Computer image analysis with artificial intelligence: a practical introduction to convolutional neural networks for medical professionals.

Artificial intelligence tools, particularly convolutional neural networks (CNNs), are transforming healthcare by enhancing predictive, diagnostic, and decision-making capabilities. This review provides an accessible and practical explanation of CNNs for clinicians and highlights their relevance in medical image analysis. CNNs have shown themselves to be exceptionally useful in computer vision, a field that enables machines to 'see' and interpret visual data. Understanding how these models work can help clinicians leverage their full potential, especially as artificial intelligence continues to evolve and integrate into healthcare. CNNs have already demonstrated their efficacy in diverse medical fields, including radiology, histopathology, and medical photography. In radiology, CNNs have been used to automate the assessment of conditions such as pneumonia, pulmonary embolism, and rectal cancer. In histopathology, CNNs have been used to assess and classify colorectal polyps, gastric epithelial tumours, as well as assist in the assessment of multiple malignancies. In medical photography, CNNs have been used to assess retinal diseases and skin conditions, and to detect gastric and colorectal polyps during endoscopic procedures. In surgical laparoscopy, they may provide intraoperative assistance to surgeons, helping interpret surgical anatomy and demonstrate safe dissection zones. The integration of CNNs into medical image analysis promises to enhance diagnostic accuracy, streamline workflow efficiency, and expand access to expert-level image analysis, contributing to the ultimate goal of delivering further improvements in patient and healthcare outcomes.

Retrospective screening of routine respiratory samples revealed undetected community transmission and missed intervention opportunities for SARS-CoV-2 in the United Kingdom.

In the early phases of the SARS coronavirus type 2 (SARS-CoV-2) pandemic, testing focused on individuals fitting a strict case definition involving a limited set of symptoms together with an identified epidemiological risk, such as contact with an infected individual or travel to a high-risk area. To assess whether this impaired our ability to detect and control early introductions of the virus into the UK, we PCR-tested archival specimens collected on admission to a large UK teaching hospital who retrospectively were identified as having a clinical presentation compatible with COVID-19. In addition, we screened available archival specimens submitted for respiratory virus diagnosis, and dating back to early January 2020, for the presence of SARS-CoV-2 RNA. Our data provides evidence for widespread community circulation of SARS-CoV-2 in early February 2020 and into March that was undetected at the time due to restrictive case definitions informing testing policy. Genome sequence data showed that many of these early cases were infected with a distinct lineage of the virus. Sequences obtained from the first officially recorded case in Nottinghamshire - a traveller returning from Daegu, South Korea - also clustered with these early UK sequences suggesting acquisition of the virus occurred in the UK and not Daegu. Analysis of a larger sample of sequences obtained in the Nottinghamshire area revealed multiple viral introductions, mainly in late February and through March. These data highlight the importance of timely and extensive community testing to prevent future widespread transmission of the virus.

Attitude of nursing students following the implementation of comprehensive computer-based nursing process in medical surgical internship: a quasi-experimental study.

BACKGROUND: The nursing process is the core and the standard of practice in nursing profession. Nowadays, the use of information technology in the field of nursing processes, education and practice has been emphasized. Since nurse's attitudes towards clinical information systems are considered as an indicator of the success rate of information systems, and nurse's attitudes about the nursing process can affect their execution of the process. So the purpose of this study was to evaluate nursing students' attitudes towards the nursing process software. METHODS: In this quasi-experimental study, 160 undergraduate nursing students (terms 4-8) in Tabriz University of Medical Sciences were selected by convenience sampling. To evaluate the effectiveness of nursing process software in this study, Mazlom and Rajabpoor (IJME 14(4):312-322, 2014) a questionnaire consisting of 21 components based on a five-point Likert scale was completed by students after using the software. Data were then analyzed by SPSS 19 software. RESULTS: The mean score of students' attitude toward nursing process software was high (80.70 ± 5.58). The nursing students' highest scoring attitudes were respectively related to "Effectiveness of software in prioritizing patient care and problems", "Completeness of patient's electronic information compared to handwritten mode" and "Software's effectiveness in saving your time". The lowest scoring attitudes towards the software was respectively related to the "feeling of fairness in labor division", "the effectiveness of the software in determining your workload" and "the feeling of satisfaction in labor division". There was a statistically significant relationship between gender and age, and student's attitude toward nursing process software. CONCLUSIONS: According to the results and analysis of nursing student's attitudes toward nursing process software, the use of such software would be welcomed by students. It seems that changing policies in the educational and clinical substructure of nursing in order to develop, adapt and use the nursing process software is an important responsibility for nursing authorities to consider. Providing educational and clinical technology equipment, periodic evaluation of software by stakeholders and promoting the use of this software, can be fundamental steps in operationalizing the findings of this research.

