Multiple Statistical Analysis Techniques Corroborate Intratumor Heterogeneity in Imaging Mass Spectrometry Datasets of Myxofibrosarcoma

MALDI mass spectrometry can generate profiles that contain hundreds of biomolecular ions directly from tissue. Spatially-correlated analysis, MALDI imaging MS, can simultaneously reveal how each of these biomolecular ions varies in clinical tissue samples. The use of statistical data analysis tools to identify regions containing correlated mass spectrometry profiles is referred to as imaging MS-based molecular histology because of its ability to annotate tissues solely on the basis of the imaging MS data. Several reports have indicated that imaging MS-based molecular histology may be able to complement established histological and histochemical techniques by distinguishing between pathologies with overlapping/identical morphologies and revealing biomolecular intratumor heterogeneity. A data analysis pipeline that identifies regions of imaging MS datasets with correlated mass spectrometry profiles could lead to the development of novel methods for improved diagnosis (differentiating subgroups within distinct histological groups) and annotating the spatio-chemical makeup of tumors. Here it is demonstrated that highlighting the regions within imaging MS datasets whose mass spectrometry profiles were found to be correlated by five independent multivariate methods provides a consistently accurate summary of the spatio-chemical heterogeneity. The corroboration provided by using multiple multivariate methods, efficiently applied in an automated routine, provides assurance that the identified regions are indeed characterized by distinct mass spectrometry profiles, a crucial requirement for its development as a complementary histological tool. When simultaneously applied to imaging MS datasets from multiple patient samples of intermediate-grade myxofibrosarcoma, a heterogeneous soft tissue sarcoma, nodules with mass spectrometry profiles found to be distinct by five different multivariate methods were detected within morphologically identical regions of all patient tissue samples. To aid the further development of imaging MS based molecular histology as a complementary histological tool the Matlab code of the agreement analysis, instructions and a reduced dataset are included as supporting information

Prospective association of social circumstance, socioeconomic, lifestyle and mental health factors with subsequent hospitalisation over 6–7 year follow up in people living with HIV

Background: Predictors of hospitalisation in people with HIV (PLHIV) in the contemporary treatment era are not well understood. / Methods: This ASTRA sub-study used clinic data linkage and record review to determine occurrence of hospitalisations among 798 PLHIV from baseline questionnaire (February to December 2011) until 1 June 2018. Associations of baseline social circumstance, socioeconomic, lifestyle, mental health, demographic and clinical factors with repeated all-cause hospitalisation from longitudinal data were investigated using Prentice-Williams-Peterson models. Associations were also assessed in 461 individuals on antiretroviral therapy (ART) with viral load ≤50 copies/ml and CD4 count ≥500 cells/ µl. / Findings: Rate of hospitalisation was 5.8/100 person-years (95% CI: 5.1–6.5). Adjusted for age, demographic group and time with diagnosed HIV, the following social circumstance, socioeconomic, lifestyle and mental health factors predicted hospitalisation: no stable partner (adjusted hazard ratio (aHR)=1.59; 95% CI=1.16–2.20 vs living with partner); having children (aHR=1.50; 1.08–2.10); non-employment (aHR=1.56; 1.07–2.27 for unemployment; aHR=2.39; 1.70–3.37 for sick/disabled vs employed); rented housing (aHR=1.72; 1.26–2.37 vs homeowner); not enough money for basic needs (aHR=1.82; 1.19–2.78 vs enough); current smoking (aHR=1.39; 1.02–1.91 vs never); recent injection-drug use (aHR=2.11; 1.30–3.43); anxiety symptoms (aHRs=1.39; 1.01–1.91, 2.06; 1.43–2.95 for mild and moderate vs none/minimal); depressive symptoms (aHRs=1.67; 1.17–2.38, 1.91; 1.30–2.78 for moderate and severe vs none/minimal); treated/untreated depression (aHRs=1.65; 1.03–2.64 for treated depression only, 1.87; 1.39–2.52 for depressive symptoms only; 1.53; 1.05–2.24; for treated depression and depressive symptoms, versus neither). Associations were broadly similar in those with controlled HIV and high CD4. / Interpretation: Social circumstance, socioeconomic disadvantage, adverse lifestyle factors and poorer mental health are strong predictors of hospitalisation in PLHIV, highlighting the need for targeted interventions and care. / Funding: British HIV Association (BHIVA) Research Award (2017); SMR funded by a PhD fellowship from the Royal Free Charity

The geoaccumulation index and enrichment factor of mercury in mangrove sediment of Port Klang, Selangor, Malaysia.

