Small carbonaceous fossils (SCFs) from the Terreneuvian (lower Cambrian) of Baltica

We describe a new assemblage of small carbonaceous fossils (SCFs) from diagenetically 9 minimally altered clays and siltstones of Terreneuvian age from the Lontova and Voosi formations of 10 Estonia, Lithuania and Russia. This is the first detailed account of an SCF assemblage from the 11 Terreneuvian, and includes a number of previously undocumented Cambrian organisms. Recognisably 12 bilaterian-derived SCFs include abundant protoconodonts (total-group Chaetognatha), and distinctive 13 cuticular spines of scalidophoran worms. Alongside these metazoan remains are a range of protistan-14 grade fossils, including Retiranus balticus gen. et sp. nov., a distinctive funnel-shaped or sheet-like 15 problematicum characterized by terminal or marginal vesicles, and Lontohystrichosphaera grandis 16 gen. et sp. nov., a large (100–550 μm) ornamented vesicular microfossil. Together these data offer a 17 fundamentally enriched view of Terreneuvian life in the epicratonic seas of Baltica, from an episode 18 where records of non-biomineralized life are currently sparse. Even so, the recovered assemblages 19 contain a lower diversity of metazoans than SCF biotas from younger (Stage 4) Baltic successions that 20 represent broadly equivalent environments, echoing the diversification signal recorded in the coeval 21 shelly and trace-fossil records. Close comparison to the biostratigraphic signal from Fortunian small 22 shelly fossils (SSFs) supports a late Fortunian age for most of the Lontova/Voosi succession, rather 23 than a younger (wholly Stage 2) range.NER

Investigating Irrational Beliefs, Cognitive Appraisals, Challenge and Threat, and Affective States in Golfers Approaching Competitive Situations

© Copyright © 2019 Chadha, Turner and Slater. On approach to competitive situations, affective states (emotions and anxiety) occur through the complex interaction of cognitive antecedents. Researchers have intimated that irrational beliefs might play an important role in the relationship between cognitive appraisals and affective states, but has ignored challenge and threat. In the current research, we examine the interaction between cognitive appraisals, irrational beliefs, and challenge and threat to predict golfers’ pre-competitive affective states. We adopted a cross-sectional atemporal design to examine how golfers approached two different competitive situations: imagined imminent golf competition (phase 1), and actual future golf competition (phase 2). Path analysis revealed how cognitive appraisals, irrational beliefs, and challenge and threat interact to predict affective states among golfers. Serial atemporal multiple mediation analysis indicated that the relationships between cognitive appraisals and affective states were mediated by irrational beliefs and challenge and threat. Further, some differences were revealed between phase 1 and phase 2 in the serial multiple atemporal mediation results with regard to challenge. That is, at phase 1 no significant serial mediation was found for any affective outcomes, but at phase 2 significant serial mediation was found for all affective states, showing that irrational beliefs and challenge serial mediated the associations between cognitive appraisals and affective states. The finding that mediation and bivariate associations differed across phase 1 and phase 2 is echoed in the phase 1-phase 2 tests of differences. The current research makes a theoretical advancement by elucidating in more detail the complex interaction between cognitive antecedents and mediators of affective states. Specifically, the inclusion of challenge and threat alongside irrational beliefs and cognitive appraisals is an important theoretical advancement that builds on work inside of sport literature (e.g., Dixon et al., 2016) and outside of sport literature (e.g., David et al., 2002, 2005), as this constellation of theoretically related antecedents of affective states has not been examined together in the extant research

Oxygen minimum zones in the early Cambrian ocean

The relationship between the evolution of early animal 26 communities and oceanic oxygen levels remains unclear. In particular, uncertainty persists in reconstructions of redox conditions during the pivotal early Cambrian (541-510 million years ago, Ma), where conflicting datasets from deeper marine settings suggest either ocean anoxia or fully oxygenated conditions. By coupling geochemical palaeoredox proxies with a record of organic-walled fossils from exceptionally well-defined successions of the early Cambrian Baltic Basin, we provide evidence for the early establishment of modern-type oxygen minimum zones (OMZs). Both inner- and outer shelf environments were pervasively oxygenated, whereas mid-depth settings were characterized by spatially oscillating anoxia. As such, conflicting redox signatures recovered from individual sites most likely derive from sampling bias, whereby anoxic conditions represent mid-shelf environments with higher productivity. This picture of a spatially restricted anoxic wedge contrasts with prevailing models of globally stratified oceans, offering a more nuanced and realistic account of the Proterozoic-Phanerozoic ocean transition

