Use of high resolution microscopy (FESEM and TEM) to investigate carbonate precipitates in association with organic matter from hot spring, salt pond, and reef environments

Carbonate precipitates in biofilm were investigated from hot springs near Viterbo, Italy; Salt Pond, San Salvador; and Fowl Cay Reef, Abaco, Bahamas. Features shared by hot springs and salt ponds are supersaturation with CaCO3, abundant Spirulina, and clustered acicular aragonite crystals termed “fuzzy dumbbells.” TEM and FESEM microscopy show fuzzy dumbbells contain a core of amorphous organic matter and subhedral CaCO3 microcrystals arranged in linear fabrics. Micron- to millimeter-scale microenvironments are identified by localized dissolution, the occurrence of gothic calcite inter-grown with organic filaments, and the presence of calcite in biofilm where aragonite is chemically favored. Spherical CaCO3 precipitates in reefs were anticipated, but not encountered in TEM sections of reef biofilm. In conclusion, biofilm creates the microenvironment and organic matter provides substrate for fuzzy dumbbell precipitation. TEM is a novel technique for studying the relationship between organic matter and CaCO3 precipitation, and has potential medical, industrial, and academic applications

Lifestyle factors and cognitive ageing in the Lothian Birth Cohort 1936: exploring the role of confounding by prior cognitive ability

With an increase in life expectancy, the number of older people affected by cognitive decline and dementia is rising, causing major, global public health concerns. However, there is substantial variation in the rate and magnitude of cognitive decline experienced among ageing individuals. Evidence suggests that many age-associated changes in cognitive functioning can be explained by modifiable lifestyle factors such as smoking, physical activity and diet choices. The weight of the evidence supports the promotion of a healthy lifestyle as an effective strategy for healthy cognitive ageing. Many epidemiological studies have drawn causal conclusions with regard to the positive and direct benefits of lifestyle, yet few have considered the possible confounding role of prior cognitive ability in explaining the lifestyle and cognition relationship in older age. Given the potential for reverse causation, whereby better prior cognitive functioning leads to a greater uptake of healthy behaviours rather than vice versa, it is a mechanism which should be studied, but rarely is. The present thesis focuses on the possible confounding effect of prior cognitive ability on the cross-sectional relationships between lifestyle factors and cognitive ability domains in later-life. The core of the thesis is a series of independent, peer-reviewed (six first-author and one co-author) journal articles in the public domain. Data were derived from the Lothian Birth Cohort 1936 study (n = 1091), a sample of relatively healthy, community-dwelling men and women aged 70 years from Edinburgh, Scotland, for whom childhood (age 11) mental test scores are available. The lifestyle factors investigated were caffeine consumption, alcohol consumption, dietary patterns, body mass index, smoking, serum cholesterol, and physical activity. Cognitive function was assessed across five major ageing-related domains: age 70 IQ (based on the same test that was taken in childhood), general cognitive ability (g), processing speed, memory, and verbal ability. General linear models (ANCOVA) were adjusted for the following covariates: age; sex; childhood cognitive ability; and socioeconomic status (SES). Other potential covariates were additionally adjusted for as necessary. Overall, the positive and significant associations observed between ‘healthy’ lifestyle factors and better cognitive functions at age 70 were consistent with previous research; their effect size was around 1% of the variance in cognitive tests scores. However, these relationships were markedly attenuated (by on average 80%) by a higher childhood cognitive ability and adult SES; for the most part, associations were reduced to non-significance. None of the lifestyle factors were consistent predictors of performance across cognitive domains, though smoking avoidance, a physically active lifestyle, and moderate intake of alcohol, appeared to have the most potential. The key novel finding of this thesis is that, in addition to having predictive value for lifestyle choices over 60 years later, cognitive ability at age 11 accounted for the majority of the cross-sectional associations between lifestyle factors and cognitive abilities in later-life. This finding is consistent with the theory of confounding or even reverse causation. That is, individuals with higher lifetime ‘trait’ cognitive ability may be more likely to adopt a lifestyle which protects against cognitive decline. Rather than a unidirectional or indirect effect of health behaviours on cognitive function, the present findings suggest there may be a dynamic cycle involving cognition, self-management of health and ultimate cognitive outcomes

Impact of Common Vitamin D-Binding Protein Isoforms on Supplemental Vitamin D3 and/or Calcium Effects on Colorectal Adenoma Recurrence Risk: A Secondary Analysis of a Randomized Clinical Trial

