Miracle-dz/UniFAR-FTUs huggingface dataset:
Testing for genetic trade-offs between early- and late-life reproduction in a wild red deer population

The antagonistic pleiotropy (AP) theory of ageing predicts genetically based trade-offs between investment in reproduction in early life and survival and performance in later life. Laboratory-based research has shown that such genetic trade-offs exist, but little is currently known about their prevalence in natural populations. We used random regression ‘animal model’ techniques to test the genetic basis of trade-offs between early-life fecundity (ELF) and maternal performance in late life in a wild population of red deer (Cervus elaphus) on the Isle of Rum, Scotland. Significant genetic variation for both ageing rates in a key maternal performance measure (offspring birth weight) and ELF was present in this population. We found some evidence for a negative genetic covariance between the rate of ageing in offspring birth weight and ELF, and also for a negative environmental covariance. Our results suggest rare support for the AP theory of ageing from a wild population.
Predictors of the Discharge Dosage of an Atypical Antipsychotic Agent Among Hospitalized, Treatment-Naive, First-Episode Psychosis Patients in Naturalistic, Public-Sector Settings

Objective: Little is known about determinants of second-generation antipsychotic dosages during initial hospitalization of first-episode psychosis. This study examined potential predictors of dosage of an atypical antipsychotic agent, risperidone, at hospital discharge after initial evaluation and treatment of first-episode nonaffective psychosis in 3 naturalistic, public-sector treatment settings. Methods: The number of psychotropic agents prescribed and discharge antipsychotic dosage were abstracted from the medical record. Demographic and extensive clinical characteristics were assessed through a clinical research study conducted at the 3 sites. One-way analyses of variance, trend tests using specific linear combinations of estimates, and &khgr;2 tests assessed for associations between atypical antipsychotic dosage and 5 hypothesized predictors, as well as 12 exploratory variables. Results: Among 155 hospitalized first-episode patients, 121 (78.1%) were discharged on risperidone, and subsequent analyses focused on that subset. The mean risperidone dosage among those 121 patients was 4.26 mg; 31 received 1 to 2 mg, 45 received 3 to 4 mg, 37 received 5 to 6 mg, and 8 received more than 6 mg. Analyses suggested that older age at hospitalization, the number of psychotropic agents prescribed, excited symptoms, and premorbid social functioning may be predictors of the discharge dosage. Conclusions: Although several factors emerged, in general, predictors of discharge dosages of second-generation agents, here exemplified by risperidone, in real-world practice settings remain to be clarified. Given the importance of antipsychotic initiation during first hospitalization, future research should test an even broader array of potential predictors.
Diversity and evolution of secondary metabolism in the marine actinomycete genus Salinispora

Significance Microbial natural products are a major source of new drug leads, yet discovery efforts are constrained by the lack of information describing the diversity and distributions of the associated biosynthetic pathways among bacteria. Using the marine actinomycete genus Salinispora as a model, we analyzed genome sequence data from 75 closely related strains. The results provide evidence for high levels of pathway diversity, with most being acquired relatively recently in the evolution of the genus. The distributions and evolutionary histories of these pathways provide insight into the mechanisms that generate new chemical diversity and the strategies used by bacteria to maximize their population-level capacity to produce diverse secondary metabolites. Access to genome sequence data has challenged traditional natural product discovery paradigms by revealing that the products of most bacterial biosynthetic pathways have yet to be discovered. Despite the insight afforded by this technology, little is known about the diversity and distributions of natural product biosynthetic pathways among bacteria and how they evolve to generate structural diversity. Here we analyze genome sequence data derived from 75 strains of the marine actinomycete genus Salinispora for pathways associated with polyketide and nonribosomal peptide biosynthesis, the products of which account for some of today’s most important medicines. The results reveal high levels of diversity, with a total of 124 pathways identified and 229 predicted with continued sequencing. Recent horizontal gene transfer accounts for the majority of pathways, which occur in only one or two strains. Acquired pathways are incorporated into genomic islands and are commonly exchanged within and between species. Acquisition and transfer events largely involve complete pathways, which subsequently evolve by gene gain, loss, and duplication followed by divergence. The exchange of similar pathway types at the precise chromosomal locations in different strains suggests that the mechanisms of integration include pathway-level homologous recombination. Despite extensive horizontal gene transfer there is clear evidence of species-level vertical inheritance, supporting the concept that secondary metabolites represent functional traits that help define Salinispora species. The plasticity of the Salinispora secondary metabolome provides an effective mechanism to maximize population-level secondary metabolite diversity while limiting the number of pathways maintained within any individual genome.
Cure of Hookworm Infection with a Cysteine Protease Inhibitor

