A Survey of Electron Probe Microanalysis Using Soft Radiations: Difficulties and Presentation of a New Computer Program for Wavelength Dispersive Spectrometry

This paper aims to demonstrate that on-line peak integral technique with wavelength dispersive spectroscopy (WDS) provides accurate results with intensity measurement counting times as short as one or two minutes, owing to the high counting rates obtained with multilayer analyzers. A great advantage of a new computer program using this technique (available on SUN/UNIX work-stations operating Cameca SX-50 microprobes) consists in the original way that peak overlaps are treated. For each analytical point, overlapping counts emerging from an element B (B counts) are removed on-line from the measured raw counts in order to obtain the net counts corresponding to the element to be analyzed (element A). B counts are first measured on a proper standard containing B but not A. The effects of chemical bonding on the shape and the shift of peaks is clearly seen in the analysis of fluorine in topaz and lithium fluoride. Self-absorption effects, which usually distort the high energy side of L-series soft radiations, are generally inconsistent with the direct measurements of peak area fork-ratio determination. A method based on the conventional area/peak factor concept is proposed for this purpose

Spectral Decomposition of Wavelength Dispersive X-Ray Spectra: Implications for Quantitative Analysis in the Electron Probe Microanalyzer

The line shapes of Kα, Lα,β and Mα X-ray peaks of pure elements were analyzed by means of commercial wavelength dispersive spectrometers (WDS) attached to an electron probe micro-analyzer (EPMA). A pseudo-Voigt function, i.e., a linear combination of Gaussian and Lorentzian distributions, was used as a fitting profile for the X-ray peaks, with Gaussian offsets incorporated in the short wavelength (high energy) side to describe the observed asymmetry. The asymmetry of X-ray peaks resulting from both instrumental distortions and satellite bands may lead to discrepancies in quantitative analysis with the EPMA as a function of the procedure used for deriving X-ray intensities from WDS spectra, e.g., peak height, peak area, or peak decomposition. These effects have been illustrated by analyzing gold-copper metallic alloys and minerals containing gold at trace levels

Electron Microprobe Analysis and Proton Induced X-Ray Spectrometry Applied to Trace Element Analysis in Sulfides: Problems and Prospects

The complementary techniques of EPMA and micro-PIXE are reviewed in the context of spatially resolved trace element analysis of sulfide minerals. Attention is focussed on methods of standardization and of fitting EDX spectra. Sphalerites and chalcopyrites from various sources are used as specimens. For Ag in chalcopyrites, the two techniques agree well. Sphalerites pose problems such as Zn-Fe replacement and the presence of minor elements, both of which influence matrix corrections ; these are addressed in detail. The necessity for absorbers in the micro-PIXE work prevents detection of minor elements lighter than Zn ; these are determined by EPMA and the results used in the micro-PIXE fitting and matrix corrections. For Cd, Ag, Ga, Ge there is acceptable agreement between the two techniques given uncertainties and constraints on samples, but EPMA results for Hg are notably lower than micro-PIXE results. The improvement in detection limits afforded by micro-PIXE over EPMA in these sulfide minerals ranges from ~ 3 for Ga, Ge, Hg to 10-30 for Se, Ag, Cd, In ; possible further gains are discussed for both techniques

A rapid review of the evidence on models of service delivery for correctional centre-based mothers and children's units: does our approach need to change?

BACKGROUND: Incarcerated mothers are a marginalised group who experience substantial health and social disadvantage and routinely face disruption of family relationships, including loss of custody of their children. To support the parenting role, mothers and children's units (M&Cs) operate in 97 jurisdictions internationally with approximately 19 000 children reported to be residing with their mothers in custody-based settings. AIM: This rapid review aims to describe the existing evidence regarding the models of service delivery for, and key components of, custodial M&Cs. METHOD: A systematic search was conducted of four electronic databases to identify peer-reviewed literature published from 2010 onwards that reported quantitative and qualitative primary studies focused on custody-based M&Cs. Extracted data included unit components, admission and eligibility criteria, evaluations and recommendations. RESULTS: Of 3075 records identified, 35 met inclusion criteria. M&Cs accommodation was purpose-built, incorporated elements of domestic life and offered a family-like environment. Specific workforce training in caring for children and M&Cs evaluations were largely absent. Our systematic synthesis generated a list of key components for M&C design and service delivery. These components include timely and transparent access to information and knowledge for women, evaluation of the impact of the prison environment on M&C, and organisational opportunities and limitations. CONCLUSION: The next generation of M&Cs requires evidence-based key components that are implemented systematically and is evaluated. To achieve this, the use of codesign is a proven method for developing tailored programmes. Such units must offer a net benefit to both mothers and their children

