The cost-effectiveness of providing antenatal lifestyle advice for women who are overweight or obese: the LIMIT randomised trial

Background: Overweight and obesity during pregnancy is common, although robust evidence about the economic implications of providing an antenatal dietary and lifestyle intervention for women who are overweight or obese is lacking. We conducted a health economic evaluation in parallel with the LIMIT randomised trial. Women with a singleton pregnancy, between 10+0-20+0weeks, and BMI ≥ 25 kg/m2were randomised to Lifestyle Advice (a comprehensive antenatal dietary and lifestyle intervention) or Standard Care. The economic evaluation took the perspective of the health care system and its patients, and compared costs encountered from the additional use of resources from time of randomisation until six weeks postpartum. Increments in health outcomes for both the woman and infant were considered in the cost-effectiveness analysis. Mean costs and effects in the treatment groups allocated at randomisation were compared, and incremental cost effectiveness ratios (ICERs) and confidence intervals (95%) calculated. Bootstrapping was used to confirm the estimated confidence intervals, and to generate acceptability curves representing the probability of the intervention being cost-effective at alternative monetary equivalent values for the outcomes avoiding high infant birth weight, and respiratory distress syndrome. Analyses utilised intention to treat principles. Results: Overall, the increase in mean costs associated with providing the intervention was offset by savings associated with improved immediate neonatal outcomes, rendering the intervention cost neutral (Lifestyle Advice Group 11261.19±14573.97 versus Standard Care Group 11306.70±14562.02; p=0.094). Using a monetary value of $20,000 as a threshold value for avoiding an additional infant with birth weight above 4 kg, the probability that the antenatal intervention is cost-effective is 0.85, which increases to 0.95 when the threshold monetary value increases to$45,000. Conclusions: Providing an antenatal dietary and lifestyle intervention for pregnant women who are overweight or obese is not associated with increased costs or cost savings, but is associated with a high probability of cost effectiveness. Ongoing participant follow-up into childhood is required to determine the medium to long-term impact of the observed, short-term endpoints, to more accurately estimate the value of the intervention on risk of obesity, and associated costs and health outcomes

Genetic variation across RNA metabolism and cell death gene networks is implicated in the semantic variant of primary progressive aphasia

The semantic variant of primary progressive aphasia (svPPA) is a clinical syndrome characterized by neurodegeneration and progressive loss of semantic knowledge. Unlike many other forms of frontotemporal lobar degeneration (FTLD), svPPA has a highly consistent underlying pathology composed of TDP-43 (a regulator of RNA and DNA transcription metabolism). Previous genetic studies of svPPA are limited by small sample sizes and a paucity of common risk variants. Despite this, svPPA\xe2\x80\x99s relatively homogenous clinicopathologic phenotype makes it an ideal investigative model to examine genetic processes that may drive neurodegenerative disease. In this study, we used GWAS metadata, tissue samples from pathologically confirmed frontotemporal lobar degeneration, and in silico techniques to identify and characterize protein interaction networks associated with svPPA risk. We identified 64 svPPA risk genes that interact at the protein level. The protein pathways represented in this svPPA gene network are critical regulators of RNA metabolism and cell death, such as SMAD proteins and NOTCH1. Many of the genes in this network are involved in TDP-43 metabolism. Contrary to the conventional notion that svPPA is a clinical syndrome with few genetic risk factors, our analyses show that svPPA risk is complex and polygenic in nature. Risk for svPPA is likely driven by multiple common variants in genes interacting with TDP-43, along with cell death,x` working in combination to promote neurodegeneration

Reconstructing sea-level change from the internal architecture of stromatolite reefs: an example from the Mesoproterozoic Sulky Formation, Dismal Lakes Group, arctic Canada

