Spatiotemporal prediction of Escherichia coli and Enterococci for the Commonwealth Games triathlon event using Bayesian Networks.

A number of Bayesian Networks were developed in order to nowcast and forecast, up to 4 days ahead and in different locations, the likelihood of water quality within the 2018 Commonwealth Games Triathlon swim course exceeding the critical limits for Enterococci and Escherichia coli. The models are data-driven, but the identification of potential inputs and optimal model structure was performed through the parallel contribution of several stakeholders and experts, consulted through workshops. The models, whose main nodes were discretised with a customised discretisation algorithm, were validated over a test set of data and deployed in real-time during the Commonwealth Games in support to a traditional water quality monitoring program. The proposed modelling framework proved to be cost-effective and less time-consuming than process-based models while still achieving high accuracy; in addition, the added value of a continuous stakeholder engagement guarantees a shared understanding of the model outputs and its future deployment.

Association of tumor-infiltrating lymphocytes with distant disease-free survival in the ShortHER randomized adjuvant trial for patients with early HER2+ breast cancer.

BACKGROUND: There is the need to identify new prognostic markers to refine risk stratification for HER2-positive early breast cancer patients. The aim of this study was to evaluate the association of tumor-infiltrating lymphocytes (TILs) with distant disease-free survival (DDFS) in patients with HER2-positive early breast cancer enrolled in the ShortHER adjuvant trial which compared 9 weeks versus 1-year trastuzumab in addition to chemotherapy, and to test the interaction between TILs and treatment arm. PATIENTS AND METHODS: Stromal TILs were assessed for 866 cases on centralized hematoxylin and eosin-stained tumor slides. The association of TILs as 10% increments with DDFS was assessed with Cox models. Kaplan-Meier curves were estimated for patients with TILs ≥20% and TILs <20%. Median follow-up was 6.1 years. RESULTS: Median TILs was 5% (Q1-Q3 1%-15%). Increased TILs were independently associated with better DDFS in multivariable model [hazard ratio (HR) 0.73, 95% confidence interval (CI) 0.59-0.89, P = 0.006, for each 10% TILs increment]. Five years DDFS rates were 91.1% for patients with TILs <20% and 95.7% for patients with TILs ≥20% (P = 0.025). The association between 10% TILs increments and DDFS was significant for patients randomized to 9 weeks of trastuzumab (HR 0.60, 95% CI 0.41-0.88) but not for patients treated with 1 year of trastuzumab (HR 0.89, 95% CI 0.71-1.12; test for interaction P = 0.088). For patients with TILs <20%, the HR for the comparison between the short versus the long arm was 1.75 (95% CI 1.09-2.80, P=0.021); whereas, for patients with TILs ≥20% the HR for the comparison of short versus long arm was 0.23 (95% CI 0.05-1.09, P = 0.064), resulting in a significant interaction (P = 0.015). CONCLUSIONS: TILs are an independent prognostic factor for HER2-positive early breast cancer patients treated with adjuvant chemotherapy and trastuzumab and may refine the ability to identify patients at low risk of relapse eligible for de-escalated adjuvant therapy.

Nanogrooves and keratin nanofibers on titanium surfaces aimed at driving gingival fibroblasts alignment and proliferation without increasing bacterial adhesion.

Periimplantitis and epithelial downgrowth are nowadays the main conditions associated to transmucosal dental implants. Gingival fibroblasts can play an important role in periimplantitis because they are the promoters of the inflammatory process and eventual tissue homeostasis and destruction. Moreover, the related inflammatory state is commonly driven also to counteract bacteria implants colonization. In the present research, a new technology based on mechanically produced nanogrooves (0.1-0.2µm) and keratin nanofibers deposited by electrospinning has been proposed in order to obtain titanium surfaces able to drive gingival fibroblasts alignment and proliferation without increasing bacterial adhesion. The prepared surfaces have been characterized for their morphology (FESEM), chemical composition (FTIR, XPS), surface charge (zeta potential) and wettability (contact angle). Afterwards, their performances in terms of cells (human primary gingival fibroblasts) and bacteria (Staphylococcus aureus) adhesion were compared to mirror-like polished titanium surfaces. Results revealed that gingival fibroblasts viability was not negatively affected by the applied surface roughness or by keratin nanofibers. On the opposite, cells adhesion and spread were strongly influenced by surface roughness revealing a significant cell orientation along the produced nanogrooves. However, the keratin influence was clearly predominant with respect to surface topography, thus leading to increased cells proliferation on the surfaces with nanofibers, disregarding the presence of the surfaces grooves. Moreover, nor nanogrooves nor keratin nanofibers increase bacterial biofilm adhesion in comparison with mirror polished surfaces. Thus, the present research represents a promising innovative strategy and technology for a surface modification finalized to match the main requirements for transmucosal dental implants.