How do people in prison feel about opt-out hepatitis C virus testing?

The prison population is central to the campaign to eliminate hepatitis C virus as a public health threat. In the UK, this has led to the introduction of a national 'opt-out' policy, requiring people in prison to be tested for HCV unless they decline, with a target to test 75% of those admitted. However, in a representative prison estate in the East Midlands of England (20,000 prison entrants per annum) testing rates were only 13.4%. This qualitative study explains why the rates of test uptake are so far short of target. This qualitative study examines the experiences of 45 people in prison about hepatitis C virus testing in an English category C (low security) prison. The data collection method was semi-structured interviews. The data were coded and analysed according to the research questions, and interpretation of the data was aided by the use of a thematic network approach. The themes Fear, Insufficient Knowledge, Stigma, Privacy, Choice and Prison Life emerged as the principal barriers to test uptake. Test Uptake Facilitators that promoted testing were identified by participants and benefits presented of prison health care being a Health Farm. In order to increase hepatitis C virus test uptake, significant changes and flexibility in the timing, location, and staff deployed to test are required. Providing information to people in prison about hepatitis C virus transmission and treatment may reduce fears and enable the test uptake target to be met and sustained.

Reliable anatase-titania nanoclusters functionalized GaN sensor devices for UV assisted NO2 gas-sensing in ppb level.

Internet of Things applications require ultra-low power, integrable into electronic circuits and mini-sized chemical sensors for automated remote air quality monitoring system. In this work, a highly sensitive and selective detection of nitrogen dioxide (NO2) has been demonstrated by functionalizing gallium nitride (GaN) submicron wire with titania (TiO2) nanoclusters. The two-terminal GaN/TiO2 sensor device was fabricated by top-down approach. The photo-enabled sensing makes it possible to operate this sensor at room-temperature, resulting in a significant reduction in operating power. The GaN/TiO2 sensor was able to detect NO2 concentrations as low as 10 ppb in air at room temperature (20 °C) with a quick response-recovery process. The sensor was found highly selective toward NO2 against other interfering gases, such as ethanol (C2H5OH), ammonia (NH3), sulfur dioxide (SO2), methane (CH4) and carbon dioxide (CO2). Furthermore, principal component analysis has been performed to address the cross-sensitive nature of TiO2. The sensor device exhibited excellent long-term stability at room temperature and humidity and was quite stable and reliable at various environmental conditions. Continuous exposure of the device to siloxane for a one-month period has shown a very small degradation in sensor response to NO2. Finally, interaction of NO2 gas molecules with the GaN/TiO2 sensor has been modeled and explained under the light of energy band diagram. The photoinduced oxygen desorption and subsequent charge transfer between TiO2 nanoclusters and NO2 molecules modulate the depletion region width within the GaN, thus contributing to a high performance NO2 gas sensing.

Testing for hepatitis C virus infection in UK prisons: What actually happens?

Prisons are a key demographic in the drive to eradicate hepatitis C virus (HCV) as a major public health threat. We have assessed the impact of the recently introduced national opt-out policy on the current status of HCV testing in 14 prisons in the East Midlands (UK). We analysed testing rates pre- and post-introduction of opt-out testing, together with face-to-face interviews with prison healthcare and management staff in each prison. In the year pre-opt-out, 1972 people in prison (PIP) were tested, compared to 3440 in the year following opt-out. From July 2016 to June 2017, 2706 people were tested, representing 13.5% of all prison entrants (median 16.6%, range 7.6%-40.7%). Factors correlating with testing rates were as follows: pre-admission location of the PIP (another prison or the community, OR 2.2, 95% CI 1.9-2.3, P < 0.001); whether the PIP could access health care independently of prison officers (OR 1.7, 95% CI 1.5-1.8, P < 0.001); the absence of out-reach services for HCV treatment (OR 1.3, 95% CI 1.2-1.5, P < 0.001), whether >50% of PIP reported ease of access to a nurse (OR 2.0, 95% CI 1.8-2.2, P < 0.001), and whether prison health care was supplied by private or NHS providers (OR 1.3, 95% CI 1.2-1.5, P < 0.001). Testing rates remained far below the minimum national opt-out target of 50%. Inadequacy of healthcare facilities and constraints imposed by adherence to prison regimens were cited by healthcare and management staff at all prisons. Without radical change, the prison estate may be intrinsically incapable of supporting NHSE to deliver the HCV elimination strategy.