Background Hookworm disease is a major global health problem and principal among a number of soil-transmitted helminthiases (STHs) for the chronic disability inflicted that impacts both personal and societal productivity. Mass drug administration most often employs single-dose therapy with just two drugs of the same chemical class to which resistance is a growing concern. New chemical entities with the appropriate single-dose efficacy are needed. Methods and Findings Using various life-cycle stages of the hookworm Ancylostoma ceylanicum in vitro and a hamster model of infection, we report the potent, dose-dependent cidal activities of the peptidyl cysteine protease inhibitors (CPIs) K11002 (4-mopholino-carbonyl-phenylalanyl-homophenylalanyl- vinyl sulfone phenyl) and K11777 (N-methylpiperazine-phenylalanyl-homophenylalanyl-vinylsulfone phenyl). The latter is in late pre-clinical testing for submission as an Investigational New Drug (IND) with the US Federal Drug Administration as an anti-chagasic. In vitro, K11002 killed hookworm eggs but was without activity against first-stage larvae. The reverse was true for K11777 with a larvicidal potency equal to that of the current anti-hookworm drug, albendazole (ABZ). Both CPIs produced morbidity in ex vivo adult hookworms with the activity of K11777 again being at least the equivalent of ABZ. Combinations of either CPI with ABZ enhanced morbidity compared to single compounds. Strikingly, oral treatment of infected hamsters with 100 mg/kg K11777 b.i. d. (i.e., a total daily dose of 200 mg/kg) for one day cured infection: a single 100 mg/kg treatment removed >90% of worms. Treatment also reversed the otherwise fatal decrease in blood hemoglobin levels and body weights of hosts. Consistent with its mechanism of action, K11777 decreased by >95% the resident CP activity in parasites harvested from hamsters 8 h post-treatment with a single 100 mg/kg oral dose. Conclusion A new, oral single-dose anthelmintic that is active in an animal model of hookworm infection and that possesses a distinct mechanism of action from current anthelmintics is discovered. The data highlight both the possibility of repurposing the anti-chagasic K11777 as a treatment for hookworm infection and the opportunity to further develop CPIs as a novel anthelmintic class to target hookworms and, possibly, other helminths.
Educating for Eco-Justice and Community

Reading, writing, arithmetic - and eco-justice; We believe in social justice. We support educational reform. Yet unless we reframe our approaches to both, says C. A. Bowers, the social justice attained through educational reform will only lead to more intractable forms of consumerism and further impoverishment of our communities. In Educating for Eco-Justice and Community Bowers outlines a strategy for educational reform that confronts the rapid degradation of our ecosystems by renewing the face-to-face, intergenerational traditions that can serve as alternatives to our hyper-consumerist, technology-driven worldview. Bowers explains how current technological and progressive programs of educational reform operate on deep cultural assumptions that came out of the Enlightenment and led to the Industrial Revolution. These beliefs frame our relationship with nature in adversarial terms, view progress as inevitable, and elevate the individual over community, expertise over intergenerational knowledge, and profit over reciprocity. By making eco-justice a priority of educational reform, we can begin to democratize developments in science and technology in ways that eliminate ecoracism; reverse the global processes that are worsening the economic and political inequities between the hemispheres; expose the cultural forces that turn aspects of daily life - from education and entertainment to work and leisure - into market-dependent relationships; uplift knowledge and traditions of intergenerationally connected communities; and develop a sense of moral responsibility for the long-term consequences of our excessive material demands. In the tradition of Wendell Berry, David Orr, and Kirkpatrick Sale, Bowers thinks about our place in the natural world and the current economies to show how we can reform education and create a less consumer-driven society.
Topic models with power-law using Pitman-Yor process

