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Objectives: Our aim was to evaluate changes in prostate cancer diagnosis and management and to examine changes in the stage and grade of newly diagnosed prostate cancer in the North West of England over a 10-year period. Materials and methods: Data was collected concerning the diagnosis (including stage and grade) and management of newly diagnosed prostate cancer in the North West of England. There were three time points: 2003, 2007 and 2011 including a total of 648 patients. For assessment of median time changes Spearman’s Rank correlation test was used, for the assessment of changes in Gleason grade and clinical stage Mann–Whitney U test was used, and assessment of positive margin rates was done with Fisher’s test. Results: Median time from management decision to surgery has reduced from 46 (2003), 34 (2007) to 27 days (2011) (p=0.074). The proportion of patients managed with active surveillance has remained relatively constant over time (18%, 16% and 21% respectively). More minimally invasive, nerve-sparing prostatectomies are now performed, and positive margin rates have significantly reduced from 53% (2003) to 23% (2011) (p<0.001). Gleason grade significantly increased over time (p<0.001); Gleason 7 disease was diagnosed in 23% of patients in 2003, 32% in 2007 and 49% in 2011 (p<0.001). There was an increase in Gleason 8 disease; 6% (2003) to 8.6% (2011), but this was not significant (p=0.27). Increase in clinical stage was also noted over time; identification of T3 disease rose from 2% (2003 and 2007) to 5% (2011) (p=0.045) (excluding cases with non-recorded stage). Conclusion: Prostate cancer management in the North West of England has evolved over the last decade, with overall improvements in management quality. We have demonstrated an increase in the presenting stage and grade of prostate cancer over a 10-year period. [ABSTRACT FROM AUTHOR]

Background:A high percentage of stroma predicts poor survival in triple-negative breast cancers but is diminished in studies of unselected cases. We determined the prognostic significance of tumour-stroma ratio (TSR) in oestrogen receptor (ER)-positive male and female breast carcinomas.Methods:TSR was measured in haematoxylin and eosin-stained tissue sections (118 female and 62 male). Relationship of TSR (cutoff 49%) to overall survival (OS) and relapse-free survival (RFS) was analysed.Results:Tumours with 49% stroma were associated with better survival in female (OS P=0.008, HR=0.2-0.7; RFS P=0.006, HR=0.1-0.6) and male breast cancer (OS P=0.005, HR=0.05-0.6; RFS P=0.01, HR=0.87-5.6), confirmed in multivariate analysis.Conclusions:High stromal content was related to better survival in ER-positive breast cancers across both genders, contrasting data in triple-negative breast cancer and highlighting the importance of considering ER status when interpreting the prognostic value of TSR. [ABSTRACT FROM AUTHOR]

The detection of quantitative changes in genomic DNA, i.e. deletions and duplications or Copy Number Variants (CNVs), has recently gained considerable interest. First, detailed analysis of the human genome showed a surprising amount of CNVs, involving thousands of genes. Second, it was realised that the detection of CNVs as a cause of genetic disease was often neglected, but should be an essential part of a complete screening strategy. In both cases new efficient CNV screening methods, covering the entire range from specific loci to genome-wide, were behind these developments. This paper will briefly review the methods that are available to detect CNVs, discuss their strong and weak points, show some new developments and look ahead. Methods covered include microscopy, fluorescence in situ hybridization (including fiber-FISH), Southern blotting, PCR-based methods (including MLPA), array technology and massive parallel sequencing. In addition, we will show some new developments, including a 1400-plex CNV bead assay, fast-MLPA (from DNA to result in ∼6 h) and a simple Melting Curve Analysis assay to confirm potential CNVs. Using the 1400-plex CNV bead assay, targeting selected chromosomal regions only, we detected confirmed rearrangements in 9% of 320 mental retardation patients studied. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Abstract Background Serial Analysis of Gene Expressions (SAGE) produces gene expression measurements on a discrete scale, due to the finite number of molecules in the sample. This means that part of the variance in SAGE data should be understood as the sampling error in a binomial or Poisson distribution, whereas other variance sources, in particular biological variance, should be modeled using a continuous distribution function, i.e. a prior on the intensity of the Poisson distribution. One challenge is that such a model predicts a large number of genes with zero counts, which cannot be observed. Results We present a hierarchical Poisson model with a gamma prior and three different algorithms for estimating the parameters in the model. It turns out that the rate parameter in the gamma distribution can be estimated on the basis of a single SAGE library, whereas the estimate of the shape parameter becomes unstable. This means that the number of zero counts cannot be estimated reliably. When a bivariate model is applied to two SAGE libraries, however, the number of predicted zero counts becomes more stable and in approximate agreement with the number of transcripts observed across a large number of experiments. In all the libraries we analyzed there was a small population of very highly expressed tags, typically 1% of the tags, that could not be accounted for by the model. To handle those tags we chose to augment our model with a non-parametric component. We also show some results based on a log-normal distribution instead of the gamma distribution. Conclusion By modeling SAGE data with a hierarchical Poisson model it is possible to separate the sampling variance from the variance in gene expression. If expression levels are reported at the gene level rather than at the tag level, genes mapped to multiple tags must be kept separate, since their expression levels show a different statistical behavior. A log-normal prior provided a better fit to our data than the gamma prior, but except for a small subpopulation of tags with very high counts, the two priors are similar.

Abstract Background In experimental biology, including retrovirology and molecular biology, replicate measurement sessions very often show similar proportional differences between experimental conditions, but different absolute values, even though the measurements were presumably carried out under identical circumstances. Although statistical programs enable the analysis of condition effects despite this replication error, this approach is hardly ever used for this purpose. On the contrary, most researchers deal with such between-session variation by normalisation or standardisation of the data. In normalisation all values in a session are divided by the observed value of the 'control' condition, whereas in standardisation, the sessions' means and standard deviations are used to correct the data. Normalisation, however, adds variation because the control value is not without error, while standardisation is biased if the data set is incomplete. Results In most cases, between-session variation is multiplicative and can, therefore, be removed by division of the data in each session with a session-specific correction factor. Assuming one level of multiplicative between-session error, unbiased session factors can be calculated from all available data through the generation of a between-session ratio matrix. Alternatively, these factors can be estimated with a maximum likelihood approach. The effectiveness of this correction method, dubbed "factor correction", is demonstrated with examples from the field of molecular biology and retrovirology. Especially when not all conditions are included in every measurement session, factor correction results in smaller residual error than normalisation and standardisation and therefore allows the detection of smaller treatment differences. Factor correction was implemented into an easy-to-use computer program that is available on request at: biolab-services@amc.uva.nl?subject=factor. Conclusion Factor correction is an effective and efficient way to deal with between-session variation in multi-session experiments.

