Premature ovarian insufficiency: the need for evidence on the effectiveness of hormonal therapy

Premature ovarian insufficiency (POI) – the loss of ovarian function before the age of 40 years, a decade before natural menopause – is a life-changing diagnosis for women. POI causes significant short-term and long-term morbidity related to estrogen deficiency. The condition is managed by providing exogenous estrogen replacement, usually as the oral contraceptive pill or hormone therapy. These preparations have different estrogen formulations and may have differing benefits and risks. At present, there are no robust data to inform clinical recommendations and women’s decision-making about treatment that they may be taking for many years. The POISE study (Premature Ovarian Insufficiency Study of Effectiveness of hormonal therapy) has been designed to determine whether hormone therapy is superior to combined oral contraceptives on important clinical outcomes and patient-reported symptoms, based on the hypothesis that hormone therapy provides more physiological continuous hormone supplementation with natural estrogens. The study is an open and pragmatic, parallel, randomized controlled trial. The primary outcome is absolute bone mineral density assessed by dual-energy X-ray absorptiometry of the lumbar spine after 2 years of treatment. The study will also investigate cardiovascular markers, symptom relief and acceptability of treatment, and will continue to collect long-term data on fractures and cardiovascular events. Results will inform future guidance on management of POI

Seasonal phosphorus and carbon dynamics in a temperate shelf sea (Celtic Sea): uptake, partitioning, release, turnover and stoichiometry.

The seasonal cycle of resource availability in shelf seas has a strong selective pressure on phytoplankton diversity and the biogeochemical cycling of key elements, such as carbon (C) and phosphorus (P). Shifts in carbon consumption relative to P availability, via changes in cellular stoichiometry for example, can lead to an apparent ‘excess’ of carbon production. We made measurements of inorganic P (Pi) uptake, in parallel to C-fixation, by plankton communities in the Celtic Sea (NW European Shelf) in spring (April 2015), summer (July 2015) and autumn (November 2014). Short-term (< 8 h) Pi-uptake coupled with dissolved organic phosphorus (DOP) release, in parallel to net (24 h) primary production (NPP), were all measured across an irradiance gradient designed to typify vertically and seasonally varying light conditions. Rates of Pi-uptake were highest during spring and lowest in the low light conditions of autumn, although biomass-normalised Pi-uptake was highest in the summer. The release of DOP was highest in November and declined to low levels in July, indicative of efficient utilization and recycling of the low levels of Pi available. Examination of daily turnover times of the different particulate pools, including estimates of phytoplankton and bacterial carbon, indicated a differing seasonal influence of autotrophs and heterotrophs in P-dynamics, with summer conditions associated with a strong bacterial influence and the early spring period with fast growing phytoplankton. These seasonal changes in autotrophic and heterotrophic influence, coupled with changes in resource availability (Pi, light) resulted in seasonal changes in the stoichiometry of NPP to daily Pi-uptake (C:P ratio); from relatively C-rich uptake in November and late April, to P-rich uptake in early April and July. Overall, these results highlight the seasonally varying influence of both autotrophic and heterotrophic components of shelf sea ecosystems on the relative uptake of C and P

Seasonal and spatial variability in the optical characteristics of DOM in a temperate shelf sea

The Celtic Sea is a productive temperate sea located on the Northwest European Shelf. It is an important pathway for the delivery of land-derived material to the North Atlantic Ocean, including dissolved organic matter (DOM). The aim of this study was to determine the seasonal and spatial variability in the magnitude, source and composition of DOM at three sites representing on shelf, central shelf and shelf edge regions in the Celtic Sea, using observations collected during the UK Shelf Sea Biogeochemistry (SSB) research programme (November 2014 – August 2015). The concentration of dissolved organic carbon (DOC) alongside DOM absorbance and fluorescence indices were measured and fluorescence Excitation and Emission Matrices (EEMs) combined with Parallel Factor Analysis (PARAFAC) were used to assess DOM composition and lability. The PARAFAC model identified four unique fluorescent components for autumn (November 2014), winter (March 2015), spring (April 2015) and summer (July 2015) consisting of two humic-like components attributed to terrestrial (C1) and marine sources (C2), and two protein components identified as tyrosine-like (C3) and tryptophan-like (C4) attributed to in situ production. DOC varied seasonally and there were strong cross shelf trends. The protein components (C3 and C4) exhibited large seasonal and within season variability particularly during productive periods. In contrast, there were persistent cross shelf gradients in the CDOM absorption coefficient at 305 nm (a305), the UV specific absorbance at 280 nm (SUVA280), the humification index (HIX), and the humic-like fluorescent components (C1 and C2), which were higher in the on shelf region and decreased towards the shelf edge. The humic-like components and the slope ratio (SR) were significantly correlated with salinity throughout all seasons, indicating a strong influence of terrestrially-derived organic matter in the Celtic Sea, with potentially up to 35% of DOC in the central shelf during winter originating from terrestrial inputs. Results from this study illustrate the importance of monitoring DOM quantitatively and qualitatively for a better understanding of the supply, production, cycling and export of this dynamic organic carbon pool in shelf seas