One important approach for knowledge discovery and data mining is to estimate unobserved variables because latent variables can indicate hidden specific properties of observed data. The latent factor model assumes that each item in a record has a latent factor; the co-occurrence of items can then be modeled by latent factors. In document modeling, a record indicates a document represented as a "bag of words," meaning that the order of words is ignored, an item indicates a word and a latent factor indicates a topic. Latent Dirichlet allocation (LDA) is a widely used Bayesian topic model applying the Dirichlet distribution over the latent topic distribution of a document having multiple topics. LDA assumes that latent topics, i.e., discrete latent variables, are distributed according to a multinomial distribution whose parameters are generated from the Dirichlet distribution. LDA also models a word distribution by using a multinomial distribution whose parameters follows the Dirichlet distribution. This Dirichlet-multinomial setting, however, cannot capture the power-law phenomenon of a word distribution, which is known as Zipf's law in linguistics. We therefore propose a novel topic model using the Pitman-Yor(PY) process, called the PY topic model. The PY topic model captures two properties of a document; a power-law word distribution and the presence of multiple topics. In an experiment using real data, this model outperformed LDA in document modeling in terms of perplexity.
Differences in cerebral blood flow and glucose utilization in vegetative versus locked‐in patients

Positron emission tomographic studies of regional cerebral metabolic rate for glucose (rCMRGlc) and cerebral blood flow were performed in 7 vegetative and 3 locked‐in patients to determine objectively the level of brain function underlying these clinical states. Cortical gray rCMRGlc in the vegetative patients was 2.73 ± 0.13 (mean ± SEM) mg/100 gm/min, less than half the normal value of 6.82 ± 0.23 (p < 0.001). Cerebral blood flow exhibited similar but more variable reductions. By contrast, cortical rCMRGlc in the locked‐in patients was 5.08 ± 0.69, a 25% reduction (p < 0.02) from normal. The massive reduction in vegetative rCMRGlc involved not only the cerebral cortex but also the basal nuclei and cerebellum. Such metabolic hypoactivity has precedent only in deep anesthesia and supports clinical evidence that cerebral cognitive function is lost in the vegetative state, leaving a body that can no longer think or experience pain.
Strategies to Overcome Bypass Mechanisms Mediating Clinical Resistance to EGFR Tyrosine Kinase Inhibition in Lung Cancer

The vast majority of patients with metastatic lung cancers who initially benefit from EGFR-targeted therapies eventually develop resistance. An increasing understanding of the number and complexity of resistance mechanisms highlights the challenge of treating tumors resistant to EGFR inhibitors. Resistance mechanisms include new, second-site mutations within EGFR (e.g., T790M and C797S), upregulation of MET kinase, upregulation of insulin growth factor receptor (IGFR), HER2 amplification, increased expression of AXL, BIM modulation, NF-κB activation, histologic switch to small-cell cancer, epithelial-to-mesenchymal transition, PDL1 expression with subsequent immune tolerance, and release of cytokines such as TGFβ and IL6. Herein, we review the growing body of knowledge regarding EGFR bypass pathways, and the development of new drugs and combination treatment strategies to overcome resistance. Mol Cancer Ther; 16(2); 265–72. ©2017 AACR.
The role of the leptin in reproduction