Abstract Background Recent analyses of prokaryotic genome sequences have demonstrated the important force horizontal gene transfer constitutes in genome evolution. Horizontally acquired sequences are detectable by, among others, their dinucleotide composition (genome signature) dissimilarity with the host genome. Genomic islands (GIs) comprise important and interesting horizontally transferred sequences, but information about acquisition events or relatedness between GIs is scarce. In Vibrio vulnificus CMCP6, 10 and 11 GIs have previously been identified in the sequenced chromosomes I and II, respectively. We assessed the compositional similarity and putative acquisition account of these GIs using the genome signature. For this analysis we developed a new algorithm, available as a web application. Results Of 21 GIs, VvI-1 and VvI-10 of chromosome I have similar genome signatures, and while artificially divided due to a linear annotation, they are adjacent on the circular chromosome and therefore comprise one GI. Similarly, GIs VvI-3 and VvI-4 of chromosome I together with the region between these two islands are compositionally similar, suggesting that they form one GI (making a total of 19 GIs in chromosome I + chromosome II). Cluster analysis assigned the 19 GIs to 11 different branches above our conservative threshold. This suggests a limited number of compositionally similar donors or intragenomic dispersion of ancestral acquisitions. Furthermore, 2 GIs of chromosome II cluster with chromosome I, while none of the 19 GIs group with chromosome II, suggesting an unidirectional dispersal of large anomalous gene clusters from chromosome I to chromosome II. Conclusion From the results, we infer 10 compositionally dissimilar donors for 19 GIs in the V. vulnificus CMCP6 genome, including chromosome I donating to chromosome II. This suggests multiple transfer events from individual donor types or from donors with similar genome signatures. Applied to other prokaryotes, this approach may elucidate the acquisition account in their genome sequences, and facilitate donor identification of GIs.

Abstract Background Correlation between the expression levels of genes which are located close to each other on the genome has been found in various organisms, including yeast, drosophila and humans. Since such a correlation could be explained by several biochemical, evolutionary, genetic and technological factors, there is a need for statistical models that correspond to specific biological models for the correlation structure. Results We modelled the pairwise correlation between the expressions of the genes in a Drosophila microarray experiment as a normal mixture under Fisher's z-transform, and fitted the model to the correlations of expressions of adjacent as well as non-adjacent genes. We also analyzed simulated data for comparison. The model provided a good fit to the data. Further, correlation between the activities of two genes could, in most cases, be attributed to either of two factors: the two genes both being active in the same age group (adult or embryo), or the two genes being in proximity of each other on the chromosome. The interaction between these two factors was weak. Conclusions Correlation between the activities of adjacent genes is higher than between non-adjacent genes. In the data we analyzed, this appeared, for the most part, to be a constant effect that applied to all pairs of adjacent genes.

Abstract Background When DNA microarray data are used for gene clustering, genotype/phenotype correlation studies, or tissue classification the signal intensities are usually transformed and normalized in several steps in order to improve comparability and signal/noise ratio. These steps may include subtraction of an estimated background signal, subtracting the reference signal, smoothing (to account for nonlinear measurement effects), and more. Different authors use different approaches, and it is generally not clear to users which method they should prefer. Results We used the ratio between biological variance and measurement variance (which is an F-like statistic) as a quality measure for transformation methods, and we demonstrate a method for maximizing that variance ratio on real data. We explore a number of transformations issues, including Box-Cox transformation, baseline shift, partial subtraction of the log-reference signal and smoothing. It appears that the optimal choice of parameters for the transformation methods depends on the data. Further, the behavior of the variance ratio, under the null hypothesis of zero biological variance, appears to depend on the choice of parameters. Conclusions The use of replicates in microarray experiments is important. Adjustment for the null-hypothesis behavior of the variance ratio is critical to the selection of transformation method.

Abstract: Array comparative genomic hybridisation (aCGH) profiling is currently the gold standard for genetic diagnosis of copy number. Next generation sequencing technologies provide an alternative and adaptable method of detecting copy number by comparing the number of sequence reads in non-overlapping windows between patient and control samples. Detection of copy number using the BlueGnome 8×60k oligonucleotide aCGH platform was compared with low resolution next generation sequencing using the Illumina GAIIx on 39 patients with developmental delay and/or learning difficulties who were referred to the Leeds Clinical Cytogenetics Laboratory. Sensitivity and workflow of the two platforms were compared. Customised copy number algorithms assessed sequence counts and detected changes in copy number. Imbalances detected on both platforms were compared. Of the thirty-nine patients analysed, all eleven imbalances detected by array CGH and confirmed by FISH or Q-PCR were also detected by CNV-seq. In addition, CNV-seq reported one purported pathogenic copy number variant that was not detected by array CGH. Non-pathogenic, unconfirmed copy number calls were detected by both platforms; however few were concordant between the two. CNV-seq offers an alternative to array CGH for copy number analysis with resolution and future costs comparable to conventional array CGH platforms and with less stringent sample requirements. [Copyright &y& Elsevier]

Background: People with problems in functioning following severe injury or illness often need multiple and combined interventions in their rehabilitation processes. In these processes, communication and collaboration between the involved healthcare professionals are essential. Despite efforts in research and policy, communication across hospital and primary healthcare services and within the primary healthcare settings remains challenging. In one region of Norway, a new intermunicipal rehabilitation team has been established to supplement the traditional services and context-bound research is needed to gain insight into the complexity of the new communication structures that are developing. The aim of this study was to explore facilitators and barriers to communication to inform further improvement of the services., Methods: A qualitative case study design was used to explore the exchange of patient information in the rehabilitation processes of four patients. Data collection included participant observations in communication situations and an exploration of the electronic patient records of these four patients. Reflexive thematic analysis was used to analyse the empirical data., Results: The complex rehabilitation processes explored involved a large number of actors across healthcare organisational levels. Lacking a common culture for rehabilitation, poor access to written information and unclear responsibility for sharing information across organisational boundaries seemed to represent barriers to interprofessional communication. Joint meetings, the use of common rehabilitation tools and language and establishing informal communication channels served to facilitate communication., Conclusion: The intermunicipal team collaborating across different organisational levels added complexity to communication structures, but also facilitated interprofessional communication by promoting formal and informal ways of exchanging information. However, the intricate organisational divisions of healthcare provision in the Norwegian context represent boundaries which can be difficult to overcome. Therefore, cross-organisational coordination services should be developed., (© 2023. The Author(s).)

