Endocrine therapy for breast cancer: a model of hormonal manipulation

Oestrogen receptor (ER) is the driving transcription factor in 70% of breast cancer. Endocrine therapies targeting the ER represent one of the most successful anticancer strategies to date. In the clinic, novel targeted agents are now being exploited in combination with established endocrine therapies to maximise efficacy. However, clinicians must balance this gain against the risk to patients of increased side effects with combination therapies. This article provides a succinct outline of the principles of hormonal manipulation in breast cancer, alongside the key evidence that underpins current clinical practice. As the role of endocrine therapy in breast cancer continues to expand, the challenge is to interpret the data and select the optimal strategy for a given clinical scenario

Options for early breast cancer follow-up in primary and secondary care : a systematic review

Background Both incidence of breast cancer and survival have increased in recent years and there is a need to review follow up strategies. This study aims to assess the evidence for benefits of follow-up in different settings for women who have had treatment for early breast cancer. Method A systematic review to identify key criteria for follow up and then address research questions. Key criteria were: 1) Risk of second breast cancer over time - incidence compared to general population. 2) Incidence and method of detection of local recurrence and second ipsi and contra-lateral breast cancer. 3) Level 1–4 evidence of the benefits of hospital or alternative setting follow-up for survival and well-being. Data sources to identify criteria were MEDLINE, EMBASE, AMED, CINAHL, PSYCHINFO, ZETOC, Health Management Information Consortium, Science Direct. For the systematic review to address research questions searches were performed using MEDLINE (2011). Studies included were population studies using cancer registry data for incidence of new cancers, cohort studies with long term follow up for recurrence and detection of new primaries and RCTs not restricted to special populations for trials of alternative follow up and lifestyle interventions. Results Women who have had breast cancer have an increased risk of a second primary breast cancer for at least 20 years compared to the general population. Mammographically detected local recurrences or those detected by women themselves gave better survival than those detected by clinical examination. Follow up in alternative settings to the specialist clinic is acceptable to women but trials are underpowered for survival. Conclusions Long term support, surveillance mammography and fast access to medical treatment at point of need may be better than hospital based surveillance limited to five years but further large, randomised controlled trials are needed

How people with dementia and their families decide about moving to a care home and support their needs: development of a decision aid, a qualitative study

yesBackground: People with dementia and their relatives find decisions about the person with dementia living in a care home difficult. Methods: We interviewed 20 people with dementia or family carers around the time of this decision in order to design a decision-aid. Results: Decision-makers balanced the competing priorities of remaining somewhere familiar, family’s wish they remain at home, reduction of risk and effects on carer’s and person with dementia’s physical health. The person with dementia frequently resented their lack of autonomy as decisions about care home moves were made after insight and judgment were impaired. Family consultation usually helped carers but sometimes exacerbated tensions. Direct professional support was appreciated where it was available. There is a need for healthcare professionals to facilitate these conversations around decision-making and to include more than signposting to other organisations. Conclusions: There is a need for a healthcare professional facilitated decision-aid. This should detail what might change for the person with dementia and their carer, possible resources and alternatives and assist in facilitating discussion with the wider family; further research will develop and test a tool to facilitate decision making about place of care needs

Search for Second-Generation Scalar Leptoquarks in ppˉ\bm{p \bar{p}} Collisions at s\sqrt{s}=1.96 TeV

Results on a search for pair production of second generation scalar leptoquark in $p \bar{p}$ collisions at $\sqrt{s}$=1.96 TeV are reported. The data analyzed were collected by the CDF detector during the 2002-2003 Tevatron Run II and correspond to an integrated luminosity of 198 pb$^{-1}$. Leptoquarks (LQ) are sought through their decay into (charged) leptons and quarks, with final state signatures represented by two muons and jets and one muon, large transverse missing energy and jets. We observe no evidence for $LQ$ production and derive 95% C.L. upper limits on the $LQ$ production cross sections as well as lower limits on their mass as a function of $\beta$, where $\beta$ is the branching fraction for $LQ \to \mu q$.Comment: 9 pages (3 author list) 5 figure

Measurement of the B0 anti-B0 oscillation frequency using l- D*+ pairs and lepton flavor tags

