Imaging biomarkers of lung ventilation in interstitial lung disease from ¹²⁹Xe and oxygen enhanced ¹H MRI

PURPOSE: To compare imaging biomarkers from hyperpolarised 129Xe ventilation MRI and dynamic oxygen-enhanced MRI (OE-MRI) with standard pulmonary function tests (PFT) in interstitial lung disease (ILD) patients. To evaluate if biomarkers can separate ILD subtypes and detect early signs of disease resolution or progression. STUDY TYPE: Prospective longitudinal. POPULATION: Forty-one ILD (fourteen idiopathic pulmonary fibrosis (IPF), eleven hypersensitivity pneumonitis (HP), eleven drug-induced ILD (DI-ILD), five connective tissue disease related-ILD (CTD-ILD)) patients and ten healthy volunteers imaged at visit 1. Thirty-four ILD patients completed visit 2 (eleven IPF, eight HP, ten DIILD, five CTD-ILD) after 6 or 26 weeks. FIELD STRENGTH/SEQUENCE: MRI performed at 1.5 T. Inversion recovery T1 mapping, dynamic MRI acquisition with varying oxygen levels, and hyperpolarised 129Xe ventilation MRI. Subjects underwent standard spirometry and gas transfer testing. ASSESSMENT: Five 1H MRI and two 129Xe MRI ventilation metrics were compared with spirometry and gas transfer measurements. STATISTICAL TEST: To evaluate differences at visit 1 among subgroups: ANOVA or Kruskal-Wallis rank tests with correction for multiple comparisons. To assess the relationships between imaging biomarkers, PFT, age and gender, at visit 1 and for the change between visit 1 and 2: Pearson correlations and multilinear regression models. RESULTS: The global PFT tests could not distinguish ILD subtypes. Ventilated volumes were lower in ILD patients than in HVs when measured with 129Xe MRI (HV 97.4 ± 2.6, CTD-ILD: 91.0 ± 4.8 p = 0.017, DI-ILD 90.1 ± 7.4 p = 0.003, HP 92.6 ± 4.0 p = 0.013, IPF 88.1 ± 6.5 p < 0.001), but not with OE-MRI. 129Xe reported more heterogeneous ventilation in DI-ILD and IPF than in HV, and OE-MRI reported more heterogeneous ventilation in DI-ILD and IPF than in HP or CTD-ILD. The longitudinal changes reported by the imaging biomarkers did not correlate with the PFT changes between visits. DATA CONCLUSION: Neither 129Xe ventilation nor OE-MRI biomarkers investigated in this study were able to differentiate between ILD subtypes, suggesting that ventilation-only biomarkers are not indicated for this task. Limited but progressive loss of ventilated volume as measured by 129Xe-MRI may be present as the biomarker of focal disease progresses. OE-MRI biomarkers are feasible in ILD patients and do not correlate strongly with PFT. Both OE-MRI and 129Xe MRI revealed more spatially heterogeneous ventilation in DI-ILD and IPF

Identifying enablers and barriers to individually tailored prescribing: a survey of healthcare professionals in the UK.

BACKGROUND: Many people now take multiple medications on a long-term basis to manage health conditions. Optimising the benefit of such polypharmacy requires tailoring of medicines use to the needs and circumstances of individuals. However, professionals report barriers to achieving this in practice. In this study, we examined health professionals' perceptions of enablers and barriers to delivering individually tailored prescribing. METHODS: Normalisation Process Theory (NPT) informed an on-line survey of health professionals' views of enablers and barriers to implementation of Individually Tailored Prescribing (ITP) of medicines. Links to the survey were sent out through known professional networks using a convenience/snowball sampling approach. Survey questions sought to identify perceptions of supports/barriers for ITP within the four domains of work described by NPT: sense making, engagement, action and monitoring. Analysis followed the framework approach developed in our previous work. RESULTS: Four hundred and nineteen responses were included in the final analysis (67.3% female, 32.7% male; 52.7% nurse prescribers, 19.8% pharmacists and 21.8% GPs). Almost half (44.9%) were experienced practitioners (16+ years in practice); around one third reported already routinely offering ITP to their patients. GPs were the group least likely to recognise this as consistent usual practice. Findings revealed general support for the principles of ITP but significant variation and inconsistency in understanding and implementation in practice. Our findings reveal four key implications for practice: the need to raise understanding of ITP as a legitimate part of professional practice; to prioritise the work of ITP within the range of individual professional activity; to improve the consistency of training and support for interpretive practice; and to review the impact of formal and informal monitoring processes on practice. CONCLUSION: The findings will inform the ongoing development of our new complex intervention (PRIME Prescribing) to support the individual tailoring of medicines needed to address problematic polypharmacy

