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This article explores the connection between the ecclesiology and the beliefs on church-state relations of Baptists in the mid-twentieth-century United States. The author analyzes white Baptists’ reactions to the US Supreme Court rulings in Everson v. Board of Education (1947) and McCollum v. Board of Education (1948), both of which inaugurated the modern era of strict separationist Establishment Clause jurisprudence. The author also traces the development of Baptist beliefs on how the institutional church relates to individual salvation—beliefs that distinguished Baptists from both Catholics and most other Protestants—and statements from US Baptist leadership supporting church-state separation. The author demonstrates that Baptists’ beliefs on the internal, individualistic, and non-sacramental nature of salvation induced them to see any government-sponsored religious activity as likely corrupting of a person’s genuine choice of salvation. Furthermore, Baptists’ origins as a persecuted minority in Europe and the United States reinforced their idea that government-sponsored religion would lead to the suppression of true Christianity. For both reasons, then, state-sponsored religion was not God’s design. Beginning with Everson and McCollum and continuing with later cases through the 1960s, Baptist’s strict separationism became the binding interpretation of the First Amendment’s Establishment Clause through Justice Hugo Black, who authored both the Everson and McCollum majority opinions. Although no longer a Baptist when the rulings were issued, Black retained his Baptist influence on church-state issues and enshrined strict separationism into American case law for decades, leading to a Baptist triumph that many Baptists themselves would later regret and attempt to reverse.

Sexual education and its relationship to issues of morality, religion, contraception, abortion, and eugenics have generated controversy in the United States for the last two centuries. During the Progressive Era (roughly late 1880s-early 1920s) and the Reagan Era (roughly late 1970s-early 1990s) this controversy garnered more national spotlight as the tone became more urgent for the same reason: epidemics of incurable sexually transmitted diseases (STDs). Syphilis and gonorrhea forced Progressive-Era Americans—as AIDS, herpes, and teenage pregnancy forced Reagan-Era Americans—to fervently search for cures as the numbers of those dead, diseased, and disadvantaged grew rapidly. This thesis explores the common division of opinion that occurred in both eras between those who sought a moral solution to the epidemics (moralists) and those who promoted a medical solution (hygienists). Moralists desired a national revival of Christian sexual ethics and believed that to expect anything less constituted a tacit approval of immorality. Hygienists saw such revivalist visions as naïve and sought to develop medical treatments for STDs and to educate the public on the best ways of avoiding infection even if sexually active. This division only sharpened as both camps formed public activist groups, as more issues of sexuality inevitably became involved in the debates, and as the issue of educating the nation’s children became a point of extra contention. Throughout it all, religious rhetoric (and opposition to it) characterized much of the public debate, as religious and irreligious people stood on both sides of the conflict.

Brain activation in response to spoken motor commands can be detected by electroencephalography (EEG) in clinically unresponsive patients. The prevalence and prognostic importance of a dissociation between commanded motor behavior and brain activation in the first few days after brain injury are not well understood. We studied a prospective, consecutive series of patients in a single intensive care unit who had acute brain injury from a variety of causes and who were unresponsive to spoken commands, including some patients with the ability to localize painful stimuli or to fixate on or track visual stimuli. Machine learning was applied to EEG recordings to detect brain activation in response to commands that patients move their hands. The functional outcome at 12 months was determined with the Glasgow Outcome Scale-Extended (GOS-E; levels range from 1 to 8, with higher levels indicating better outcomes). A total of 16 of 104 unresponsive patients (15%) had brain activation detected by EEG at a median of 4 days after injury. The condition in 8 of these 16 patients (50%) and in 23 of 88 patients (26%) without brain activation improved such that they were able to follow commands before discharge. At 12 months, 7 of 16 patients (44%) with brain activation and 12 of 84 patients (14%) without brain activation had a GOS-E level of 4 or higher, denoting the ability to function independently for 8 hours (odds ratio, 4.6; 95% confidence interval, 1.2 to 17.1). A dissociation between the absence of behavioral responses to motor commands and the evidence of brain activation in response to these commands in EEG recordings was found in 15% of patients in a consecutive series of patients with acute brain injury. (Supported by the Dana Foundation and the James S. McDonnell Foundation.).

