The likely implications of the 1997 Coroners Ordinance on the autopsy service of a teaching hospital

The new Hong Kong Coroners Ordinance was published in April 1997. It introduced an expanded set of guidelines for reporting deaths to the coroner as well as the threat of criminal proceedings for non-compliance. The Ordinance is due to be implemented in early 1998. The aim of this study is to determine the likely effect of the new law on the relative proportion of coroner's and hospital (consent) autopsies. A total of 352 consecutive autopsy cases were reviewed; 170 (48.3%) were referred for coroner's autopsies and 182 (51.7%) for hospital autopsies. But applying the criteria of the current ordinance, there should have been 213 (60.5%) coroner's cases and 139 (39.5%) hospital autopsiesԸ?that is, 43 hospital autopsies should have been coroner's autopsies. Under the new Coroners Ordinance, there would be 300 (85.2%) coroner's autopsies and only 52 (14.8%) hospital autopsies. The new Coroners Ordinance is likely to result in a greater number of requests for coroner's autopsies with a corresponding decline in hospital autopsiesԸ?in our case, a shift from 48.3% of all autopsies performed to 85.2%! This increase would be due largely to the requirement for reporting stillbirths but would also be due to increased reporting for fear of Ը?criminal proceedings' for non-compliance. An absolute increase in the number of autopsies is also anticipated, although the magnitude cannot as yet be predicted.published_or_final_versio

SILAC-based proteomic quantification of chemoattractant-induced cytoskeleton dynamics on a second to minute timescale

Cytoskeletal dynamics during cell behaviours ranging from endocytosis and exocytosis to cell division and movement is controlled by a complex network of signalling pathways, the full details of which are as yet unresolved. Here we show that SILAC-based proteomic methods can be used to characterize the rapid chemoattractant-induced dynamic changes in the actin–myosin cytoskeleton and regulatory elements on a proteome-wide scale with a second to minute timescale resolution. This approach provides novel insights in the ensemble kinetics of key cytoskeletal constituents and association of known and novel identified binding proteins. We validate the proteomic data by detailed microscopy-based analysis of in vivo translocation dynamics for key signalling factors. This rapid large-scale proteomic approach may be applied to other situations where highly dynamic changes in complex cellular compartments are expected to play a key role

Enrichment analysis of Alu elements with different spatial chromatin proximity in the human genome

Transposable elements (TEs) have no longer been totally considered as “junk DNA” for quite a time since the continual discoveries of their multifunctional roles in eukaryote genomes. As one of the most important and abundant TEs that still active in human genome, Alu, a SINE family, has demonstrated its indispensable regulatory functions at sequence level, but its spatial roles are still unclear. Technologies based on 3C(chromosomeconformation capture) have revealed the mysterious three-dimensional structure of chromatin, and make it possible to study the distal chromatin interaction in the genome. To find the role TE playing in distal regulation in human genome, we compiled the new released Hi-C data, TE annotation, histone marker annotations, and the genome-wide methylation data to operate correlation analysis, and found that the density of Alu elements showed a strong positive correlation with the level of chromatin interactions (hESC: r=0.9, P<2.2×1016; IMR90 fibroblasts: r = 0.94, P < 2.2 × 1016) and also have a significant positive correlation withsomeremote functional DNA elements like enhancers and promoters (Enhancer: hESC: r=0.997, P=2.3×10−4; IMR90: r=0.934, P=2×10−2; Promoter: hESC: r = 0.995, P = 3.8 × 10−4; IMR90: r = 0.996, P = 3.2 × 10−4). Further investigation involving GC content and methylation status showed the GC content of Alu covered sequences shared a similar pattern with that of the overall sequence, suggesting that Alu elements also function as the GC nucleotide and CpG site provider. In all, our results suggest that the Alu elements may act as an alternative parameter to evaluate the Hi-C data, which is confirmed by the correlation analysis of Alu elements and histone markers. Moreover, the GC-rich Alu sequence can bring high GC content and methylation flexibility to the regions with more distal chromatin contact, regulating the transcription of tissue-specific genes

CFTR founder mutation causes protein trafficking defects in Chinese patients with cystic fibrosis

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Assessment of HIF-1α expression and release following endothelial injury in-vitro and in-vivo