Background: Telehealth seems feasible for use in home-based palliative care (HBPC). It may improve access to health care professionals (HCPs) at patients' homes, reduce hospital admissions, enhance patients' feelings of security and safety, and increase the time spent at home for patients in HBPC. HBPC requires the involvement of various HCPs such as nurses, physicians, allied health professionals, dietitians, psychologists, religious counselors, and social workers. Acceptance of the use of technology among HCPs is essential for the successful delivery of telehealth in practice. No scoping review has mapped the experiences and perspectives of HCPs regarding the use of telehealth in HBPC., Objective: The aim of this review was to systematically map published studies on HCPs' experiences and perspectives on the use of telehealth in HBPC., Methods: A scoping review was conducted using the methodology of Arksey and O'Malley. The review was reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews. A systematic search was performed in AMED, CINAHL, Embase, MEDLINE, PsycINFO, and Web of Science for studies published in peer-reviewed journals between January 1, 2000, and August 23, 2022. The reference lists of the included papers were hand searched to identify additional studies. The inclusion criteria were (1) studies using qualitative, quantitative, or mixed methods; (2) studies including HCPs using telehealth with patients in HBPC; (3) studies on HCPs' experiences and perspectives on the use of telehealth in HBPC; (4) studies published between January 1, 2000, and August 23, 2022; and (5) studies published in English, Portuguese, Norwegian, Danish, Swedish, or Spanish. Pairs of authors independently included studies and extracted data. The first 2 stages of thematic synthesis were used to thematically organize the data., Results: This scoping review included 29 papers from 28 studies. Four descriptive themes were identified: (1) easy to use but technological issues undermine confidence, (2) adds value but personal and organizational barriers challenge adoption, (3) potential to provide useful and meaningful patient-reported data, and (4) mutual trust as a prerequisite for interpersonal relationships., Conclusions: Telehealth in HBPC seems to be easy to use and may improve the coordination of care, time efficiency, clinical assessments, and help build and enhance personal and professional relationships. However, the introduction of technology in HBPC is complex, as it may not align well with the overall aim of palliative care from HCPs' point of view. Further, changes in practice and requirements for HCPs may reduce motivation for the use of telehealth in HBPC. HCPs consider themselves to have central roles in implementing telehealth, and a lack of acceptance and motivation is a key barrier to telehealth adoption. Policy makers and telehealth developers should be aware of this potential barrier when developing or implementing new technology for use in HBPC., International Registered Report Identifier (irrid): RR2-10.2196/33305., (©Elias David Lundereng, Andréa Aparecida Gonçalves Nes, Heidi Holmen, Anette Winger, Hilde Thygesen, Nina Jøranson, Christine Råheim Borge, Olav Dajani, Kari L Mariussen, Simen A Steindal. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 29.03.2023.)

18 F-FDG positron emission tomography with computed tomography (PET/CT) is a standard imaging modality for the nodal staging of non-small cell lung cancer (NSCLC). To improve the accuracy of pre-operative staging, we compare the staging accuracy of mediastinal lymph node (LN) standard uptake values (SUV) with four derived SUV ratios based on the SUV values of primary tumours (TR), the mediastinal blood pool (MR), liver (LR), and nodal size (SR). In 2015-2017, 53 patients (29 women and 24 men, mean age 67.4 years, range 53-87) receiving surgical resection have pre-operative evidence of mediastinal nodal involvement (cN2). Among these, 114 mediastinal nodes are resected and available for correlative PET/CT analysis. cN2 status accuracy is low, with only 32.5% of the cN2 cases confirmed pathologically. Using receiver operating characteristic (ROC) curve analyses, a SUVmax of N2 LN performs well in predicting the presence of N2 disease (AUC, 0.822). Based on the respective selected thresholds for each ROC curve, normalisation of LN SUVmax to that for mediastinum, liver and tumour improved sensitivities of LN SUVmax from 68% to 81.1-89.2% while maintaining acceptable specificity (68-70.1%). In conclusion, normalised SUV ratios (particularly LR) improve current pre-operative staging performance in detecting mediastinal nodal involvement.