Prison officers' views about hepatitis C testing and treatment: a qualitative enquiry.

AIMS AND OBJECTIVES: To explore the views of prison officers in an English category B male prison about people in prison being tested and treated for hepatitis C. BACKGROUND: Hepatitis C testing and treatment in English prisons remain low with the reasons being poorly understood. Prison officers are in continuous contact with prisoners so might observe factors that may influence people in prisons' choice in whether to accept hepatitis C testing and treatment. DESIGN: A qualitative design within an interpretative framework was employed. METHODS: Semistructured interviews were conducted with 10 prison officers at an English male category B prison. The interviews were audiorecorded and transcribed at the prison. RESULTS: Four themes emerged Safeguarding, Stigma, Confidentiality and Education. Hepatitis C testing and treatment were supported in principle but if a person in prison poses a threat to the overall security of a prison, any health issues that are not immediately life threatening will be overridden, irrespective of the financial or health consequences. The prison officers respected people in prisons' confidentiality regarding health matters, but this could be compromised during violent incidents. All of the prison officers displayed limited knowledge about hepatitis C. CONCLUSIONS: This qualitative enquiry illustrates that prison security transcends health. This suggests that health providers may need to offer greater flexibility and collaboration across the network of National Health Service hospitals to maintain continuity in treatment if a prisoner is moved to a different establishment or liberated. RELEVANCE TO CLINICAL PRACTICE: This study introduces the notion that prison security staff may have a potential role in promoting or discouraging hepatitis C testing and treatment by the ways in which their knowledge impacts on their interactions with people in prison. Engaging this staff group in educational opportunities should be a component of commissioned hepatitis service delivery in prisons.

Rare, low-frequency, and common variants in the protein-coding sequence of biological candidate genes from GWASs contribute to risk of rheumatoid arthritis.

The extent to which variants in the protein-coding sequence of genes contribute to risk of rheumatoid arthritis (RA) is unknown. In this study, we addressed this issue by deep exon sequencing and large-scale genotyping of 25 biological candidate genes located within RA risk loci discovered by genome-wide association studies (GWASs). First, we assessed the contribution of rare coding variants in the 25 genes to the risk of RA in a pooled sequencing study of 500 RA cases and 650 controls of European ancestry. We observed an accumulation of rare nonsynonymous variants exclusive to RA cases in IL2RA and IL2RB (burden test: p = 0.007 and p = 0.018, respectively). Next, we assessed the aggregate contribution of low-frequency and common coding variants to the risk of RA by dense genotyping of the 25 gene loci in 10,609 RA cases and 35,605 controls. We observed a strong enrichment of coding variants with a nominal signal of association with RA (p < 0.05) after adjusting for the best signal of association at the loci (p(enrichment) = 6.4 × 10(-4)). For one locus containing CD2, we found that a missense variant, rs699738 (c.798C>A [p.His266Gln]), and a noncoding variant, rs624988, reside on distinct haplotypes and independently contribute to the risk of RA (p = 4.6 × 10(-6)). Overall, our results indicate that variants (distributed across the allele-frequency spectrum) within the protein-coding portion of a subset of biological candidate genes identified by GWASs contribute to the risk of RA. Further, we have demonstrated that very large sample sizes will be required for comprehensively identifying the independent alleles contributing to the missing heritability of RA.

Genetic basis of autoantibody positive and negative rheumatoid arthritis risk in a multi-ethnic cohort derived from electronic health records.