The structure and composition of bacterial communities can compromise antibiotic efficacy. For example, the secretion of β-lactamase by individual bacteria provides passive resistance for all residents within a polymicrobial environment. Here, we uncover that collective resistance can also develop via intracellular antibiotic deactivation. Real-time luminescence measurements and single-cell analysis demonstrate that the opportunistic human pathogen Streptococcus pneumoniae grows in medium supplemented with chloramphenicol (Cm) when resistant bacteria expressing Cm acetyltransferase (CAT) are present. We show that CAT processes Cm intracellularly but not extracellularly. In a mouse pneumonia model, more susceptible pneumococci survive Cm treatment when coinfected with a CAT-expressing strain. Mathematical modeling predicts that stable coexistence is only possible when antibiotic resistance comes at a fitness cost. Strikingly, CAT-expressing pneumococci in mouse lungs were outcompeted by susceptible cells even during Cm treatment. Our results highlight the importance of the microbial context during infectious disease as a potential complicating factor to antibiotic therapy.

Measures aimed at conservation or restoration of ecosystems are often seen as net‐cost projects by governments and businesses because they are based on incomplete and often faulty cost‐benefit analyses. After screening over 200 studies, we examined the costs (94 studies) and benefits (225 studies) of ecosystem restoration projects that had sufficient reliable data in 9 different biomes ranging from coral reefs to tropical forests. Costs included capital investment and maintenance of the restoration project, and benefits were based on the monetary value of the total bundle of ecosystem services provided by the restored ecosystem. Assuming restoration is always imperfect and benefits attain only 75% of the maximum value of the reference systems over 20 years, we calculated the net present value at the social discount rates of 2% and 8%. We also conducted 2 threshold cum sensitivity analyses. Benefit‐cost ratios ranged from about 0.05:1 (coral reefs and coastal systems, worst‐case scenario) to as much as 35:1 (grasslands, best‐case scenario). Our results provide only partial estimates of benefits at one point in time and reflect the lower limit of the welfare benefits of ecosystem restoration because both scarcity of and demand for ecosystem services is increasing and new benefits of natural ecosystems and biological diversity are being discovered. Nonetheless, when accounting for even the incomplete range of known benefits through the use of static estimates that fail to capture rising values, the majority of the restoration projects we analyzed provided net benefits and should be considered not only as profitable but also as high‐yielding investments. Beneficios de Invertir en la Restauración de Ecosistemas

BACKGROUND: The benefit of intradiscal glucocorticoid injection (IGI) for discogenic low back pain (LBP) remains controversial. OBJECTIVES: The objective of this study was to systematically assess and meta-analyze the efficacy of IGI compared with these control groups. STUDY DESIGN: Systematic review and meta-analysis. METHODS: A comprehensive literature search was performed screening PubMed and Embase through May 2022. Only randomized controlled trials (RCTs) comparing IGI to control groups in adult patients with discogenic lumbar back pain were included. A random effects model was used to pool mean differences of pain intensity (visual analaog scale [VAS] 0-100), and physical function assessed with the Oswestry Disability Index (ODI). Subgroup analyses were stratified by Modic magnetic resonance imaging findings. RESULTS: Seven studies met inclusion criteria with a total of 626 patients. The short-term (< 3 months) follow-up showed a significant pooled mean difference in both pain intensity (-20.1; 95% CI, -25.5 to -14.7) and physical function (-9.9; 95% CI, -16.1 to -3.6). In the intermediate -term follow-up (3 to < 6 months), only physical function remained significantly better in the glucocorticoid group (-13.1; 95% CI, -22.3 to -3.9). There was no clinically meaningful or significant difference in pain scores and physical function at the long-term (>= 6 months) follow-up. A subgroup analysis did not demonstrate an effect of Modic (type I) changes on the efficacy of IGI. LIMITATIONS: A limited number of studies was available and consequently publication bias could not be evaluated using a funnel plot. Statistical heterogeneity was detected among the included studies. CONCLUSION: We conclude that IGI reduces discogenic LBP intensity and improves physical function effectively at short-term follow-up, and continues to improve physical function at intermediate-term. However, 6 months posttreatment, outcomes are similar in comparison to the control groups. The type of Modic change does not appear to be related with the response to IGI. KEY WORDS: Low back pain, lumbar back pain, intradiscal glucocorticoid injection, modic changes, meta-analysis

