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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.
The cardiovascular adaptations associated with structured exercise training in Fontan patients remain unknown. We hypothesised that short-term training causes cardiac remodelling and parallel improvement in maximal exercise capacity (VO2 max) in these patients.
Methods and Results:
Five patients, median age 19.5 (17.6–21.3) years, with a history of Fontan operation meeting inclusion/exclusion criteria, participated in a 3-month training programme designed to improve endurance. Magnetic resonance images for assessment of cardiac function, fibrosis, cardiac output, and liver elastography to assess stiffness were obtained at baseline and after training. Maximal exercise capacity (VO2 max) and cardiac output Qc (effective pulmonary blood flow) at rest and during exercise were measured (C2H2 rebreathing) at the same interval. VO2 max increased from median (IQR) 27.2 (26–28.7) to 29.6 (28.5–32.2) ml/min/kg (p = 0.04). There was an improvement in cardiac output (Qc) during maximal exercise testing from median (IQR) 10.3 (10.1–12.3) to 12.3 (10.9–14.9) l/min, but this change was variable (p = 0.14). Improvement in VO2 max correlated with an increase in ventricular mass (r = 0.95, p = 0.01), and improvement in Quality-of-life inventory (PedsQL) Cardiac scale scores for patient-reported symptoms (r = 0.90, p = 0.03) and cognitive problems (r = 0.89, p = 0.04). The correlation between VO2 max and Qc showed a positive trend but was not significant (r = 0.8, p = 0.08). No adverse cardiac or liver adaptations were noted.
Short-term training improved exercise capacity in this Fontan pilot without any adverse cardiac or liver adaptations. These results warrant further study in a larger population and over a longer duration of time.
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.
This work describes the mineralogy of dolomite carbonatite occurring at the Newania carbonatite complex, Rajasthan, north-western India. The mineralogy records the textural and compositional features of magmatic and post-magmatic stages of carbonatite evolution. Ferroan dolomite is the principal constituent and displays variable degrees of deformation, ranging from brittle-to-ductile deformation regimes. Apatite exhibits textural and compositional evolutionary trends from early-to-late stages of carbonatite evolution. Two varieties of amphibole are reported for the first time from this complex, ferri-winchite and cummingtonite; the former is magmatic and the latter is metamorphic in origin. The columbite–tantalite-series minerals are columbite-(Fe), and their paragenesis evolves from composite grains with pyrochlore to individual crystals. Pyrochlore is magmatic with U–Ta–Ti-rich compositions and shows evolution from calciopyrochlore to kenopyrochlore, followed by alteration during late-stages of carbonatite evolution. Monazite and baryte constitute the post-magmatic mineral assemblage; the former is hydrothermal and crystallised after precursor apatite, whereas the latter is associated exclusively with columbite–pyrochlore composites. On the basis of the mineralogy of the carbonatite, it is concluded that the parent magma was generated by low-degree partial melting of magnesite–phlogopite-bearing peridotite.
Socioeconomic disadvantage is a major correlate of low political participation. This association is among the most robust findings in political science. However, it is based largely on observational data. The causal effects of early-life disadvantage in particular are even less understood, because long-term data on the political consequences of randomized early-life anti-poverty interventions is nearly nonexistent. We leverage the Moving to Opportunity (MTO) experiment to test the long-term effect of moving out of disadvantaged neighborhoods—and thus out of deep poverty—on turnout. MTO is one of the most ambitious anti-poverty experiments ever implemented in the United States. Although MTO ameliorated children’s poverty long term, we find that, contrary to expectations, the intervention did not increase children’s likelihood of voting later in life. Additional tests show the program did not ameliorate their poverty enough to affect turnout. These findings speak to the complex relationship between neighborhood disadvantage and low political participation.
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.
Background: Our aim was to develop a National Quality Indicators Set for the Care of Adults Hospitalized for Neurological Problems, to serve as a foundation to build regional or national quality initiatives in Canadian neurology centres. Methods: We used a national eDelphi process to develop a suite of quality indicators and a parallel process of surveys and patient focus groups to identify patient priorities. Canadian content and methodology experts were invited to participate. To be included, >70% of participants had to rate items as critical and <15% had to rate it as not important. Two rounds of surveys and consensus meetings were used identify and rank indicators, followed by national consultation with members of the Canadian Neurological Society. Results: 38 neurologists and methodologists and 56 patients/caregivers participated in this project. An initial list of 91 possible quality indicators was narrowed to 40 indicators across multiple categories of neurological conditions. 21 patient priorities were identified. Conclusions: This quality indicators suite can be used regionally or nationally to drive improvement initiatives for inpatient neurology care. In addition, we identified multiple opportunities for further research where evidence was lacking or patient and provider priorities did not align.