IMPORTANCE: Variants in the vitamin D-binding protein (DBP) gene (GC) encode DBP isoforms that may affect vitamin D metabolism. However, whether these isoforms modify the effects of vitamin D3 and/or calcium supplementation on colorectal adenoma recurrence is unclear. We hypothesized that supplementation effects may be stronger among those with the DBP2 isoform (encoded by the rs4588*A allele), which is associated with vitamin D deficiency and modified the associations of circulating vitamin D with risk for colorectal neoplasms in observational studies. OBJECTIVE: To estimate supplemental vitamin D3 and/or calcium effects on colorectal adenoma recurrence according to 3 common DBP isoforms (DBP1s, DBP1f, DBP2) encoded by 2 missense variants: rs7041 (NG_012837.3:g.57904T\u3eG NP_001191235.1:p.Asp432Glu) and rs4588 (NG_012837.3:g.57915C\u3eA NP_001191235.1:p.Thr436Lys). DESIGN, SETTING, AND PARTICIPANTS: Secondary analysis of a randomized, double-blind, placebo-controlled clinical trial of 2259 participants with a recently diagnosed adenoma and no remaining polyps after complete colonoscopy in the US from July 1, 2004, to August 31, 2013. The current analyses were performed from August 12, 2019, to July 16, 2022. INTERVENTIONS: Daily vitamin D3 (1000 IU), calcium (1200 mg), both, or placebo. MAIN OUTCOMES AND MEASURES: One or more adenomas diagnosed during 3 to 5 years of follow-up. Treatment effects were estimated according to DBP isoform as risk ratios (RRs) and 95% CIs using Poisson regression analysis. RESULTS: Of the 2259 participants randomized (mean [SD] age, 58 [6.8] years; 1033 [64%] men), 1604 non-Hispanic White participants (chosen to avoid population stratification bias) were included in the analysis. Among those with the DBP2 isoform (rs4588*AC or AA), the RRs (95% CI) for adenoma recurrence were 0.84 (0.72-1.00) with vitamin D3 relative to no vitamin D3, 0.83 (95% CI, 0.70-0.99) with calcium relative to no calcium, and 0.76 (95% CI, 0.59-0.98) with both agents relative to neither agent. Conversely, among those without DBP2 (rs4588*CC), the corresponding values were 1.08 (95% CI, 0.93-1.26; P = .03 for interaction) with vitamin D3 relative to no vitamin D3, 0.98 (95% CI, 0.84-1.14; P = .37 for interaction) with calcium relative to no calcium, and 1.09 (0.88-1.36; P = .03 for interaction) with both agents relative to neither agent. Among DBP2 homozygotes (rs4588*AA), the RR for adenoma recurrence was 0.57 (95% CI, 0.31-1.08) with both agents relative to neither agent. CONCLUSIONS AND RELEVANCE: The findings of this secondary analysis of a randomized clinical trial suggest that individuals with the DBP2 isoform-encoding rs4588*A allele may particularly benefit from vitamin D3 and/or calcium supplementation for colorectal adenoma prevention. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00153816

In politics, caricatures can become facts, and that is bad for everyone

The distortion of facts is nothing new to politics and election campaigns. But, with the rise of the internet and 24-hour news cycle, rumors and conspiracy theories can now spread easier than ever through social networks to reach potential voters. Michael Cacciatore and co-authors look at two examples from the 2008 presidential election campaign to better understand how unsubstantiated rumors can become facts in voters’ minds. They find that values, including political ideology and evangelical Christian status, were primarily responsible for propelling misperceptions about President Barack Obama’s faith, while media use played a more important role in driving the misperception that Sarah Palin, and not Saturday Night Live’s Tina Fey, was responsible for the “I can see Russia from my house” quote. The latter finding lends some credibility to the so-called “lamestream media” effect often espoused by prominent Republican figures

Carotid disease at age 73 and cognitive change from age 70 to 76 years. A longitudinal cohort study

