Dinoflagellate Taxonomy and Biostratigraphy of the Mid- to Late Eocene and Early Oligocene of New Zealand

This document presents results from a study of the Mid- to Late Eocene and earliest Oligocene marine palynomorphs from on-shore and near-shore New Zealand. Eighty samples of appropriate age from across mainland New Zealand were examined for fossil dinoflagellates. Acritarchs encountered in the study are described, also, and the phenetic taxonomy of the Acritarcha provides an interesting contrast to the present 'mixed' state of dinoflagellate taxonomy: phylogenetic above the genus rank, and arguably below it, but predominantly phenetic at the genus rank. Extensive single mount collections were harvested from a number of samples which were found to be especially rich, well preserved, or which contained new taxa. The outcome has included descriptions of 25 new species, in addition to two (Corrudinium regulare and Corrudinium otagoense) published in an earlier paper (Clowes & Wilson 2006), namely: Achilleodinium echinatum, Achilleodinium improcerum, ?Areoligera hampdenensis, Batiacasphaera perforata, Chlamydophorella neopilata, Chlamydophorella pilata, Corrudinium bujakii, Deflandrea totara, Disphaerogena morgansii, Graptodinium inconditum, Graptodinium reticulatum, Nummus inornatus, Operculodinium crouchii, Operculodinium schioleri, Operculodinium pulcher, Operculodinium vulgare, Phthanoperidinium aculeatum, Phthanoperidinium australe, Phthanoperidinium dentatum, Phthanoperidinium granulatum, Phthanoperidinium spumosum, Phthanoperidinium tenuimurum, Pyxidinopsis mundus, Pyxidinopsis teuriensis, Samlandia tenuis. Although there remain some difficulties where the adopted suprageneric phylogeny meets the traditionally phenetic generic constructs, adopting an explicitly phylogenetic approach to dinoflagellate taxonomy was found to be a fruitful approach. Investigation into some of the new taxa described herein was first prompted by geographic or temporal occurrence criteria which hinted that relationships might be other than those immediately suggested by gross morphology. Only upon closer inspection were subtler morphological distinctions noticed. To adopt a wholly phylogenetic approach almost certainly requires the abandonment of taxa, particularly genera, which are uniquely defined by mutually exclusive morphological criteria. Other clues to phylogeny, such as stratigraphic and regional occurrence data, may also have to be recognised. Notwithstanding, all taxa described herein are, in fact, defined by means of conventional morphological distinctions. This study does not take the bold step to suggest a new taxon based wholly on geographical and temporal criteria. Doing so, however, is clearly a rational extension to the ideas presented herein, and is thought worthy of further investigation. A subordinate goal of this study was to further refine the younger part of Wilson's dinoflagellate biozonation for New Zealand (Wilson 1984d, 1987, 1988; Morgans et al. 2004), to: improve resolution, if possible; clarify an ambiguous boundary remaining in the literature, between the Wetzeliella hampdenensis and Wilsonidium tabulatum zones; incorporate more common taxa, which are not restricted to particular ecological settings. This has been progressed by a number of measures, including adopting a consistent approach to defining zone boundaries; replacement of the Wilsonidium echinosuturatum and Wilsonidium lineidentatum Zones with three new zones, Deflandrea convexa (early Porangan - late Porangan), Graptodinium inconditum (late Porangan - early Bortonian), and Impagidinium elegans (early Bortonian - late Bortonian); and the establishment of an additional new zone, the Stoveracysta kakanuiensis Zone, straddling the Eocene-Oligocene boundary

Developments in Polish trade with the European Union and Germany since transition

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Mixed-methods evaluation of an enhanced asthma biologics clinical pathway in the West Midlands UK

Biologic treatments can alleviate severe asthma symptoms and reduce health service use. However, service capacity limits and low referral rates from primary care indicate unmet patient need. We report a mixed-methods evaluation of an enhanced severe asthma pathway implemented in Staffordshire and Stoke-on-Trent, UK which aimed to optimise primary care referrals through training/education, and increased capacity in specialist clinics. Quantitative analysis assessed patient wait times between pathway stages, prescribing changes, exacerbations, hospital admissions and asthma control. Interviews with 12 stakeholders evaluated perceptions of the enhanced pathway across settings. In 12 months, 564 patients from 28 general practices were reviewed for biologics eligibility, of whom 125 (22.2%) were referred for specialist assessment. Wait times were significantly lower under the enhanced pathway when compared against historic patients following the standard pathway, and reduced overall from a mean of 76.4 to 26.7 weeks between referral and biologics initiation (p  <  0.001). Patients commencing biologics (n = 46) showed significantly reduced reliever inhaler prescribing rates (p  =  0.037), 60% lower oral steroid use (p  <  0.001), significantly reduced exacerbation rates (p  <  0.001) and fewer hospital admissions (p < 0.001) compared with the 12 months pre-treatment. Mean asthma control scores reduced from 3.13 pre-initiation to 1.89 post-initiation (p  <  0.001) – a clinically significant improvement. Interviewees viewed the enhanced pathway positively, although ongoing issues related to difficulties engaging primary care amid concerns around increased workloads and pathway capacity. The large number of referrals generated from a comparatively small number of general practices confirms substantial unmet need that an enhanced severe asthma pathway could help address if implemented routinely

