Objective
To systematically review evidence for the association between trauma experienced in childhood or adolescence, and the subsequent experience of affective or psychotic mental disorders in ...adulthood.
Methods
Electronic databases (Scopus, Medline (for Ovid), EMBASE and PsychINFO) were searched for peer‐reviewed, longitudinal cohort studies in the English language examining child or adolescent exposure to trauma, and adult‐diagnosed depression, anxiety, psychotic disorder or bipolar disorder. A total of 23 manuscripts were retained.
Results
Results revealed a significant association between the following childhood exposures and adult mental disorder: bullying (victimhood, perpetration and frequency); emotional abuse; physical neglect; parental loss; and general maltreatment (unspecified and/or multiple trauma exposure). There was some evidence of a dose‐response relationship with those exposed to multiple forms of maltreatment having more than three times the odds of developing a mental disorder (Odds ratio = 3.11, 95% CI = 1.36–7.14). There was no significant association found between physical or sexual abuse and adult mental disorder; however, this is likely an artefact of how these adversities were assessed.
Conclusion
There is strong evidence of an association between childhood trauma and later mental illness. This association is particularly evident for exposure to bullying, emotional abuse, maltreatment and parental loss. The evidence suggests that childhood and adolescence are an important time for risk for later mental illness, and an important period in which to focus intervention strategies.
The main protease, M
(or 3CL
) in SARS-CoV-2 is a viable drug target because of its essential role in the cleavage of the virus polypeptide. Feline infectious peritonitis, a fatal coronavirus ...infection in cats, was successfully treated previously with a prodrug GC376, a dipeptide-based protease inhibitor. Here, we show the prodrug and its parent GC373, are effective inhibitors of the M
from both SARS-CoV and SARS-CoV-2 with IC
values in the nanomolar range. Crystal structures of SARS-CoV-2 M
with these inhibitors have a covalent modification of the nucleophilic Cys145. NMR analysis reveals that inhibition proceeds via reversible formation of a hemithioacetal. GC373 and GC376 are potent inhibitors of SARS-CoV-2 replication in cell culture. They are strong drug candidates for the treatment of human coronavirus infections because they have already been successful in animals. The work here lays the framework for their use in human trials for the treatment of COVID-19.
The evolution of misbelief McKay, Ryan T; Dennett, Daniel C
Behavioral and brain sciences,
12/2009, Volume:
32, Issue:
6
Journal Article
Peer reviewed
Open access
From an evolutionary standpoint, a default presumption is that true beliefs are adaptive and misbeliefs maladaptive. But if humans are biologically engineered to appraise the world accurately and to ...form true beliefs, how are we to explain the routine exceptions to this rule? How can we account for mistaken beliefs, bizarre delusions, and instances of self-deception? We explore this question in some detail. We begin by articulating a distinction between two general types of misbelief: those resulting from a breakdown in the normal functioning of the belief formation system (e.g., delusions) and those arising in the normal course of that system's operations (e.g., beliefs based on incomplete or inaccurate information). The former are instances of biological dysfunction or pathology, reflecting "culpable" limitations of evolutionary design. Although the latter category includes undesirable (but tolerable) by-products of "forgivably" limited design, our quarry is a contentious subclass of this category: misbeliefs best conceived as design features. Such misbeliefs, unlike occasional lucky falsehoods, would have been systematically adaptive in the evolutionary past. Such misbeliefs, furthermore, would not be reducible to judicious - but doxastically noncommittal - action policies. Finally, such misbeliefs would have been adaptive in themselves, constituting more than mere by-products of adaptively biased misbelief-producing systems. We explore a range of potential candidates for evolved misbelief, and conclude that, of those surveyed, only positive illusions meet our criteria.
Over the past two decades, nuclear magnetic resonance (NMR) has emerged as one of the three principal analytical techniques used in metabolomics (the other two being gas chromatography coupled to ...mass spectrometry (GC-MS) and liquid chromatography coupled with single-stage mass spectrometry (LC-MS)). The relative ease of sample preparation, the ability to quantify metabolite levels, the high level of experimental reproducibility, and the inherently nondestructive nature of NMR spectroscopy have made it the preferred platform for long-term or large-scale clinical metabolomic studies. These advantages, however, are often outweighed by the fact that most other analytical techniques, including both LC-MS and GC-MS, are inherently more sensitive than NMR, with lower limits of detection typically being 10 to 100 times better. This review is intended to introduce readers to the field of NMR-based metabolomics and to highlight both the advantages and disadvantages of NMR spectroscopy for metabolomic studies. It will also explore some of the unique strengths of NMR-based metabolomics, particularly with regard to isotope selection/detection, mixture deconvolution via 2D spectroscopy, automation, and the ability to noninvasively analyze native tissue specimens. Finally, this review will highlight a number of emerging NMR techniques and technologies that are being used to strengthen its utility and overcome its inherent limitations in metabolomic applications.
Urban parks play a crucial role in conserving the biophysical environment, yet conservation efforts mostly focus on biodiversity hotspots, iconic mammal species, and nature conservation areas. A ...challenge in enhancing the role of urban parks in conservation relates to the varied, and often conflicted, priorities of communities and city authorities in the engagement process. Using a qualitative research approach through in-depth interviews with community leaders, councilors, community-based organizations, and youth organizations, this study explores stakeholder engagement in the planning and management of Mofolo Park in Soweto, Johannesburg. Results indicate that although the City of Johannesburg wanted to add food gardens to the park, the community was not united in support of this. Rather, the community wanted better safety, security and ablutions in the park, in contrast to the City of Johannesburg officials. Community members also expressed concerns about water pollution, sewerage spills, security and vandalism within the park, noting this inhibited their full enjoyment of the park. The study also revealed that women's voices were mostly silenced during community discussions. The facilitator, who represented the City of Johannesburg, a few extroverted, vocal people and men dominated the discourse. This study concludes that although community engagement through stakeholder dialogues can, and should, play a crucial role in managing urban parks, the priorities and voices of the various stakeholders need to be carefully considered if the park is to be sustainably managed and fit for purpose as an urban green recreational space for local communities.
