Evidence of decreased HPV vaccine acceptance in Polish communities within Scotland.

Human papillomavirus (HPV) vaccines are currently utilised globally in national immunisation programmes. Many new European migrants have settled in the United Kingdom (UK) since the 2004 European Union expansion with approximately 91,000 Polish people resident in Scotland. Following anecdotal reports from several NHS Boards within Scotland of lower HPV vaccine uptake in Polish communities compared with other ethnic minorities, an extract containing both forename and surname, was taken from the Scottish Immunisation Recall System (SIRS) for all girls in S2 and S3 in school years 2014/15 to 2016/17. We then used the OnoMap algorithm software to derive ethnicity. OnoMap identified between 289 and 321 age-eligible girls as Polish with significant disparity noted for completed HPV vaccine uptake between UK (87.2-89.8%) and Polish ethnicities (69.7-77.2%) (P < 0.01). Preliminary discussions with Polish families suggest that vaccine programme differences, trust in medical/healthcare practitioners, and cultural influences may be important drivers of acceptance.

Multidisciplinary managed care networks-Life-saving interventions for hepatitis C patients.

Successful hepatitis C virus (HCV) therapy depends on effective pathways of care. Over two decades, we have developed four sequential models of care latterly using a multidisciplinary managed care network to improve HCV testing, care and treatment. This was a cohort study to evaluate the effectiveness of care pathways, carried out using all HCV antibody-positive individuals tested in a geographical region between 1994 and 2014. The study involved 3122 HCV-positive patients. They were divided into four subgroups representing different care pathways defined by their date of HCV antibody diagnosis. The number who accessed treatment services within 1 year of diagnosis increased from 77 of 292 (26.3%) to 521 of 821 (72.9%). The rate of treatment starts within 1 year of diagnosis increased from 6 of 292 (2.0%) to 133 of 821 (16.2%), and the sustained viral response rate improved from 61.6% to 77.4%. All-cause mortality decreased from 232 of 688 (33.7%) in subgroup A to 55 of 1207 (4.5%) in subgroup D, and multivariate analysis showed that pathway type was an independent predictor of mortality irrespective of age, sex, SVR status or HIV co-infection with pathway in D having an odds ratio of 0.53(0.40-0.77; P<.001) compared to pathway in A. At study end, 78% (3122) of an estimated 4000 HCV positive had been diagnosed. In total, 97.5% of HCV caseload was referred to specialist services and 89% attended for assessment. The introduction of a managed care network increased access to care and reduced all-cause mortality.

Salinity Preference in the Estuarine Teleost Fish Mummichog (Fundulus heteroclitus): Halocline Behavior.

Mummichogs prefer seawater (SW) but have wide ability to acclimate to extreme temperatures and salinities. In the field, minnow trapping revealed that mummichogs move progressively into low-salinity warmer water during early spring after ice melt and show significant aversion to colder temperatures and high salinity. First appearance in estuarine shallows occurred above 10°C, and catch increased to 21°C over 4 wk. Three-spine sticklebacks (Gasterosteus aculeatus) also preferred warmer low-salinity locations but preferred slowing streams, whereas mummichogs preferred tidal ponds. In the laboratory, artificial haloclines tested isothermal salinity preference, between 28‰ full-strength SW (below) and 10% SW (3.0‰; above). Mummichogs of both sexes acclimated to 5°C in SW strongly preferred SW. Freshwater (0% SW)-acclimated mummichogs at 21°C also preferred SW, but of sexually mature fish acclimated to 21°C SW, only the males preferred SW; the females showed no significant preference for SW, meaning they freely entered low salinity. SW preference was manifested by a stereotypic passive aversion to the dilute upper layer at the halocline. We conclude that the overall movement of mummichogs into summer breeding grounds of low salinity is driven by maturation of females and their preference for warmer water regardless of salinity.

Insights into the nanoscale lateral and vertical phase separation in organic bulk heterojunctions via scanning probe microscopy.