Discovering and following up on genetic associations with complex phenotypes require large patient cohorts. This is particularly true for patient cohorts of diverse ancestry and clinically relevant subsets of disease. The ability to mine the electronic health records (EHRs) of patients followed as part of routine clinical care provides a potential opportunity to efficiently identify affected cases and unaffected controls for appropriate-sized genetic studies. Here, we demonstrate proof-of-concept that it is possible to use EHR data linked with biospecimens to establish a multi-ethnic case-control cohort for genetic research of a complex disease, rheumatoid arthritis (RA). In 1,515 EHR-derived RA cases and 1,480 controls matched for both genetic ancestry and disease-specific autoantibodies (anti-citrullinated protein antibodies [ACPA]), we demonstrate that the odds ratios and aggregate genetic risk score (GRS) of known RA risk alleles measured in individuals of European ancestry within our EHR cohort are nearly identical to those derived from a genome-wide association study (GWAS) of 5,539 autoantibody-positive RA cases and 20,169 controls. We extend this approach to other ethnic groups and identify a large overlap in the GRS among individuals of European, African, East Asian, and Hispanic ancestry. We also demonstrate that the distribution of a GRS based on 28 non-HLA risk alleles in ACPA+ cases partially overlaps with ACPA- subgroup of RA cases. Our study demonstrates that the genetic basis of rheumatoid arthritis risk is similar among cases of diverse ancestry divided into subsets based on ACPA status and emphasizes the utility of linking EHR clinical data with biospecimens for genetic studies.

Meta-analysis of genome-wide association studies in celiac disease and rheumatoid arthritis identifies fourteen non-HLA shared loci.

Epidemiology and candidate gene studies indicate a shared genetic basis for celiac disease (CD) and rheumatoid arthritis (RA), but the extent of this sharing has not been systematically explored. Previous studies demonstrate that 6 of the established non-HLA CD and RA risk loci (out of 26 loci for each disease) are shared between both diseases. We hypothesized that there are additional shared risk alleles and that combining genome-wide association study (GWAS) data from each disease would increase power to identify these shared risk alleles. We performed a meta-analysis of two published GWAS on CD (4,533 cases and 10,750 controls) and RA (5,539 cases and 17,231 controls). After genotyping the top associated SNPs in 2,169 CD cases and 2,255 controls, and 2,845 RA cases and 4,944 controls, 8 additional SNPs demonstrated P<5 × 10(-8) in a combined analysis of all 50,266 samples, including four SNPs that have not been previously confirmed in either disease: rs10892279 near the DDX6 gene (P(combined) =  1.2 × 10(-12)), rs864537 near CD247 (P(combined) =  2.2 × 10(-11)), rs2298428 near UBE2L3 (P(combined) =  2.5 × 10(-10)), and rs11203203 near UBASH3A (P(combined) =  1.1 × 10(-8)). We also confirmed that 4 gene loci previously established in either CD or RA are associated with the other autoimmune disease at combined P<5 × 10(-8) (SH2B3, 8q24, STAT4, and TRAF1-C5). From the 14 shared gene loci, 7 SNPs showed a genome-wide significant effect on expression of one or more transcripts in the linkage disequilibrium (LD) block around the SNP. These associations implicate antigen presentation and T-cell activation as a shared mechanism of disease pathogenesis and underscore the utility of cross-disease meta-analysis for identification of genetic risk factors with pleiotropic effects between two clinically distinct diseases.

Osteopontin is a novel downstream target of SOX9 with diagnostic implications for progression of liver fibrosis in humans.

UNLABELLED: Osteopontin (OPN) is an important component of the extracellular matrix (ECM), which promotes liver fibrosis and has been described as a biomarker for its severity. Previously, we have demonstrated that Sex-determining region Y-box 9 (SOX9) is ectopically expressed during activation of hepatic stellate cells (HSC) when it is responsible for the production of type 1 collagen, which causes scar formation in liver fibrosis. Here, we demonstrate that SOX9 regulates OPN. During normal development and in the mature liver, SOX9 and OPN are coexpressed in the biliary duct. In rodent and human models of fibrosis, both proteins were increased and colocalized to fibrotic regions in vivo and in culture-activated HSCs. SOX9 bound a conserved upstream region of the OPN gene, and abrogation of Sox9 in HSCs significantly decreased OPN production. Hedgehog (Hh) signaling has previously been shown to regulate OPN expression directly by glioblastoma (GLI) 1. Our data indicate that in models of liver fibrosis, Hh signaling more likely acts through SOX9 to modulate OPN. In contrast to Gli2 and Gli3, Gli1 is sparse in HSCs and is not increased upon activation. Furthermore, reduction of GLI2, but not GLI3, decreased the expression of both SOX9 and OPN, whereas overexpressing SOX9 or constitutively active GLI2 could rescue the antagonistic effects of cyclopamine on OPN expression. CONCLUSION: These data reinforce SOX9, downstream of Hh signaling, as a core factor mediating the expression of ECM components involved in liver fibrosis. Understanding the role and regulation of SOX9 during liver fibrosis will provide insight into its potential modulation as an antifibrotic therapy or as a means of identifying potential ECM targets, similar to OPN, as biomarkers of fibrosis.