The aim of this study was to determine if the protozoa that cause dysentery might have been present in Jerusalem, the capital of the Kingdom of Judah, during the Iron Age. Sediments from 2 latrines pertaining to this time period were obtained, 1 dating from the 7th century BCE and another from the 7th to early 6th century BCE. Microscopic investigations have previously shown that the users were infected by whipworm (Trichuris trichiura), roundworm (Ascaris lumbricoides), Taenia sp. tapeworm and pinworm (Enterobius vermicularis). However, the protozoa that cause dysentery are fragile and do not survive well in ancient samples in a form recognizable using light microscopy. Enzyme-linked immunosorbent assay kits designed to detect the antigens of Entamoeba histolytica, Cryptosporidium sp. and Giardia duodenalis were used. Results for Entamoeba and Cryptosporidium were negative, while Giardia was positive for both latrine sediments when the analysis was repeated three times. This provides our first microbiological evidence for infective diarrhoeal illnesses that would have affected the populations of the ancient near east. When we integrate descriptions from 2nd and 1st millennium BCE Mesopotamian medical texts, it seems likely that outbreaks of dysentery due to giardiasis may have caused ill health throughout early towns across the region.
Perinatal substance abuse (PSA) is associated with increased risk of prematurity, low birth weight, neonatal abstinence syndrome, behavioral issues and learning difficulties. It is imperative that robust care pathways are in place for these high-risk pregnancies and that staff and patient education are optimized. The present study explores the knowledge and attitudes of healthcare professionals toward PSA to identify knowledge gaps to enhance care and reduce stigma.
This is a cross-sectional study using questionnaires to survey healthcare professionals (HCPs) working in a tertiary maternity unit (n = 172).
The majority of HCPs were not confident in the antenatal management (75.6%, n = 130) or postnatal management (67.5%, n = 116) of PSA. More than half of HCPs surveyed (53.5%, n = 92) did not know the referral pathway and 32% (n = 55) did not know when to make a TUSLA referral. The vast majority (96.5%, n = 166) felt that they would benefit from further training, and 94.8% (n = 163) agreed or strongly agreed that the unit would benefit from a drug liaison midwife. Among study participants, 54.1% (n = 93) agreed or strongly agreed that PSA should be considered a form of child abuse and 58.7% (n = 101) believe that the mother is responsible for damage done to her child.
Our study highlights the urgent need for increased training on PSA to enhance care and reduce stigma. It is imperative that staff training, drug liaison midwives and dedicated clinics are introduced to hospitals as a matter of high priority.
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.
Underrepresented researchers face more challenges than their well-represented counterparts. Perseverance and consistency of interest are associated with career success in well-represented physicians. Therefore, we examined associations of perseverance and consistency of interest with Clinical Research Appraisal Inventory (CRAI), science identity, and other factors related to career success among underrepresented post-doctoral fellows and early-career faculty.
This is a cross-sectional analysis of data collected from September to October 2020 among 224 underrepresented early-career researchers at 25 academic medical centers in the Building Up Trial. We used linear regression to test associations of perseverance and consistency of interest scores with CRAI, science identity, and effort/reward imbalance (ERI) scores.
The cohort is 80% female, 33% non-Hispanic Black, and 34% Hispanic. The median perseverance and consistency of interest scores were 3.8 (25th–75th percentile: 3.7,4.2) and 3.7 (25th–75th percentile: 3.2, 4.0), respectively. Higher perseverance was associated with a higher CRAI score (β = 0.82; 95% CI = 0.30, 1.33, p = 0.002) and science identity (β = 0.44; 95% CI = 0.19, 0.68, p = 0.001). Higher consistency of interest was associated with a higher CRAI score (β = 0.60; 95% CI = 0.23, 0.96, p = 0.001) and higher science identity score (β = 0.20; 95% CI = 0.03, 0.36, p = 0.02), while lower consistency of interest was associated with imbalance favoring effort (β = –0.22; 95% CI = –0.33, –0.11, p = 0.001).