Solution processed polymer (donor) and fullerene (acceptor) bulk heterojunctions are widely used as the photo active layer in organic solar cells. Intimate mixing of these two materials is essential for efficient charge separation and transport. Identifying relative positions of acceptor and donor rich regions in the bulk heterojunction with nanometer scale precision is crucial in understanding intricate details of operation. In this work, a combination of Ar(+)2000 gas cluster ion beam and scanning probe microscopy is used to examine the lateral and vertical phase separation within regio-regular poly(3-hexylthiophene)(P3HT):phenyl-C60-butyric acid methyl ester (PCBM) bulk heterojunction. While the Ar(+)2000 gas cluster ion beam is used as a sputter tool to expose the underneath layers, scanning probe microscopy techniques are used to obtain two-dimensional (2D) electrical maps (with sub-2 nm lateral resolution). The electrical mapping is decoded to chemical composition, essentially producing lateral and vertical maps of phase separation. Thermal stress causes large PCBM-rich hillocks to form, and consequently affecting the balance of P3HT:PCBM heterojunctions, hence a negative impact on the efficiency of the solar cell. We further developed a method to analyze the efficiency of exciton dissociation based on the current maps and a loss of 20% in efficiency is observed for thermally degraded samples compared to fresh un-annealed samples.

Identifying viable regulatory and innovation pathways for regenerative medicine: a case study of cultured red blood cells.

The creation of red blood cells for the blood transfusion markets represents a highly innovative application of regenerative medicine with a medium term (5-10 year) prospect for first clinical studies. This article describes a case study analysis of a project to derive red blood cells from human embryonic stem cells, including the systemic challenges arising from (i) the selection of appropriate and viable regulatory protocols and (ii) technological constraints related to stem cell manufacture and scale up to clinical Good Manufacturing Practice (GMP) standard. The method used for case study analysis (Analysis of Life Science Innovation Systems (ALSIS)) is also innovative, demonstrating a new approach to social and natural science collaboration to foresight product development pathways. Issues arising along the development pathway include cell manufacture and scale-up challenges, affected by regulatory demands emerging from the innovation ecosystem (preclinical testing and clinical trials). Our discussion reflects on the efforts being made by regulators to adapt the current pharmaceuticals-based regulatory model to an allogeneic regenerative medicine product and the broader lessons from this case study for successful innovation and translation of regenerative medicine therapies, including the role of methodological and regulatory innovation in future development in the field.

Review article: 2014 UK consensus guidelines - hepatitis C management and direct-acting anti-viral therapy.

BACKGROUND: Therapeutic options for the management of hepatitis C virus (HCV) infection have evolved rapidly over the past two decades, with a consequent improvement in cure rates. Novel therapeutic agents are an area of great interest in the research community, with a number of these agents showing promise in the clinical setting. AIMS: To assess and present the available evidence for the use of novel therapeutic agents for the treatment of HCV, updating previous guidelines. METHODS: All Phase 2 and 3 studies, as well as abstract presentations from international Hepatology meetings were identified and reviewed for suitable inclusion, based on studies of new therapies in HCV. Treatment-naïve and experienced individuals, as well as cirrhotic and co-infected individuals were included. RESULTS: Sofosbuvir, simeprevir and faldaprevir, along with pegylated interferon and ribavirin, have a role in the treatment of chronic HCV infection. The precise regimens are largely dependent on the patient characteristics, patient and physician preferences, and cost implication. CONCLUSIONS: Therapies for chronic HCV have evolved dramatically in recent years. Interferon-free regimens are now possible without compromise in the rate of sustained viral response. The decision as to which regimen is most appropriate is multifactorial, and based on efficacy, safety and cost.

Dangling conversations: reflections on the process of creating digital stories during a workshop with people with early-stage dementia.