A 3D Voronoi+Gapper Galaxy Cluster Finder in Redshift Space to z∼ 0.2 I: an Algorithm Optimized for the 2dFGRS

This paper is the first in a series, presenting a new galaxy cluster finder based on a three-dimensional Voronoi Tesselation plus a maximum likelihood estimator, followed by gapping-filtering in radial velocity(VoML+G). The scientific aim of the series is a reassessment of the diversity of optical clusters in the local universe. A mock galaxy database mimicking the southern strip of the magnitude(blue)-limited 2dF Galaxy Redshift Survey (2dFGRS), for the redshift range 0.009 N g ≥ 5, and 14% with N g < 5. The ensemble of VoML+G clusters has a ~59% completeness and a ~66% purity, whereas the subsample with N g ≥ 10, to z ~ 0.14, has greatly improved mean rates of ~75% and ~90%, respectively. The VoML+G cluster velocity dispersions are found to be compatible with those corresponding to "Millennium clusters" over the 300–1000 km s−1 interval, i.e., for cluster halo masses in excess of ~3.0 × 1013 M ⊙ h −1

A single nucleotide polymorphism in the p27Kip1 gene is associated with primary patency of lower extremity vein bypass grafts

ObjectiveFactors responsible for the variability in outcomes after lower extremity vein bypass grafting (LEVBG) are poorly understood. Recent evidence has suggested that a single nucleotide polymorphism (SNP) in the promoter region of the p27Kip1 gene, a cell-cycle regulator, is associated with coronary in-stent restenosis. We hypothesized an association with vein graft patency.MethodsThis was a retrospective genetic association study nested within a prospective cohort of 204 patients from three referral centers undergoing LEVBG for claudication or critical ischemia. The main outcome measure was primary vein graft patency.ResultsAll patients were followed up for a minimum of 1 year with duplex graft surveillance (median follow-up, 893 days; interquartile range, 539-1315). Genomic DNA was isolated and SNP analysis for the p27Kip1-838C>A variants was performed. Allele frequencies were correlated with graft outcome using survival analysis and Cox proportional hazards modeling. The p27Kip1-838C>A allele frequencies observed were CA, 53%; CC, 30%; and AA, 17%, satisfying Hardy-Weinberg equilibrium. Race (P = .025) and history of coronary artery disease (P = .027) were different across the genotypes; all other baseline variables were similar. Primary graft patency was greater among patients with the -838AA genotype (75% AA vs 55% CA/CC at 3 years; P = .029). In a Cox proportional hazards model including age, sex, race, diabetes, critical limb ischemia, redo (vs primary) bypass, vein type, and baseline C-reactive protein level, the p27Kip1-838AA genotype was significantly associated with higher graft patency (hazard ratio for failure, 0.4; 95% confidence interval, 0.17-0.93). Genotype was also associated with early (0-1 month) changes in graft lumen diameter by ultrasound imaging.ConclusionsThese data suggest that the p27Kip1-838C>A SNP is associated with LEVBG patency and, together with previous reports, underscore a central role for p27Kip1 in the generic response to vascular injury

Elevated local senescence in diabetic wound healing is linked to pathological repair via CXCR2.

© 2019 The Authors Cellular senescence can be broadly defined as a stable, but essentially irreversible, loss of proliferative capacity. Historically, senescence has been described as a negative outcome of advanced cellular age. It is now clear, however, that senescence represents a dynamic autonomous stress response, integral to long-term tumor suppression. Transient induction of a senescent phenotype has actually been suggested to promote regeneration in both liver and skin. Here, we explored the role of senescence in pathological aged and diabetic murine wound healing. Aged and diabetic wounds had greater numbers of senescent cells, and diabetic macrophages maintained altered retention of polarization and produced a CXCR2-enriched senescence-associated secretory phenotype (i.e., SASP). Of translational relevance, targeted expression of CXCR2 in primary human dermal fibroblasts led to paracrine induction of nuclear p21. Furthermore, a selective agonist to CXCR2 was able to reverse delayed healing in diabetic mice and accelerate ex vivo human skin wound healing. Collectively, these data suggest a hitherto unappreciated role for CXCR2 in mediating cellular senescence in pathological wound repair

Photocatalytic proton reduction by a computationally identified, molecular hydrogen-bonded framework