How do wettability, zeta potential and hydroxylation degree affect the biological response of biomaterials?

It is well known that composition, electric charge, wettability and roughness of implant surfaces have great influence on their interaction with the biological fluids and tissues, but systematic studies of different materials in the same experimental conditions are still lacking in the scientific literature. The aim of this research is to investigate the correlations between some surface characteristics (wettability, zeta potential and hydroxylation degree) and the biological response (protein adsorption, blood wettability, cell and bacterial adhesion) to some model biomaterials. The resulting knowledge can be applied for the development of future innovative surfaces for implantable biomaterials. Roughness was not considered as a variable because it is a widely explored feature: smooth surfaces prepared by a controlled protocol were compared in order to have no roughness effects. Three oxides (ZrO2, Al2O3, SiO2), three metals (316LSS steel, Ti, Nb) and two polymers (corona treated polystyrene for cell culture and untreated polystyrene for bacteria culture), widely used for biomedical applications, were considered. The surfaces were characterized by contact profilometry, SEM-EDS, XPS, FTIR, zeta potential and wettability with different fluids. Protein adsorption, blood wettability, bacterial and cell adhesion were evaluated in order to investigate the correlations between the surface physiochemical properties and biological responses. From a methodological standpoint, XPS and electrokinetic measurements emerged as the more suitable techniques respectively for the evaluation of hydroxylation degree and surface charge/isoelectric point. Moreover, determination of wettability by blood appeared a specific and crucial test, the results of which are not easily predictable by using other type of tests. Hydroxylation degree resulted correlated to the wettability by water, but not directly to surface charge. Wetting tests with different media showed the possibility to highlight some differences among look-alike materials. A dependence of protein absorption on hydroxylation degree, charge and wettability was evidenced and its maximum was registered for surfaces with low wettability in both water based and protein containing media and a moderate surface charge. As far as bacterial adhesion is concerned, no effect of surface charge or protein adsorption was evidenced, while the presence of a high acid component of the surface energy appeared significant. Finally, the combination of hydroxylation degree, wettability, surface charge and energy (polar component) emerged as a key parameter for cell adhesion and viability.

Screening-detected breast carcinoma in a patient with Cowden syndrome.

Cowden syndrome is a hereditary genetic disease whose incidence is still not precisely defined; it is due to a germline mutation in the PTEN gene. We reported a case of breast tumor caused by a PTEN gene mutation, which was detected within a National Screening Program; the diagnosis of Cowden syndrome was made on the basis of patient's particular clinical history. The identification of new genetic mutations has allowed clarification of some of the mechanisms that increase the risk of developing some types of tumors. Furthermore, new kind of mutations recently reported in the literature raise questions about their prognostic significance and how their carriers can be better screened, counseled and managed. These problematic issues will be encountered with increasing frequency in the near future, since many other more mutations are sure to be discovered. The PTEN gene mutation has been implicated in various human tumors, mainly in the breast and the thyroid gland. In the course of a screening program, the early identification of patients affected by a genetic mutation, which is rare, improves the definition of the prognosis and the therapeutic options.

p53 expression and environmental tobacco smoke exposure in feline oral squamous cell carcinoma.

The purpose of this study was to determine the prevalence of p53 overexpression in feline oral squamous cell carcinomas (SCC) and to determine, if any, the association between p53 overexpression and lifestyle factors and environmental exposures, including exposure to environmental tobacco smoke (ETS). Questionnaires concerning exposure to ETS and other environmental factors were sent to owners of cats presenting to the Harrington Oncology Program with a diagnosis of oral SCC between 1991 and 2000. Additionally, 23 formalin-fixed biopsy samples from these cats, with information regarding ETS, were evaluated immunohistochemically for p53 expression using the CM-1 clone and the avidin-biotin-horseradish peroxidase method. Of the 23 samples evaluated, 15 (65%) showed positive nuclear staining for the CM-1 clone. Tumor biopsy samples from cats exposed to any ETS were 4.5 times more likely to overexpress p53 than were tumors from unexposed cats (P = 0.19). Among cats with any ETS exposure, those with 5 years or longer of exposure were 7.0 times more likely to overexpress p53 (P = 0.38). Longhaired cats (P = 0.18) and female cats (P = 0.35) were also more likely to show p53 expression in their tumors. These results provide additional support for a relationship between oral SCC development and exposure to household ETS and may implicate p53 as a potential site for carcinogen-related mutation in this tumor.