Care and compassion are key features of the NHS Constitution. Recent reports have identified a lack of compassion in the care and treatment of older people. Nurses draw on aesthetic knowledge, developed through engagement with the experience of others, when providing compassionate care. Patient Voices reflective digital stories are used in healthcare education to facilitate student engagement with the patient experience. Digital stories were made with seven people with early-stage dementia as part of a learning package for student nurses. In this paper the authors reflect on their experience and observations from facilitating the 4-day digital story-making workshop. Social theories of dementia provide a theoretical framework for understanding these reflections. Despite considerable challenges in developing a story, and anxiety about using the technology, reading and speaking, all participants engaged in creating their own digital stories. Positive changes in the participants' interactions were observed. These improvements appeared to be the product of the person-centred facilitation and the creative process which supported self-expression and a sense of identity. Nurses working in this way could facilitate ability of the person with dementia to participate in their care, and improve their sense of well-being by supporting self-expression.

Ferret lung transplant: an orthotopic model of obliterative bronchiolitis.

Obliterative bronchiolitis (OB) is the primary cause of late morbidity and mortality following lung transplantation. Current animal models do not reliably develop OB pathology. Given the similarities between ferret and human lung biology, we hypothesized an orthotopic ferret lung allograft would develop OB. Orthotopic left lower lobe transplants were successfully performed in 22 outbred domestic ferrets in the absence of immunosuppression (IS; n = 5) and presence of varying IS protocols (n = 17). CT scans were performed to evaluate the allografts. At intervals between 3-6 months the allografts were examined histologically for evidence of acute/chronic rejection. IS protects allografts from acute rejection and early graft loss. Reduction of IS dosage by 50% allowed development of controlled rejection. Allografts developed infiltrates on CT and classic histologic acute rejection and lymphocytic bronchiolitis. Cycling of IS, to induce repeated episodes of controlled rejection, promoted classic histologic hallmarks of OB including fibrosis-associated occlusion of the bronchiolar airways in all allografts of long-term survivors. In conclusion, we have developed an orthotopic lung transplant model in the ferret with documented long-term functional allograft survival. Allografts develop acute rejection and lymphocytic bronchiolitis, similar to humans. Long-term survivors develop histologic changes in the allografts that are hallmarks of OB.

Dry blood spot testing for hepatitis C in people who injected drugs: reaching the populations other tests cannot reach.

OBJECTIVE: The aim of the study was to evaluate the effectiveness of Dry Blood Spot testing (DBST) for hepatitis C within a geographical area. DESIGN: This is a prospective cohort study of all individuals living in Tayside who had received a hepatitis C virus (HCV) DBST between 2009 and 2011. RESULTS: During the study, 1123 DBSTs were carried out. 946 individuals had one test. 295 (31.2%) of these individuals were HCV antibody positive on their first test. Overall, 94.3% (902/956) individuals returned for the results of their test. During the course of the study 177 individuals were retested and 29 new cases of hepatitis C were detected. 249 individuals attended for further follow-up, and 164 (65.5%) were PCR positive. All 164 PCR-positive individuals were offered referral into specialist HCV services for further assessment. Data showed 62.5% were genotype 3, 65.1% had a low viral load (<600 000 iu/ml) and 77.5% had a Fibroscan score below 7 KPa. To date, 40 have commenced treatment and a further 16 are currently in the assessment period. Overall, we have retained in services or treated 63.6% (105/164) of patients who were initially referred and with effective support mechanisms in place we have achieved sustained viral response rates of 90%. CONCLUSIONS: The study has shown that DBST is a complementary technique to conventional venepuncture for the diagnosis of HCV. The majority of patients have low viral loads and low fibrosis scores, so that while this group of patients may be difficult to reach and may be challenging to maintain in therapy, they are easier to cure.

Intravenous drug use: not a barrier to achieving a sustained virological response in HCV infection.

