Introduction 1. Woman's Place in Man's Life Cycle 2. Images of Relationship 3. Concepts of Self and Morality 4. Crisis and Transition 5. Women's Rights and Women's Judgment 6. Visions of Maturity References Index of Study Participants General Index

In a Different Voice. Psychological Theory and Women’s Development. Cambridge, MA (Harvard University Press) 1982.

Trust: The Social Virtues and the Creation of Prosperity

Evidence from clinical and experimental studies indicates that macrophages promote solid-tumour progression and metastasis. Macrophages are educated by the tumour microenvironment, so that they adopt a trophic role that facilitates angiogenesis, matrix breakdown and tumour-cell motility — all of which are elements of the metastatic process. During an inflammatory response, macrophages also produce many compounds — ranging from mutagenic oxygen and nitrogen radicals to angiogenic factors — that can contribute to cancer initiation and promotion. Macrophages therefore represent an important drug target for cancer prevention and cure.

Tumour-educated macrophages promote tumour progression and metastasis

1described the presence of cell-free nucleic acid (cfNA) in human blood for the first time. This attracted little attention in the scientific community and it was not until 1994 that the importance of cfNA was recognized as a result of the detection of mutated RAS gene fragments in the blood of cancer patients 2,3 (TIMELINE). In 1996, microsatellite alterations on cell-free DNA (cfDNA) were shown in cancer patients 4

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Cell-free nucleic acids as biomarkers in cancer patients

DNA containing somatic mutations is highly tumor specific and thus, in theory, can provide optimum markers. However, the number of circulating mutant gene fragments is small compared to the number of normal circulating DNA fragments, making it difficult to detect and quantify them with the sensitivity required for meaningful clinical use. We apply a highly sensitive approach to quantify circulating tumor DNA (ctDNA) in body samples of patients. Measurements of ctDNA can be used to reliably monitor tumor dynamics in subjects with cancer, especially those who are undergoing surgery or chemotherapy. This personalized genetic approach can be generally applied.

Circulating Mutant DNA to Assess Tumor Dynamics

Background and study aims Small bowel capsule endoscopy [SBCE) has an established role in investigating suspected small bowel bleeding [SSBB). Identification of a biomarker to predict pathology would maximize utility of this valuable diagnostic modality. This study aimed to investigate if fecal immunochemical test [FIT) could predict likelihood of small bowel pathology on SBCE. Patients and methods Patients referred for SBCE to investigate anaemia or suspected small bowel bleeding were prospectively recruited. All patients had negative upper and lower endoscopy prior to referral. A FIT ≥ 45 ug Hb/g was considered positive. SBCE was positive if a potential source of SSBB was identified. The primary endpoint was correlation between FIT and positive SBCE. Secondary endpoints were correlation between anemia and SBCE and a combination of anemia plus FIT and SBCE. Results Fifty-one patients were included in the final study cohort. 29.4 % had a positive FIT, 33.3 % were anemic, and 25.5 % patients had significant SBCE findings. There was a statistically significant association between positive FIT and pathology on SBCE (OR 12, 95 % CI [2.8 – 51.9), P = 0.001). Sensitivity and specificity of positive FIT in predicting SBCE findings were 69 % and 84 %, respectively. A normal Hb had an NPV of 83 % (OR 0.30, P = 0.09). Combining Hb and FIT was statistically significant in predicting pathology on SBCE (OR 9.14, 67 % PPV, 82 % NPV, P = 0.025). Conclusion FIT ≥ 45 ug Hb/g is a useful tool in predicting small bowel pathology on SBCE. Use of this biomarker alone, or in combination with serum haemoglobin, has value as a screening tool and may help to better triage patients referred for SBCE.

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Predicting pathology on small bowel capsule endoscopy: a good FIT.

Background and study aims The completeness of a polyp resection is an important determinant of quality in colonoscopy, and may reduce incidence of interval cancers. Incomplete resection rates (IRR) vary widely and range from 6.5 % to 22.7 %. Residual disease is more likely with larger polyps, for sessile serrated adenomas, and with more proximal lesions. Chromoendoscopy is increasingly employed in lesion detection. The aims of this study were to assess local IRR, and to determine whether chromoendoscopy could correctly identify residual disease post polypectomy. Patients and methods This was a prospective study examining post polypectomy sites. Chromoendoscopy (0.13 % indigo carmine) was applied to resection bases to identify residual disease. Targeted base biopsies were taken from identified residual disease (positive group) or random base biopsies were taken when a clear base was visualised (negative group). Overall rates of incomplete resection were documented. Reported rates post chromoendoscopy and actual histological rates were documented and compared. Results A total of 102 polyps were identified for inclusion, of which 15 % (n = 16) were excluded. Resection quality was evaluated in 86 polyps of 61 patients (female n = 33 54 %; mean Age 62.3 years). Polyps were mainly removed by cold snare (n = 71, 82.5 %). Most polyps (n = 58, 67 %) measured between 5 to 10 mm. Polyps were largely located in the right colon (n = 57, 66 %). Overall histological residual disease occurred in 17 /86 (19.6 %). Chromoendoscopy correctly identified residual disease in 13 of 17 bases (76.5 %). Only four of /86 (4.6 %) of polyp bases were missclassified post-chromoendoscopy (odds ratio 0.284 (95 % CI 0.0857–0.9409), P = 0.03). Conclusion Indigo carmine chromoendoscopy improves early detection of residual disease post polypectomy, reducing incomplete resection rates.