Cognitive decline and carotid artery atheroma are common at older ages. In community-dwelling subjects, we assessed cognition at ages 70, 73 and 76 and carotid Doppler ultrasound at age 73, to determine whether carotid stenosis was related to cognitive decline. We used latent growth curve models to examine associations between four carotid measures (internal carotid artery stenosis, velocity, pulsatility and resistivity indices) and four cognitive ability domains (memory, visuospatial function, crystallised intelligence, processing speed) adjusted for cognitive ability at age 11, current age, gender and vascular risk factors. Amongst 866 participants, carotid stenosis (median 12.96%) was not associated with cognitive abilities at age 70 or cognitive decline from age 70 to 76. Increased ICA pulsatility and resistivity indices were associated with slower processing speed (both P &lt; 0.001) and worse visuospatial function ( P = 0.036, 0.031, respectively) at age 70, and declining crystallised intelligence from ages 70 to 76 ( P = 0.008, 0.006, respectively). The findings suggest that vascular stiffening, rather than carotid luminal narrowing, adversely influences cognitive ageing and provides a potential target for ameliorating age-related cognitive decline. </jats:p

Inhibition of Protein-protein Interactions in Mycobacterium tuberculosis

Tuberculosis is a highly contagious, infectious disease that kills about 1.8 million people annually. Current chemotherapeutic regimens are both inefficient and taxing to the patient. In addition, the disease has suboptimal treatment due to the rise of multidrug resistant strains of Mycobacterium tuberculosis (Mtb), the causative bacterial agent of tuberculosis. Therefore, we established a critical assay to identify novel drugs that interfere with specific Mtb virulence mechanisms. The mycobacterial protein fragment complementation (M-PFC) assay was developed to screen 725 compound drug panel to find candidate drugs that interfered with important virulence-causing protein interactions of Mtb. We targeted the EsxA EsxB and EsxMEsxN interactions of the type VII secretion systems of Mtb. Our screen identified 46 small molecules that inhibited both virulence interactions, exhibiting nonspecific activity against a model cell line in vitro as well as seven hits specific to one of the two cell lines. In the future, we hope to retest the seven unique positive hits to confirm their ability to inhibit specific proteinprotein interactions of Mtb

A nationwide evaluation of bevacizumab-based treatments in pediatric low-grade glioma in the UK: safety, efficacy, visual morbidity, and outcomes

BACKGROUND: Bevacizumab is increasingly used in children with pediatric low-grade glioma (PLGG) despite limited evidence. A nationwide UK service evaluation was conducted to provide larger cohort "real life" safety and efficacy data including functional visual outcomes. METHODS: Children receiving bevacizumab-based treatments (BBT) for PLGG (2009-2020) from 11 centers were included. Standardized neuro-radiological (RANO-LGG) and visual (logMAR visual acuity) criteria were used to assess clinical-radiological correlation, survival outcomes and multivariate prognostic analysis. RESULTS: Eighty-eight children with PLGG received BBT either as 3rd line with irinotecan (85%) or alongside 1st/2nd line chemotherapies (15%). Toxicity was limited and minimal. Partial response (PR, 40%), stable disease (SD, 49%), and progressive disease (PD, 11%) were seen during BBT. However, 65% progressed at 8 months (median) from BBT cessation, leading to a radiology-based 3 yr-progression-free survival (PFS) of 29%. Diencephalic syndrome (P = .03) was associated with adverse PFS. Pre-existing visual morbidity included unilateral (25%) or bilateral (11%) blindness. Improvement (29%) or stabilization (49%) of visual acuity was achieved, more often in patients' best eyes. Vision deteriorated during BBT in 14 (22%), with 3-year visual-PFS of 53%; more often in patients' worst eyes. A superior visual outcome (P = .023) was seen in neurofibromatosis type 1-associated optic pathway glioma (OPG). Concordance between visual and radiological responses was 36%; optimized to 48% using only best eye responses. CONCLUSIONS: BBTs provide effective short-term PLGG control and delay further progression, with a better sustained visual (best > worst eye) than radiological response. Further research could optimize the role of BBT toward a potentially sight-saving strategy in OPG