Hepatitis C virus (HCV) is commonly transmitted by intravenous drug use (IDU) but drug users are under represented in many treatment cohorts, this is because of the assumption of lowered treatment success. We assessed HCV treatment outcomes in active intravenous drug users and patients on opiate substitution therapy. The Tayside HCV treatment database was retrospectively analysed for consecutively treated patients based on risk factor for acquisition of HCV. Primary end point was sustained virological response (SVR). Two hundred and ninety-one consecutively treated patients were assessed. The overall SVR rate was 55.3%. The SVR rates by risk factor were; Non-IDU 61.4%, Ex-IDU 54.8% and Active IDU 47.1% (P = n/s). In the groups G1 patients SVR was; Non-IDU 52.7%, Ex-IDU 30.7% and active IDU 35.4% (P = n/s). In the non-G1 patients: non-IDU 65.1%, Ex-IDU 76.7% and active IDU 53.5%. Ex-IDU had a significantly better SVR than active IDU, other differences were not significant. Our results demonstrate that SVR rates in the active drug users and those on opiate substitution therapy can be achieved which are comparable with non-IDU infected individuals. Intravenous drug use in those engaged with treatment services should not be seen as a barrier to treatment of HCV.

A new microparticle size calibration standard for use in measuring smaller microparticles using a new flow cytometer.

BACKGROUND: Microparticle size measurements are often calibrated on flow cytometers using polystyrene microspheres that forward scatter more light vs. particle diameter than cellular microparticles. METHODS: We compared theoretical with measured forward angle light scattering on the LSRII, FC500 and Apogee A40 using polystyrene and silica microspheres vs. synthetic lipid vesicles and platelets, then compared plasma microparticle counts using different calibration strategies. RESULTS: Polystyrene and silica microspheres with higher refractive indices forward scattered more light with a wavelength of 488 nm for a given size microparticle than did lipid vesicles or platelets. The LSRII and FC500 did not count many, and were unable to separate by size, polystyrene microspheres <0.5 µm in diameter. On the Apogee A40, polystyrene microspheres could be separated by size down to 0.2 µm, and a polystyrene microsphere 0.4 µm in diameter produced the same forward scatter relative intensity as a 1-µm lipid or cellular microparticle. Using the new calibrator, the Apogee A40 found 80 000-4 000 000 µL(-1) total microparticles, 11 000-350 000 µL(-1) annexin V positive microparticles and 6000-350 000 µL(-1) platelet microparticles <1 µm in plasma samples. CONCLUSIONS: The Apogee A40 was able to resolve size differences in polystyrene microspheres down to 0.2 µm and microparticles down to 0.4 µm. On the Apogee A40 we propose using a 0.4-µm polystyrene microsphere as equivalent to a 1-µm cellular microparticle for size calibration. Using this calibrator, the Apogee A40 detected higher numbers of total, platelet and annexin V positive microparticles than were found using a Megamix gate.

The impact of a managed care network on attendance, follow-up and treatment at a hepatitis C specialist centre.

Infection with the hepatitis C virus commonly occurs in patient groups who have difficulty accessing conventional medical care, reducing their chance of successful antiviral therapy. Managed care networks (MCNs) have been suggested as a mechanism of improving access to care; however, there is little evidence to support their use in patients with hepatitis C. The aim of this study was to evaluate the impact of a MCN for patients with hepatitis C. This was a retrospective cohort study of all individuals in our area who had received a positive hepatitis C antibody test between August 1994 and June 2008. The MCN introduced a new referral pathway, which included nonmedical referrals and outreach nurse-led clinics. These interventions were introduced in 2004 and evaluated in 2008. After the introduction of the MCN, the proportion of individuals who accessed care increased from 61% (280/430) to 82.4% (721/875). There was an increase in nonmedical referrals with 81 (18.3%) being directly referred from Drug Problem Services and 75 (17%) from the Prison Service. The changes to referral did not have a negative impact on treatment outcomes as the number who completed treatment increased from 66.1% (43/65) to 73.7% (98/133) and the sustained virological response increased from 50.7% (33/65) to 60.9% (81/133). This study provides evidence that the collaboration of health care professionals within a network can have a radical effect in improving access to care in a traditionally hard to reach population. This has been achieved with little additional resource, but rather working smarter with existing staff.

Examination of the secondary palate on stored 3D ultrasound volumes of the fetal face.