FOXA pioneer transcription factors (TFs) associate with primed enhancers in endodermal organ precursors. Using a human stem cell model of pancreas differentiation, we here discover that only a subset of pancreatic enhancers is FOXA-primed, whereas the majority is unprimed and engages FOXA upon lineage induction. Primed enhancers are enriched for signal-dependent TF motifs and harbor abundant and strong FOXA motifs. Unprimed enhancers harbor fewer, more degenerate FOXA motifs, and FOXA recruitment to unprimed but not primed enhancers requires pancreatic TFs. Strengthening FOXA motifs at an unprimed enhancer near NKX6.1 renders FOXA recruitment pancreatic TF-independent, induces priming, and broadens the NKX6.1 expression domain. We make analogous observations about FOXA binding during hepatic and lung development. Our findings suggest a dual role for FOXA in endodermal organ development: first, FOXA facilitates signal-dependent lineage initiation via enhancer priming, and second, FOXA enforces organ cell type-specific gene expression via indirect recruitment by lineage-specific TFs. Enhancers for endodermal organs are primed at the chromatin level prior to lineage induction by FOXA pioneer transcription factors; how pervasive this is, is not well known. Here the authors show that only a small subset of organ-specific enhancers are bound and primed by FOXA prior to lineage induction, whereas the majority do not undergo chromatin priming and engage FOXA upon lineage induction.

Single-nucleus assay for transposase-accessible chromatin using sequencing (snATAC-seq) creates new opportunities to dissect cell type–specific mechanisms of complex diseases. Since pancreatic islets are central to type 2 diabetes (T2D), we profiled 15,298 islet cells by using combinatorial barcoding snATAC-seq and identified 12 clusters, including multiple alpha, beta and delta cell states. We cataloged 228,873 accessible chromatin sites and identified transcription factors underlying lineage- and state-specific regulation. We observed state-specific enrichment of fasting glucose and T2D genome-wide association studies for beta cells and enrichment for other endocrine cell types. At T2D signals localized to islet-accessible chromatin, we prioritized variants with predicted regulatory function and co-accessibility with target genes. A causal T2D variant rs231361 at the KCNQ1 locus had predicted effects on a beta cell enhancer co-accessible with INS and genome editing in embryonic stem cell–derived beta cells affected INS levels. Together our findings demonstrate the power of single-cell epigenomics for interpreting complex disease genetics. Single-cell ATAC-seq analysis of human pancreatic islet cells identifies different cell clusters and transcription factors that underlie lineage- and state-specific regulation and helps prioritize type 2 diabetes risk variants.

Extreme phenotype sequencing has led to the identification of high-impact rare genetic variants for many complex disorders but has not been applied to studies of severe schizophrenia. We sequenced 112 individuals with severe, extremely treatment-resistant schizophrenia, 218 individuals with typical schizophrenia, and 4,929 controls. We compared the burden of rare, damaging missense and loss-of-function variants between severe, extremely treatment-resistant schizophrenia, typical schizophrenia, and controls across mutation intolerant genes. Individuals with severe, extremely treatment-resistant schizophrenia had a high burden of rare loss-of-function (odds ratio, 1.91; 95% CI, 1.39 to 2.63; P = 7.8 × 10−5) and damaging missense variants in intolerant genes (odds ratio, 2.90; 95% CI, 2.02 to 4.15; P = 3.2 × 10−9). A total of 48.2% of individuals with severe, extremely treatment-resistant schizophrenia carried at least one rare, damaging missense or loss-of-function variant in intolerant genes compared to 29.8% of typical schizophrenia individuals (odds ratio, 2.18; 95% CI, 1.33 to 3.60; P = 1.6 × 10−3) and 25.4% of controls (odds ratio, 2.74; 95% CI, 1.85 to 4.06; P = 2.9 × 10−7). Restricting to genes previously associated with schizophrenia risk strengthened the enrichment with 8.9% of individuals with severe, extremely treatment-resistant schizophrenia carrying a damaging missense or loss-of-function variant compared to 2.3% of typical schizophrenia (odds ratio, 5.48; 95% CI, 1.52 to 19.74; P = 0.02) and 1.6% of controls (odds ratio, 5.82; 95% CI, 3.00 to 11.28; P = 2.6 × 10−8). These results demonstrate the power of extreme phenotype case selection in psychiatric genetics and an approach to augment schizophrenia gene discovery efforts.

Coxiella burnetii, the causative bacterium of the zoonotic disease Q fever, has been documented in many different species. We describe documented turtles that were PCR positive for C. burnetii from multiple locations in Illinois and Wisconsin, USA. Assessing the conservation implications, reservoir potential, and zoonotic risk requires further research.