Hepatitis C therapy at home: a hospital and home care partnership.

Hepatitis C virus (HCV) is a significant public health threat in the UK, and is both underdiagnosed and undertreated. The treatment episode takes between 12 and 48 weeks. In the UK, HCV management is undertaken in secondary and tertiary centres. This does not meet the needs of all patients; they may have to travel long distances, incur travel costs, wait a long time to be seen and negotiate time off work while not divulging their illness. Providing care at home can increase patients' access to and acceptability of treatment, especially in areas remote from specialist centres. This paper describes the feasibility, safety and efficacy of treating HCV infected patients at home by a partnership between secondary care and an clinical home care company. The home care model had a significantly higher attendance rate than the clinic model. It allowed the trust to improve care at no extra cost. This model can optimise specialist nurses' time, allowing them to focus on patients with more complex needs.

Male Nursing Students' Perception of Gender Barriers in Nursing Curricula in an Iranian University of Medical Sciences.

OBJECTIVES: The present study aimed to determine male nursing students' perception of gender barriers in nursing curricula. METHODS: This descriptive study was conducted on 150 B.Sc. and M.Sc. nursing students at Tabriz School of Nursing and Midwifery, Tabriz university of medical sciences, Tabriz, Iran that were selected through convenience sampling. The study data were collected using Inventory of Male Friendliness in Nursing Programs-Short (IMFNP-S). This scale has 17 items for investigating male nursing students' perception of gender barriers in nursing curricula. Each item is a 5-point Likert-type scale scored from 0 to 4; total scale score could range from 0 to 68, higher scores representing male nursing students' perception of less gender barriers in nursing curricula. RESULTS: The total mean score of gender barriers was 35.11+6.15. The most important barriers included different requirements/limitations in obstetrics apprenticeship (Median=1), and need for proving oneself because of people's expectation of nurses to be female (Median=2). On the other hand, the least important barriers were lack of important people's support on one's career decisions (Median=3), and lack of opportunity to work with other male nurses (Median=3). The scale score was not associated with the socio-demographic characteristics studied. CONCLUSIONS: The most male nursing students feel various gender issues in the nursing curriculum in a medium level that may negatively impact on their learning, professional performance and motivation and tendency to nursing. Furthermore, this vicious cycle can lead to lack of professional development, leaving the job and burnout. Thus, creating a gender-neutral environment can make nursing programs more male friendly.

Most common single-nucleotide polymorphisms associated with rheumatoid arthritis in persons of European ancestry confer risk of rheumatoid arthritis in African Americans.

OBJECTIVE: Large-scale genetic association studies have identified >20 rheumatoid arthritis (RA) risk alleles among individuals of European ancestry. The influence of these risk alleles has not been comprehensively studied in African Americans. We therefore sought to examine whether these validated RA risk alleles are associated with RA risk in an African American population. METHODS: Twenty-seven candidate single-nucleotide polymorphisms (SNPs) were genotyped in 556 autoantibody-positive African Americans with RA and 791 healthy African American control subjects. Odds ratios (ORs) and 95% confidence intervals (95% CIs) for each SNP were compared with previously published ORs for RA patients of European ancestry. We then calculated a composite genetic risk score (GRS) for each individual based on the sum of all risk alleles. RESULTS: Overlap of the ORs and 95% CIs between the European and African American populations was observed for 24 of the 27 candidate SNPs. Conversely, 3 of the 27 SNPs (CCR6 rs3093023, TAGAP rs394581, and TNFAIP3 rs6920220) demonstrated ORs in the opposite direction from those reported for RA patients of European ancestry. The GRS analysis indicated a small but highly significant probability that African American patients relative to control subjects were enriched for the risk alleles validated in European RA patients (P = 0.00005). CONCLUSION: The majority of RA risk alleles previously validated for RA patients of European ancestry showed similar ORs in our population of African Americans with RA. Furthermore, the aggregate GRS supports the hypothesis that these SNPs are risk alleles for RA in the African American population. Future large-scale genetic studies are needed to validate these risk alleles and identify novel RA risk alleles in African Americans.