Purpose of review Since its discovery in 1994, leptin has appeared to be a pleiotrophic hormone, governing energy homeostasis and affecting many tissues in the body. Numerous pieces of evidence have accumulated showing that leptin potentially plays an important role in the control of the reproductive function. Recent findings This review presents the major concepts for the role of leptin in the modulation of reproductive function. As a marker of the nutritional status, leptin affects the hypothalamo–pituitary–gonadal axis, regulating gonadotrophin-releasing hormone and luteinising hormone secretion, and appears to be a permissive factor in the onset of the puberty. This protein and its receptor have been found in the reproductive tissues, indicating that this system could be also implicated in several processes such as embryo development, implantation and pregnancy. Moreover, disorders of the leptin system have been related to some reproductive pathologies such as pre-eclampsia and polycystic ovary syndrome. However, controversy surrounds several aspects of the action of leptin in reproduction that require a deeper investigation of this system. Summary Results to date suggest that this system could be implicated in important reproductive processes such as embryonic development and implantation. Moreover, understanding the role of leptin might be useful for new treatments in reproductive pathologies.
Recombinase polymerase amplification: Emergence as a critical molecular technology for rapid, low-resource diagnostics

Isothermal molecular diagnostics are bridging the technology gap between traditional diagnostics and polymerase chain reaction-based methods. These new techniques enable timely and accurate testing, especially in settings where there is a lack of infrastructure to support polymerase chain reaction facilities. Despite this, there is a significant lack of uptake of these technologies in developing countries where they are highly needed. Among these novel isothermal technologies, recombinase polymerase amplification (RPA) holds particular potential for use in developing countries. This rapid nucleic acid amplification approach is fast, highly sensitive and specific, and amenable to countries with a high burden of infectious diseases. Implementation of RPA technology in developing countries is critically required to assess limitations and potentials of the diagnosis of infectious disease, and may help identify impediments that prevent adoption of new molecular technologies in low resource- and low skill settings. This review focuses on approaching diagnosis of infectious disease with RPA.
Oral health status, salivary pH status, and Streptococcus mutans counts in dental plaques and saliva of children with acute lymphoblastic leukemia

Background: Acute lymphoblastic leukemia (ALL), accounting for 23% of all malignancies in children, is the most prevalent pediatric malignancy. This study compared dental caries, oral hygiene status, salivary pH, and Streptococcus mutans counts in dental plaques and saliva of children with leukemia with those of healthy controls. Materials and Methods: This case–control cross-sectional study assessed 32 children with ALL and 32 healthy children (4–9-year-old) for gingival bleeding index (GBI), decayed, missing, and filled/decayed, missing, and filled surfaces (DMF/dmfs), and plaque index (PI). Sampling was performed to determine salivary pH and S. mutans counts of the participants. The two groups matched in terms of age, gender, and socioeconomic status. The groups were compared using independent t-test, Mann–Whitney test, Chi-square test, and Spearman's and Pearson's correlation analyses. Results: The mean DMF/dmfs and GBI were significantly higher in the ALL group (PDMF/dmfs= 0.03; PGBI= 0.04). However, the two groups were not significantly different in the mean PI values (P = 0.47). The mean S. mutans counts in dental plaques and saliva of the children with leukemia were significantly lower than the healthy controls (P < 0.01). Moreover, the mean salivary pH was significantly lower in the ALL group compared to the control group (P < 0.01). Conclusion: Higher caries and gingival bleeding rates, higher dental plaque accumulation in children with ALL, decreased salivary pH, and cumulative effects of other risk factors highlight the significance of oral hygiene training programs (for the parents of these children) and regular dental examinations for these children.
Direct numerical simulations of the double scalar mixing layer. Part I: Passive scalar mixing and dissipation

The double scalar mixing layer (DSML) is a canonical problem for studying the mixing of multiple streams and, with reaction, combustion of the partially premixed type. In a DSML, a third stream consisting of a premixture of the reactants is introduced in between the pure fuel and air streams of the classic twin-feed or binary mixing problem. The well-known presumed probability density function (PDF), such as the β-PDF, can adequately model passive scalar mixing for the binary mixing problem on which state-of-the-art turbulent combustion models such as conditional moment closure and flamelet approaches rely. However, the β-PDF model, now a standard in CFD simulation, cannot describe turbulent mixing involving multiple streams; e.g., the asymmetric three-stream mixing characterizing the DSML. In this paper, direct numerical simulations of the DSML are performed to make available a high-fidelity database for developing more general, fine-scale mixing models required to compute turbulent combustion problems o.
Endorsing benevolent sexism magnifies willingness to dissolve relationships when facing partner-ideal discrepancies