Dissolution Dominates Silica Cycling in a Shelf Sea Autumn Bloom

Autumn phytoplankton blooms represent key periods of production in temperate and high‐latitude seas. Biogenic silica (bSiO2) production, dissolution, and standing stocks were determined in the Celtic Sea (United Kingdom) during November 2014. Dissolution rates were in excess of bSiO2 production, indicating a net loss of bSiO2. Estimated diatom bSiO2 contributed ≤10% to total bSiO2, with detritalbSiO2 supportingrapidSicycling.Basedontheaveragebiomass‐specificdissolutionrate(0.2day−1), 3weekswouldbeneededtodissolve99%ofthebSiO2 present.NegativenetbSiO2 productionwasassociated with low‐light conditions (<4 E·m−2·day−1). Our observations imply that dissolution dominates Si cycling during autumn, with low‐light conditions also likely to influence Si cycling during winter and early spring

Stime di emissioni di inquinanti provenienti da sorgenti di traffico nell’area veneziana.

Purpose: Wnt signalling has been implicated in breast cancer, and in particular aberrant β-catenin-independent Wnt signalling has been associated with breast cancer metastasis and Tamoxifen resistance. Despite Wnt pathway involvement in many human cancers, attempts to target the pathway therapeutically have been disappointing. The recent discovery that the receptor tyrosine kinase-like orphan receptor 2 (ROR2) is a novel Wnt receptor provides a potential new therapeutic and diagnostic target

Field assessment of the potential for small scale co-cultivation of seaweed and shellfish to regulate nutrients and plankton dynamics

This is the final version. Available on open access from Elsevier via the DOI in this recordData Availability; Data will be made available on request.The co-cultivation of seaweed alongside shellfish has the potential to regulate local dissolved nutrient concentrations and consequently affect plankton dynamics. Evidence for this has until now come largely from computational modelling and laboratory studies, rather than field studies. Here we report on weekly/bi-weekly profiling of inorganic nutrient concentrations (nitrate, nitrite, ammonium, phosphate, and silicate) over two years (2019–2020) at three sampling stations across a small-scale (16 ha) kelp and mussel farm in Porthallow Bay, Cornwall, UK. Nutrient concentrations were measured in conjunction with a range of related environmental variables, including water temperature, salinity, clarity, and phyto- and zoo- plankton abundance, biomass and community composition. These environmental data were also supplemented with river discharge data. Our results indicate typical seasonal variations in chemical (nutrient), physical (hydrographic), and biological (plankton) parameters across all three sampling stations and no significant reductions in inorganic nutrient concentrations in the water column downstream from the integrated kelp and shellfish farm. We conclude that the effectiveness of nutrient regulation by integrating seaweed and shellfish aquaculture will depend on local climatic and hydro-geochemical conditions (affecting background nutrient inputs), as well as the design and scale of integrated multi–trophic aquaculture (IMTA) systems.Natural Environment Research Council (NERC)European Maritime and Fisheries FundFishmongers' Company's Charitable Trust, UKCornish Seaweed CompanyWestcountry Mussels of FoweyCornwall Inshore Fisheries Conservation AuthorityUKR

Normal levels of p27Xic1 are necessary for somite segmentation and determining pronephric organ size

The Xenopus laevis cyclin dependent kinase inhibitor p27Xic1 has been shown to be involved in exit from the cell cycle and differentiation of cells into a quiescent state in the nervous system, muscle tissue, heart and retina. We show that p27Xic1 is expressed in the developing kidney in the nephrostomal regions. Using over-expression and morpholino oligonucleotide (MO) knock-down approaches we show normal levels of p27Xic1 regulate pronephros organ size by regulating cell cycle exit. Knock-down of p27Xic1 expression using a MO prevented myogenesis, as previously reported; an effect that subsequently inhibits pronephrogenesis. Furthermore, we show that normal levels of p27Xic1 are required for somite segmentation also through its cell cycle control function. Finally, we provide evidence to suggest correct paraxial mesoderm segmentation is not necessary for pronephric induction in the intermediate mesoderm. These results indicate novel developmental roles for p27Xic1, and reveal its differentiation function is not universally utilised in all developing tissues

Wave vision

The basic applications of radio waves are communication an

Do adults with high functioning autism or Asperger Syndrome differ in empathy and emotion recognition?

The present study examined whether adults with high functioning autism (HFA) showed greater difficulties in (i) their self-reported ability to empathise with others and/or (ii) their ability to read mental states in others’ eyes than adults with Asperger syndrome (AS). The Empathy Quotient (EQ) and ‘Reading the Mind in the Eyes’ Test (Eyes Test) were compared in 43 adults with AS and 43 adults with HFA. No significant difference was observed on EQ score between groups, while adults with AS performed significantly better on the Eyes Test than those with HFA. This suggests that adults with HFA may need more support, particularly in mentalizing and complex emotion recognition, and raises questions about the existence of subgroups within autism spectrum conditions