Since the beginning of the Covid-19 pandemic in January 2020 the need for rapid information spread grew and social media became the ultimate platform for information exchange as well as a tool for connection and entertainment. With the rapid information spread along came the various public misconceptions and misinformation which consequently influenced perceptions and behaviors of the public towards the coronavirus pandemic. Thus, there was a need for identification and collation of public perceptions information to address future public health initiatives. This cross-national study aimed to examine the challenges and benefits of using social media during the Covid-19 pandemic outbreak. This study was a content analysis of the open-ended questions from a wider cross-sectional online survey conducted in Norway, UK, USA, and Australia during October/November 2020. 2368 participants out of 3474 respondents to the survey provided the open text responses included in the qualitative analysis. Thematic analysis was conducted independently by two researchers. All statements were coded to positive and negative sentiments. Three overarching themes were identified: 1. Mental health and emotional exhaustion 2. Information and misinformation; 3. Learning and inspiration.While providing a powerful mode of connection during the pandemic, social media also led to negative impact on public perceptions, including mistrust and confusion. Clarity in communications by institutions and education about credible information sources should be considered in the future. Further research is required in exploring and documenting social media narratives around COVID-19 in this and any subsequent incidents of pandemic restrictions. Understanding the public perceptions and their social narratives can support the designing of appropriate support and services for people in the future, while acknowledging the uncertainty and overwhelming impact of the pandemic that may have skewed the experiences of social media., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Schoultz et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: We aimed to examine the association between social media use and loneliness two years after the COVID-19 pandemic outbreak., Methods: Participants were 1649 adults who completed a cross-sectional online survey disseminated openly in Norway, United Kingdom, USA, and Australia between November 2021 and January 2022. Linear regressions examined time spent on social media and participants' characteristics on loneliness, and interactions by motives for social media use., Results: Participants who worried more about their health and were younger, not employed, and without a spouse or partner reported higher levels of loneliness compared to their counterparts. More time spent on social media was associated with more loneliness ( β  = 0.12, p  < 0.001). Three profile groups emerged for social media use motives: 1) social media use motive ratings on avoiding difficult feelings higher or the same as for maintaining contact; 2) slightly higher ratings for maintaining contact; and 3) substantially higher ratings for maintaining contact. Time spent on social media was significant only in motive profile groups 2 and 3 ( β  = 0.12 and β  = 0.14, both p  < 0.01)., Conclusions: Our findings suggest that people who use social media for the motive of maintaining their relationships feel lonelier than those who spend the same amount of time on social media for other reasons. While social media may facilitate social contact to a degree, they may not facilitate the type of contact sought by those who use social media primarily for this reason., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

We aimed to gain knowledge of possible sociodemographic predictors of long COVID and whether long COVID was associated with health outcomes almost two years after the pandemic outbreak. There were 1649 adults who participated in the study by completing a cross-sectional online survey disseminated openly in Norway, the UK, the USA, and Australia between November 2021 and January 2022. Participants were defined as having long COVID based on self-reports that they had been infected by COVID-19 and were experiencing long-lasting COVID symptoms. Logistic regression analyses were used to examine possible sociodemographic predictors, and multivariate analysis of variance was used to examine whether long COVID status was associated with health outcomes. None of the sociodemographic variables was significantly associated with reporting long COVID. Having long COVID was associated with higher levels of psychological distress, fatigue, and perceived stress. The effect of long COVID on health outcomes was greater among men than among women. In conclusion, long COVID appeared across sociodemographic groups. People with long COVID reported worsened health outcomes compared to those who had had COVID-19 but without long-term symptoms. Men experiencing long COVID appear to be particularly vulnerable to experiencing poorer health outcomes; health services may pay extra attention to potentially unnoticed needs for support among men experiencing long COVID.

During the COVID-19 pandemic, much research has been devoted to assessing mental health in a variety of populations. Students in higher education appear to be particularly vulnerable to experiencing reduced mental health. The purpose of the study was to assess whether higher education students experienced poorer mental health compared to the general population and examine the factors associated with students' mental health during the COVID-19 pandemic. A cross-national sample of students ( n = 354) and non-students ( n = 3120) participated in a survey in October/November 2020. Mental health outcomes among students and non-students were compared with independent t -tests. Multiple linear regression analysis and general linear estimation were used to assess the impact of student status on mental health outcomes while adjusting for sociodemographic factors. Students reported poorer mental health than non-students. The difference in mental health between students and non-students was bigger for participants aged 30 years or older. More social media use was associated with poorer mental health outcomes. In conclusion, students had poorer mental health than the wider population. Aspects of life as a student, beyond what can be attributed to life stage, appears to increase mental health problems.

Background: The aim of the study was to explore and articulate how meaning-making appears and how meaningfulness is experienced in persons with severe dementia. Although there is little knowledge about meaning-making and experience of meaningfulness for this group, this article assumes that persons with dementia are as much in need of meaningfulness in life as any others, and hence, that they are involved in the process of meaning-making., Methods: The study was conducted using a qualitative method with exploratory design. Ten patients with severe dementia at a specialized dementia ward at an old age psychiatric department in hospital were observed through participant observation performed over four months. The field-notes from the observation contained narratives carrying with them a dimension of meaning played out in an everyday setting and thus named Meaning-making dramas . The narratives were analyzed looking for expressions where experiences of meaning-making and meaningfulness could be identified., Results: The narratives demonstrate that persons with severe dementia are involved in processes of meaning-making. The narratives include expressions of meaning-making, and of interactions that include apparent crises of meaning, but also transitions into what may be interpreted as meaningfulness based on experiences of significance, orientation and belonging. The role of the body and the senses has proved significant in these processes. The findings also suggest that experiences of meaning contribute to experience of personhood., Conclusions: The relevance to clinical practice indicates that working from a person-centred approach in dementia care also includes paying attention to the dimension of meaning. This dimension is important both for the person living with dementia and for the people caring for them. Acknowledging meaning as a central human concern, it is crucial to seek understanding and knowledge about the significance of meaning in vulnerable groups such as persons with dementia.

Background: The covid-19 pandemic has impacted the health and well-being of millions across the globe. Strict social distancing policies and periodic lockdowns has led to an increased reliance on alternative online means of communication, including social media., Objectives: to examine (i) social media use and mental health in the general population 9 months after the COVID-19 pandemic outbreak and (ii) mental health in relation to motives for and extent of social media use, while adjusting for sociodemographic variables., Methods: A cross-national online survey was conducted in Norway, UK, USA and Australia. Participants ( n = 3,474) reported extent of and motives for social media use and completed the 12-item General Health Questionnaire. The data were analyzed by chi-square tests, one-way analyses of variance, and multiple linear regression analysis., Results: Poorer mental health was associated with using social media to decrease loneliness and for entertainment motives, while better mental health was associated with using social media for personal contact and maintaining relationships. Overall increased daily time on social media was associated with poorer mental health. The social media use variables were responsible for a substantial proportion of the outcome variance explained. These findings were consistent across the four countries, with only minor variations., Conclusions: Motives for using, and time spent using, social media were associated with the participants' mental health. Guidance and recommendations for social media usage to the general public for prevention and intervention for behavioral health may be beneficial., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Thygesen, Bonsaksen, Schoultz, Ruffolo, Leung, Price and Geirdal.)

