User experience analysis of AbC-19 Rapid Test via lateral flow immunoassays for self-administrated SARS-CoV-2 antibody testing

Abstract Lateral flow immunoassays are low cost, rapid and highly efficacious point-of-care devices, which have been used for SARS-CoV-2 antibody testing by professionals. However, there is a lack of understanding about how self-administered tests are used by the general public for mass testing in different environmental settings. The purpose of this study was to assess the user experience (UX) (including usability) of a self-testing kit to identify COVID-19 antibodies used by a representative sample of the public in their cars, which included 1544 participants in Northern Ireland. The results based on 5-point Likert ratings from a post-test questionnaire achieved an average UX score of 96.03% [95% confidence interval (CI) 95.05–97.01%], suggesting a good degree of user experience. The results of the Wilcoxon rank sum tests suggest that UX scores were independent of the user’s age and education level although the confidence in this conclusion could be strengthened by including more participants aged younger than 18 and those with only primary or secondary education. The agreement between the test result as interpreted by the participant and the researcher was 95.85% [95% CI 94.85–96.85%], Kappa score 0.75 [95% CI 0.69–0.81] (indicating substantial agreement). Text analysis via the latent Dirichlet allocation model for the free text responses in the survey suggest that the user experience could be improved for blood-sample collection, by modifying the method of sample transfer to the test device and giving clearer instructions on how to interpret the test results. The overall findings provide an insight into the opportunities for improving the design of SARS-CoV-2 antibody testing kits to be used by the general public and therefore inform protocols for future user experience studies of point-of-care tests

Single feature polymorphisms (SFPs) for drought tolerance in pigeonpea (Cajanus spp.)

Single feature polymorphisms (SFPs) are microarray-based molecular markers that are detected by hybridization of DNA or cRNA to oligonucleotide probes. With an objective to identify the potential polymorphic markers for drought tolerance in pigeonpea [Cajanus cajan (L.) Millspaugh], an important legume crop for the semi-arid tropics but deficient in genomic resources, Affymetrix Genome Arrays of soybean (Glycine max), a closely related species of pigeonpea were used on cRNA of six parental genotypes of three mapping populations of pigeonpea segregating for agronomic traits like drought tolerance and pod borer (Helicoverpa armigiera) resistance. By using robustified projection pursuit method on 15 pair-wise comparisons for the six parental genotypes, 5,692 SFPs were identified. Number of SFPs varied from 780 (ICPL 8755 × ICPL 227) to 854 (ICPL 151 × ICPL 87) per parental combination of the mapping populations. Randomly selected 179 SFPs were used for validation by Sanger sequencing and good quality sequence data were obtained for 99 genes of which 75 genes showed sequence polymorphisms. While associating the sequence polymorphisms with SFPs detected, true positives were observed for 52.6% SFPs detected. In terms of parental combinations of the mapping populations, occurrence of true positives was 34.48% for ICPL 151 × ICPL 87, 41.86% for ICPL 8755 × ICPL 227, and 81.58% for ICP 28 × ICPW 94. In addition, a set of 139 candidate genes that may be associated with drought tolerance has been identified based on gene ontology analysis of the homologous pigeonpea genes to the soybean genes that detected SFPs between the parents of the mapping populations segregating for drought tolerance

Resolving a gender and language problem in women’s leadership:consultancy research in workplace discourse

This article considers the contribution that consultancy research might make to resolving communication problems that women have identified in their leadership practices. Within the intersecting fields of gender and language and workplace discourse, consultancy research-that is, practitioner-commissioned research to resolve work-related, communication problems-is still uncommon. This article presents a study of Monika, a senior leader in an engineering company, who commissioned me to find out why she was experiencing communication problems with her teams. By using interactional sociolinguistic analysis, I was able to show Monika how her authority was being resisted on gendered, linguistic grounds. In making the case for more consultancy research, I discuss how we might use insights from discourse analysis to offer guidance to practitioners seeking our help

The HUSH complex is a gatekeeper of type I interferon through epigenetic regulation of LINE-1s

The Human Silencing Hub (HUSH) complex is necessary for epigenetic repression of LINE-1 elements. We show that HUSH-depletion in human cell lines and primary fibroblasts leads to induction of interferon-stimulated genes (ISGs) through JAK/STAT signaling. This effect is mainly attributed to MDA5 and RIG-I sensing of double-stranded RNAs (dsRNAs). This coincides with upregulation of primate-conserved LINE-1s, as well as increased expression of full-length hominid-specific LINE-1s that produce bidirectional RNAs, which may form dsRNA. Notably, LTRs nearby ISGs are derepressed likely rendering these genes more responsive to interferon. LINE-1 shRNAs can abrogate the HUSH-dependent response, while overexpression of an engineered LINE-1 construct activates interferon signaling. Finally, we show that the HUSH component, MPP8 is frequently downregulated in diverse cancers and that its depletion leads to DNA damage. These results suggest that LINE-1s may drive physiological or autoinflammatory responses through dsRNA sensing and gene-regulatory roles and are controlled by the HUSH complex