The Mesoproterozoic Dismal Lakes Group, arctic Canada, contains a relatively thin, yet regionally extensive stromatolitic reef complex that developed subtidally during a major transgression, shoaled to sea level, and was overlain by intertidal to supratidal carbonate and evaporite strata. The September Lake reef complex exhibits a complex internal architecture that records the interaction between stromatolite growth and changes in accommodation space derived from both higher order (4th- or 5th-order, parasequence-scale) changes in sea level and the variable bathymetry of the sea floor. Reef growth, which was initiated during three sea-level cycles, records progressive marine transgression over depositional lows that were formed during pre-reef subaerial exposure and erosion of the underlying strata. A fourth sea-level cycle, represented by spectacular coniform stromatolites with \u3e10 m of synoptic relief, marks a more dramatic rise in sea level and establishment of the main reef complex. Aggradation and eventual shoaling of the reef complex occurred over an additional six sea-level cycles. Only basinward regions of the September Lake reef complex preserve vertical stacking of reefal packages in response to sea-level fluctuations. In contrast, in the main reef core, sea-level fluctuations resulted in subaerial exposure of the reef top, variable karst development, and the progressive infilling of reef topography by progradational reef elements. Assessment of stromatolite growth patterns reveals the complex nature of the reef architecture and permits the determination of higher order changes in relative sea level that were responsible for reef development. Le Groupe de Dismal Lakes (Mésoprotérozoïque), de l’Arctique canadien, contient un complexe récifal de stromatolithes, relativement mince mais d’une grande étendue, qui s’est développé sous le niveau des hautes marées durant une transgression majeure; il a été remonté au niveau de la mer et ensuite il a été recouvert par des strates de carbonate et d’évaporites intertidales à supratidales. Le complexe récifal de September Lake possède une architecture interne complexe qui enregistre l’interaction entre la croissance des stromatolithes et les changements dans les lieux habités, lesquels découlent de changements du niveau de la mer d’ordres supérieurs (4e ou 5e ordre à l’échelle de la paraséquence) et de la bathymétrie variable du plancher océanique. La récif a commencé à croître durant trois cycles de changement du niveau de la mer qui enregistrent une transgression marine progressive par-dessus des creux de déposition crées durant l’exposition sub-aérienne, avant la formation du récif, et l’érosion des strates sous-jacentes. Un quatrième cycle de fluctuation du niveau de la mer, représenté par des stromatolithes remarquables de forme conique ayant plus de 10 mètres de relief synoptique, marque une élévation du niveau de la mer plus spectaculaire et l’établissement du principal complexe récifal. L’aggradation et l’éventuelle remontée du complexe récifal se sont produites au cours de six autres cycles de changement du niveau de la mer. Uniquement les régions du côté du bassin du complexe récifal de September Lake gardent l’empilement vertical des ensembles récifaux en réponse aux fluctuations du niveau de la mer. À titre de comparaison, dans le noyau du récif principal, les fluctuations du niveau de la mer ont causé l’exposition subaérienne du sommet du récif, le développement variable de karsts et le remplissage progressif de la topographie du récif par des éléments récifaux de progradation. L’évaluation des patrons de croissance des stromatolithes révèle la nature complexe de l’architecture du récif et permet de déterminer les changements d’ordre supérieur des niveaux relatifs de la mer qui sont responsables du développement du récif

Molar Tooth Structures in Calcareous Nodules, Early Neoproterozoic Burovaya Formation, Turukhansk Region, Siberia

Molar tooth structures are abundant in large (1-2 m diameter) carbonate nodules within fine-grained, subtidal carbonates of the early Neoproterozoic (lower Upper Riphean) Burovaya Formation along the Sukhaya Tunguska River, Turukhansk Uplift, northwestern Siberia. Although molar tooth structures are regionally abundant in this unit, here they occur only within the nodules. Stable isotopic compositions of molar-tooth-filling dolomicrospar cements and of thinly bedded dolomicrite within and surrounding the nodules are indistinguishable from one another. The carbon isotopic compositions (mean δ13C= + 2.8% PDB+/- 0.4) reflect mean average oceanic surface water composition during their formation; the light oxygen isotopic compositions (mean δ18O = -6.4% PDB+/- 2.2) are generally similar to those of other little-altered Meso- to Neoproterozoic limestones and dolostones. These molar tooth structures have no features that would support a tectonic origin; they more likely formed through bacterial processes. Carbonate cement filling of these voids occurred soon after their fort-nation, but the mechanism responsible for this carbonate precipitation is currently uncertain. Local restriction of molar tooth structures to early diagenetic nodules suggests that penecontemporaneous lithification was required for the formation, or at least preservation, of these widespread Mesoproterozoic to Neoproterozoic features.Organismic and Evolutionary Biolog

Microbialites in a high-altitude andean lake: multiple controls in carbonate precipitation and lamina accretion