Background: Telehealth seems feasible for use in home-based palliative care. However, acceptance among health care professionals (HCPs) is essential for the successful delivery of telehealth in practice. No scoping review has mapped the experiences and perspectives of HCPs on the use of telehealth for home-based palliative care., Objective: The aim of this review is to systematically map published studies on HCPs' experiences and perspectives on the use of telehealth in home-based palliative care., Methods: The proposed scoping review will employ the methodology of Arksey and O'Malley. This protocol is guided by the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocol (PRISMA-P). A systematic search will be performed in MEDLINE, PsycINFO, EMBASE, CINAHL, Allied and Complementary Medicine (AMED), and Web of Science for studies published between January 2000 and July 5, 2021. We will also hand search the reference lists of included papers to identify additional studies of relevance. The search will be updated in 2022. Pairs of authors will independently assess the eligibility of studies and extract data. The first 2 stages of thematic synthesis will be used to thematically organize the data. Because the scoping review methodology consists of reviewing and collecting data from publicly available materials, this study does not require ethics approval., Results: The database searches; testing of eligibility criteria; and screening of titles, abstracts, and full-text papers will be performed by fall 2021. The results from this scoping review will be presented as a descriptive summary of the results from all included papers, and will be inductively organized into descriptive themes. A frequency table illustrating which papers were included in which descriptive themes will be made. Results are anticipated by the fall of 2022., Conclusions: A mapping of studies could identify research gaps regarding HCPs' experiences and perspectives on the use of telehealth in home-based palliative care and may determine the value and feasibility of conducting a full systematic review., International Registered Report Identifier (irrid): PRR1-10.2196/33305., (©Elias David Lundereng, Andrea Aparecida Goncalves Nes, Heidi Holmen, Anette Winger, Hilde Thygesen, Nina Jøranson, Chrstine Råheim Borge, Weiqin Chen, Olav Dajani, Kari L Mariussen, Simen A Steindal. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 29.10.2021.)

The need for meaning in life is a key aspect of being human, and a central issue in the psychology of religion. Understanding experience of meaning for persons with severe dementia is challenging due to the impairments associated with the illness. Despite these challenges, this article argues that meaning in life is as important for a person with severe dementia as it is for everyone else. This study was conducted in a Norwegian hospital and nursing home context and was part of a research project on meaning in life for persons with severe dementia. The study builds on two other studies which focused on how meaning-making and experience of meaningfulness appeared in patients with severe dementia. By presenting the findings from these two studies for a group of healthcare professionals and introducing them to research on meaning in life, the aim of this study was to explore how healthcare professionals interpret the patients' experience of meaning in life in practise for patients with severe dementia in a hospital and nursing home context, and to highlight its clinical implications. The study was conducted using a qualitative method with exploratory design. The data were collected at a round table conference, a method inspired by a mode of action research called "co-operative inquiry." Altogether 27 professional healthcarers, from a variety of professions, with high competence in dementia care participated together with six researchers authoring this article. This study revealed that healthcare professionals were constantly dealing with different forms of meaning in their everyday care for people with dementia. The findings also showed clear connexions between understanding of meaning and fundamental aspects of good dementia care. Meaning corresponded well with the principles of person-centred care, and this compatibility allowed the healthcare professionals to associate meaning in life as a perspective into their work without having much prior knowledge or being familiar with the use of this perspective. The study points out that awareness of meaning in life as an integrated perspective in clinical practise will contribute to a broader and enhanced repertoire, and hence to improved dementia care. Facilitating experience of meaning calls for increased resources in personnel and competence in future dementia care., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Isene, Kjørven Haug, Stifoss-Hanssen, Danbolt, Ødbehr and Thygesen.)

Objective: The objective of this study was to examine differences in worry, loneliness, and mental health between those individuals infected by COVID-19 or having someone their family infected, and the rest of the population., Methods: A cross-sectional online survey was conducted in Norway, UK, USA, and Australia during April/May 2020. Participants ( n = 3810) were recruited via social media postings by the researchers and the involved universities. Differences between those with and without infection in the family were investigated with chi-square tests and independent t -tests. Multiple regression analyses were used to assess associations between sociodemographic variables and psychological outcomes (worry, loneliness, and mental health) in both groups., Results: Compared to their counterparts, participants with infection in the family reported higher levels of worries about themselves ( p < 0.05) and their family members ( p < 0.001) and had poorer mental health ( p < 0.05). However, the effect sizes related to the differences were small. The largest effect ( d = 0.24) concerned worries about their immediate family. Poorer psychological outcomes were observed in those who were younger, female, unemployed, living alone and had lower levels of education, yet with small effect sizes., Conclusions: In view of the small differences between those with and without infection, we generally conclude that the mental health effects of the COVID-19 situation are not limited to those who have been infected or have had an infection within the family but extend to the wider population.

Background : Due to the COVID-19 pandemic and the strict national policies regarding social distancing behavior in Europe, America and Australia, people became reliant on social media as a means for gathering information and as a tool for staying connected to family, friends and work. This is the first trans-national study exploring the qualitative experiences and challenges of using social media while in lockdown or shelter-in-place during the current pandemic. Methods : This study was part of a wider cross-sectional online survey conducted in Norway, the UK, USA and Australia during April/May 2020. The manuscript reports on the qualitative free-text component of the study asking about the challenges of social media users during the COVID-19 pandemic in the UK, USA and Australia. A total of 1991 responses were included in the analysis. Thematic analysis was conducted independently by two researchers. Results : Three overarching themes identified were: Emotional/Mental Health, Information and Being Connected. Participants experienced that using social media during the pandemic amplified anxiety, depression, fear, panic, anger, frustration and loneliness. They felt that there was information overload and social media was full of misleading or polarized opinions which were difficult to switch off. Nonetheless, participants also thought that there was an urge for connection and learning, which was positive and stressful at the same time. Conclusion : Using social media while in a shelter-in-place or lockdown could have a negative impact on the emotional and mental health of some of the population. To support policy and practice in strengthening mental health care in the community, social media could be used to deliver practical advice on coping and stress management. Communication with the public should be strengthened by unambiguous and clear messages and clear communication pathways. We should be looking at alternative ways of staying connected.