We found that perseverance and consistency of interest are related to CRAI and science identity, indicating that these factors may positively influence one’s decision to stay in research.
In this book we explore how different kinds of parasites affected the key civilizations that flourished across the world over the last 10,000 years. Ancient parasites can be recovered from mummies, skeletons, latrines, coprolites, and chamber pots. Analysis may involve microscopy, ELISA, proteomics, and recovery of DNA. A huge range of parasites can infect humans, ranging from helminths (worms), single-celled protozoa such as malaria and dysentery, and ectoparasites such as lice and fleas. Different parasites will have varying impact upon health depending upon the proportion of a society affected and the physiological consequences of infection upon the body. Here the concept of Disabilit-Adjusted Life Years (DALYs) is employed to estimate the health impact of parasites in past societies, and compare them. This should allow us for the first time to propose which past civilizations may have experienced the greatest health burden from the parasites affecting their populations.
In ancient China, Japan, and Korea it is clear that roundworm and whipworm were the most common parasites present. Where data are available to estimate how common these parasites were, they suggest that more than half of the population were infected. Flukes spread by eating raw fish and crustaceans were a significant health risk, but less than half of individuals appear to have been affected. These include Chinese liver fluke, Fasciolopsis, Gymnophalloides, Metagonimus, and Paragonimus. The range of species of flukes present seem to have been higher in Korea and Japan than China, which may reflect the range of species endemic there, or the range of foods traditionally eaten raw in each culture. Oriental schistosomiasis is contracted by wading in still freshwater, so farmers growing rice in paddy fields were at particular risk. Major trade routes such as the Silk Road have been shown to act as conduits for the spread of intestinal parasites across East Asia.
The most widespread evidence for parasite infection in medieval Europe is for species spread by poor sanitation, such as whipworm, roundworm, and the protozoa Entamoeba histolytica and Giardia duodenalis, likely related to the common use of human faeces as a crop fertilizer. The prevalence of infection by intestinal helminths has been shown to be at least a quarter to a third of the medieval population, with a broad north–south divide in the dominant types of parasite. While species spread by poor sanitation were present throughout the continent, in northern Europe where eating raw, smoked, dried, or pickled fish was common, fish tapeworm resulted. The use of dogs by farmers put them at risk of infection by Echinococcus granulosus as shown by calcified hydatid cysts. Human fleas and body lice helped spread the Black Death pandemic from the fourteenth century onwards. Medical practitioners thought intestinal worms were formed due to an excess of phlegm (one of the four bodily humours), while ectoparasites were formed due to putrefying humours, sweat, and grime. Delousing combs were widely used to remove head lice, while the wealthy in Italy applied mercury ointments to their hair.
A broad range of parasites were present in ancient Egypt and Nubia, with 15 different species, including ectoparasites, helminths, and protozoa. Some are spread directly from one person to another (such as pinworm and head lice), some pass through animals as part of their life cycle (such as Taenia tapeworms, fish tapeworm, and trichinella), while others require biting insect vectors to spread them (such as malaria, leishmaniasis, and filariasis). Around 40% of ancient Nubians had head lice, 10% of Nubians were infected by visceral leishmaniasis, 22% of Egyptian mummies were positive for malaria, and 17% were positive for schistosomiasis. As malaria and schistosomiasis cause chronic anaemia and fatigue during physical work, they must have been responsible for a considerable drain upon the capabilities of the workforce in these civilizations along the Nile.
When we consider intestinal parasites, early societies to the east of the Andes were mainly infected by hookworm, whipworm, and to a lesser degree roundworm, thorny-headed worm, and Echinostoma. In contrast, to the west of the Andes fish tapeworm and pinworm were the dominant intestinal parasites, with lower levels of hookworm, dwarf tapeworm, and roundworm. This variation between cultures on either side of the Andes may indicate different approaches to sanitation, as well as the contrasting climate with high rainfall in the east and arid climate to the west. Head lice were found in 60–80% of mummies from Pacific coast societies such as the Chinchorro. Chagas’ disease, spread by the bite of bed bugs, affected 40–50% of Pacific coast civilizations including the Chiribaya and Inca. This causes a slow death from heart failure and intestinal failure. Mucocutaneous leishmaniasis spread by sandfly bites was also endemic in civilizations along the Pacific coast, causing ulcerating destruction of the face.