CTC-5: A novel digital pathology approach to characterise circulating tumour cell biodiversity.

Metastatic progression and tumor evolution complicates the clinical management of cancer patients. Circulating tumor cell (CTC) characterization is a growing discipline that aims to elucidate tumor metastasis and evolution processes. CTCs offer the clinical potential to monitor cancer patients for therapy response, disease relapse, and screen 'at risk' groups for the onset of malignancy. However, such clinical utility is currently limited to breast, prostate, and colorectal cancer patients. Further understanding of the basic CTC biology of other malignancies is required to progress them towards clinical utility. Unfortunately, such basic clinical research is often limited by restrictive characterization methods and high-cost barrier to entry for CTC isolation and imaging infrastructure. As experimental clinical results on applications of CTC are accumulating, it is becoming clear that a two-tier system of CTC isolation and characterization is required. The first tier is to facilitate basic research into CTC characterization. This basic research then informs a second tier specialised in clinical prognostic and diagnostic testing. This study presented in this manuscript describes the development and application of a low-cost, CTC isolation and characterization pipeline; CTC-5. This approach uses an established 'isolation by size' approach (ScreenCell Cyto) and combines histochemical morphology stains and multiparametric immunofluorescence on the same isolated CTCs. This enables capture and characterization of CTCs independent of biomarker-based pre-selection and accommodates both single CTCs and clusters of CTCs. Additionally, the developed open-source software is provided to facilitate the synchronization of microscopy data from multiple sources (https://github.com/CTC5/). This enables high parameter histochemical and immunofluorescent analysis of CTCs with existing microscopy infrastructure without investment in CTC specific imaging hardware. Our approach confirmed by the number of successful tests represents a potential major advance towards highly accessible low-cost technology aiming at the basic research tier of CTC isolation and characterization. The biomarker independent approach facilitates closing the gap between malignancies with poorly, and well-defined CTC phenotypes. As is currently the case for some of the most commonly occurring breast, prostate and colorectal cancers, such advances will ultimately benefit the patient, as early detection of relapse or onset of malignancy strongly correlates with their prognosis.

Intimate partner violence among HIV-positive women in Nairobi, Kenya.

PURPOSE: This study was conducted to identify the prevalence and sociodemographic factors associated with four forms of intimate partner violence (IPV) among HIV-positive women attending the Comprehensive Care Centre at the Kenyatta National Hospital in Nairobi, Kenya. METHODS: A cross-sectional study was conducted among 600 sexually active HIV-positive women aged 18-69 years from May to August of 2012. A structured questionnaire including questions pertaining to sociodemographic characteristics, health care decisions, and forms of IPV (controlling behavior, emotional abuse, physical violence, and sexual violence) was administered to each woman. RESULTS: All women reported experiencing emotional abuse; 20%, 17%, and 15% experienced controlling behavior, physical violence, and sexual violence, respectively. Women who reported low/below average socioeconomic status (SES) had a greater likelihood of experiencing controlling behavior than women with high/average SES (adjusted odds ratio [aOR] =1.62, 95% CI 1.05-2.51). Women who were unemployed had greater odds of experiencing physical violence than those who were employed (aOR =2.35, 95% CI 1.31-4.23). Non-Christian women had higher odds of experiencing controlling behavior, physical violence, and sexual violence than Christian women (aOR =4.41, 95% CI 1.81-10.76 and aOR =3.33, 95% CI 1.43-7.80). CONCLUSION: Based on the prevalence of IPV and the sociodemographic factors identified to be associated with IPV among women in this study it may be beneficial to include IPV screening as part of routine clinic visits for HIV-positive and other women. Furthermore, women who report emotional abuse or controlling behavior from spouse should not be overlooked, as these two forms of IPV may precede or accompany physical and sexual IPV. Women who report experiencing IPV during clinic visits may be referred to organizations and resources available to battered women in Kenya. Increased funding for anti-IPV programs and changes in policy may also contribute to a reduction in IPV among HIV-positive and other women in Kenya.

Development of a consumer product ingredient database for chemical exposure screening and prioritization.

Consumer products are a primary source of chemical exposures, yet little structured information is available on the chemical ingredients of these products and the concentrations at which ingredients are present. To address this data gap, we created a database of chemicals in consumer products using product Material Safety Data Sheets (MSDSs) publicly provided by a large retailer. The resulting database represents 1797 unique chemicals mapped to 8921 consumer products and a hierarchy of 353 consumer product "use categories" within a total of 15 top-level categories. We examine the utility of this database and discuss ways in which it will support (i) exposure screening and prioritization, (ii) generic or framework formulations for several indoor/consumer product exposure modeling initiatives, (iii) candidate chemical selection for monitoring near field exposure from proximal sources, and (iv) as activity tracers or ubiquitous exposure sources using "chemical space" map analyses. Chemicals present at high concentrations and across multiple consumer products and use categories that hold high exposure potential are identified. Our database is publicly available to serve regulators, retailers, manufacturers, and the public for predictive screening of chemicals in new and existing consumer products on the basis of exposure and risk.

Copper(II)-mediated oxidative coupling of 2-aminonaphthalene homologues. Competition between the straight dimerization and the formation of carbazoles.

Whereas the Cu(II)-mediated oxidative coupling of 2-aminonaphthalenes 7a and 7b results in the clean formation of 1,1'-binaphthyls 13a and 13b, respectively, their higher homologues and congeners 8-12 have been found to exhibit a different reaction pattern. Thus, 2-aminoanthracene (8) gave a approximately 1:1 mixture of the expected bianthryl derivative 15 and the carbazole 16, whereas the 9-aminophenanthrene (10), 3-phenyl-1-aminonaphthalene (11), and 2-aminochrysene (12) produced almost exclusively the corresponding carbazoles 19, 20, and 21, respectively. By contrast, the isomeric 3-aminophenanthrene (9) gave rise to the azo compound 17 as a result of the preferential oxidation on the nitrogen. The carbazoles have been shown to arise directly from the coupling reactions rather than from the primarily formed binaphthyls. Alternatively, carbazole 19 can also be prepared from 1b on reaction with hydrazine. On the other hand, treatment of 3a with hydrazine resulted in the formation of a approximately 2:7 mixture of amine 11 and arylhydrazine 22. 2,2'-Diamino-1,1'-bianthryl (15) has been resolved into enantiomers via cocrystallization with (-)-N-benzylcinchonidinium chloride and shown to have (R)-(-)-15 configuration by X-ray crystallography.

A replication of Rorschach and MMPI-2 convergent validity.

We replicated prior research on Rorschach and MMPI-2 convergent validity by testing 8 hypotheses in a new sample of patients. We also extended prior research by developing criteria to include more patients and by applying the same procedures to 2 self-report tests: the MMPI-2 and the MCMI-II. Results supported our hypotheses and paralleled the prior findings. Furthermore, 3 different tests for methodological artifacts could not account for the results. Thus, the convergence of Rorschach and MMPI-2 constructs seems to be partially a function of how patients interact with the tests. When patients approach each test with a similar style, conceptually aligned constructs tend to correlate. Although this result is less robust, when patients approach each test in an opposing manner, conceptually aligned constructs tend to be negatively correlated. When test interaction styles are ignored, MMPI-2 and Rorschach constructs tend to be uncorrelated, unless a sample just happens to possess a correlation between Rorschach and MMPI-2 stylistic variables. Remaining ambiguities and suggestions for further advances are discussed.