The drive to ensure regular and reliable access to domestic water supplies is a major challenge for governments across sub-Saharan Africa. This study investigated the rural water systems in ...North-West Cameroon across rural districts using the lenses of Cultural Theory and Systems Thinking Analysis (STA). Different social groups were classified using Cultural Theory to assist in appreciating and presenting solutions to preventing water resources becoming degraded and ensure water supplies are maintained. STA focuses on causal feedback principles and therefore, was used to evaluate relationships between the stakeholders and systems. Thereby allowing the development of a suggested policy intervention mechanism for sustainable community-based Water Management (CBWM) in the region under study. Findings revealed that in Cameroon, the provisioning of domestic water to rural residents faces significant hurdles. This is due, in part, to the centralisation of governance, where the national government determines how water resources are managed throughout the country. This is despite the promulgation of laws that support the decentralisation of decision-making. It was found that CBWM systems prevailed due to the enormous contributions of local inhabitants, extended community networks and the diaspora. However, CBWM serve to reinforce the status and situational power of local elites, government officials and, to a lesser degree, men. Therefore, a concerted effort to implement a more democratic and transparent politico-cultural mechanism to manage water resources could serve both to resolve water management conflicts and develop suitable policy intervention mechanisms for sustainable CBWM.
Reducing the scatter between cluster mass and optical richness is a key goal for cluster cosmology from photometric catalogs. We consider various modifications to the red-sequence-matched filter ...richness estimator of Rozo et al. implemented on the maxBCG cluster catalog and evaluate the impact of these changes on the scatter in X-ray luminosity (L sub(X)) at fixed richness, using L sub(X) from the ROSAT All-Sky Catalog as the best mass proxy available for the large area required. Most significantly, we find that deeper luminosity cuts can reduce the recovered scatter, finding that sigma sub(lnLX|lambda) = 0.63+ or -0.02 for clusters with M sub(500c) > ~ 1.6 x 10 super(14) h sub(70) super(-1) M sub(middot in circle). The corresponding scatter in mass at fixed richness is sigma sub(ln M|lambda) approx = 0.2-0.3 depending on the richness, comparable to that for total X-ray luminosity. We find that including blue galaxies in the richness estimate increases the scatter, as does weighting galaxies by their optical luminosity. We further demonstrate that our richness estimator is very robust. Specifically, the filter employed when estimating richness can be calibrated directly from the data, without requiring a priori calibrations of the red sequence. We also demonstrate that the recovered richness is robust to up to 50% uncertainties in the galaxy background, as well as to the choice of photometric filter employed, so long as the filters span the 4000 A break of red-sequence galaxies. Consequently, our richness estimator can be used to compare richness estimates of different clusters, even if they do not share the same photometric data. Appendix A includes "easy-bake" instructions for implementing our optimal richness estimator, and we are releasing an implementation of the code that works with Sloan Digital Sky Survey data, as well as an augmented maxBCG catalog with the lambda richness measured for each cluster.
Studying disease models at the molecular level is vital for drug development in order to improve treatment and prevent a wide range of human pathologies. Microbial infections are still a major ...challenge because pathogens rapidly and continually evolve developing drug resistance. Cancer cells also change genetically, and current therapeutic techniques may be (or may become) ineffective in many cases. The pathology of many neurological diseases remains an enigma, and the exact etiology and underlying mechanisms are still largely unknown. Viral infections spread and develop much more quickly than does the corresponding research needed to prevent and combat these infections; the present and most relevant outbreak of SARS-CoV-2, which originated in Wuhan, China, illustrates the critical and immediate need to improve drug design and development techniques. Modern day drug discovery is a time-consuming, expensive process. Each new drug takes in excess of 10 years to develop and costs on average more than a billion US dollars. This demonstrates the need of a complete redesign or novel strategies. Nuclear Magnetic Resonance (NMR) has played a critical role in drug discovery ever since its introduction several decades ago. In just three decades, NMR has become a "gold standard" platform technology in medical and pharmacology studies. In this review, we present the major applications of NMR spectroscopy in medical drug discovery and development. The basic concepts, theories, and applications of the most commonly used NMR techniques are presented. We also summarize the advantages and limitations of the primary NMR methods in drug development.
Lecture is prominent, but practices vary
A large body of evidence demonstrates that strategies that promote student interactions and cognitively engage students with content (
1
) lead to gains in ...learning and attitudinal outcomes for students in science, technology, engineering, and mathematics (STEM) courses (
1
,
2
). Many educational and governmental bodies have called for and supported adoption of these student-centered strategies throughout the undergraduate STEM curriculum. But to the extent that we have pictures of the STEM undergraduate instructional landscape, it has mostly been provided through self-report surveys of faculty members, within a particular STEM discipline e.g., (
3
–
6
). Such surveys are prone to reliability threats and can underestimate the complexity of classroom environments, and few are implemented nationally to provide valid and reliable data (
7
). Reflecting the limited state of these data, a report from the U.S. National Academies of Sciences, Engineering, and Medicine called for improved data collection to understand the use of evidence-based instructional practices (
8
). We report here a major step toward a characterization of STEM teaching practices in North American universities based on classroom observations from over 2000 classes taught by more than 500 STEM faculty members across 25 institutions.
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