On several key issues we agree with the commentators. Perhaps most importantly, everyone seems to agree that psychology has an important role to play in building better models of human vision, and (most) everyone agrees (including us) that deep neural networks (DNNs) will play an important role in modelling human vision going forward. But there are also disagreements about what models are for, how DNN–human correspondences should be evaluated, the value of alternative modelling approaches, and impact of marketing hype in the literature. In our view, these latter issues are contributing to many unjustified claims regarding DNN–human correspondences in vision and other domains of cognition. We explore all these issues in this response.

Medieval hospitals were founded to provide charity, but poverty and infirmity were broad and socially determined categories and little is known about the residents of these institutions and the pathways that led them there. Combining skeletal, isotopic and genetic data, the authors weave a collective biography of individuals buried at the Hospital of St John the Evangelist, Cambridge. By starting with the physical remains, rather than historical expectations, they demonstrate the varied life courses of those who were ultimately buried in the hospital's cemetery, illustrating the diverse faces of medieval poverty and institutional notions of charity. The findings highlight the value of collective osteobiography when reconstructing the social landscapes of the past.

Liquid immiscibility has become the preferred mode of genesis for the carbonatite rocks, which commonly, but not exclusively, accompany silicate rocks in alkaline-rock complexes. This concept has been universally based on the presumption that nephelinitic and phonolitic magmas can evolve to a stage where two conjugate immiscible liquids separate. It is assumed that these two liquids separate quickly, or even instantaneously, into discrete bodies of magma capable of being intruded or extruded with subsequent independent crystallization. Supporting evidence generally given is: alleged consanguinity as discrete occurrence of the two rock types; similarity of radiogenic isotope ratios; trace element contents similar to those predicted from experimentally derived partition coefficients. We do not accept that a general case for liquid immiscibility has been demonstrated; although we do accept that silicate and carbonate liquids are inherently immiscible, we maintain that they are not conjugate in a petrogenetic context. We have reviewed and critically examined the experimental data purporting to establish liquid immiscibility and find that when applied to natural rocks, they are based on inappropriate experimental designs, which are not relevant to the genesis of calcite or dolomite carbonatites, although they might have some relevance to Oldoinyo Lengai nyerereite–gregoryite lavas. The design of these experiments guarantees immiscibility and ensures that the carbonate liquids formed will be calcitic or sodium-rich. We dispute the validity of comparing the trace element contents of natural rocks, which in many instances do not represent liquid compositions, to experimentally determine partition coefficients. We consider that experimental design inadequacies, principally assuming but not proving, that the liquids involved are conjugate, indicate that these coefficients are merely an expression of the preference of certain elements for particular liquids, regardless of how the liquids formed. Proof of consanguinity in alkaline complexes requires more accurate age determinations on the relevant rock types than has generally been the case, and in most complexes, consanguinity can be discounted. We dispute the contention that melt inclusions represent parental melts, although they might elucidate the character of magmas undergoing fractional crystallization from magmatic to carbothermal stages. Radiogenic isotope data are shown to be too widely variable to support a case for liquid immiscibility. We address the contention that calcite cannot crystallize from a dolomitic liquid formed by direct mantle melting, and must therefore have crystallized from a calcite carbonate liquid generated by liquid immiscibility, and demonstrate that it is an unsupported hypothesis as calcite can readily crystallize from dolomitic liquids. We observe that, because immiscible dolomite liquids have never been produced experimentally, the liquid immiscibility proposition could at best be applied only to calcite carbonatites, thus leaving unexplained the large number of dolomite carbonatites and those of either type, which are not accompanied by alkaline silicate rocks. The assumed bimodality of alkaline-rock carbonatite complexes is considered to be fallacious and no actual geological or petrographic evidence for immiscibility processes is evident in these complexes. Several examples of alkaline rock carbonatite complexes for which immiscibility has been proposed are evaluated critically and shown to fail in attempts to establish them as exemplifying immiscibility. We conclude that no actual geological or experimental data exist to establish liquid immiscibility being involved in the genesis of calcite or dolomite carbonatite-forming magmas.

The Eighth World Congress of Pediatric Cardiology and Cardiac Surgery (WCPCCS) will be held in Washington DC, USA, from Saturday, 26 August, 2023 to Friday, 1 September, 2023, inclusive. The Eighth World Congress of Pediatric Cardiology and Cardiac Surgery will be the largest and most comprehensive scientific meeting dedicated to paediatric and congenital cardiac care ever held. At the time of the writing of this manuscript, The Eighth World Congress of Pediatric Cardiology and Cardiac Surgery has 5,037 registered attendees (and rising) from 117 countries, a truly diverse and international faculty of over 925 individuals from 89 countries, over 2,000 individual abstracts and poster presenters from 101 countries, and a Best Abstract Competition featuring 153 oral abstracts from 34 countries. For information about the Eighth World Congress of Pediatric Cardiology and Cardiac Surgery, please visit the following website: [www.WCPCCS2023.org]. The purpose of this manuscript is to review the activities related to global health and advocacy that will occur at the Eighth World Congress of Pediatric Cardiology and Cardiac Surgery.

Acknowledging the need for urgent change, we wanted to take the opportunity to bring a common voice to the global community and issue the Washington DC WCPCCS Call to Action on Addressing the Global Burden of Pediatric and Congenital Heart Diseases. A copy of this Washington DC WCPCCS Call to Action is provided in the Appendix of this manuscript. This Washington DC WCPCCS Call to Action is an initiative aimed at increasing awareness of the global burden, promoting the development of sustainable care systems, and improving access to high quality and equitable healthcare for children with heart disease as well as adults with congenital heart disease worldwide.

