917 research outputs found
Ki67 and breast cancer mortality in women with invasive breast cancer
Background: The percentage of cells staining positive for Ki67 is sometimes used for decision-making in patients with early invasive breast cancer (IBC). However, there is uncertainty regarding the most appropriate Ki67 cut points and the influence of interlaboratory measurement variability. We examined the relationship between breast cancer mortality and Ki67 both before and after accounting for interlaboratory variability and 8 patient and tumor characteristics.
Methods: A multicenter cohort study of women with early IBC diagnosed during 2009-2016 in more than 20 NHS hospitals in England and followed until December 31, 2020.
Results: Ki67 was strongly prognostic of breast cancer mortality in 8212 women with estrogen receptor (ER)–positive, human epidermal growth factor receptor 2 (HER2)–negative early IBC (Ptrend < .001). This relationship remained strong after adjustment for patient and tumor characteristics (Ptrend < .001). Standardization for interlaboratory variability did little to alter these results. For women with Ki67 scores of 0%-5%, 6%-10%, 11%-19%, and 20%-29% the corresponding 8-year adjusted cumulative breast cancer mortality risks were 3.3% (95% confidence interval [CI] = 2.8% to 4.0%), 3.7% (95% CI = 3.0% to 4.4%), 3.4% (95% CI = 2.8% to 4.1%), and 3.4% (95% CI = 2.8% to 4.1%), whereas for women with Ki67 scores of 30%-39% and 40%-100%, these risks were higher, at 5.1% (95% CI = 4.3% to 6.2%) and 7.7% (95% CI = 6.6% to 9.1) (Ptrend < .001). Similar results were obtained when the adjusted analysis was repeated with omission of pathological information about tumor size and nodal involvement, which would not be available preoperatively for patients being considered for neoadjuvant therapy.
Conclusion: Our findings confirm the prognostic value of Ki67 scores of 30% or more in women with ER-positive, HER2-negative early IBC, irrespective of interlaboratory variability. These results also suggest that Ki67 may be useful to aid decision-making in the neoadjuvant setting
Extended analysis of benchmark datasets for Agilent two-color microarrays
<p>Abstract</p> <p>Background</p> <p>As part of its broad and ambitious mission, the MicroArray Quality Control (MAQC) project reported the results of experiments using External RNA Controls (ERCs) on five microarray platforms. For most platforms, several different methods of data processing were considered. However, there was no similar consideration of different methods for processing the data from the Agilent two-color platform. While this omission is understandable given the scale of the project, it can create the false impression that there is consensus about the best way to process Agilent two-color data. It is also important to consider whether ERCs are representative of all the probes on a microarray.</p> <p>Results</p> <p>A comparison of different methods of processing Agilent two-color data shows substantial differences among methods for low-intensity genes. The sensitivity and specificity for detecting differentially expressed genes varies substantially for different methods. Analysis also reveals that the ERCs in the MAQC data only span the upper half of the intensity range, and therefore cannot be representative of all genes on the microarray.</p> <p>Conclusion</p> <p>Although ERCs demonstrate good agreement between observed and expected log-ratios on the Agilent two-color platform, such an analysis is incomplete. Simple loess normalization outperformed data processing with Agilent's Feature Extraction software for accurate identification of differentially expressed genes. Results from studies using ERCs should not be over-generalized when ERCs are not representative of all probes on a microarray.</p
Mapping the UK renal psychosocial workforce : the first comprehensive workforce survey
Background: Emerging evidence of psychosocial problems in CKD patients has led to an acceptance that a focus
on the emotional wellbeing of the patient should be included in the provision of comprehensive CKD care. It is
unclear if an increased attention for psychosocial needs in guidelines and policy documents has led to a rise in
psychosocial staffing levels or change in composition of staff since the last workforce mapping in 2002. This paper
offers a critical analysis and in-depth discussion of findings and their implications, in addition to providing an
international perspective and exposing gaps in current knowledge.
Methods: Data on psychosocial staffing levels was taken from a survey based on the Scottish Renal Association’s
(SRA) staffing survey that was sent to all units in England, Wales and Northern-Ireland in 2016. In addition, data
from a psychosocial staffing survey designed by and distributed via psychosocial professional groups was used. This data was then completed with Freedom of Information (FOI) requests and collated to describe the current renal
psychosocial workforce in all 84 UK renal units. This was compared to results from the last renal workforce mapping
in 2002.