Melanoma in congenital melanocytic naevi

Congenital melanocytic naevi (CMN) are a known risk factor for melanoma, with the greatest risk currently thought to be in childhood. There has been controversy over the years about the incidence, and therefore over clinical management of CMN, due partly to the difficulties of histological diagnosis and partly to publishing bias towards cases of malignancy. Large cohort studies have demonstrated that risk in childhood is related to the severity of the congenital phenotype, not only cutaneous but neuroradiological. New understanding of the genetics of CMN offers the possibility of improvement in diagnosis of melanoma, identification of those at highest risk, and new treatment options. We review the world literature and our centre's experience over the last 25 years, including the molecular characteristics of melanoma in these patients and new melanoma incidence and outcome data from our prospective cohort. Management strategies are proposed for presentation of suspected melanoma of the skin and the CNS in patients with CMN, including use of oral MEK inhibitors in NRAS-mutated tumours. This article is protected by copyright. All rights reserved

IGFBP-1 in Cardiometabolic Pathophysiology—Insights From Loss-of-Function and Gain-of-Function Studies in Male Mice

We have previously reported that overexpression of human insulin-like growth factor binding protein (IGFBP)-1 in mice leads to vascular insulin sensitization, increased nitric oxide bioavailability, reduced atherosclerosis, and enhanced vascular repair, and in the setting of obesity improves glucose tolerance. Human studies suggest that low levels of IGFBP-1 are permissive for the development of diabetes and cardiovascular disease. Here we seek to determine whether loss of IGFBP-1 plays a causal role in the predisposition to cardiometabolic disease. Metabolic phenotyping was performed in transgenic mice with homozygous knockout of IGFBP-1. This included glucose, insulin, and insulin-like growth factor I tolerance testing under normal diet and high-fat feeding conditions. Vascular phenotyping was then performed in the same mice using vasomotor aortic ring studies, flow cytometry, vascular wire injury, and angiogenesis assays. These were complemented with vascular phenotyping of IGFBP-1 overexpressing mice. Metabolic phenotype was similar in IGFBP-1 knockout and wild-type mice subjected to obesity. Deletion of IGFBP-1 inhibited endothelial regeneration following injury, suggesting that IGFBP-1 is required for effective vascular repair. Developmental angiogenesis was unaltered by deletion or overexpression of IGFBP-1. Recovery of perfusion following hind limb ischemia was unchanged in mice lacking or overexpressing IGFBP-1; however, overexpression of IGFBP-1 stimulated hindlimb perfusion and angiogenesis in insulin-resistant mice. These findings provide new insights into the role of IGFBP-1 in metabolic and vascular pathophysiology. Irrespective of whether loss of IGFBP-1 plays a causal role in the development of cardiometabolic disorders, increasing IGFBP-1 levels appears effective in promoting neovascularization in response to ischemia

Multiple congenital melanocytic nevi and neurocutaneous melanosis are caused by postzygotic mutations in codon 61 of NRAS

Congenital melanocytic nevi (CMN) can be associated with neurological abnormalities and an increased risk of melanoma. Mutations in NRAS, BRAF, and Tp53 have been described in individual CMN samples; however, their role in the pathogenesis of multiple CMN within the same subject and development of associated features has not been clear. We hypothesized that a single postzygotic mutation in NRAS could be responsible for multiple CMN in the same individual, as well as for melanocytic and nonmelanocytic central nervous system (CNS) lesions. From 15 patients, 55 samples with multiple CMN were sequenced after site-directed mutagenesis and enzymatic digestion of the wild-type allele. Oncogenic missense mutations in codon 61 of NRAS were found in affected neurological and cutaneous tissues of 12 out of 15 patients, but were absent from unaffected tissues and blood, consistent with NRAS mutation mosaicism. In 10 patients, the mutation was consistently c.181C>A, p.Q61K, and in 2 patients c.182A>G, p.Q61R. All 11 non-melanocytic and melanocytic CNS samples from 5 patients were mutation positive, despite NRAS rarely being reported as mutated in CNS tumors. Loss of heterozygosity was associated with the onset of melanoma in two cases, implying a multistep progression to malignancy. These results suggest that single postzygotic NRAS mutations are responsible for multiple CMN and associated neurological lesions in the majority of cases

The “dirty dozen” of freshwater science: Detecting then reconciling hydrological data biases and errors