Standardized observation of bed baths and showers for 100 residents in 8 nursing homes revealed inadequate cleansing of body sites (88%–100% failure) and >90% process failure involving lather, firm massage, changing dirty wipes or cloths, and following clean-to-dirty sequence. Insufficient water warmth affected 86% of bathing opportunities. Bathing training and adequate resources are needed.

OBJECTIVES/GOALS: Glioblastomas (GBMs) are heterogeneous, treatment-resistant tumors that are driven by populations of cancer stem cells (CSCs). In this study, we perform an epigenetic-focused functional genomics screen in GBM organoids and identify WDR5 as an essential epigenetic regulator in the SOX2-enriched, therapy resistant cancer stem cell niche. METHODS/STUDY POPULATION: Despite their importance for tumor growth, few molecular mechanisms critical for CSC population maintenance have been exploited for therapeutic development. We developed a spatially resolved loss-of-function screen in GBM patient-derived organoids to identify essential epigenetic regulators in the SOX2-enriched, therapy resistant niche. Our niche-specific screens identified WDR5, an H3K4 histone methyltransferase responsible for activating specific gene expression, as indispensable for GBM CSC growth and survival. RESULTS/ANTICIPATED RESULTS: In GBM CSC models, WDR5 inhibitors blocked WRAD complex assembly and reduced H3K4 trimethylation and expression of genes involved in CSC-relevant oncogenic pathways. H3K4me3 peaks lost with WDR5 inhibitor treatment occurred disproportionally on POU transcription factor motifs, required for stem cell maintenance and including the POU5F1(OCT4)::SOX2 motif. We incorporated a SOX2/OCT4 motif driven GFP reporter system into our CSC cell models and found that WDR5 inhibitor treatment resulted in dose-dependent silencing of stem cell reporter activity. Further, WDR5 inhibitor treatment altered the stem cell state, disrupting CSC in vitro growth and self-renewal as well as in vivo tumor growth. DISCUSSION/SIGNIFICANCE: Our results unveiled the role of WDR5 in maintaining the CSC state in GBM and provide a rationale for therapeutic development of WDR5 inhibitors for GBM and other advanced cancers. This conceptual and experimental framework can be applied to many cancers, and can unmask unique microenvironmental biology and rationally designed combination therapies.

Deep neural networks (DNNs) have had extraordinary successes in classifying photographic images of objects and are often described as the best models of biological vision. This conclusion is largely based on three sets of findings: (1) DNNs are more accurate than any other model in classifying images taken from various datasets, (2) DNNs do the best job in predicting the pattern of human errors in classifying objects taken from various behavioral datasets, and (3) DNNs do the best job in predicting brain signals in response to images taken from various brain datasets (e.g., single cell responses or fMRI data). However, these behavioral and brain datasets do not test hypotheses regarding what features are contributing to good predictions and we show that the predictions may be mediated by DNNs that share little overlap with biological vision. More problematically, we show that DNNs account for almost no results from psychological research. This contradicts the common claim that DNNs are good, let alone the best, models of human object recognition. We argue that theorists interested in developing biologically plausible models of human vision need to direct their attention to explaining psychological findings. More generally, theorists need to build models that explain the results of experiments that manipulate independent variables designed to test hypotheses rather than compete on making the best predictions. We conclude by briefly summarizing various promising modeling approaches that focus on psychological data.

The study of political participation in Latin America has, until very recently, been too narrowly conceived by social scientists, focusing largely on elites and violence. The former is illustrated by studies of the military (Lieuwen, 1961, 1966; Johnson, 1964; Horowitz, 1967; Fagen and Cornelius, 1970; Schmitter, 1973), the Church (Dillon Soares, 1967; Solari, 1967; Petersen, 1970; Suchlicki, 1972), industrialists (Cardoso, 1967; Polit, 1968; Petras and Cook, 1973), and large landholders (Whetten, 1948; Carroll, 1966; Feder, 1971; Cockroft, 1972). Attention to violent forms of political participation is found in studies of revolution and the military coup d'état (Payne, 1965; Needler, 1968; Von Lazar and Kaufman, 1969; Moreno and Mitrani, 1971; Kohl and Litt, 1974). Those studies that have centered on nonviolent mass participation (Horowitz, 1970) have generally been limited to elections (for example, Martz, 1967; Petras, 1970), political parties (Fitzgibbon, 1957; Ciria, 1974), and labor unions (Payne, 1965; Angell, 1972; Erickson et al., 1974). As a result of the narrowness of these approaches, we have only a partial image of the faces of the Latin American citizen political activity; we have underestimated the scope of such activity and have failed to investigate its many forms.

Despite certain early efforts to interpret Mexico as a pluralist constitutional democracy, or democracy-in-the-making (Scott 1959; Tucker 1957), scholars today almost universally agree that the political system of Mexico is authoritarian. The trappings of Mexico's liberal constitution and elections notwithstanding, Mexico's Partido Revolucionario Institucional (PRI) serves to integrate the polity under the highly centralized control of a single institution that dominates access to all public office. At the apex of the PRI is the Mexican president, who not only chooses his own successor but controls access to the PRI's candidate lists for all other public offices and therefore dominates both the party and the congress. In sum, as Coleman and Davis argue, Mexico fits the ideal type of authoritarian political organization because “decisions are made almost exclusively by the ruling elite rather than by democratic, pluralist processes” and because “there are severe restrictions placed upon political mobilization” (1976, 195).

Cerebrospinal fluid shunt–associated surgical site infection surveillance for 3 months compared to 12 months after surgery captures 83% of cases with no significant differences in patient characteristics, surgery types, or pathogens. A shorter 3-month follow-up can reduce resource use and allow for more timely reporting of healthcare-associated infection rates for hospitals.