Results: The results from this mapping show great variability in models of service provision, significant exceeding of benchmarks for staffing levels, and a change in staffing patterns over the past 15 years. Adult psychology services have increased in number, but provision remains low due to increased patient numbers, whereas adult social work and paediatric services have decreased.
Conclusion: A lack in the provision of renal psychosocial services has been identified, together with the absence of
a general service provision model. These findings provide a valuable benchmark for units, a context from which to
review and monitor provision alongside patient need. Along with recommendations, this paper forms a foundation
for future research and workforce planning. Research into best practice models of service provision and the
psychosocial needs of CKD patients lies at the heart of the answers to many identified questions
Remanufacturing as a means for achieving low-carbon SMEs in Indonesia
Remanufacturing can reduce the energy intensity and associated greenhouse gas (GHG) emissions significantly and increase the eco-efficiency of product systems by utilizing recovered end-of-life parts. This paper presents the GHG mitigation potential of technically feasible remanufactured alternators in Indonesian small- and medium-sized enterprizes. Life cycle assessment approach and Weibull ++8 software have been used to calculate environmental and quality parameters. Since existing remanufactured alternators have not been found to meet the technical criterion for customers’ satisfaction, a number of alternative remanufacturing strategies have been explored to identify an option that has not only reduced GHG emissions but also has satisfied reliability, durability and warranty period criterion. Three improvement scenarios involving three different remanufacturing strategies were investigated in this case study, and yielded useful insights in order to come up with a technically feasible remanufacturing strategy for reducing a significant amount of GHG emissions. The improvement scenario III, which maximizes the use of used components, was found to offer technically and environmentally feasible remanufacturing solutions. Overall, this research has found that about 7207 t of CO2 -eq GHG emissions and 111.7 TJ embodied energy consumption could potentially be avoided if 10 % of alternators in Indonesian automobile sector are remanufactured using technically feasible remanufacturing strategy
Enhanced electron acceleration by high-intensity lasers in extended (confined) preplasma in cone targets
Characteristics of outdoor falls among older people: A qualitative study
Background Falls are a major threat to older people’s health and wellbeing. Approximately half of falls occur in outdoor environments but little is known about the circumstances in which they occur. We conducted a qualitative study to explore older people’s experiences of outdoor falls to develop understanding of how they may be prevented. Methods We conducted nine focus groups across the UK (England, Wales, and Scotland). Our sample was from urban and rural settings and different environmental landscapes. Participants were aged 65+ and had at least one outdoor fall in the past year. We analysed the data using framework and content analyses. Results Forty-four adults aged 65 – 92 took part and reported their experience of 88 outdoor falls. Outdoor falls occurred in a variety of contexts, though reports suggested the following scenarios may have been more frequent: when crossing a road, in a familiar area, when bystanders were around, and with an unreported or unknown attribution. Most frequently, falls resulted in either minor or moderate injury, feeling embarrassed at the time of the fall, and anxiety about falling again. Ten falls resulted in fracture, but no strong pattern emerged in regard to the contexts of these falls. Anxiety about falling again appeared more prevalent among those that fell in urban settings and who made more visits into their neighbourhood in a typical week. Conclusions This exploratory study has highlighted several aspects of the outdoor environment that may represent risk factors for outdoor falls and associated fear of falling. Health professionals are recommended to consider outdoor environments as well as the home setting when working to prevent falls and increase mobility among older people
Autoimmune and autoinflammatory mechanisms in uveitis
The eye, as currently viewed, is neither immunologically ignorant nor sequestered from the systemic environment. The eye utilises distinct immunoregulatory mechanisms to preserve tissue and cellular function in the face of immune-mediated insult; clinically, inflammation following such an insult is termed uveitis. The intra-ocular inflammation in uveitis may be clinically obvious as a result of infection (e.g. toxoplasma, herpes), but in the main infection, if any, remains covert. We now recognise that healthy tissues including the retina have regulatory mechanisms imparted by control of myeloid cells through receptors (e.g. CD200R) and soluble inhibitory factors (e.g. alpha-MSH), regulation of the blood retinal barrier, and active immune surveillance. Once homoeostasis has been disrupted and inflammation ensues, the mechanisms to regulate inflammation, including T cell apoptosis, generation of Treg cells, and myeloid cell suppression in situ, are less successful. Why inflammation becomes persistent remains unknown, but extrapolating from animal models, possibilities include differential trafficking of T cells from the retina, residency of CD8(+) T cells, and alterations of myeloid cell phenotype and function. Translating lessons learned from animal models to humans has been helped by system biology approaches and informatics, which suggest that diseased animals and people share similar changes in T cell phenotypes and monocyte function to date. Together the data infer a possible cryptic infectious drive in uveitis that unlocks and drives persistent autoimmune responses, or promotes further innate immune responses. Thus there may be many mechanisms in common with those observed in autoinflammatory disorders