Oestrogen blocks the nuclear entry of SOX9 in the developing gonad of a marsupial mammal

<p>Abstract</p> <p>Background</p> <p>Hormones are critical for early gonadal development in nonmammalian vertebrates, and oestrogen is required for normal ovarian development. In contrast, mammals determine sex by the presence or absence of the <it>SRY </it>gene, and hormones are not thought to play a role in early gonadal development. Despite an XY sex-determining system in marsupial mammals, exposure to oestrogen can override <it>SRY </it>and induce ovarian development of XY gonads if administered early enough. Here we assess the effect of exogenous oestrogen on the molecular pathways of mammalian gonadal development.</p> <p>Results</p> <p>We examined the expression of key testicular (<it>SRY</it>, <it>SOX9</it>, <it>AMH </it>and <it>FGF9</it>) and ovarian (<it>WNT4</it>, <it>RSPO1</it>, <it>FOXL2 </it>and <it>FST</it>) markers during gonadal development in the marsupial tammar wallaby (<it>Macropus eugenii</it>) and used these data to determine the effect of oestrogen exposure on gonadal fate. During normal development, we observed male specific upregulation of <it>AMH </it>and <it>SOX9 </it>as in the mouse and human testis, but this upregulation was initiated before the peak in <it>SRY </it>expression and 4 days before testicular cord formation. Similarly, key genes for ovarian development in mouse and human were also upregulated during ovarian differentiation in the tammar. In particular, there was early sexually dimorphic expression of <it>FOXL2 </it>and <it>WNT4</it>, suggesting that these genes are key regulators of ovarian development in all therian mammals. We next examined the effect of exogenous oestrogen on the development of the mammalian XY gonad. Despite the presence of <it>SRY</it>, exogenous oestrogen blocked the key male transcription factor SOX9 from entering the nuclei of male somatic cells, preventing activation of the testicular pathway and permitting upregulation of key female genes, resulting in ovarian development of the XY gonad.</p> <p>Conclusions</p> <p>We have uncovered a mechanism by which oestrogen can regulate gonadal development through the nucleocytoplasmic shuttling of SOX9. This may represent an underlying ancestral mechanism by which oestrogen promotes ovarian development in the gonads of nonmammalian vertebrates. Furthermore, oestrogen may retain this function in adult female mammals to maintain granulosa cell fate in the differentiated ovary by suppressing nuclear translocation of the SOX9 protein.</p> <p>See commentary: http://www.biomedcentral.com/1741-7007/8/110</p

Identification of chemokine receptors as potential modulators of endocrine resistance in oestrogen receptor–positive breast cancers

Introduction Endocrine therapies target oestrogenic stimulation of breast cancer (BC) growth, but resistance remains problematic. Our aims in this study were (1) to identify genes most strongly associated with resistance to endocrine therapy by intersecting global gene transcription data from patients treated presurgically with the aromatase inhibitor anastrazole with those from MCF7 cells adapted to long-term oestrogen deprivation (LTED) (2) to assess the clinical value of selected genes in public clinical data sets and (3) to determine the impact of targeting these genes with novel agents. Methods Gene expression and Ki67 data were available from 69 postmenopausal women with oestrogen receptor–positive (ER+) early BC, at baseline and 2 weeks after anastrazole treatment, and from cell lines adapted to LTED. The functional consequences of target genes on proliferation, ER-mediated transcription and downstream cell signalling were assessed. Results By intersecting genes predictive of a poor change in Ki67 with those upregulated in LTED cells, we identified 32 genes strongly correlated with poor antiproliferative response that were associated with inflammation and/or immunity. In a panel of LTED cell lines, C-X-C chemokine receptor type 7 (CXCR7) and CXCR4 were upregulated compared to their wild types (wt), and CXCR7, but not CXCR4, was associated with reduced relapse-free survival in patients with ER+ BC. The CXCR4 small interfering RNA variant (siCXCR4) had no specific effect on the proliferation of wt-SUM44, wt-MCF7 and their LTED derivatives. In contrast, siCXCR7, as well as CCX733, a CXCR7 antagonist, specifically suppressed the proliferation of MCF7-LTED cells. siCXCR7 suppressed proteins associated with G1/S transition and inhibited ER transactivation in MCF7-LTED, but not wt-MCF7, by impeding association between ER and proline-, glutamic acid– and leucine-rich protein 1, an ER coactivator. Conclusions These data highlight CXCR7 as a potential therapeutic target warranting clinical investigation in endocrine-resistant BC