HIV-associated neurocognitive disorders before and during the era of combination antiretroviral therapy: differences in rates, nature, and predictors

Combination antiretroviral therapy (CART) has greatly reduced medical morbidity and mortality with HIV infection, but high rates of HIV-associated neurocognitive disorders (HAND) continue to be reported. Because large HIV-infected (HIV+) and uninfected (HIV−) groups have not been studied with similar methods in the pre-CART and CART eras, it is unclear whether CART has changed the prevalence, nature, and clinical correlates of HAND. We used comparable methods of subject screening and assessments to classify neurocognitive impairment (NCI) in large groups of HIV + and HIV − participants from the pre-CART era (1988–1995; N = 857) and CART era (2000–2007; N = 937). Impairment rate increased with successive disease stages (CDC stages A, B, and C) in both eras: 25%, 42%, and 52% in pre-CART era and 36%, 40%, and 45% in CART era. In the medically asymptomatic stage (CDC-A), NCI was significantly more common in the CART era. Low nadir CD4 predicted NCI in both eras, whereas degree of current immunosuppression, estimated duration of infection, and viral suppression in CSF (on treatment) were related to impairment only pre-CART. Pattern of NCI also differed: pre-CART had more impairment in motor skills, cognitive speed, and verbal fluency, whereas CART era involved more memory (learning) and executive function impairment. High rates of mild NCI persist at all stages of HIV infection, despite improved viral suppression and immune reconstitution with CART. The consistent association of NCI with nadir CD4 across eras suggests that earlier treatment to prevent severe immunosuppression may also help prevent HAND. Clinical trials targeting HAND prevention should specifically examine timing of ART initiation

Assessing the perceived impact of post Minamata amalgam phase down on oral health inequalities: a mixed-methods investigation

Background: Data from countries that have implemented a complete phase out of dental amalgam following the Minamata agreement suggest increased costs and time related to the placement of alternatives with consumers absorbing the additional costs. This aim of this study was to investigate the impact of a complete phase out of dental amalgam on oral health inequalities in particular for countries dependent on state run oral health services. Methods: A mixed methods component design quantitative and qualitative study in the United Kingdom. The quantitative study involved acquisition and analysis of datasets from NHS Scotland to compare trends in placement of dental amalgam and a survey of GDPs in Yorkshire, UK. The qualitative study involved analysis of the free text of the survey and a supplementary secondary analysis of semi-structured interviews and focus groups with GDPs (private and NHS), dental school teaching leads and NHS dental commissioners to understand the impact of amalgam phase down on oral health inequalities. Results: Time-trends for amalgam placement showed that there was a significant (p < 0.05) reduction in amalgam use compared with composites and glass ionomers. However dental amalgam still represented a large proportion (42%) of the restorations (circa 1.8 million) placed in the 2016–2017 financial year. Survey respondents suggest that direct impacts of a phase down were related to increased costs and time to place alternative restorations and reduced quality of care. This in turn would lead to increased tooth extractions, reduced access to care and privatisation of dental services with the greatest impact on deprived populations. Conclusion: Amalgam is still a widely placed material in state run oral health services. The complete phase down of dental amalgam poses a threat to such services and threatens to widen oral health inequalities. Our data suggest that a complete phase out is not currently feasible unless appropriate measures are in place to ensure cheaper, long-lasting and easy to use alternatives are available and can be readily adopted by primary care oral health providers

Promoting patient engagement with self-management support information: a qualitative meta-synthesis of processes influencing uptake