/pdf/dye-based-chromoendoscopy-following-polypectomy-reduces-37ec3f1lri.pdf

Dye-based chromoendoscopy following polypectomy reduces incomplete polyp resection

In 2010, Ryan and Matheson (2010) compiled evidence to quantify the importance of communication activities to emergency management. The study involved a comprehensive content analysis of emergency incident and emergency exercise debriefing sessions and reports spanning 2003 to 2008. Six years on, this 2015 study replicates that work to determine the current significance of communication in emergency management. It also identifies trends in issues that occur during emergency events. This study considers recommendations and findings from 22 reviews of recent disaster events and training exercises from around Australia. Using content analysis, 20.4 per cent of the findings relate to issues with communicating with communities. This represents an increase of 1.3 per cent on the 2010 study. Resourcing, skills in social media, and community consultation and engagement feature in the study results.

The significance of communication in emergency management: What's changed since 2010?

We present a salutary lesson learned from three cases with significant complications that followed anorectal intervention in the presence of radiation proctitis due to prior radiotherapy for adenocarcinoma of the prostate. After apparent routine rubber band ligation for painful haemorrhoids, one patient developed a colo-cutaneous fistula. Following laser coagulation for radiation proctitis, one patient required a pelvic exenteration for a fistula, while another developed a rectal stenosis. Those diagnosing and treating colonic conditions should be mindful of the increased prevalence of patients who have had radiotherapy for prostate cancer and the potential for complications in treating these patients.

The pitfalls of treating anorectal conditions after radiotherapy for prostate cancer.

Pancreatic ductal adenocarcinoma (PDAC) has a 5-year survival rate below 5%. Carbohydrate antigen 19-9 (CA19-9) is the most commonly used blood-based biomarker for PDAC in current clinical practice, despite having been shown repeatedly to be inaccurate and have poor diagnostic performance. This review aims to assess the reported diagnostic accuracy of all blood-based biomarkers investigated to date in PDAC, by directly comparing individual biomarkers and multi-biomarker panels, both containing CA19-9 and not (novel). A systematic review was conducted in accordance with PRISMA standards in July 2020. Individualized search strategies for three academic databases identified 5,885 studies between the years 1973 and 2020. After two rounds of screening, 250 studies were included. Data were extracted and assessed for bias. A multivariate three-level meta-analysis with subgroup moderators was run in R using AUC values as effect size. On the basis of this model, the pooled AUC value for all multi-biomarker panels (AUC = 0.898; 95% confidence interval (CI): 0.88–0.91) was significantly higher than all single biomarkers (AUC = 0.803; 95% CI: 0.78–0.83; P < 0.0001). The pooled AUC value for CA19-9 alone was significantly lower compared with the multi-biomarker panels containing CA19-9 (P < 0.0001). For the novel biomarkers, the pooled AUC for single biomarkers was also significantly lower compared with multi-biomarker panels (P < 0.0001). Novel biomarkers that have been repeatedly examined across the literature, such as TIMP-1, CEA, and CA125, are highlighted as promising. These results suggest that CA19-9 may be best used as an addition to a panel of biomarkers rather than alone, and that multi-biomarker panels generate the most robust results in blood-based PDAC diagnosis. Significance: In a systematic review and three-level multivariate meta-analysis, it is shown for the first time that blood-based multi-biomarker panels for the diagnosis of PDAC exhibit superior performance in comparison with single biomarkers. CA19-9 is demonstrated to have limited utility alone, and to perform poorly in patient control cohorts of both healthy and benign individuals. Multi-biomarker panels containing CA19-9 produce the best diagnostic performance overall.

https://aacrjournals.org/cancerrescommun/article-pdf/2/10/1229/3214789/crc-22-0190.pdf

Barbara Ryan

Papers

Predicting pathology on small bowel capsule endoscopy: a good FIT.

Dye-based chromoendoscopy following polypectomy reduces incomplete polyp resection

The significance of communication in emergency management: What's changed since 2010?

The pitfalls of treating anorectal conditions after radiotherapy for prostate cancer.

Diagnostic Accuracy of Blood-based Biomarkers for Pancreatic Cancer: A Systematic Review and Meta-analysis