Rheumatoid arthritis risk allele PTPRC is also associated with response to anti-tumor necrosis factor alpha therapy.

OBJECTIVE: Anti-tumor necrosis factor alpha (anti-TNF) therapy is a mainstay of treatment in rheumatoid arthritis (RA). The aim of the present study was to test established RA genetic risk factors to determine whether the same alleles also influence the response to anti-TNF therapy. METHODS: A total of 1,283 RA patients receiving etanercept, infliximab, or adalimumab therapy were studied from among an international collaborative consortium of 9 different RA cohorts. The primary end point compared RA patients with a good treatment response according to the European League Against Rheumatism (EULAR) response criteria (n = 505) with RA patients considered to be nonresponders (n = 316). The secondary end point was the change from baseline in the level of disease activity according to the Disease Activity Score in 28 joints (triangle upDAS28). Clinical factors such as age, sex, and concomitant medications were tested as possible correlates of treatment response. Thirty-one single-nucleotide polymorphisms (SNPs) associated with the risk of RA were genotyped and tested for any association with treatment response, using univariate and multivariate logistic regression models. RESULTS: Of the 31 RA-associated risk alleles, a SNP at the PTPRC (also known as CD45) gene locus (rs10919563) was associated with the primary end point, a EULAR good response versus no response (odds ratio [OR] 0.55, P = 0.0001 in the multivariate model). Similar results were obtained using the secondary end point, the triangle upDAS28 (P = 0.0002). There was suggestive evidence of a stronger association in autoantibody-positive patients with RA (OR 0.55, 95% confidence interval [95% CI] 0.39-0.76) as compared with autoantibody-negative patients (OR 0.90, 95% CI 0.41-1.99). CONCLUSION: Statistically significant associations were observed between the response to anti-TNF therapy and an RA risk allele at the PTPRC gene locus. Additional studies will be required to replicate this finding in additional patient collections.

The role of IGFs in the regulation of ovarian follicular growth in the brushtail possum (Trichosurus vulpecula).

IGFs are known to be key regulators of ovarian follicular growth in eutherian mammals, but little is known regarding their role in marsupials. To better understand the potential role of IGFs in the regulation of follicular growth in marsupials, expression of mRNAs encoding IGF1, IGF2, IGF1R, IGF-binding protein 2 (IGFBP2), IGFBP4 and IGFBP5 was localized by in situ hybridization in developing ovarian follicles of the brushtail possum. In addition, the effects of IGF1 and IGF2 on granulosa cell function were tested in vitro. Both granulosa and theca cells synthesize IGF mRNAs, with the theca expressing IGF1 mRNA and granulosa cell expressing IGF2 mRNA. Oocytes and granulosa cells express IGF1R. Granulosa and theca cells expressed IGFBP mRNAs, although the pattern of expression differed between the BPs. IGFBP5 mRNA was differentially expressed as the follicles developed with granulosa cells of antral follicles no longer expressing IGFBP5 mRNA, suggesting an increased IGF bioavailability in the antral follicle. The IGFBP protease, PAPPA mRNA, was also expressed in granulosa cells of growing follicles. Both IGF1 and IGF2 stimulated thymidine incorporation but had no effect on progesterone production. Thus, IGF may be an important regulator of ovarian follicular development in marsupials as has been shown in eutherian mammals.

Hepatitis C virus: the growing challenge.

BACKGROUND: Hepatitis C virus (HCV) is a major cause of liver disease worldwide. In industrialized countries, intravenous drug users (IDUs) are the main reservoir of infection. Relatively little information is available on HCV in the developing world. SOURCES OF DATA: Peer reviewed publications and presentations at major academic meetings. AREAS OF AGREEMENT: HCV-related cirrhosis and death from hepatocellular carcinoma are likely to rise dramatically in the next three decades. Urgent intervention is required both to minimize the burden of disease in those already infected and to reduce the incidence of new infections, particularly in the IDU population. AREAS OF CONTROVERSY: Current models of care and commissioning in the UK and other countries do not adequately identify or treat HCV infection in IDUs. Most strategies focus on disease prevention and do not target new infections. GROWING POINTS: New models of care are currently being developed and validated. AREAS TIMELY FOR DEVELOPING RESEARCH: The development of new models of HCV replication will transform our understanding and capacity to treat HCV infection.