Potential for airborne transmission of infection in the waiting areas of healthcare premises: stochastic analysis using a Monte Carlo model
BACKGROUND: Although many infections that are transmissible from person to person are acquired through direct contact between individuals, a minority, notably pulmonary tuberculosis (TB), measles and influenza are known to be spread by the airborne route. Airborne infections pose a particular threat to susceptible individuals whenever they are placed together with the index case in confined spaces. With this in mind, waiting areas of healthcare facilities present a particular challenge, since large numbers of people, some of whom may have underlying conditions which predispose them to infection, congregate in such spaces and can be exposed to an individual who may be shedding potentially pathogenic microorganisms. It is therefore important to understand the risks posed by infectious individuals in waiting areas, so that interventions can be developed to minimise the spread of airborne infections. METHOD: A stochastic Monte Carlo model was constructed to analyse the transmission of airborne infection in a hypothetical 132 m3 hospital waiting area in which occupancy levels, waiting times and ventilation rate can all be varied. In the model the Gammaitoni-Nucci equation was utilized to predict probability of susceptible individuals becoming infected. The model was used to assess the risk of transmission of three infectious diseases, TB, influenza and measles. In order to allow for stochasticity a random number generator was applied to the variables in the model and a total of 10000 individual simulations were undertaken. The mean quanta production rates used in the study were 12.7, 100 and 570 per hour for TB, influenza and measles, respectively. RESULTS: The results of the study revealed the mean probability of acquiring a TB infection during a 30-minute stay in the waiting area to be negligible (i.e. 0.0034), while that for influenza was an order of magnitude higher at 0.0262. By comparison the mean probability of acquiring a measles infection during the same period was 0.1349. If the duration of the stay was increased to 60 minutes then these values increased to 0.0087, 0.0662 and 0.3094, respectively. CONCLUSION: Under normal circumstances the risk of acquiring a TB infection during a visit to a hospital waiting area is minimal. Likewise the risks associated with the transmission of influenza, although an order of magnitude greater than those for TB, are relatively small. By comparison, the risks associated with measles are high. While the installation of air disinfection may be beneficial, when seeking to prevent the transmission of airborne viral infection it is important to first minimize waiting times and the number of susceptible individuals present before turning to expensive technological solutions
The European Legal Framework on Cybercrime
This article analyzes the European legal framework on cybercrime. Initially, it argues the challenges of cybercrime to traditional criminal justice systems. Subsequently, it focuses on the criminal law framework on cybercrime with a mainly European perspective. The European legal framework provides a three-path solution: the reduction of frictions among national legislations, the introduction of new investigative powers and the facilitation of international cooperation. The article presents and discusses each solution. Further, it argues that the effective implementation of the main legal instruments does not seem to depend on the legal enforceability of these international measures. Contrarily, other, non legal, factors such as national security, politics, the economy and the public opinion appear to stimulate the spontaneous implementation of the European legal framework. In this context, the added value of the EU action is rather low, although the Treaty of Lisbon and the Stockholm Programme may improve this situation in the long ter
How do ADHD children perceive their cognitive, affective, and behavioral aspects of anger expression in school setting?
<p>Abstract</p> <p>Background</p> <p>Anger is an ignored research area in children and young adolescents with Attention deficit hyperactivity disorder (ADHD) in the school setting. This study compares school anger dimensions in children and young adolescents with ADHD and a control group.</p> <p>Methods</p> <p>The subjects were a clinical sample of 67 children and young adolescents with ADHD and their parents, with a sample of 91 children from the community of similar age and gender as control group. Anger was measured by the Farsi version of the Multidimensional School Anger Inventory (MSAI).</p> <p>Results</p> <p>The scores of the two components of "Hostile Outlook" and "Positive Coping" were different between the groups. The mean scores for the Anger components did not statistically differ between the children with ADHD and ODD and ADHD without ODD, boys and girls, or different types of ADHD.</p> <p>Conclusion</p> <p>Children with ADHD do not report higher rates of experience of anger and they do not apply destructive strategies more than the control group. However, children with ADHD appear to have a more hostile outlook toward school and their coping strategy is weaker than that of the control group.</p
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