OBJECTIVES: To examine the use of oblique planes from stored three-dimensional (3D) ultrasound volumes of the fetal face for viewing the secondary palate at various gestational ages. METHODS: 3D ultrasound volumes of the fetal face acquired with surface rendering at 15-35 weeks' gestation in 31 fetuses with confirmed normal secondary palates were reviewed. The secondary palate was viewed in three oblique planes targeted at the uvula: the oblique axial, the oblique sagittal and the reverse face view. The detection and appearance of the secondary palate, including the soft palate, with these views at various gestational ages were compared. RESULTS: The various surfaces of the secondary palate could be viewed in all 31 fetuses in the oblique axial and the reverse face views, and in all except two fetuses in the oblique sagittal view. Both of these were < 19 weeks' gestation, at which age the uvula could not be identified clearly in this plane. CONCLUSIONS: The oblique axial, the oblique sagittal and the reverse face view targeted at the uvula allow visualization of the various aspects of the fetal secondary palate on 3D ultrasound in the second and third trimesters of pregnancy. The uvula could be used as a landmark for viewing the soft palate, but was not always easily identifiable before 19 weeks' gestation.

Sonographic study of the decidua basalis in the first trimester of pregnancy.

OBJECTIVES: To describe the sonographic appearance of the decidua basalis and its changes in the first trimester of pregnancy. METHODS: We reviewed images from 159 first-trimester ultrasound examinations in 105 women with uncomplicated pregnancies who later delivered at term. The appearance of the decidua basalis layer and the sonographic changes that it underwent, including in echogenicity and thickness, were analyzed with respect to gestational age. RESULTS: A distinct decidual layer could be identified consistently at 5-6 weeks' gestation and its thickness peaked at 6-7 weeks. It was seen inconsistently at 8-9 weeks and was not identifiable by 10 weeks. Its appearance changed over time, from a uniformly echogenic layer at 5-6 weeks to a heterogeneous echogenic layer at 7 weeks, corresponding to the histological evidence of trophoblast penetration. The layer then became less echogenic with time until it became unidentifiable. CONCLUSIONS: There is a window of opportunity in the first trimester for sonographic examination of the decidua. This may allow screening, at an early stage, for conditions that affect the decidua during pregnancy.

A case of amyoplasia in a monochorionic twin pregnancy: a sequela from twin-twin transfusion syndrome?

OBJECTIVE: To present and discuss the sonographic and clinical findings in one twin of a monochorionic pair affected by amyoplasia. METHODS: On ultrasound examination at 21 weeks in a monochorionic twin pregnancy, twin I was smaller, hydropic, with multiple contractures consistent with amyoplasia and oligohydramnios. Twin II was anatomically normal with polyhydramnios. RESULTS: The twins were delivered at 28 weeks' gestation. The clinical findings were consistent with twin-twin transfusion syndrome (TTTS). CONCLUSION: It is postulated that TTTS may be a causative factor in the excessive incidence of amyoplasia in monozygotic twin pregnancy.

Mapping the future dynamics of disease transmission: risk analysis in the United Kingdom Foresight Programme on the detection and identification of infectious diseases.

This paper reflects on the qualitative risk analysis framework developed for a Foresight study on the Detection and Identification of Infectious Diseases, which was coordinated in 2005 by the United Kingdom (UK) under what is now the Government Office for Science, Department for Innovation, Universities and Skills. The risk assessment covered human, plant and animal diseases in the UK and Africa in the years 2015 and 2030. Through engaging a diverse pool of experts, we developed a model conceptualising disease spread as the outcome of interactions among sources, pathways and drivers. We then used this model to conduct a Delphi survey of experts. The factors perceived most likely to contribute to infectious disease spread in 2015 and 2030 included geographic extension of existing pathogens (partially due to climate change), over-use of antibiotics/antivirals/pesticides leading to drug resistance, and zoonoses. Our methodology provides a framework for those who need to integrate a wide range of perspectives and factors into their planning and analyses.

Viewing of the soft and the hard palate on routine 3-D ultrasound sweep of the fetal face--a feasibility study.