Kappa opioid receptor screen with the Tango beta-arrestin recruitment technology and characterization of hits with second-messenger assays.

Assays for high-throughput screening of G-protein-coupled receptors (GPCRs) have typically revolved around receptor binding, guanine nucleotide binding, and second-messenger assays measuring intracellular cAMP and calcium levels. New assay development has been directed toward G-protein-independent signaling pathways, including protein redistribution in response to activated receptors. beta-arrestin recruitment to agonist-stimulated GPCRs is the basis for the Transfluor, PathHunter, and Tango GPCR screening platforms. In the Tango GPCR technology, receptor activation results in the recruitment of a TEV protease:beta-arrestin fusion protein to the activated receptor where the TEV protease releases the GAL4-VP16 tethered to the target GPCR by a 7-amino acid TEV protease site. The release of the transcription factor results in expression of the beta-lactamase (bla) reporter gene. The authors performed a small library screen with a Tango cell line expressing the kappa opioid receptor and identified a series of compounds with a similar core chemical structure that were selective agonists for the kappa opioid receptor over the Amicro and delta opioid receptors. These compounds were validated in additional second-messenger assays, confirming the agonist activity of the identified compounds. These results provide insight into the value of screening compounds in multiple assay technologies to better characterize the compound's potency and efficacy.

Cost-effectiveness of pegylated interferon and ribavirin for patients with chronic hepatitis C treated in routine clinical practice.

OBJECTIVES: This study assesses whether pegylated interferon and ribavirin is cost-effective compared with no antiviral treatment provided in routine clinical practice, for different patient subgroups. METHODS: The cost-effectiveness analysis (CEA) uses a Markov decision model to estimate the lifetime cost per quality-adjusted life-year (QALY) of antiviral treatment compared with no treatment. The model is populated with data on sustained virological responses, costs, and transition probabilities all taken from a large representative sample of UK cases and centers (Trent HCV database). RESULTS: The CEA found that pegylated interferon and ribavirin was cost-effective for most patient subgroups. The CEA found that for patients with genotype non-1, the intervention led to cost reductions and gains of at least 0.5 QALYs. For genotype 1 cases with mild or moderate disease, and younger cirrhotic patients (aged 40 or less), costs per QALY remained below 20,000 pound sterling ($40,000 or 29,000 euro). For genotype 1 cases with cirrhosis aged 50, the mean cost per QALY rose to over 60,000 pound sterling ($120,000 or 87,000 euro). CONCLUSIONS: The study concludes that, based on cost and effectiveness data collected from routine clinical practice, treatment with pegylated interferon and ribavirin is generally cost-effective. The study shows that there are variations according to patient subgroup and for older (aged 50 or over) genotype 1 patients with cirrhosis, antiviral treatment appears less cost-effective.

Young adults' attitudes to sharing whole-genome sequencing information: a university-based survey.

BACKGROUND: Genomic services are increasingly accessible to young adults starting their independent lives with responsibility for their self-care, yet their attitudes to sharing genomic information remain under-researched. This study explored attitudes of university-based 18-25 year-olds towards sharing personal whole-genome sequencing (WGS) information with relatives. METHODS: We surveyed 112 young adults. Hypotheses were tested regarding the relationships between their preferences for sharing personal WGS information with relatives and factors including their gender, previous genetics-specific education, general educational attainment level and current study in a science, technology, engineering, maths or medicine (STEMM) field. RESULTS: Most participants were positive about both their intention to share their WGS results with their parents and siblings, and their desire to know their relatives' results. Being female and having a university-level genetics education were consistently positively correlated with intention to share one's results with parents and with siblings as well as the desire to know relatives' results. Additionally, females who had undertaken a genetics course at university had significantly greater intentions and desires than females who had not. Lower general educational attainment was related to a lower intention to share with siblings. Participants who were in a STEMM field had a greater desire to know their relatives' results. CONCLUSIONS: Participants' gender and prior genetics education were consistently related to their intentions to share WGS results with relatives and their desire to know relatives' results. Educational attainment was found to be positively correlated with intention to share with siblings. Being in a STEMM field was related to participants' desire to know their relatives' results. These findings indicate that gender and genetics education are particularly important influencers on young adults' stated sharing preferences. More research is required to examine the dependent variables studied to further understand their influence on attitudes to sharing WGS results. These findings are particularly interesting for information provision and support before genomic sequencing and post-results to improve the outcomes for individuals and their relatives.