Microbialites comprise the mineralized record of early life on Earth and preserve a spectrum of fabrics that reflect complex physical, chemical, and biological interactions. The relatively rarity of microbialites in modern environments, however, challenges our interpretation of ancient structures. Here we report the occurrence of microbial mats, mineral precipitates, and stromatolitic oncolites in the Laguna Negra, a high-altitude Andean lake in Catamarca Province,Argentina. Extreme environmental conditions, including high UV-radiation, salinity, and temperature extremes, restrict multicellular life so that mineralization reflects a combination of local hydrologic conditions, lake geochemistry, and microbial activity. The resulting carbonate microtextures are strikingly similar to those observed in Proterozoic stromatolites, providing insight into potential mechanisms of mineralization. Here, increased saturation in carbonate minerals due to mixing of spring-fed inlets and lake waters favors microbialite formation and preservation. This highlights the importance of hydrological mixing zones in microbialites formation and as taphonomic windows to record microbial activity. Recent discoveries of minerals related to evaporating playa-lake systems on Mars further highlights the potential of Laguna Negra to provide critical insight into biosignature preservation in both terrestrial and extraterrestrial settings.Fil: Gomez, Fernando Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Ciencias de la Tierra. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Centro de Investigaciones en Ciencias de la Tierra; ArgentinaFil: Kah, Linda C.. University of Tennessee; Estados UnidosFil: Bartley, Julie K.. Gustavus Adolphus College; Estados UnidosFil: Astini, Ricardo Alfredo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Ciencias de la Tierra. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Centro de Investigaciones en Ciencias de la Tierra; Argentin

A Vendian-Cambrian Boundary Succession from the Northwestern Margin of the Siberian Platform: Stratigraphy, Palaeontology, Chemostratigraphy and Correlation

Siberia contains several key reference sections for studies of biological and environmental evolution across the Proterozoic-Phanerozoic transition. The Platonovskaya Formation, exposed in the Turukhansk region of western Siberia, is an uppermost Proterozoic to Cambrian succession whose trace and body fossils place broad limits on the age of deposition, but do not permit detailed correlation with boundary successions elsewhere. In contrast, a striking negative carbon isotopic excursion in the lower part of the Platonovskaya Formation permits precise chemostratigraphic correlation with uppermost Yudomian successions in Siberia, and possibly worldwide. In addition to providing a tool for correlation, the isotopic excursion preserved in the Platonovskaya and contemporaneous successions documents a major biogeochemical event, likely involving the world ocean. The excursion coincides with the palaeontological breakpoint between Ediacaran- and Cambrian-style assemblages, suggesting a role for biogeochemical change in evolutionary events near the Proterozoic-Cambrian boundary.Organismic and Evolutionary Biolog

A toxic epidermal necrolysis-like presentation of linear IgA bullous dermatosis treated with dapsone

Linear IgA bullous dermatosis is a rare autoimmune vesiculobullous disease characterized by linear deposition of IgA along the basement membrane zone. It is classically idiopathic, but may also arise secondary to drug exposure. A heterogeneous spectrum of clinical features has been described, including a rare, morbid variant mimicking toxic epidermal necrolysis. Herein, we present a case of vancomycin-induced linear IgA bullous dermatosis that manifested clinically as toxic epidermal necrolysis and resolved with dapsone therapy

Global Events Across the Mesoproterozoic-Neoproterozoic Boundary: C and Sr Isotopic Evidence from Siberia

Thick, unmetamorphosed successions of siliciclastic and carbonate rocks in eastern and western Siberia preserve a record of Middle Riphean to Early Upper Riphean sedimentary environments and geochemistry. Consistent with data from other continents, our studies in the Uchur-Maya region in southeastern Siberia and the Turukhansk Uplift in northwestern Siberia suggest a first-order shift in delta C-13 from values near 0 parts per thousand in the early Mesoproterozoic to values near +3.5 parts per thousand after about 1300 Ma. Over this same interval, primary Sr-87/Sr-86 values decrease from > 0.7060 to < 0.7053. Combining lithologic, biostratigraphic, and geochemical data sets with available geochronologic constraints, we present a refined correlation between these two key Proterozoic successions in Siberia and add this dataset to a growing body of C and Sr isotopic data from this time interval, Carbon isotope chemostratigraphy from these regions supports the occurrence and timing of a first-order, similar to 3.5 parts per thousand positive shift ca. 1250-1300 Ma, approximately coeval with the onset of active margin activity that predates the main phase of Rodinia assembly. Sr isotopic data may also be interpreted within the context of the evolving Mesoproterozoic tectonic regime. Available data suggest that no dramatic rise in Sr-87/Sr-86 heralds the main phase of Rodinia assembly in the terminal Mesoproterozoic, suggesting that significant juvenile crust was involved in mountain building, that relative hydrothermal flux from mid-ocean ridges remained high throughout the assembly of Rodinia and/or that increased continental runoff related to intense erosion of Grenvillian mountain belts terminated shortly after orogeny.Earth and Planetary SciencesOrganismic and Evolutionary Biolog