Benevolent sexism (BS) contains prescriptive partner expectations that should foster an intolerance of discrepancies between partners and warmth/trustworthiness ideal standards. This longitudinal study tested whether endorsing BS magnifies the degree to which warmth/trustworthiness partner-ideal discrepancies are associated with willingness to dissolve relationships. Heterosexual couples (N = 88) reported their partner-ideal discrepancies, willingness to dissolve the relationship, and their partner’s willingness to dissolve the relationship every 3 months for 1 year. Greater partner-ideal discrepancies were associated with subsequent increases in willingness to dissolve the relationship, but this was stronger for people who endorsed BS. Partners of women who endorsed BS also perceived this greater willingness to dissolve the relationship. These results demonstrate that the prescriptions within BS undermine the stability of ongoing relationships.
Annals of Clinical Microbiology and Antimicrobials Open Access Prevalence and Antimicrobial Resistance Pattern of Bacterial Meningitis in Egypt

Infectious diseases are the leading cause of morbidity and mortality in the developing world. In Egypt bacterial diseases constitute a great burden, with several particular bacteria sustaining the leading role of multiple serious infections. This article addresses profound bacterial agents causing a wide array of infections including but not limited to pneumonia and meningitis. The epidemiology of such infectious diseases and the prevalence of Streptococcus pneumoniae, Neisseria meningitidis and Haemophilus influenzae are reviewed in the context of bacterial meningitis. We address prevalent serotypes in Egypt, antimicrobial resistance patterns and efficacy of vaccines to emphasize the importance of periodic surveillance for appropriate preventive and treatment strategies.
Children's Ability to Coordinate Spatial Perspectives Through Linguistic Descriptions.

ABSTRACT In this study, two rival accounts of the mental operations used to solve Piaget's three-mountain perspective task are tested. One hypothesis is that if children use some form of mental rotation through anticipatory imagery, scores should improve as the angle of separation between the child and the other viewer is decreased. A second hypothesis is that if children simply construct a linguistic description of the view adjacent to the other viewer, scores should instead reflect the complexity of the linguistic description of the other's view. 2n addition, if a linguistic strategy is used, a linguistic response mode should optimize correct responses; if an imagery solution is employed, a non-linguistic response mode would presumably be more appropriate. A total of 120 children in grades K, 2 and 4 were asked to identify another's view either verbally or by picture selection. Results indicate that the verbal response mode leads to substantially more correct responses (82% vs. 45%) and has a minimum of egocentric errors (4% vs. 38%). Correct responses in both verbal and pictorial modes are shown to increase as a function of the linguistic complexity, not the angle of separation. It is suggested that the egocentric perspective errors noted by Piaget can be seen as the by-product of a non-linguistic response mode which does not map onto the linguistic mental operations typically used to solve the task. Spatial egocentrism emerges as a function of one particular mode of response (pictorial) rather than as a general characteristic of pre-operational thought. Analogously, perspective taking seems better described as the handling of increasingly complex linguistic descriptions rather than as a simple present/absent phenomenon. (Author/MS)
Visual Space Perception: A Primer

The problem of visual space perception. Part 1 Binocular perception: spatial localization - visual directions stereopsis -fusion and horopters stereopsis - traditional stereograms cyclopean perception. Part 2 Monocular perception: stimulus inadequacy - the fundamental problem of monocular perception pictorial cues, oculomotor adjustments, automatic organizing processes and observer tendencies empiricist view - perceived size and shape Gibson's psychophysics - basic concepts lateral or parallactic motion motion in depth perceived object motions detecting motion concluding thoughts appendix - angular measures.