Why is it difficult to implement e-health initiatives? A qualitative study

&lt;b&gt;Background&lt;/b&gt; The use of information and communication technologies in healthcare is seen as essential for high quality and cost-effective healthcare. However, implementation of e-health initiatives has often been problematic, with many failing to demonstrate predicted benefits. This study aimed to explore and understand the experiences of implementers - the senior managers and other staff charged with implementing e-health initiatives and their assessment of factors which promote or inhibit the successful implementation, embedding, and integration of e-health initiatives.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Methods&lt;/b&gt; We used a case study methodology, using semi-structured interviews with implementers for data collection. Case studies were selected to provide a range of healthcare contexts (primary, secondary, community care), e-health initiatives, and degrees of normalization. The initiatives studied were Picture Archiving and Communication System (PACS) in secondary care, a Community Nurse Information System (CNIS) in community care, and Choose and Book (C&#38;B) across the primary-secondary care interface. Implementers were selected to provide a range of seniority, including chief executive officers, middle managers, and staff with 'on the ground' experience. Interview data were analyzed using a framework derived from Normalization Process Theory (NPT).&lt;p&gt;&lt;/p&gt; &lt;b&gt;Results&lt;/b&gt; Twenty-three interviews were completed across the three case studies. There were wide differences in experiences of implementation and embedding across these case studies; these differences were well explained by collective action components of NPT. New technology was most likely to 'normalize' where implementers perceived that it had a positive impact on interactions between professionals and patients and between different professional groups, and fit well with the organisational goals and skill sets of existing staff. However, where implementers perceived problems in one or more of these areas, they also perceived a lower level of normalization.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Conclusions&lt;/b&gt; Implementers had rich understandings of barriers and facilitators to successful implementation of e-health initiatives, and their views should continue to be sought in future research. NPT can be used to explain observed variations in implementation processes, and may be useful in drawing planners' attention to potential problems with a view to addressing them during implementation planning

Absence of influenza vaccination among high-risk older adults in Taiwan

<p>Abstract</p> <p>Background</p> <p>Older adults, who often have more than one chronic disease, are at greater risk of influenza and its complications. However, because they often see physicians for other more pressing complaints, their physicians, focusing on one condition, may forget to suggest preventive measures for other diseases such as influenza. This study investigates what major factors affect an older adult with more than one chronic condition missing a vaccination opportunity.</p> <p>Methods</p> <p>Retrospectively reviewing a nationally representative random sample of medical claims from Taiwan's National Health Insurance Research Database during the period 2004 - 2006, we first identified patients sixty-five years or older who had visited physicians. Each patient was assigned a proxy for health status, the Charlson Comorbidity Index (CCI) score. An older claimant was defined has having "absence of a vaccination" when he or she had visited a physician during an influenza season but did not receive an influenza vaccination. Multivariate logistic regression was performed to estimate how likely it would be for older adults with various CCI scores to miss a vaccination.</p> <p>Results</p> <p>Out of 200,000 randomly selected claims, 20,923 older adults were included in our final analysis. We found older adults with higher CCIs to be more likely to have an absence of vaccination (<it>p </it>< 0.01). Our multivariate logistic regression results revealed CCI to be the greatest predictor of absence of vaccination, after controlling for individual factors and medical setting. Older adults with CCI scores three or higher were nearly five times more likely to miss a vaccination than those with a CCI of zero [OR: 4.93 (95%CI, 4.47-5.42)]. Those with CCIs of one and two were 2.53 and 3.92 times more likely to miss vaccination than those with a CCI of zero [OR 2.53 (95%CI, 2.26-2.84) and OR 3.92 (95%CI, 3.51-4.38), respectively].</p> <p>Conclusions</p> <p>The greater the number of certain comorbid conditions, the greater the likelihood a flu vaccination will be missed. Physicians would be well advised to not let the presenting problems of older patients distract from other possible health problems that might also need attention, in this case influenza vaccinations.</p

Systematic evaluation of implementation fidelity of complex interventions in health and social care

<p>Abstract</p> <p>Background</p> <p>Evaluation of an implementation process and its fidelity can give insight into the 'black box' of interventions. However, a lack of standardized methods for studying fidelity and implementation process have been reported, which might be one reason for the fact that few prior studies in the field of health service research have systematically evaluated interventions' implementation processes.</p> <p>The aim of this project is to systematically evaluate implementation fidelity and possible factors influencing fidelity of complex interventions in health and social care.</p> <p>Methods</p> <p>A modified version of The Conceptual Framework for Implementation Fidelity will be used as a conceptual model for the evaluation. The modification implies two additional moderating factors: context and recruitment. A systematic evaluation process was developed. Multiple case study method is used to investigate implementation of three complex health service interventions. Each case will be investigated in depth and longitudinally, using both quantitative and qualitative methods.</p> <p>Discussion</p> <p>This study is the first attempt to empirically test The Conceptual Framework for Implementation Fidelity. The study can highlight mechanism and factors of importance when implementing complex interventions. Especially the role of the moderating factors on implementation fidelity can be clarified.</p> <p>Trial Registration</p> <p>Supported Employment, SE, among people with severe mental illness -- a randomized controlled trial: NCT00960024.</p