A Genetic Epidemiological Mega Analysis of Smoking Initiation in Adolescents

Introduction. Previous studies in adolescents were not adequately powered to accurately disentangle genetic and environmental influences on smoking initiation across adolescence. Methods. Mega-analysis of pooled genetically informative data on smoking initiation was performed, with structural equation modeling, to test equality of prevalence and correlations across cultural backgrounds, and to estimate the significance and effect size of genetic and environmental effects according to the classical twin study, in adolescent male and female twins from same-sex and opposite-sex twin pairs (N=19 313 pairs) between age 10 and 19, with 76 358 longitudinal assessments between 1983 and 2007, from 11 population-based twin samples from the US, Europe and Australia. Results. Although prevalences differed between samples, twin correlations did not, suggesting similar etiology of smoking initiation across developed countries. The estimate of additive genetic contributions to liability of smoking initiation increased from approximately 15% to 45% from age 13 to 19. Correspondingly, shared environmental factors accounted for a substantial proportion of variance in liability to smoking initiation at age 13 (70%) and gradually less by age 19 (40%). Conclusions. Both additive genetic and shared environmental factors significantly contribute to variance in smoking initiation throughout adolescence. The present study, the largest genetic epidemiological study on smoking initiation to date, found consistent results across 11 studies for the etiology of smoking initiation. Environmental factors, especially those shared by siblings in a family, primarily influence smoking initiation variance in early adolescence, while an increasing role of genetic factors is seen at later ages, which has important implications for prevention strategies. IMPLICATIONS: This is the first study to find evidence of genetic factors in liability to smoking initiation at ages as young as 12. It also shows the strongest evidence to date for decay of effects of the shared environment from early adolescence to young adulthood. We found remarkable consistency of twin correlations across studies reflecting similar etiology of liability to initiate smoking across different cultures and time periods. Thus familial factors strongly contribute to individual differences in who starts to smoke with a gradual increase in the impact of genetic factors and a corresponding decrease in that of the shared environment

Decoding the Molecular Universe -- Workshop Report

On August 9-10, 2023, a workshop was convened at the Pacific Northwest National Laboratory (PNNL) in Richland, WA that brought together a group of internationally recognized experts in metabolomics, natural products discovery, chemical ecology, chemical and biological threat assessment, cheminformatics, computational chemistry, cloud computing, artificial intelligence, and novel technology development. These experts were invited to assess the value and feasibility of a grand-scale project to create new technologies that would allow the identification and quantification of all small molecules, or to decode the molecular universe. The Decoding the Molecular Universe project would extend and complement the success of the Human Genome Project by developing new capabilities and technologies to measure small molecules (defined as non-protein, non-polymer molecules less than 1500 Daltons) of any origin and generated in biological systems or produced abiotically. Workshop attendees 1) explored what new understanding of biological and environmental systems could be revealed through the lens of small molecules; 2) characterized the similarities in current needs and technical challenges between each science or mission area for unambiguous and comprehensive determination of the composition and quantities of small molecules of any sample; 3) determined the extent to which technologies or methods currently exist for unambiguously and comprehensively determining the small molecule composition of any sample and in a reasonable time; and 4) identified the attributes of the ideal technology or approach for universal small molecule measurement and identification. The workshop concluded with a discussion of how a project of this scale could be undertaken, possible thrusts for the project, early proof-of-principle applications, and similar efforts upon which the project could be modeled

Of risks and regulations: how leading U.S. nanoscientists form policy stances about nanotechnology

Even though there is a high degree of scientific uncertainty about the risks of nanotechnology, many scholars have argued that policy-making cannot be placed on hold until risk assessments are complete (Faunce, Med J Aust 186(4):189–191, 2007; Kuzma, J Nanopart Res 9(1):165–182, 2007; O’Brien and Cummins, Hum Ecol Risk Assess 14(3):568–592, 2008; Powell et al., Environ Manag 42(3):426–443, 2008). In the absence of risk assessment data, decision makers often rely on scientists’ input about risks and regulation to make policy decisions. The research we present here goes beyond the earlier descriptive studies about nanotechnology regulation to explore the heuristics that the leading U.S. nanoscientists use when they make policy decisions about regulating nanotechnology. In particular, we explore the relationship between nanoscientists’ risk and benefit perceptions and their support for nanotech regulation. We conclude that nanoscientists are more supportive of regulating nanotechnology when they perceive higher levels of risks; yet, their perceived benefits about nanotechnology do not significantly impact their support for nanotech regulation. We also find some gender and disciplinary differences among the nanoscientists. Males are less supportive of nanotech regulation than their female peers and materials scientists are more supportive of nanotechnology regulation than scientists in other fields. Lastly, our findings illustrate that the leading U.S. nanoscientists see the areas of surveillance/privacy, human enhancement, medicine, and environment as the nanotech application areas that are most in need of new regulations