Immunohistochemical detection of ERβ in breast cancer: towards more detailed receptor profiling?

Oestrogen receptor (ER) is used routinely to predict endocrine responsiveness in patients with breast cancer. A second ER, ERβ has been described but its significance remains undefined; most studies have described mRNA levels rather than protein expression. Here, we demonstrate for the first time, immunohistochemical detection of ERβ in archival breast tumours. © 2001 Cancer Research Campaignhttp://www.bjcancer.co

Oestrogen receptor beta: how should we measure this?

British Journal of Cancer (2002) 87, 687–687. doi:10.1038/sj.bjc.6600534 www.bjcancer.co

A brave new world: the new normal for general practice after the COVID-19 pandemic

General practice in the UK transformed almost overnight in March 2020 in response to the COVID-19 pandemic. Practices largely shut their doors, face-to-face consultations almost exclusively became remote consultations, research evidence was implemented within days of being published, and much routine work postponed and labelled ‘non-essential’. As we settle into this (temporary) new way of working, we have a unique opportunity to reflect on our old and new working practices and decide what we should continue, change, and stop doing. Specifically, we consider what this ‘new normal’ could be in terms of remote consulting, practice re-organisation, use and implementation of evidence, advanced care planning, patient behaviour and chronic disease management, and implications for future practice, research, and policy

Estimating primary production at depth from remote sensing

By use of a common primary-production model and identical photosynthetic parameters, four different methods were used to calculate quanta 1Q2 and primary production 1P2 at depth for a study of high-latitude North Atlantic waters. The differences among the four methods relate to the use of pigment information in the upper water column. Methods 1 and 2 use pigment biomass 1B2 as an input and a subtropical, empirical relation between K d 1diffuse attenuation coefficient2 and B to estimate Q at depth. Method 1 uses measured B, but Method 2 uses B derived from the Coastal Zone Color Scanner 1subtropical algorithm2 as inputs. Methods 3 and 4 use the phytoplankton absorption coefficient 1a ph 2 instead of B as input, and Method 3 uses empirically derived a ph 14402 and K d values, and Method 4 uses analytically derived a ph 14402 and a 1total absorption coefficient2 values based on the same remote measurements as Method 2. When the calculated and the measured values of Q1z2 and P1z2 were compared, Method 4 provided the closest results 3for P1z2, r 2 5 0.95 1n 5 242, and for Q1z2, r 2 5 0.92 1n 5 1124. Method 1 yielded the worst results 3for P1z2, r 2 5 0.56 and for Q1z2, r 2 5 0.814. These results indicate that one of the greatest uncertainties in the remote estimation of P can come from a potential mismatch of the pigment-specific absorption coefficient 1a ph *2, which is needed implicitly in current models or algorithms based on B. We point out that this potential mismatch can be avoided if we arrange the models or algorithms so that they are based on the pigment absorption coefficient 1a ph 2. Thus, except for the accuracy of the photosynthetic parameters and the above-surface light intensity, the accuracy of the remote estimation of P depends on how accurately a ph can be estimated, but not how accurately B can be estimated. Also, methods to derive a ph empirically and analytically from remotely sensed data are introduced. Curiously, combined application of subtropical algorithms for both B and K d to subarctic waters apparently compensates to some extent for effects that are due to their similar and implicit pigment-specific absorption coefficients for the calculation of Q1z2

The association of cold weather and all-cause and cause-specific mortality in the island of Ireland between 1984 and 2007

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.This article has been made available through the Brunel Open Access Publishing Fund.Background This study aimed to assess the relationship between cold temperature and daily mortality in the Republic of Ireland (ROI) and Northern Ireland (NI), and to explore any differences in the population responses between the two jurisdictions. Methods A time-stratified case-crossover approach was used to examine this relationship in two adult national populations, between 1984 and 2007. Daily mortality risk was examined in association with exposure to daily maximum temperatures on the same day and up to 6 weeks preceding death, during the winter (December-February) and cold period (October-March), using distributed lag models. Model stratification by age and gender assessed for modification of the cold weather-mortality relationship. Results In the ROI, the impact of cold weather in winter persisted up to 35 days, with a cumulative mortality increase for all-causes of 6.4% (95%CI=4.8%-7.9%) in relation to every 1oC drop in daily maximum temperature, similar increases for cardiovascular disease (CVD) and stroke, and twice as much for respiratory causes. In NI, these associations were less pronounced for CVD causes, and overall extended up to 28 days. Effects of cold weather on mortality increased with age in both jurisdictions, and some suggestive gender differences were observed. Conclusions The study findings indicated strong cold weather-mortality associations in the island of Ireland; these effects were less persistent, and for CVD mortality, smaller in NI than in the ROI. Together with suggestive differences in associations by age and gender between the two Irish jurisdictions, the findings suggest potential contribution of underlying societal differences, and require further exploration. The evidence provided here will hope to contribute to the current efforts to modify fuel policy and reduce winter mortality in Ireland