OBJECTIVES: To report a technique to view the fetal soft and hard palates, utilizing acquired routine 3-D volumes of the fetal face. METHOD: The axial, sagittal and coronal planes in acquired volumes of 3-D surface rendering of 5 normal fetal faces obtained at 19, 21, 23, 26 and 28 weeks, respectively, were reviewed by focusing on the uvula. RESULTS: The surfaces of the soft and the hard palate could be viewed in oblique axial, oblique sagittal and targeted coronal planes in all fetuses. CONCLUSION: Rotating or tilting of the axial, sagittal and coronal planes of the fetal head allows the visualization of the various aspects of the soft and hard palates, with the uvula as a useful landmark.

Antenatal diagnosis of anophthalmia by three-dimensional ultrasound: a novel application of the reverse face view.

The prenatal diagnosis of anophthalmia can be made on the demonstration of absent eye globe and lens on the affected side(s) on two-dimensional ultrasound examination, but when the fetal head position is unfavorable three-dimensional (3D) ultrasound may reveal additional diagnostic sonographic features, including sunken eyelids and small or hypoplastic orbit on the affected side(s). We present two cases of isolated anophthalmia diagnosed on prenatal ultrasound examination in which 3D ultrasound provided additional diagnostic information. The reverse face view provides valuable information about the orbits and the eyeballs for prenatal diagnosis and assessment of anophthalmia.

A case of thanatophoric dysplasia: the early prenatal 2D and 3D sonographic findings and molecular confirmation of diagnosis.

OBJECTIVE: To present the early 2D and 3D ultrasound findings and the molecular confirmation in a case of thanatophoric dysplasia. METHODS: On ultrasound examination, there was frontal bossing, increased nuchal translucency and short limbs at 12 weeks' gestation and a small thorax and short and bowed long bones on 3D at 16 weeks. Amniocentesis and DNA analysis confirmed the mutation of FGFR3 gene indicating thanatophoric dysplasia. RESULTS: After medical termination of pregnancy, the postmortem X-ray and pathology examination findings were consistent with the diagnosis. CONCLUSION: 3D anatomy scan and molecular confirmation may be helpful in early diagnosis and genetic counseling of thanatophoric dysplasia.

Primordial radionuclides in Canadian background sites: secular equilibrium and isotopic differences.

A literature review and field sampling were done to obtain information on primordial (natural-series) radionuclide concentrations in terrestrial environments in diverse locations across Canada. Of special interest was the degree of secular equilibrium among members of decay series. The analytes measured in soils and plants were (nat)U by neutron activation-delayed neutron counting, (228)Th, (230)Th, (232)Th, (226)Ra and (210)Po by alpha spectroscopy, (210)Pb by gas flow proportional counting, (228)Ra by beta counting and (137)Cs by gamma spectroscopy. In addition, ICP-MS was used to obtain concentrations of about 50 analytes including elemental U, Pb, and Th. Samples were from seven representative background sites with a total of 162 plant samples from 38 different species. These data were supplemented by a review that gathered a large portion of the similar data from published sources. The sites chosen were semi-natural, far from any nuclear industry, although several were specifically located in areas with slightly elevated natural U concentrations. As might be expected, there were many cases of non-detectable concentrations. However, certain trends were evident. The activity ratio (210)Po/(210)Pb was unity in soils and non-annual plant tissues such as lichens. It was about 0.6 in annual plant tissues. These results are consistent with the time required for ingrowth of (210)Po to reach secular equilibrium. There was evidence from several sources that (210)Pb in plants came predominantly from deposition of (210)Pb from air after the decay of airborne (222)Rn. This was expected. Somewhat unexpected was the observation that (228)Th seemed to be much more plant available than (232)Th, even though both are in the same decay series and should be chemically similar. The difference was attributed to the combined effects of ingrowth from (228)Ra in the plant and effects of alpha recoil in mobilizing (228)Th in the soil. In general, the results of this study will benefit risk assessment, both in providing background concentrations, but also some indication of where isotope activity ratios can and cannot be used to estimate concentrations.