The aim of the study was to examine the use of video-based communication and its association with loneliness, mental health and quality of life in older adults (60-69 years versus 70+ years) during the COVID-19 pandemic. A cross-sectional online survey was conducted in Norway, UK, USA and Australia during April/May 2020, and 836 participants in the relevant age groups were included in the analysis. Multiple regression analyses were conducted to examine associations between the use of video-based communication tools and loneliness, mental health and quality of life within age groups, while adjusting by sociodemographic variables. Video-based communication tools were found to be more often used among participants aged 60-69 years (60.1%), compared to participants aged 70 or above (51.8%, p < 0.05). Adjusting for all variables, the use of video-based communication was associated with less loneliness ( β = -0.12, p < 0.01) and higher quality of life ( β = 0.14, p < 0.01) among participants aged 60-69 years, while no associations were observed for participants in the oldest age group. The use of video-based communication tools was therefore associated with favorable psychological outcomes among participants in their sixties, but not among participants in the oldest age group. The study results support the notion that age may influence the association between the use of video-based communication tools and psychological outcomes amongst older people.

This cross-national study explored stability and change in mental health, quality of life, well-being and loneliness during the early stage and nine months after the implementation of COVID-19 pandemic social distancing measures and periodic lockdowns as adjusted by demographic variables. In the USA, the UK, Australia and Norway, 7284 individuals responded to the invitation to take part in two cross-sectional web-based surveys (April and November 2020), including questions about sociodemographic variables and psychosocial outcomes. Independent t -tests and generalized linear models (GLM) and estimated marginal means were used to analyze differences between subgroups and countries, multiple linear regression analyses were conducted on the psychosocial outcome measures by demographic variables and time in each country and mean responses presented by time after adjusting for all demographic variables in the model. Age, gender, civil status, education, employment, place of work and living area were all significant factors for psychosocial health across the countries. Differences in mental health, quality of life, well-being and loneliness were found between the countries in both April and November 2020, while time did not contribute to reducing the toll in any of the four countries over the nine-month period.

Background: The COVID-19 outbreak raised questions about how people experience their mental health, quality of life (QoL), wellbeing and loneliness in the context of social distancing, and the use of social media during this time., Aims: To examine the experience of mental health, QoL, wellbeing and loneliness and use of social media among people living in Norway, USA, UK and Australia., Methods: A cross-country comparative survey of people living in Norway, USA, UK and Australia. Relevant statistical analyses were used to examine differences between the countries and to explore associations between demographic, mental health and psychosocial variables and use of social media., Results: There were 3810 respondents from four countries, of which 50 - 74% showed a high level of emotional distress. The Norwegian population reported significantly better mental health, QoL and wellbeing and lower levels of loneliness compared to the other countries. High-frequent use of social media after the COVID-19 outbreak was associated with poorer mental- and psychosocial health., Conclusions: The results suggest that the COVID-19 outbreak took a toll on people's experience of mental health, QoL, wellbeing and experienced loneliness, and high-frequent use of social media was associated with these factors.

COVID-19 has been a global healthcare concern impacting multiple aspects of individual and community wellness. As one moves forward with different methods to reduce the infection and mortality rates, it is critical to continue to study the impact that national and local "social distancing" policies have on the daily lives of individuals. The aim of this study was to examine loneliness in relation to risk assessment, measures taken against risks, concerns, and social media use, while adjusting for sociodemographic variables. The cross-sectional study collected data from 3474 individuals from the USA, the UK, Norway, and Australia. Loneliness was measured with the de Jong Gierveld Loneliness Scale. Multiple linear regression was used in the analysis of associations between variables. The results showed that concerns about finances were more strongly associated with social loneliness, while concerns about the future was more strongly associated with emotional loneliness. Longer daily time spent on social media was associated with higher emotional loneliness. In conclusion, pandemic-related concerns seem to affect perceptions of loneliness. While social media can be used productively to maintain relationships, and thereby prevent loneliness, excessive use may be counterproductive.

Background: Social distancing during the COVID-19 pandemic has resulted in changes in the work environment and employment uncertainty. This paper reports on a cross-national comparison of four countries (Norway, UK, USA and Australia) and examines the differences in mental health between those individuals employed and those not employed during the social distancing implementation., Methods: Participants ( N  = 3,810) were recruited through social media in April/May 2020 and were invited to complete a self-administered electronic survey over a 3-week period. Differences between those employed and those not employed with regard to their sociodemographic characteristics and mental health were investigated with chi-square tests, independent t tests, and one-way analysis of variances (ANOVAs)., Results: Compared with their counterparts, participants who were employed reported lower levels of mental health distress ( p  < 0.001), higher levels of psychosocial well-being ( p  < 0.001), better overall quality of life ( p  < 0.001), and lower levels of overall loneliness, social loneliness, and emotional loneliness ( p  < 0.001). Small to medium but consistent differences (Cohen's d  = 0.23-0.67) in mental health favor those with employment or those who were retired., Conclusion: Further study is needed to assess mental health over time as the COVID-19 pandemic and employment uncertainty continues., (© The Author(s) 2021.)

To (i) examine the use of social media before and after the COVID-19 outbreak; (ii) examine the self-perceived impact of social media before and after the outbreak; and (iii) examine whether the self-perceived impacts of social media after the outbreak varied by levels of mental health. A cross-national online survey was conducted in Norway, UK, USA and Australia. Participants ( n  = 3810) reported which social media they used, how frequently they used them before and after the COVID-19 outbreak, and the degree to which they felt social media contributed to a range of outcomes. The participants also completed the 12-item General Health Questionnaire. The data were analyzed by chi-square tests and multiple linear regression analysis. Social media were used more frequently after the pandemic outbreak than compared to before the outbreak. Self-perceived effects from using social media increased after the COVID-19 outbreak, and in particular stress and concern for own and others' health. Emotional distress was associated with being more affected from using social media, in particular in terms of stress and concern for own or others' health. The use of social media has increased during the coronavirus outbreak, as well as its impacts on people. In particular, the participants reported more stress and health concerns attributed to social media use after the COVID-19 outbreak. People with poor mental health appear to be particularly vulnerable to experiencing more stress and concern related to their use of social media., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© The Author(s) 2021.)