Background: Endothelial injury is an early and enduring feature of cardiovascular disease. Inflammation and hypoxia may be responsible for this, and are often associated with the up-regulation of several transcriptional factors that include Hypoxia Inducible Factor-1 (HIF-1). Although it has been reported that HIF-1α is detectable in plasma, it is known to be unstable. Our aim was to optimize an assay for HIF-1α to be applied to in vitro and in vivo applications, and to use this assay to assess the release kinetics of HIF-1 following endothelial injury. Methods: An ELISA for the measurement of HIF in cell-culture medium and plasma was optimized, and the assay used to determine the best conditions for sample collection and storage. The results of the ELISA were validated using Western blotting and immunohistochemistry (IHC). In vitro, a standardized injury was produced in a monolayer of rat aortic endothelial cells (RAECs) and intracellular HIF-1α was measured at intervals over 24 hours. In vivo, a rat angioplasty model was used. The right carotid artery was injured using a 2F Fogarty balloon catheter. HIF-1α was measured in the plasma and in the arterial tissue (0, 1, 2, 3 and 5 days post injury). Results: The HIF-1α ELISA had a limit of detection of 2.7 pg/ mL and was linear up to 1000 pg/ mL. Between and within-assay coefficient of variation values were less than 15%. HIF-1α was unstable in cell lysates and plasma, and it was necessary to add a protease inhibitor immediately after collection, and to store samples at -800C prior to analysis. The dynamics of HIF-1α release were different for the in vitro and in vivo models. In vitro, HIF-1α reached maximum concentrations approximately 2h post injury, whereas peak values in plasma and tissues occurred approximately 2 days post injury, in the balloon injury model. Conclusion: HIF-1α can be measured in plasma, but this requires careful sample collection and storage. The carotid artery balloon injury model is associated with the transient release of HIF-1α into the circulation that probably reflects the hypoxia induced in the artery wall

The AFLOW Fleet for Materials Discovery

The traditional paradigm for materials discovery has been recently expanded to incorporate substantial data driven research. With the intent to accelerate the development and the deployment of new technologies, the AFLOW Fleet for computational materials design automates high-throughput first principles calculations, and provides tools for data verification and dissemination for a broad community of users. AFLOW incorporates different computational modules to robustly determine thermodynamic stability, electronic band structures, vibrational dispersions, thermo-mechanical properties and more. The AFLOW data repository is publicly accessible online at aflow.org, with more than 1.7 million materials entries and a panoply of queryable computed properties. Tools to programmatically search and process the data, as well as to perform online machine learning predictions, are also available.Comment: 14 pages, 8 figure

COVID-19 Vaccine Booster Hesitancy among the Elderly in Malaysian Residential Care Homes: A Cross-Sectional Study in Klang Valley

Abstract: The elderly are considered a high-risk group for severe outcomes and death from COVID-19 infection. Given the emergence of new COVID variants and the immunity provided by vaccines waning over time, booster doses of the vaccine have been advocated for those at risk to stay protected. This study aimed to determine the factors associated with hesitancy toward the second booster of the COVID-19 vaccine among the elderly residing in residential care homes. A cross-sectional study was conducted in 24 residential care homes in the Klang Valley using a face-to-face interview questionnaire. The study population included individuals aged 60 and above who had been fully vaccinated against COVID-19 up to the first booster dose. Second-booster hesitancy was assessed using the Oxford Vaccine Hesitancy Scale with seven items, the aggregate score of which ranges from seven to thirty-five; the higher the score, the greater the level of hesitancy. Multivariate linear regression was employed to determine factors associated with second-booster hesitancy, and a p-value &lt; 0.05 was considered statistically significant. Data from 401 elderly individuals were included for analysis. The mean score of the Oxford Vaccine Hesitancy Scale was 21.6 \ub1 7.2. Predictors of second booster hesitancy were identified. Age, Indian ethnicity, being a recipient of the Sinovac vaccine as the first COVID-19 booster, experiencing the death of close friends or immediate family members following COVID-19 vaccination, and negative messages (indicating that taking a booster dose is harmful) from caregivers, friends, or family members were found to be associated with an increased second-booster-hesitancy score. Conversely, positive messages (indicating that taking a booster is helpful) from the government and caregivers, friends, or family members were identified as predictors associated with a reduction in the second-booster-hesitancy score. While vaccines effectively combat severe COVID-19, the majority of the elderly hesitate before taking the second booster. Their hesitancy, rooted in the perception of a low self risk and reliance on protection from the initial doses, emphasizes the need for intervention by relevant bodies. Taking into consideration the risk, albeit relatively low, of potentially serious side effects following COVID-19 vaccinations, it is imperative that transparent, appropriate, and positive messaging regarding booster vaccines, particularly in the context of the elderly from residential care homes, be available. Encouraging this high-risk group to embrace the second booster aligns with the goal of maximizing protection within the vulnerable elderly populatio