Sound water policy and management rests on sound hydrometeorological and ecological data. Conversely, unrepresentative, poorly collected or erroneously archived data introduces uncertainty regarding the magnitude, rate and direction of environmental change, in addition to undermining confidence in decision-making processes. Unfortunately, data biases and errors can enter the information flow at various stages, starting with site selection, instrumentation, sampling/ measurement procedures, post-processing and ending with archiving systems. Techniques such as visual inspection of raw data, graphical representation and comparison between sites, outlier and trend detection, and referral to metadata can all help uncover spurious data. Tell-tale signs of ambiguous and/or anomalous data are highlighted using 12 carefully chosen cases drawn mainly from hydrology (‘the dirty dozen’). These include evidence of changes in site or local conditions (due to land management, river regulation or urbanisation); modifications to instrumentation or inconsistent observer behaviour; mismatched or misrepresentative sampling in space and time; treatment of missing values, post-processing and data storage errors. As well as raising awareness of pitfalls, recommendations are provided for uncovering lapses in data quality after the information has been gathered. It is noted that error detection and attribution are more problematic for very large data sets, where observation networks are automated, or when various information sources have been combined. In these cases, more holistic indicators of data integrity are needed that reflect the overall information life-cycle and application(s) of the hydrological data

The rationale and plan for creating a World Antimalarial Resistance Network (WARN)

Drug resistant malaria was a major factor contributing to the failure of a worldwide campaign to eradicate malaria in the last century, and now threatens the large investment being made by the global community in the rollout of effective new drug combinations to replace failed drugs. Four related papers in this issue of Malaria Journal make the case for creating the World Antimalarial Resistance Network (WARN), which will consist of four linked open-access global databases containing clinical, in vitro, molecular and pharmacological data, and networks of reference laboratories that will support these databases and related surveillance activities. WARN will serve as a public resource to guide antimalarial drug treatment and prevention policies and to help confirm and characterize the new emergence of new resistance to antimalarial drugs and to contain its spread

Acceleration of generalized hypergeometric functions through precise remainder asymptotics

We express the asymptotics of the remainders of the partial sums {s_n} of the generalized hypergeometric function q+1_F_q through an inverse power series z^n n^l \sum_k c_k/n^k, where the exponent l and the asymptotic coefficients {c_k} may be recursively computed to any desired order from the hypergeometric parameters and argument. From this we derive a new series acceleration technique that can be applied to any such function, even with complex parameters and at the branch point z=1. For moderate parameters (up to approximately ten) a C implementation at fixed precision is very effective at computing these functions; for larger parameters an implementation in higher than machine precision would be needed. Even for larger parameters, however, our C implementation is able to correctly determine whether or not it has converged; and when it converges, its estimate of its error is accurate.Comment: 36 pages, 6 figures, LaTeX2e. Fixed sign error in Eq. (2.28), added several references, added comparison to other methods, and added discussion of recursion stabilit

Key features of palliative care service delivery to Indigenous peoples in Australia, New Zealand, Canada and the United States: A comprehensive review

Background: Indigenous peoples in developed countries have reduced life expectancies, particularly from chronic diseases. The lack of access to and take up of palliative care services of Indigenous peoples is an ongoing concern. Objectives: To examine and learn from published studies on provision of culturally safe palliative care service delivery to Indigenous people in Australia, New Zealand (NZ), Canada and the United States of America (USA); and to compare Indigenous peoples’ preferences, needs, opportunities and barriers to palliative care. Methods: A comprehensive search of multiple databases was undertaken. Articles were included if they were published in English from 2000 onwards and related to palliative care service delivery for Indigenous populations; papers could use quantitative or qualitative approaches. Common themes were identified using thematic synthesis. Studies were evaluated using Daly’s hierarchy of evidence-for-practice in qualitative research. Results: Of 522 articles screened, 39 were eligible for inclusion. Despite diversity in Indigenous peoples’ experiences across countries, some commonalities were noted in the preferences for palliative care of Indigenous people: to die close to or at home; involvement of family; and the integration of cultural practices. Barriers identified included inaccessibility, affordability, lack of awareness of services, perceptions of palliative care, and inappropriate services. Identified models attempted to address these gaps by adopting the following strategies: community engagement and ownership; flexibility in approach; continuing education and training; a whole-of-service approach; and local partnerships among multiple agencies. Better engagement with Indigenous clients, an increase in number of palliative care patients, improved outcomes, and understanding about palliative care by patients and their families were identified as positive achievements. Conclusions: The results provide a comprehensive overview of identified effective practices with regards to palliative care delivered to Indigenous populations to guide future program developments in this field. Further research is required to explore the palliative care needs and experiences of Indigenous people living in urban areas