Background: Seasonal variability in mortality has been studied in various regions globally. Proper evaluation of seasonally fluctuating mortality is important to establish effective public health measures. We investigated the overall, age-specific, and cause-specific seasonality of deaths in Chitral District in Pakistan., Method: Data on 2577 deaths were provided by the Agha Khan Health Support Program. Seasonal mortality patterns concerning age and causes were examined using the X-12 ARIMA pseudo-additive decomposition method., Results: Of the total deceased, 59.6% were males. The proportion of deceased males was significantly higher than the female (40.4%, p< 0.001). The average age at death was 57.7 years (SD = 28.7). On average, approximately 43 deaths occurred each month. More than 10% of the deaths occurred in children less than 5-years-of-age. Among all the causes of death, the most frequent was cardiovascular disease (n = 666, 25.8%) followed by respiratory disease (n = 482, 18.7%). Significant seasonality in the overall deaths was evident, with a peak in winter. Deaths in people ≥ 55-years-of-age were significantly seasonal and peaked in winter. Deaths due to cardiovascular, respiratory, and kidney related diseases were also significantly seasonal with winter peaks. Further, deaths due to external causes were significantly seasonal with summer peak., Conclusion: In the winter season, all-cause, except external, and age-specific mortality peaks in Chitral District, Pakistan. Deaths due to external causes and cardiovascular, respiratory, and kidney related diseases were significant seasonal effects., Competing Interests: The authors have declared that no competing interests exist.

Background: Physical restraint is a coercive intervention used to prevent individuals from harming themselves or others. However, serious adverse effects have been reported. Minimising the use of restraint requires a multimodal approach to target both organisational and individual factors. The 'Six Core Strategies' developed in America, underpinned by prevention and trauma informed principles, is one such approach., Objective: An adapted version of the Six Core Strategies was developed and its impact upon physical restraint usage in mental health Trusts in the United Kingdom evaluated. This became known as 'REsTRAIN YOURSELF. The hypothesis was that restraint would be reduced by 40% on the implementation wards over a six-month period., Design: A non-randomised controlled trial design was employed., Setting: Fourteen, adult, mental health wards from seven mental health hospitals in the North West of England took part in the study. Two acute care wards were targeted from all eligible acute wards within each site in negotiation with each Trust. The intervention wards (total n = 144 beds, mean = 20.1 beds per ward) and control wards (total n = 147 beds, mean = 21.0 beds per ward) were primarily mixed gender but included single sex wards also (2 female-only and 1 male-only in each group). All wards offered pharmacological and psychosocial interventions over short admission durations (circa 15 days) for patients with a mixture of enduring mental health problems., Method: As part of a pre and post-test method, physical restraint figures were collected using prospective, routine hospital records before and 6 months after the intervention. Restraint rates on seven wards receiving the REsTRAIN YOURSELF intervention were compared with those on seven control wards over three study phases (baseline, implementation and adoption)., Results: In total, 1680 restraint incidents were logged over the study period. The restraint rate was significantly lower on the intervention wards in the adoption phase (6.62 events/1000 bed-days, 95% CI 5.53-7.72) compared to the baseline phase (9.38, 95% CI 8.19-10.55). Across all implementation wards there was an average reduction of restraint by 22%, with some wards showing a reduction of 60% and others less so (8%). The association between ward type and study phase was statistically significant., Conclusion: In conclusion, it is possible that reductions in the use of physical restraint are achievable using a model such as the Six Core Strategies. This approach can be adapted for global settings and changes can be sustained over time with continued support., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Systematic tumour profiling is essential for biomarker research and clinically for assessing response to therapy. Solving the challenge of delivering informative copy number (CN) profiles from formalin-fixed paraffin embedded (FFPE) material, the only likely readily available biospecimen for most cancers, involves successful processing of small quantities of degraded DNA. To investigate the potential for analysis of such lesions, whole-genome CNVseq was applied to 300 FFPE primary tumour samples, obtained from a large-scale epidemiological study of melanoma. The quality and the discriminatory power of CNVseq was assessed. Libraries were successfully generated for 93% of blocks, with input DNA quantity being the only predictor of success (success rate dropped to 65% if <20 ng available); 3% of libraries were dropped because of low sequence alignment rates. Technical replicates showed high reproducibility. Comparison with targeted CN assessment showed consistency with the Next Generation Sequencing (NGS) analysis. We were able to detect and distinguish CN changes with a resolution of ≤10 kb. To demonstrate performance, we report the spectrum of genomic CN alterations (CNAs) detected at 9p21, the major site of CN change in melanoma. This successful analysis of CN in FFPE material using NGS provides proof of principle for intensive examination of population-based samples.

Recently, increased attention has been paid to biodiversity conservation provided by blue-green solutions such as engineered ponds that are primarily established for water treatment and flood control. However, little research has been done to analyse the factors that affect biodiversity in such ponds. The purpose of this study was to evaluate the influence of environmental factors on aquatic biodiversity, mainly macroinvertebrate communities, in road sedimentation ponds in order to provide a foundation for recommendations on aquatic biodiversity conservation. Multivariate statistical methods, including unconstrained and constrained analysis, were applied to examine the relationships between organisms and the water quality as well as physical factors (including plant cover). Stepwise multiple regressions indicated that the most important variables governing the variation in the biological community composition were pond size, average annual daily traffic, metals, chloride, distance to the closest pond from study pond, dissolved oxygen, hydrocarbons, and phosphorus. The presence of most taxa was positively correlated with pond size and negatively correlated with metals. Small ponds with high pollutant loadings were associated with a low diversity and dominated by a few pollution tolerant taxa such as oligochaetes. A comprehensive understanding of impacts of various environmental factors on aquatic biodiversity is important to effectively promote and conserve aquatic biodiversity in such sedimentation ponds. Our results indicate that road sedimentation ponds should be designed large enough, because large ponds are likely to provide a more heterogeneous habitat and thus contain a species rich fauna. In addition, larger ponds seem to be less contaminated due to dilution compared to smaller ponds, thereby maintaining a higher biodiversity. Finally, creating some additional ponds in the vicinity of the sedimentation ponds in areas with few water bodies would increase the connectivity that facilitates the movement of invertebrates between ponds., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Introduction: Haematospermia is an uncommon clinical condition that may be associated with prostate cancer. The optimal investigation of haematospermia is unknown. The aim of this study was to investigate haematospermia as a presenting symptom of significant pathology and to assess the diagnostic value of magnetic resonance imaging (MRI)., Material and Methods: Patient and treatment parameters were collected from a practice cohort of men referred to a urology center presenting with haematospermia. We used a multivariate logistic regression model to test the independent significance of MRI in detecting prostate cancer (PCa) after adjusting for other known predictors of PCa detection., Results: A total of 125 men (median age 58 years) were evaluated between 2012-2015. In the univariate and multivariate logistic regression model MRI was a significant predictor of PCa diagnosis after adjusting for age, prostate specific antigen (PSA) and digital rectal examination (DRE) results (Odds Ratio (OR) 14.15, p = 0.001). Of 107 patients who underwent MRI prostate imaging, 31 (28.9%) had reports suspicious of PCa. In 26 patients, other benign conditions were detected on MRI. PCa was detected in 12 (25.5%) of the 47 men (median age 61 years; range 43 to 85) who underwent prostate biopsies. Eight (17%) of these patients had Gleason ≥7 grade cancer. The persistence of haematospermia was not an independent predictor of cancer diagnosis (OR 0.20, p = 0.15)., Conclusions: PCa is not commonly associated with haematospermia. MRI seems to be improving detection rate of a significant PCa, particularly in patients presenting with haematospermia and normal PSA levels and DRE examination. Duration of haematospermia does not predict the presence of PCa.