Mangrove areas are important to the ecosystem. One of its crucial functions is as a sink of pollutants, especially metal ions. However, the accumulation of metals in mangrove sediment can generate negative impacts on plant growth, microbial activity, and soil fertility. Apart from that, the severity of the impact is highly influenced by the type of metal found in the sediment and the quality of sediment itself. One of the metals that have adverse effects on the environment is mercury. The objectives of this study are to determine the concentration and distribution of mercury and to assess the enrichment of mercury in Port Klang mangrove sediment by using geoaccumulation index and enrichment factor. Sediment samples were collected from 30 sampling points that cover Langat River and Klang River estuaries, Lumut Straits, Pulau Klang, and Pulau Indah. During sampling, water parameters such as pH, salinity, electrical conductivity, and total dissolved solids were measured in situ, whereas the total mercury in sediment samples was determined at the laboratory using inductively coupled plasma mass spectrometry. In this study, mercury was found to be concentrated along Lumut Strait especially in the mixing zone near the confluence of Langat River and at the jetty to Pulau Ketam. The geoaccumulation index and enrichment factor (calculated using logarithmized data of the reference element) found that three stations were enriched with mercury. In addition, geoaccumulation index was also observed to be more objective compared to enrichment factor whose results were influenced by the concentration of reference element used

A cross-sector analysis of human and organisational factors in the deployment of data-driven predictive maintenance

Domains such as utilities, power generation, manufacturing and transport are increasingly turning to data-driven tools for management and maintenance of key assets. Whole ecosystems of sensors and analytical tools can provide complex, predictive views of network asset performance. Much research in this area has looked at the technology to provide both sensing and analysis tools. The reality in the field, however, is that the deployment of these technologies can be problematic due to user issues, such as interpretation of data or embedding within processes, and organisational issues, such as business change to gain value from asset analysis. 13 experts from the field of remote condition monitoring, asset management and predictive analytics across multiple sectors were interviewed to ascertain their experience of supplying data-driven applications. The results of these interviews are summarised as a framework based on a predictive maintenance project lifecycle covering project motivations and conception, design and development, and operation. These results identified critical themes for success around having a target or decision-led, rather than data-led, approach to design; long-term resourcing of the deployment; the complexity of supply chains to provide data-driven solutions and the need to maintain knowledge across the supply chain; the importance of fostering technical competency in end-user organisations; and the importance of a maintenance-driven strategy in the deployment of data-driven asset management. Emerging from these themes are recommendations related to culture, delivery process, resourcing, supply chain collaboration and industry-wide cooperation

Reversed-phase liquid chromatography coupled on-line to estrogen receptor bioaffinity detection based on fluorescence polarization

We describe the development and validation of a high-resolution screening (HRS) platform which couples gradient reversed-phase high-performance liquid chromatography (RP-HPLC) on-line to estrogen receptor α (ERα) affinity detection using fluorescence polarization (FP). FP, which allows detection at high wavelengths, limits the occurrence of interference from the autofluorescence of test compounds in the bioassay. A fluorescein-labeled estradiol derivative (E2-F) was synthesized and a binding assay was optimized in platereader format. After subsequent optimization in flow-injection analysis (FIA) mode, the optimized parameters were translated to the on-line HRS bioassay. Proof of principle was demonstrated by separating a mixture of five compounds known to be estrogenic (17β-estradiol, 17α-ethinylestradiol and the phytoestrogens coumestrol, coumarol and zearalenone), followed by post-column bioaffinity screening of the individual affinities for ERα. Using the HRS-based FP setup, we were able to screen affinities of off-line-generated metabolites of zearalenone for ERα. It is concluded that the on-line FP-based bioassay can be used to screen for the affinity of compounds without the disturbing occurrence of autofluorescence

Breast cancer oestrogen independence mediated by BCAR1 or BCAR3 genes is transmitted through mechanisms distinct from the oestrogen receptor signalling pathway or the epidermal growth factor receptor signalling pathway

INTRODUCTION: Tamoxifen is effective for endocrine treatment of oestrogen receptor-positive breast cancers but ultimately fails due to the development of resistance. A functional screen in human breast cancer cells identified two BCAR genes causing oestrogen-independent proliferation. The BCAR1 and BCAR3 genes both encode components of intracellular signal transduction, but their direct effect on breast cancer cell proliferation is not known. The aim of this study was to investigate the growth control mediated by these BCAR genes by gene expression profiling. METHODS: We have measured the expression changes induced by overexpression of the BCAR1 or BCAR3 gene in ZR-75-1 cells and have made direct comparisons with the expression changes after cell stimulation with oestrogen or epidermal growth factor (EGF). A comparison with published gene expression data of cell models and breast tumours is made. RESULTS: Relatively few changes in gene expression were detected in the BCAR-transfected cells, in comparison with the extensive and distinct differences in gene expression induced by oestrogen or EGF. Both BCAR1 and BCAR3 regulate discrete sets of genes in these ZR-75-1-derived cells, indicating that the proliferation signalling proceeds along distinct pathways. Oestrogen-regulated genes in our cell model showed general concordance with reported data of cell models and gene expression association with oestrogen receptor status of breast tumours. CONCLUSIONS: The direct comparison of the expression profiles of BCAR transfectants and oestrogen or EGF-stimulated cells strongly suggests that anti-oestrogen-resistant cell proliferation is not caused by alternative activation of the oestrogen receptor or by the epidermal growth factor receptor signalling pathway