The oscillation frequency Delta-md of B0 anti-B0 mixing is measured using the partially reconstructed semileptonic decay anti-B0 -> l- nubar D*+ X. The data sample was collected with the CDF detector at the Fermilab Tevatron collider during 1992 - 1995 by triggering on the existence of two lepton candidates in an event, and corresponds to about 110 pb-1 of pbar p collisions at sqrt(s) = 1.8 TeV. We estimate the proper decay time of the anti-B0 meson from the measured decay length and reconstructed momentum of the l- D*+ system. The charge of the lepton in the final state identifies the flavor of the anti-B0 meson at its decay. The second lepton in the event is used to infer the flavor of the anti-B0 meson at production. We measure the oscillation frequency to be Delta-md = 0.516 +/- 0.099 +0.029 -0.035 ps-1, where the first uncertainty is statistical and the second is systematic.Comment: 30 pages, 7 figures. Submitted to Physical Review

Bait uptake by wild badgers and its implications for oral vaccination against tuberculosis

This is the final version. Available from Public Library of Science via the DOI in this record.Data Availability: All relevant data are within the paper and its Supporting Information files.The deployment of baits containing vaccines or toxins has been used successfully in the management of wildlife populations, including for disease control. Optimisation of deployment strategies seeks to maximise uptake by the targeted population whilst ensuring cost-effectiveness. Tuberculosis (TB) caused by infection with Mycobacterium bovis affects a broad range of mammalian hosts across the globe, including cattle, wildlife and humans. The control of TB in cattle in the UK and Republic of Ireland is hampered by persistent infection in European badgers (Meles meles). The present study aimed to determine the best strategy for maximising uptake of an oral vaccine by wild badgers, using a surrogate novel bait deployed at 40 badger social groups. Baits contained a blood-borne biomarker (Iophenoxic Acid, IPA) in order to measure consumption in badgers subsequently cage trapped at targeted setts. Evidence for the consumption of bait was found in 83% (199/240) of captured badgers. The probability that badgers had consumed at least one bait (IPA >10 μg ml-1) was significantly higher following deployment in spring than in summer. Lower uptake amongst social groups where more badgers were captured, suggested competition for baits. The probability of bait consumption was significantly higher at groups where main and outlier setts were provided with baits than at those where outliers were present but not baited. Badgers captured 10–14 days post bait feeding had significantly higher levels of bait uptake compared to those caught 24–28 days later. Uptake rates did not vary significantly in relation to badger age and whether bait was placed above ground or down setts. This study suggests that high levels of bait uptake can be achieved in wild badger populations and identifies factors influencing the potential success of different deployment strategies. The implications for the development of an oral badger vaccine are discussed.Natural Environment Research Council (NERC)Animal and Plant Health Agency (APHA

Screening for atrial fibrillation – a cross-sectional survey of healthcare professionals in primary care

Introduction: Screening for atrial fibrillation (AF) in primary care has been recommended; however, the views of healthcare professionals (HCPs) are not known. This study aimed to determine the opinions of HCP about the feasibility of implementing screening within a primary care setting. Methods: A cross-sectional mixed methods census survey of 418 HCPs from 59 inner-city practices (Nottingham, UK) was conducted between October-December 2014. Postal and web-surveys ascertained data on existing methods, knowledge, skills, attitudes, barriers and facilitators to AF screening using Likert scale and open-ended questions. Responses, categorized according to HCP group, were summarized using proportions, adjusting for clustering by practice, with 95% C.Is and free-text responses using thematic analysis. Results: At least one General Practitioner (GP) responded from 48 (81%) practices. There were 212/418 (51%) respondents; 118/229 GPs, 67/129 nurses [50 practice nurses; 17 Nurse Practitioners (NPs)], 27/60 healthcare assistants (HCAs). 39/48 (81%) practices had an ECG machine and diagnosed AF in-house. Non-GP HCPs reported having less knowledge about ECG interpretation, diagnosing and treating AF than GPs. A greater proportion of non-GP HCPs reported they would benefit from ECG training specifically for AF diagnosis than GPs [proportion (95% CI) GPs: 11.9% (6.8–20.0); HCAs: 37.0% (21.7–55.5); nurses: 44.0% (30.0–59.0); NPs 41.2% (21.9–63.7)]. Barriers included time, workload and capacity to undertake screening activities, although training to diagnose and manage AF was a required facilitator. Conclusion: Inner-city general practices were found to have adequate access to resources for AF screening. There is enthusiasm by non-GP HCPs to up-skill in the diagnosis and management of AF and they may have a role in future AF screening. However, organisational barriers, such as lack of time, staff and capacity, should be overcome for AF screening to be feasibly implemented within primary care

Erratum: Sequence data and association statistics from 12,940 type 2 diabetes cases and controls.

This corrects the article DOI: 10.1038/sdata.2017.179