Acetate as a model for aspartate-based CXCR4 chemokine receptor binding of cobalt and nickel complexes of cross-bridged tetraazamacrocycles

A number of disease states including WHIM syndrome, HIV infection and cancer have been linked to the chemokine receptor CXCR4. High-affinity CXCR4 antagonist transition metal complexes of configurationally restricted bis-tetraazamacrocyclic ligands have been identified in previous studies. Recently synthesised and structurally characterised Co2+/Co3+ and Ni2+ acetate complexes of mono-macrocycle cross-bridged ligands have been used to mimic their known coordination interaction with the aspartate side chains on binding to CXCR4. Here, X-ray crystal structures for three Co2+/Co3+ acetate complexes and five Ni2+ acetate complexes are presented and demonstrate flexibility in the mode of binding to the acetate ligand concomitantly with the requisite cis-V-configured cross-bridged tetraazamacrocyle. Complexes of the smaller Co3+ metal ion exclusively bind acetate by chelating both oxygens of acetate. Larger Co2+ and Ni2+ metal ions in cross-bridged tetraazamacrocycles show a clear tendency to coordinate acetate in a monodentate fashion with a coordinated water molecule completing the octahedral coordination sphere. However, in unbridged tetraazamacrocycle acetate structures reported in the literature, the coordination preference is to chelate both acetate oxygens. We conclude that the short ethylene cross-bridge restricts the equatorial bulk of the macrocycle, prompting the metal ion to fill the equator with the larger monodentate acetate plus water ligand set. In unbridged ligand examples, the flexible macrocycle expands equatorially and generally only allows chelation of the sterically smaller acetate alone. These results provide insight for generation of optimised bis-macrocyclic CXCR4 antagonists utilising cobalt and nickel ions

New models of care: a liaison psychiatry service for medically unexplained symptoms and frequent attenders in primary care

Aims and method: This paper describes the process of setting up and the early results from a new liaison psychiatry service in primary care for people identified as frequent general practice attenders with long-term conditions or medically unexplained symptoms. Using a rapid evidence synthesis, we identified existing service models, mechanisms to identify and refer patients, and outcomes for the service. Considering this evidence, with local contingencies we defined options and resources. We agreed a model to set up a service in three diverse general practices. An evaluation explored the feasibility of the service and of collecting data for clinical, service and economic outcomes. Results: High levels of patient and staff satisfaction, and reductions in the utilisation of primary and secondary healthcare, with associated cost savings are reported. Clinical implications: A multidisciplinary liaison psychiatry service integrated in primary care is feasible and may be evaluated using routinely collected data

An empirical algorithm for light absorption by ocean water based on color

Empirical algorithms for the total absorption coefficient and absorption coefficient by pigments for surface waters at 440 nm were developed by applying a quadratic formula that combines two spectral ratios of remote-sensing reflectance. For total absorption coefficients ranging from 0.02 to 2.0 m⁻¹, a goodness of fit was achieved between the measured and modeled data with a root-mean-squared difference between the measured and modeled values for log10 scale(RMSDₗₒ₁₀) of 0.062 (15.3% for linear scale, number of samples N = 63), while RMSDₗₒ₁₀ is 0.111 ( 29.1% for linear scale, N = 126) for pigment absorption (ranging from 0.01 to 1.0 m⁻¹). As alternatives to pigment concentration algorithms, the absorption algorithms developed can be applied to the coastal zone color scanner and sea-viewing wide-field-of-view sensor data to derive inherent optical properties of the ocean. For the same data sets, we also directly related the chlorophyll a concentrations to the spectral ratios and obtained an RMSDₗₒ₁₀ value of 0.218 (65.2% for linear scale, N = 120) for concentrations ranging from 0.06 to 50.0 mg m⁻³. These results indicate that it is more accurate to estimate the absorption coefficients than the pigment concentrations from remotely sensed data. This is likely due to the fact that for the broad range of waters studied the pigment-specific absorption coefficient at 440nm ranged from 0.02 to 0.2 m² (mg chl)⁻¹. As an indirect test of the algorithms developed, the chlorophyll a concentration algorithm is applied to an independent global dataset and an RMSDₗₒ₁₀ of 0.191( 55.2% for linear scale, N = 919) is obtained. There is no independent global absorption data set available as yet to test the absorption algorithms