Methylation levels of a novel genetic element, EgNB3 as a candidate biomarker associated with the embryogenic competency of oil palm

The association between DNA methylation status and embryogenic competency in oil palm tissue culture was examined through Representational Difference Analysis (RDA) approach, using methylation-sensitive restriction endonucleases. "Difference Products" (DPs) of RDA derived from palms of similar genetic backgrounds but exhibiting different embryogenesis rates during the regeneration process were isolated. The DPs were sequenced using a pyrosequencing platform. To our knowledge, this is the first study profiling partial HpaII methylation sites in oil palm young leaf tissues which are potentially associated with embryogenic amenability through a genomic subtractive approach. Quantitative real-time PCR analysis demonstrated that the methylation status of a novel fragment, EgNB3, was higher in highly embryogenic leaf explants compared to low embryogenesis rate materials. These differences are likely to be contributed by the 5′-mCCGG-3′ and/or 5′-mCmCGG-3′ methylation patterns. Our data suggest that the differentially methylated site in EgNB3 has potential as a molecular biomarker for the screening of oil palm leaf explants for their embryogenic potentials

Understanding patients' satisfaction with physician assistant/associate encounters through communication experiences: a qualitative study in acute hospitals in England.

BACKGROUND: Physician assistants/associates (PAs) are a recent innovation in acute hospital teams in England and many other countries worldwide. Although existing evidence indicates generally high levels of patient satisfaction with their PA hospital encounters, little is known about the factors associated with this outcome. There is a lack of evidence on the process of PA-patient communication in hospital encounters and how this might influence satisfaction. This study therefore aimed to understand patients' satisfaction with PA acute hospital encounters through PA-patient communication experiences. METHODS: A qualitative study was conducted among patients and representatives of patients seen by or receiving care from one of the PAs working in acute hospital services in England. Semi-structured interviews were undertaken face-to-face with study participants in the hospital setting and shortly after their PA encounter. Data were coded and analysed using thematic analysis. The study was framed within a theoretical model of core functions of medical encounter communication. RESULTS: Fifteen patients and patient representatives who had experienced a PA encounter participated in interviews, across five hospitals in England. Four interrelated communication experiences were important to participants who were satisfied with the encounter in general: feeling trust and confidence in the relationship, sharing relevant and meaningful information, experiencing emotional care and support, and sharing discussion on illness management and treatment. However, many participants misconceived PAs to be doctors, raising a potential risk of reduced trust in the PA relationship and negative implications for satisfaction with their PA encounter. Participants considered it beneficial that patients be informed about the PA role to prevent confusion. CONCLUSIONS: PA encounters offer a constructive example of successful clinician-patient communication experiences in acute hospital encounters from the patient's perspective. Study participants were generally naïve to the PA role. Hospital services and organisations introducing these mid-level or advanced care practitioner roles should consider giving attention to informing patients about the roles

The AURORA pilot study for molecular screening of patients with advanced breast cancer–a study of the breast international group

Several studies have demonstrated the feasibility of molecular screening of tumour samples for matching patients with cancer to targeted therapies. However, most of them have been carried out at institutional or national level. Herein, we report on the pilot phase of AURORA (NCT02102165), a European multinational collaborative molecular screening initiative for advanced breast cancer patients. Forty-one patients were prospectively enroled at four participating centres across Europe. Metastatic tumours were biopsied and profiled using an Ion Torrent sequencing platform at a central facility. Sequencing results were obtained for 63% of the patients in real-time with variable turnaround time stemming from delays between patient consent and biopsy. At least one clinically actionable mutation was identified in 73% of patients. We used the Illumina sequencing technology for orthogonal validation and achieved an average of 66% concordance of substitution calls per patient. Additionally, copy number aberrations inferred from the Ion Torrent sequencing were compared to single nucleotide polymorphism arrays and found to be 59% concordant on average. Although this study demonstrates that powerful next generation genomic techniques are logistically ready for international molecular screening programs in routine clinical settings, technical challenges remain to be addressed in order to ensure the accuracy and clinical utility of the genomic data.info:eu-repo/semantics/publishe