A randomised controlled trial of Pre-Operative Oncotype DX testing in early-stage breast cancer (PRE-DX study) - Study protocol

Background The Oncotype DX® Breast Recurrence Score assay can guide recommendations made to patients with oestrogen receptor positive (ER+), human epidermal growth factor receptor 2 negative (HER2-) breast cancer regarding post-surgery adjuvant therapy. Standard practice is to order the test in the post-operative setting on a specimen from the excised invasive carcinoma. However, it has been shown to be technically possible to perform the test on the diagnostic core biopsy. By testing the diagnostic core biopsy in the pre-operative setting, the wait for excised invasive carcinoma Recurrence Score results could be reduced allowing patients to be more accurately counselled regarding their treatment pathway sooner with any adjuvant treatment recommendations expedited. This would allow for more efficient streaming of follow up appointments. The aim of this study is to compare the impact on the patient treatment pathway of performing the Oncotype DX® test on the diagnostic core biopsy pre-operatively (intervention) as opposed to the excised invasive carcinoma (control). Methods and analysis This parallel group randomised controlled trial aims to recruit 330 newly diagnosed patients with grade 2 or grade 3, ER+, HER2-, invasive intermediate risk early-stage breast cancer. Participants will be randomised 2:1 to the preoperative testing of the diagnostic core biopsy compared to the post-operative testing of the excision specimen. The primary endpoint is number of clinical touchpoints between treating team and patient from initial approach until offer and prescription of the first adjuvant treatment. Secondary endpoints include time from diagnosis to offer and prescription of the first adjuvant treatment, patient-reported anxiety scores and health cost impact analysis collected at baseline, following the post-operative clinic and following the offer of adjuvant treatment, and number of alterations in treatment sequence from original planned surgical treatment to neoadjuvant therapy

Emigration of post-spawned twaite shad Alosa fallax, an anadromous and iteroparous fish, in a highly fragmented river

Anthropogenic barriers are widely known to negatively impact the spawning migrations of anadromous fishes, by delaying or preventing passage upstream. Although the impacts of barriers on emigrating post-spawned adults are less well studied, they could potentially impact the fitness and subsequent return rates of iteroparous species. In this study, passive acoustic telemetry was used to track the emigrations of 53 twaite shad Alosa fallax in the River Severn basin in their first spawning migration a year after being tagged, giving insights into their emigration movements and the impacts of anthropogenic weirs on these movements. A. fallax began their emigrations after spending varying amounts of time and migrating various distances within the river, with late-emigrating individuals moving fastest and most directly. Emigrations became faster and more direct the further downstream individuals were from their furthest upstream extent. Downstream passage delays at weirs increased emigration times by a median of 61%, with environmental conditions (i.e., temperature, flow, and tidal influence on river level) having little influence on downstream passage at weirs with no modifications to facilitate fish passage. As weir-induced emigration delays are suggested to deplete energy reserves (when energy levels are already depleted post-spawning), limit spawning opportunities (by preventing access to downstream spawning habitat), and expose individuals to increased predation risk and suboptimal conditions (e.g., high temperatures), these delays can potentially diminish the benefits of iteroparity. The evidence presented here suggests that more consideration should be given to the potential impacts of anthropogenic barriers on the emigrations of iteroparous species when assessing river connectivity or undertaking barrier mitigation

Proua van Gogh

Aastal 1890 sureb Vincent van Gogh rahata, tundmatuna, vaimus piinatud mehena. Tal on õnnestunud müüa vaid üksainus teos.Alles üksteist aastat hiljem pannakse tema tööd Pariisis välja. Vincent van Gogh saab maailmakuulsaks.See oli ühe naise, Johanna van Gogh-Bongeri väsimatu pingutus.Kuid kes oli see Jo, kes pühendas oma elu varalahkunud abikaasa Theo ja mehevenna Vincent van Goghi töö jätkamisele ja pärandi hoidmisele, hoolimata sellest, et ta trügis meeste maailma, kus teda sugugi ei oodatud? Mida ta tegi, et võis lõpuks kirjutada „Ma tunnen, et olen oma võitluse võitnud“