We show that a hydrogen-bonded framework, TBAP-α, with extended π-stacked pyrene columns has a sacrificial photocatalytic hydrogen production rate of up to 3108 μmol g-1 h-1. This is the highest activity reported for a molecular organic crystal. By comparison, a chemically-identical but amorphous sample of TBAP was 20-200 times less active, depending on the reaction conditions, showing unambiguously that crystal packing in molecular crystals can dictate photocatalytic activity. Crystal structure prediction (CSP) was used to predict the solid-state structure of TBAP and other functionalised, conformationally-flexible pyrene derivatives. Specifically, we show that energy-structure-function (ESF) maps can be used to identify molecules such as TBAP that are likely to form extended π-stacked columns in the solid state. This opens up a methodology for the a priori computational design of molecular organic photocatalysts and other energy-relevant materials, such as organic electronics

A 3D Voronoi+Gapper Galaxy Cluster Finder in Redshift Space to z ∼ 0.2. II. An Abundant Cluster Population Dominated by Late-type Galaxies Unveiled

We identify 1901 galaxy clusters (N g ≥ 2) with the VoML+G algorithm (Paper I) on the Two-Degree Field Galaxy Redshift Survey. We present the 341 clusters with at least 10 galaxies that are within 0.009 < z < 0.14 (the Catalog), of which 254 (~75%) have counterparts in the literature (NED), with the remainder (87) plausibly "new" because of incompleteness of previous searches or unusual galaxy contents. The 207 clusters within z = 0.04–0.09 are used to study the properties of the galaxy systems in the nearby universe, including their galaxy contents parameterized by the late-type galaxy fractions (f L ). For this nearly complete cluster subsample, we find the following: (i) 63% are dominated by early-type galaxies (i.e., the late-type-poor clusters, f L < 0.5) with corresponding mean multiplicity and logarithmic virial mass (in units of M ⊙) of 22 ± 1 and 12.91 ± 0.04, respectively; and (ii) 37% are dominated by late-type galaxies (i.e., the late-type-rich clusters, f L ≥ 0.5) with corresponding mean multiplicity and logarithmic virial mass (in units of M ⊙) of 15.7 ± 0.9 and 12.66 ± 0.07, respectively. The statistical analysis of the late-type fraction distribution supports, with a 3σ confidence level, the presence of two population components. It is suggested that the late-type-poor galaxy systems reflect and extend the class of Abell-APM-EDCC clusters and that the late-type-rich systems (~one-third of the total) belong to a new, previously unappreciated class. The late-type-rich clusters, on average high mass-to-light ratio systems, appear to be more clustered on large scales than the late-type-poor clusters. A class of late-type-rich clusters is not predicted by current theory

Adalimumab for Treating Moderate-to-Severe Hidradenitis Suppurativa: An Evidence Review Group Perspective of a NICE Single Technology Appraisal

As part of its single technology appraisal (STA) process, the UK National Institute for Health and Care Excellence (NICE) invited the manufacturer of adalimumab (AbbVie) to submit evidence on the clinical effectiveness and cost effectiveness of adalimumab for the treatment of moderate-to-severe hidradenitis suppurativa (HS). The appraisal assessed adalimumab as monotherapy in adult patients with an inadequate response to conventional systemic HS therapy. The School of Health and Related Research Technology Appraisal Group was commissioned to act as the independent Evidence Review Group (ERG). The ERG produced a critical review of the evidence for the clinical effectiveness and cost effectiveness of the technology based on the company’s submission to NICE. The evidence was mainly derived from three randomised controlled trials comparing adalimumab with placebo in adults with moderate-to-severe HS. The clinical-effectiveness review found that significantly more patients achieved a clinical response in the adalimumab groups than in the control groups but that the treatment effect varied between trials and there was uncertainty regarding its impact on a range of other relevant outcomes as well as long-term efficacy. The company’s submitted Markov model assessed the incremental cost effectiveness of adalimumab versus standard care for the treatment of HS from the perspective of the UK NHS and Personal Social Services (PSS) over a lifetime horizon. The original submitted model, including a patient access scheme (PAS), suggested that the incremental cost-effectiveness ratio (ICER) for adalimumab versus standard care was expected to be £16,162 per quality-adjusted life-year (QALY) gained. Following a critique of the model, the ERG’s preferred base case, which corrected programming errors and structural problems surrounding discontinuation rules and incorporated a lower unit cost for HS surgery, resulted in a probabilistic ICER of £29,725 per QALY gained. Based on additional analyses undertaken by the company and the ERG following the publication of the appraisal consultation document (ACD), the Appraisal Committee concluded that the maximum possible ICER for adalimumab compared with supportive care was between £28,500 and £33,200 per QALY gained but was likely to be lower. The Appraisal Committee recommended adalimumab (with the PAS) for the treatment of active moderate-to-severe HS in adults whose disease has not responded to conventional systemic therapy