The DUNDRUM Quartet: validation of structured professional judgement instruments DUNDRUM-3 assessment of programme completion and DUNDRUM-4 assessment of recovery in forensic mental health services

<p>Abstract</p> <p>Background</p> <p>Moving a forensic mental health patient from one level of therapeutic security to a lower level or to the community is influenced by more than risk assessment and risk management. We set out to construct and validate structured professional judgement instruments for consistency and transparency in decision making</p> <p>Methods</p> <p>Two instruments were developed, the seven-item DUNDRUM-3 programme completion instrument and the six item DUNDRUM-4 recovery instrument. These were assessed for all 95 forensic patients at Ireland's only forensic mental health hospital.</p> <p>Results</p> <p>The two instruments had good internal consistency (Cronbach's alpha 0.911 and 0.887). Scores distinguished those allowed no leave or accompanied leave from those with unaccompanied leave (ANOVA F = 38.1 and 50.3 respectively, p < 0.001). Scores also distinguished those in acute/high security units from those in medium or in low secure/pre-discharge units. Each individual item distinguished these levels of need significantly. The DUNDRUM-3 and DUNDRUM-4 correlated moderately with measures of dynamic risk and with the CANFOR staff rated unmet need (Spearman r = 0.5, p < 0.001).</p> <p>Conclusions</p> <p>The DUNDRUM-3 programme completion items distinguished significantly between levels of therapeutic security while the DUNDRUM-4 recovery items consistently distinguished those given unaccompanied leave outside the hospital and those in the lowest levels of therapeutic security. This data forms the basis for a prospective study of outcomes now underway.</p

Radiofrequency Heating of the Cornea: An Engineering Review of Electrodes and Applicators

This paper reviews the different applicators and electrodes employed to create localized heating in the cornea by means of the application of radiofrequency (RF) currents. Thermokeratoplasty (TKP) is probably the best known of these techniques and is based on the principle that heating corneal tissue (particularly the central part of the corneal tissue, i.e. the central stroma) causes collagen to shrink, and hence changes the corneal curvature. Firstly, we point out that TKP techniques are a complex challenge from the engineering point of view, due to the fact that it is necessary to create very localized heating in a precise location (central stroma), within a narrow temperature range (from 58 to 76ºC). Secondly, we describe the different applicator designs (i.e. RF electrodes) proposed and tested to date. This review is planned from a technical point of view, i.e. the technical developments are classified and described taking into consideration technical criteria, such as energy delivery mode (monopolar versus bipolar), thermal conditions (dry versus cooled electrodes), lesion pattern (focal versus circular lesions), and application placement (surface versus intrastromal)

HIV and HPV infections and ocular surface squamous neoplasia: systematic review and meta-analysis.

BACKGROUND: The frequency of ocular surface squamous neoplasias (OSSNs) has been increasing in populations with a high prevalence of infection with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) and infection with human papillomavirus (HPV). We aimed to quantify the association between HIV/AIDS and HPV infection and OSSN, through systematic review and meta-analysis. METHODS: The articles providing data on the association between HIV/AIDS and/or HPV infection and OSSN were identified in MEDLINE, SCOPUS and EMBASE searched up to May 2013, and through backward citation tracking. The DerSimonian and Laird method was used to compute summary relative risk (RR) estimates and 95% confidence intervals (95% CI). Heterogeneity was quantified with the I(2) statistic. RESULTS: HIV/AIDS was strongly associated with an increased risk of OSSN (summary RR=8.06, 95% CI: 5.29-12.30, I(2)=56.0%, 12 studies). The summary RR estimate for the infection with mucosal HPV subtypes was 3.13 (95% CI: 1.72-5.71, I(2)=45.6%, 16 studies). Four studies addressed the association between both cutaneous and mucosal HPV subtypes and OSSN; the summary RR estimates were 3.52 (95% CI: 1.23-10.08, I(2)=21.8%) and 1.08 (95% CI: 0.57-2.05, I(2)=0.0%), respectively. CONCLUSION: Human immunodeficiency virus infection increases the risk of OSSN by nearly eight-fold. Regarding HPV infection, only the cutaneous subtypes seem to be a risk factor