Quantum Dot Imaging Agents: Haematopoietic Cell Interactions and Biocompatibility

Quantum dots (QDs) are semi-conducting nanoparticles that have been developed for a range of biological and non-biological functions. They can be tuned to multiple different emission wavelengths and can have significant benefits over other fluorescent systems. Many studies have utilised QDs with a cadmium-based core; however, these QDs have since been shown to have poor biological compatibility. Therefore, other QDs, such as indium phosphide QDs, have been developed. These QDs retain excellent fluorescent intensity and tunability but are thought to have elevated biological compatibility. Herein we discuss the applicability of a range of QDs to the cardiovascular system. Key disease states such as myocardial infarction and stroke are associated with cardiovascular disease (CVD), and there is an opportunity to improve clinical imaging to aide clinical outcomes for these disease states. QDs offer potential clinical benefits given their ability to perform multiple functions, such as carry an imaging agent, a therapy, and a targeting motif. Two key cell types associated with CVD are platelets and immune cells. Both cell types play key roles in establishing an inflammatory environment within CVD, and as such aid the formation of pathological thrombi. However, it is unclear at present how and with which cell types QDs interact, and if they potentially drive unwanted changes or activation of these cell types. Therefore, although QDs show great promise for boosting imaging capability, further work needs to be completed to fully understand their biological compatibility

Working with wood in rivers in the Western United States

Recognition of the important physical and ecological roles played by large wood in channels and on floodplains has grown substantially during recent decades. Although large wood continues to be routinely removed from many river corridors worldwide, the practice of wood reintroduction has spread across the United States, the United Kingdom and western Europe, Australia, and New Zealand. The state-of-science regarding working with wood in rivers was discussed during a workshop held in Colorado, USA, in September 2022 with 40 participants who are scientists and practitioners from across the USA, UK, Europe, and Japan. The objectives of this paper are to present the findings from the workshop; summarize two case studies of wood in river restoration in the western United States; and provide suggestions for advancing the practice of wood in river management. We summarize the workshop results based on participant judgements and recommendations with respect to: (i) limitations and key barriers to using wood, which reflect perceptions and practicalities; (ii) gaps in the use of large wood in river management; (iii) scenarios in which wood is generally used effectively; and (iv) scenarios in which wood is generally not used effectively. The case studies illustrate the importance of the local geomorphic context, the configuration complexity of the wood, and the potential for modification of river corridor morphology to enhance desired benefits. Moving forward, we stress the importance of collaboration across disciplines and across communities of research scientists, practitioners, regulators, and potential stakeholders; accounting for stakeholder perceptions of the use of large wood; and increasing non-scientist access to the latest state-of-science knowledge

Parenteral nutrition and venting gastrostomy in the management of malignant bowel obstruction

Background: Malignant bowel obstruction (MBO) is a distressing complication of gastrointestinal, gynaecological and other cancers causing severe pain, intractable nausea and vomiting, anorexia, and death. There are no agreed best approaches for symptom control, or to improve survival.Aim: I aimed to evaluate the current practice of percutaneous venting gastrostomy (PVG) and parenteral nutrition (PN) in inoperable malignant bowel obstruction (MBO) relating to benefits and harms and the views and experiences of patients, their family carers and clinicians.Methods: In this multiple-methods thesis I used a i) mixed-methods systematic review and narrative synthesis of published literature aimed to investigate how PVG and PN in MBO affect clinical and quality-of-life (QoL) outcomes and, ii) two-site mixed-methods study; a retrospective consecutive cohort study using clinical record data (opt-out consent) to observe management and clinical outcomes of inpatients with MBO, including those making the clinical decisions; qualitative in-depth interviews of those involved in caring for people with MBO to explore the views, experiences and decision-making of MBO in health care professionals (HCPs). Mixed-methods findings were synthesised using a modified critical interpretative synthesis and then integrated with the systematic review results.Findings: Review findings from 47 included studies highlighted the lack of high-quality evidence that PN improves survival in those MBO. PN and VPG allow people valuable time at home. PN appears to improve QoL but with PN-associated burdens. PVG provides immediate and effective symptom relief and improves QoL for most. Most patients trusted their clinical team and felt they had little choice but to agree with a decision already made, often presented as ‘do or die’ or with conflicting information.Mixed-methods data (total cohort n = 143; interviews n = 14) show surgery and home PN are associated with better survival but this finding is confounded by performance status. Better performance status is associated with better clinical outcomes; HCPs use performance status to determine the interventions offered. Only a third of patients are referred to palliative care services despite severe symptoms and a very poor prognosis. Despite good symptomatic resolution with nasogastric tubes and PVG, lack of familiarity with and resources contribute to poor self-fulfilling availability. HCPs know the evidence for managing MBO is poor, and variable clinical practice is driven by local clinical culture and consensus.Conclusion: MBO is challenging for patients, carers, and HCPs, with little clinical guidance to aid them. Gut decompression appears to provide excellent symptom relief but has barriers to its use, including clinical uptake. PN is beneficial in selected MBO patients