<p>Abstract</p> <p>Background</p> <p>Patient information has been viewed as a key component of self-management. However, little attention has been given to methods of dissemination or implementation of effective information strategies. Previous problems identified with the use and implementation of patient information point to the need to explore the way in which patients engage with and use information to support self-management for chronic conditions.</p> <p>Methods</p> <p>Four published qualitative studies from a programme of research about self-management were analysed as a group; these included studies of the management of inflammatory bowel disease (IBD); self-help in anxiety and depression (SHADE); menorrhagia, treatment, information, and preference (MENTIP) study; and self-help for irritable bowel syndrome (IBS). For the analysis, we used an adapted meta-ethnographic approach to the synthesis of qualitative data in order to develop an evidence base.</p> <p>Results</p> <p>The ontological status and experience of the condition in everyday life was the most dominant theme to emerge from this synthesis. This, coupled with access to and experience of traditional health services responses, shaped the engagement with and use of information to support self-management. Five key elements were found which were likely to influence this: the perception and awareness of alternative self-management possibilities; the prior extent and nature of engagement with information; the extent of and ability to self-manage; opportunities for use of the information and the stage of the illness career; and congruence and synergy with the professional role.</p> <p>Conclusion</p> <p>People with chronic conditions need support from providers in both supply and engagement with information, in a way which gives legitimacy to the person's own self-management strategies and possible alternatives. Thus, a link could usefully be made between information offered, as well as patients' past experiences of self-management and engagement with services for their condition. The timeliness of the information should be considered, both in terms of the illness career and the type of condition (<it>i.e</it>., before depression gets too bad or time to reflect on existing knowledge about a condition and how it is to be managed) and in terms of the pre-existing relationship with services (<it>i.e</it>., options explored and tried).</p> <p>More considered use of information (how it is provided, by whom, and at what point it should be introduced) is key to facilitating patients' engagement with and therefore use of information to support self-management.</p

Evaluation of emotion processing in HIV-infected patients and correlation with cognitive performance

Background: Facial emotion recognition depends on cortical and subcortical networks. HIV infection of the central nervous system can damage these networks, leading to impaired facial emotion recognition. Methods: We performed a cross-sectional single cohort study consecutively enrolling HIV + subjects during routine outpatient visits. Age, gender and education-matched HIV-negative healthy individuals were also selected. Subjects were submitted to a Facial Emotion Recognition Test, which assesses the ability to recognize six basic emotions (disgust, anger, fear, happiness, surprise, sadness). The score for each emotion and a global score (obtained by summing scores for each emotion) were analyzed. General cognitive status of patients was also assessed. Results: A total of 49 HIV + and 20 HIV−subjects were enrolled. On the Facial Emotion Recognition Test, ANOVA revealed a significantly lower performance of HIV + subjects than healthy controls in recognizing fear. Moreover, fear facial emotion recognition was directly correlated with Immediate Recall of Rey Words. The lower the patients’ neurocognitive performance the less accurate they were in recognizing happiness. AIDS-defining events were negatively related to the correct recognition of happiness. Conclusions: Fear recognition deficit in HIV + patients might be related to the impaired function of neural networks in the frontostriatal system. AIDS events, including non-neurological ones, may have a negative effect on this system. Inclusion of an emotion recognition test in the neuropsychological test battery could help clinicians during the long term management of HIV-infected patients, to better understand the cognitive mechanisms involved in the reduction of emotion recognition ability and the impact of this impairment on daily lif

How taphonomic alteration affects the detection and imaging of striations in stab wounds

Stabbing with a kitchen knife is a common methodof homicide in Europe. Serrated knives may leave tool mark-ings (striations) in tissues. Documentation of striations is nec-essary for their use as forensic evidence. Traditional methods(physical casting and photography) have significant limita-tions, and micro-computed tomography (micro-CT) has beentrialled in cartilage toBvirtually cast^wounds. Previous re-search has shown the proportion of striations in cartilage fallsfollowing decomposition. This project has investigated theeffects of taphonomic alteration and documentation methodsof striations in porcine skin. Fresh, decomposed, mummified,burnt and waterlogged stab wounds in a porcine analoguewere excised and imaged using photography, stereo-opticalmicroscopy and micro-CT. The proportion of striations ineach taphonomic group was determined from the images byindependent analysts. Striations were observed more frequent-ly in serrated blade wounds, although they were also identifiedin non-serrated blade wounds. The proportion of woundsshowing striations declined following decomposition. An in-versely proportional linear correlation between advancing de-composition and proportion of striations existed. Dehydration(mummification and burning) rendered serrated and non-serrated blade wounds indistinguishable. Water compositionaffected the preservation of striations. Identification ofstriations gradually declined after decomposition in tap water,but persisted to a point when left in brackish water. All threetechniques imaged striations; however, the optimum tech-nique was stereo-optical microscopy due to practical advan-tages and specific limitations affecting photography and mi-cro-CT. This study demonstrates the effects of taphonomicalteration on striations and suggests stereo-optical microscopyis the optimum method for their documentation