Bladder cancer incurs a higher lifetime treatment cost than other cancers due to frequent recurrence of non-invasive disease. Improved prognostic biomarkers and localized therapy are needed for this large patient group. We defined two major genomic subtypes of primary stage Ta tumors. One of these was characterized by loss of 9q including TSC1, increased KI67 labeling index, upregulated glycolysis, DNA repair, mTORC1 signaling, features of the unfolded protein response, and altered cholesterol homeostasis. Comparison with muscle-invasive bladder cancer mutation profiles revealed lower overall mutation rates and more frequent mutations in RHOB and chromatin modifier genes. More mutations in the histone lysine demethylase KDM6A were present in non-invasive tumors from females than males., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: For patients to engage with the long-term management of liver cirrhosis, sufficient understanding of their condition is essential. The aim of this study was to assess baseline patient knowledge and to test whether a condition-specific multimedia screencast could improve this., Design: Service quality improvement study., Setting: A UK tertiary liver centre. Patients were recruited during 12 general hepatology outpatient clinics., Patients: Fifty-two patients with liver cirrhosis were included. Sixty-two per cent were male; their median age was 56 years and their median clinic attendance period was 3 years., Interventions: Participants completed a baseline questionnaire assessing their knowledge of the management and complications of cirrhosis. They then watched a tailored screencast discussing this condition, which had been developed by expert hepatologists in collaboration with patient representatives. Knowledge was reassessed using a new copy of the original questionnaire after an interval of at least one month., Main Outcome Measures: Patient scores on knowledge questionnaires at baseline and follow-up., Results: Fifty-two patients achieved a median score of 25.0% before viewing the screencast. Thirty-five patients then completed a follow-up questionnaire after an interval period. The median questionnaire score in this group improved from 25.0% to 66.7%; an increase of 41.7% compared with baseline (p<0.001)., Conclusions: Despite regular review at a specialist clinic, participants had poor baseline knowledge of liver cirrhosis. Delivering information by screencast led to a significant improvement. We therefore present an effective way to empower patients with accurate, up-to-date and retainable information that can easily be translated to many other conditions., Competing Interests: Competing interests: None declared.

Purpose: We investigated whether microRNA expression data from glioblastoma could be used to produce a profile that defines a bevacizumab responsive group of patients., Patients and Methods: TCGA microRNA expression data from tumors resected at first diagnosis of glioblastoma in patients treated with bevacizumab at any time during the course of their disease were randomly separated into training (n = 50) and test (n = 37) groups for model generation. MicroRNA-seq data for 51 patients whose treatment included bevacizumab in the BELOB trial were used as an independent validation cohort., Results: Using penalized regression we identified 8 microRNAs as potential predictors of overall survival in the training set. We dichotomized the response score based on the most prognostic minimum of a density plot of the response scores (log-rank HR = 0.16, p = 1.2e(-5)) and validated the profile in the test cohort (one-sided log-rank HR = 0.34, p = 0.026). Analysis of the profile using all samples in the TCGA glioblastoma dataset, regardless of treatment received, (n = 473) showed that the prediction of patient benefit was not significant (HR = 0.84, p = 0.083) suggesting the profile is specific to bevacizumab. Further independent validation of our microRNA profile in RNA-seq data from patients treated with bevacizumab (alone or in combination with CCNU) at glioblastoma recurrence in the BELOB trial confirmed that our microRNA profile predicted patient benefit from bevacizumab (HR = 0.59, p = 0.043)., Conclusion: We have identified and validated an 8-microRNA profile that predicts overall survival in patients with glioblastoma treated with bevacizumab. This may be useful for identifying patients who are likely to benefit from this agent., (Copyright © 2016 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.)

Chronic exposure to neonicotinoid insecticides has been linked to reduced survival of pollinating insects at both the individual and colony level, but so far only experimentally. Analyses of large-scale datasets to investigate the real-world links between the use of neonicotinoids and pollinator mortality are lacking. Moreover, the impacts of neonicotinoid seed coatings in reducing subsequent applications of foliar insecticide sprays and increasing crop yield are not known, despite the supposed benefits of this practice driving widespread use. Here, we combine large-scale pesticide usage and yield observations from oilseed rape with those detailing honey bee colony losses over an 11 year period, and reveal a correlation between honey bee colony losses and national-scale imidacloprid (a neonicotinoid) usage patterns across England and Wales. We also provide the first evidence that farmers who use neonicotinoid seed coatings reduce the number of subsequent applications of foliar insecticide sprays and may derive an economic return. Our results inform the societal discussion on the pollinator costs and farming benefits of prophylactic neonicotinoid usage on a mass flowering crop.