The impact of vaccination strategy on the spatiotemporal pattern dynamics of a COVID-19 epidemic model

In the last 3 years, mathematical modelling and computational simulations have been used to discuss and estimate key transmission parameters of the spreading COVID-19 pandemics. There are several major factors that have played a crucial role in controlling this disease. These factors include contact tracing, rapid testing, and vaccination programs. In this study, we use a developed model to understand the impact of vaccination strategy on the spatiotemporal pattern dynamics of the COVID-19. We consider a system of diffusion equations of the spreading COVID-19 with vaccinated individuals. Accordingly, we apply the local sensitivity techniques to identify the model critical parameters. Computational results show spatial distribution of individuals for different initial states and parameters to show association between vaccination and COVID-19. It can be noticed that the spatio-temporal distribution of the recovered individuals appears to be reduced by the increased vaccination rate, as evident in three different normalization results of local sensitivity. Interestingly, the vaccination and contact tracing rate can effectively reduce the reproduction number of the virus in the population rather than the other parameters. Numerical results provide a wide range of possible solutions to control the spreading of this disease

Modeling nonstationary noise in pulsar timing array data analysis

Pulsar timing array (PTA) collaborations recently reported evidence for the presence of a gravitational wave background (GWB) in their datasets. The main candidate that is expected to produce such a GWB is the population of supermassive black hole binaries. Some analyses showed that the recovered signal may exhibit time-dependent properties, i.e., nonstationarity. In this paper, we propose an approximated nonstationary Gaussian process model obtained from the perturbation of stationary processes. The presented method is applied to the second data release of the European Pulsar Timing Array to search for nonstationary features in the GWB. We analyzed the data in different time slices and showed that the inferred properties of the GWB evolve with time. We find no evidence for such nonstationary behavior and the Bayes factor in favor of the latter is ℬNS =1.5. We argue that the evolution of the GWB properties most likely comes from the improvement of the observation cadence with time and better characterization of the noise of individual pulsars. Such nonstationary GWB could also be produced by the leakage of nonstationary features in the noise of individual pulsars or by the presence of an eccentric single source

The experiences of patients attending the emergency department who were managed by physiotherapists: a person-centred perspective

Purpose: The expectation for all clinicians to deliver person-centred practices extends to the growing number of primary contact physiotherapists based in United Kingdom emergency departments (ED). Research on ED patients’ experience of this physiotherapy role has yet to consider this through the lens of person-centredness. A qualitative exploration of person-centredness among ED physiotherapists through the experiences of attending patients targeted this knowledge gap to inform future clinical practice.Methods: Semi-structured interviews with thematic analysis.Results: 13 interviews were completed with four overarching themes generated: (1) patient experience of the ED; (2) the importance of connection, competence, and time; (3) recognising the benefits of being seen by a physiotherapist in ED; and (4) patient experience of the ED physical environment.Conclusion: Novel contributions from the patient perspective, here, reflected a cognisance of certain environment limitations to PCP, as well as institutional challenges to their personhood, with a suggestion that ED patients anticipated a validation of their visit and valued the educational aspects that the physiotherapists provided. Considering this new knowledge can help ED physiotherapists to be more person-centred