Diseño y puesta en funcionamiento de un SIG como herramienta para el estudio del turismo y su planificación en las regiones del archipiélago de Las Canarreos y Cienfuegos-Trinidad-Topes de Collantes, Cuba

Today, geographic information systems are being used as a platform for managing hugh volumes of information related to the decision making process withing different fields. Given the great variety of touristic resources that Cuba has, different systems have been generated at the Faculty of Geography of the University of Havana, oriented to tourism plainning and study. In this article, two of those results are presented involving different territories: Los Canarreos Archipielago and Cienfuegos -Trinidad - Topes de Collantes region.En la época actual, los Sistemas de Información Geográfica están siendo cada vez más utilizados como plataforma para el manejo de grandes volúmenes de información relacionados con la toma de decisiones en diferentes ramas. Dada la gran variedad de recursos turísticos con que Cuba cuenta y dado el incremento de la actividad en el país, se han generado por la Facultad de Geografía de la Universidad de La Habana diferentes sistemas orientados al estudio y la planificación del turismo. En el presente trabajo se presentan dos de estos resultados vinculados con territorios específicos: El Archipiélago de los Canarreos y la región Cienfuegos-Trinidad-Topes de Collaiites

Most Lung and Colon Cancer Susceptibility Genes Are Pair-Wise Linked in Mice, Humans and Rats

Genetic predisposition controlled by susceptibility quantitative trait loci (QTLs) contributes to a large proportion of common cancers. Studies of genetics of cancer susceptibility, however, did not address systematically the relationship between susceptibility to cancers in different organs. We present five sets of data on genetic architecture of colon and lung cancer susceptibility in mice, humans and rats. They collectively show that the majority of genes for colon and lung cancer susceptibility are linked pair-wise and are likely identical or related. Four CcS/Dem recombinant congenic strains, each differing from strain BALB/cHeA by a different small random subset of ±12.5% of genes received from strain STS/A, suggestively show either extreme susceptibility or extreme resistance for both colon and lung tumors, which is unlikely if the two tumors were controlled by independent susceptibility genes. Indeed, susceptibility to lung cancer (Sluc) loci underlying the extreme susceptibility or resistance of such CcS/Dem strains, mapped in 226 (CcS-10×CcS-19)F2 mice, co-localize with susceptibility to colon cancer (Scc) loci. Analysis of additional Sluc loci that were mapped in OcB/Dem strains and Scc loci in CcS/Dem strains, respectively, shows their widespread pair-wise co-localization (P = 0.0036). Finally, the majority of published human and rat colon cancer susceptibility genes map to chromosomal regions homologous to mouse Sluc loci. 12/12 mouse Scc loci, 9/11 human and 5/7 rat colon cancer susceptibility loci are close to a Sluc locus or its homologous site, forming 21 clusters of lung and colon cancer susceptibility genes from one, two or three species. Our data shows that cancer susceptibility QTLs can have much broader biological effects than presently appreciated. It also demonstrates the power of mouse genetics to predict human susceptibility genes. Comparison of molecular mechanisms of susceptibility genes that are organ-specific and those with trans-organ effects can provide a new dimension in understanding individual cancer susceptibility