Genetic complexity of miscanthus cell wall composition and biomass quality for biofuels

BACKGROUND: Miscanthus sinensis is a high yielding perennial grass species with great potential as a bioenergy feedstock. One of the challenges that currently impedes commercial cellulosic biofuel production is the technical difficulty to efficiently convert lignocellulosic biomass into biofuel. The development of feedstocks with better biomass quality will improve conversion efficiency and the sustainability of the value-chain. Progress in the genetic improvement of biomass quality may be substantially expedited by the development of genetic markers associated to quality traits, which can be used in a marker-assisted selection program. RESULTS: To this end, a mapping population was developed by crossing two parents of contrasting cell wall composition. The performance of 182 F1 offspring individuals along with the parents was evaluated in a field trial with a randomized block design with three replicates. Plants were phenotyped for cell wall composition and conversion efficiency characters in the second and third growth season after establishment. A new SNP-based genetic map for M. sinensis was built using a genotyping-by-sequencing (GBS) approach, which resulted in 464 short-sequence uniparental markers that formed 16 linkage groups in the male map and 17 linkage groups in the female map. A total of 86 QTLs for a variety of biomass quality characteristics were identified, 20 of which were detected in both growth seasons. Twenty QTLs were directly associated to different conversion efficiency characters. Marker sequences were aligned to the sorghum reference genome to facilitate cross-species comparisons. Analyses revealed that for some traits previously identified QTLs in sorghum occurred in homologous regions on the same chromosome. CONCLUSION: In this work we report for the first time the genetic mapping of cell wall composition and bioconversion traits in the bioenergy crop miscanthus. These results are a first step towards the development of marker-assisted selection programs in miscanthus to improve biomass quality and facilitate its use as feedstock for biofuel production

Soluble and Cell-Associated Insulin Receptor Dysfunction Correlates with Severity of HAND in HIV-Infected Women

Blood sugar metabolism abnormalities have been identified in HIV-infected individuals and associated with HIV-associated neurocognitive disorders (HAND). These abnormalities may occur as a result of chronic HIV infection, long-term use of combined antiretroviral treatment (CART), aging, genetic predisposition, or a combination of these factors, and may increase morbidity and mortality in this population.To determine if changes in soluble and cell-associated insulin receptor (IR) levels, IR substrate-1 (IRS-1) levels, and IRS-1 tyrosine phosphorylation are associated with the presence and severity of HAND in a cohort of HIV-seropositive women.This is a retrospective cross-sectional study using patient database information and stored samples from 34 HIV-seropositive women and 10 controls without history of diabetes from the Hispanic-Latino Longitudinal Cohort of Women. Soluble IR subunits [sIR, ectodomain (α) and full-length or intact (αβ)] were assayed in plasma and CSF samples by ELISA. Membrane IR levels, IRS-1 levels, and IRS-1 tyrosine phosphorylation were analyzed in CSF white cell pellets (WCP) using flow cytometry. HIV-seropositive women had significantly increased levels of intact or full-length sIR in plasma (p<0.001) and CSF (p<0.005) relative to controls. Stratified by HAND, increased levels of full-length sIR in plasma were associated with the presence (p<0.001) and severity (p<0.005) of HAND. A significant decrease in IRS-1 tyrosine-phosphorylation in the WCP was also associated with the presence (p<0.02) and severity (p<0.02) of HAND.This study provides evidence that IR secretion is increased in HIV-seropositive women, and increased IR secretion is associated with cognitive impairment in these women. Thus, IR dysfunction may have a role in the progression of HAND and could represent a biomarker for the presence and severity of HAND