CIBRA identifies genomic alterations with a system-wide impact on tumor biology

Background: Genomic instability is a hallmark of cancer, leading to many somatic alterations. Identifying which alterations have a system-wide impact is a challenging task. Nevertheless, this is an essential first step for prioritizing potential biomarkers. We developed CIBRA (Computational Identification of Biologically Relevant Alterations), a method that determines the system-wide impact of genomic alterations on tumor biology by integrating two distinct omics data types: one indicating genomic alterations (e.g., genomics), and another defining a system-wide expression response (e.g., transcriptomics). CIBRA was evaluated with genome-wide screens in 33 cancer types using primary and metastatic cancer data from the Cancer Genome Atlas and Hartwig Medical Foundation. Results: We demonstrate the capability of CIBRA by successfully confirming the impact of point mutations in experimentally validated oncogenes and tumor suppressor genes. Surprisingly, many genes affected by structural variants were identified to have a strong system-wide impact (30.3%), suggesting that their role in cancer development has thus far been largely underreported. Additionally, CIBRA can identify impact with only ten cases and controls, providing a novel way to prioritize genomic alterations with a prominent role in cancer biology. Conclusions: Our findings demonstrate that CIBRA can identify cancer drivers by combining genomics and transcriptomics data. Moreover, our work shows an unexpected substantial system-wide impact of structural variants in cancer. Hence, CIBRA has the potential to preselect and refine current definitions of genomic alterations to derive more nuanced biomarkers for diagnostics, disease progression, and treatment response. CIBRA is available at https://github.com/AIT4LIFE-UU/CIBR

Early evaluation of the effectiveness and cost-effectiveness of ctDNA-guided selection for adjuvant chemotherapy in stage II colon cancer

Background: Current patient selection for adjuvant chemotherapy (ACT) after curative surgery for stage II colon cancer (CC) is suboptimal, causing overtreatment of high-risk patients and undertreatment of low-risk patients. Postoperative circulating tumor DNA (ctDNA) could improve patient selection for ACT. Objectives: We conducted an early model-based evaluation of the (cost-)effectiveness of ctDNA-guided selection for ACT in stage II CC in the Netherlands to assess the conditions for cost-effective implementation. Methods: A validated Markov model, simulating 1000 stage II CC patients from diagnosis to death, was supplemented with ctDNA data. Five ACT selection strategies were evaluated: the current guideline (pT4, pMMR), ctDNA-only, and three strategies that combined ctDNA status with pT4 and pMMR status in different ways. For each strategy, the costs, life years, quality-adjusted life years (QALYs), recurrences, and CC deaths were estimated. Sensitivity analyses were performed to assess the impact of the costs of ctDNA testing, strategy adherence, ctDNA as a predictive biomarker, and ctDNA test performance. Results: Model predictions showed that compared to current guidelines, the ctDNA-only strategy was less effective (+2.2% recurrences, −0.016 QALYs), while the combination strategies were more effective (−3.6% recurrences, +0.038 QALYs). The combination strategies were not cost-effective, since the incremental cost-effectiveness ratio was €67,413 per QALY, exceeding the willingness-to-pay threshold of €50,000 per QALY. Sensitivity analyses showed that the combination strategies would be cost-effective if the ctDNA test costs were lower than €1500, or if ctDNA status was predictive of treatment response, or if the ctDNA test performance improved substantially. Conclusion: Adding ctDNA to current high-risk clinicopathological features (pT4 and pMMR) can improve patient selection for ACT and can also potentially be cost-effective. Future studies should investigate the predictive value of post-surgery ctDNA status to accurately evaluate the cost-effectiveness of ctDNA testing for ACT decisions in stage II CC.</p

Prognostic value of microvessel density in stage II and III colon cancer patients:a retrospective cohort study

Background Microvessel density (MVD), as a derived marker for angiogenesis, has been associated with poor outcome in several types of cancer. This study aimed to evaluate the prognostic value of MVD in stage II and III colon cancer and its relation to tumour-stroma-percentage (TSP) and expression of HIF1A and VEGFA. Methods Formalin-fixed paraffin-embedded (FFPE) colon cancer tissues were collected from 53 stage II and 54 (5-fluorouracil-treated) stage III patients. MVD was scored by digital morphometric analysis of CD31-stained whole tumour sections. TSP was scored using haematoxylin-eosin stained slides. Protein expression of HIF1A and VEGFA was determined by immunohistochemical evaluation of tissue microarrays. Results Median MVD was higher in stage III compared to stage II colon cancers (11.1% versus 5.6% CD31-positive tissue area, p <0.001). High MVD in stage II patients tended to be associated with poor disease free survival (DFS) in univariate analysis (p = 0.056). In contrast, high MVD in 5FU-treated stage III patients was associated with better DFS (p = 0.006). Prognostic value for MVD was observed in multivariate analyses for both cancer stages. Conclusions MVD is an independent prognostic factor associated with poor DFS in stage II colon cancer patients, and with better DFS in stage III colon cancer patients treated with adjuvant chemotherapy