Prospective study of recreational physical activity and ovarian cancer.

BACKGROUND: It has been hypothesized that physical activity may reduce the risk of ovarian cancer by decreasing estrogen levels, reducing body fat, and reducing the frequency of ovulation. Epidemiologic studies of this relationship have obtained inconsistent results. The only prospective study to date reported a positive association between frequent vigorous exercise and ovarian cancer risk. We further evaluated this relationship in the Nurses' Health Study cohort. METHODS: Participation in recreational physical activity was assessed by questionnaire in 1980, 1982, 1986, 1988, 1992, and 1994, with questions assessing exercise frequency, duration, and intensity. Results were adjusted for age, parity, oral contraceptive use, tubal ligation, and other risk factors for ovarian cancer. All statistical tests were two-sided. RESULTS: During a 16-year follow-up (from 1980 to 1996), 1.2 million person-years were accrued by 92 825 cohort members, and 377 cases of epithelial ovarian cancer were confirmed. The relative risk (RR) of ovarian cancer for women engaging in recreational physical activity for 7 hours or more per week compared with those reporting less than 1 hour per week was 0.80 (95% confidence interval [CI] = 0.49 to 1.32; P(trend) =.59). When both the frequency and intensity of activity were taken into account, activity level was also not associated with a reduced risk of ovarian cancer. Compared with inactive women, participants reporting high activity in terms of metabolic equivalent task hours (MET hours) were at greater risk of ovarian cancer (RR for 20 to <30 MET hours/week = 1.84 [95% CI = 1.12 to 3.02]; RR for >30 MET hours/week = 1.27 [95% CI = 0.75 to 2.14]). CONCLUSIONS: Overall, results did not suggest an inverse association between recreational physical activity and ovarian cancer. The possibility of a modest increase in risk with frequent vigorous activity requires further investigation.

A population-based case-control study of carotenoid and vitamin A intake and ovarian cancer (United States).

OBJECTIVE: To evaluate the association between dietary intake of carotenoids and vitamin A and the incidence of ovarian cancer. METHODS: We conducted a population-based case-control study of ovarian cancer in Massachusetts and Wisconsin. Incident cases diagnosed between 1991 and 1994 were identified through statewide tumor registries. We selected community controls at random from lists of licensed drivers and Medicare recipients; 327 cases and 3129 controls were included in the analysis. Data were collected by telephone interview, which included an abbreviated food and supplement list to quantify typical consumption of carotenoids (lutein/zeaxanthin, alpha-carotene, beta-carotene), retinol and total vitamin A at 5 years prior to diagnosis in cases, or to a comparable reference date in controls. Results were adjusted for age, state, and other risk factors. RESULTS: Participants with the highest dietary intake of lutein/zeaxanthin (> or =24,000 microg/week) experienced a 40% lower risk of ovarian cancer (95% CI = 0.36-0.99) compared to those with the lowest intake. Intake of alpha-carotene, beta-carotene, retinol and total vitamin A was unrelated to risk. Among foods, we observed non-significantly lower risks with high consumption of spinach, carrots, skim/lowfat milk and liver. CONCLUSION: These results support previous findings suggesting an inverse relationship between carotenoid intake and ovarian cancer risk.

Family history as a risk factor for ulcerative colitis-associated colon cancer in cotton-top tamarin.

BACKGROUND & AIMS: Little is currently known about the relationship between family history of colon cancer and ulcerative colitis-associated colon cancer. A nested case-control study was performed to evaluate the association between family history of colon cancer and spontaneously occurring colon cancer in cotton-top tamarins (Saguinus oedipus). METHODS: Subjects were chosen from a colony of cotton-top tamarins held in captivity between 1968 and 1995. The cancer status of parents and grandparents was compared for 48 animals with colon cancer and 58 controls, all with histological confirmation of ulcerative colitis. Multivariate odds ratios were calculated using logistic regression. RESULTS: A parental history of colon cancer was positively associated with risk of colon cancer (multivariate odds ratio, 2.7; 95% confidence interval, 1.1-6.3). Risk also increased as an animal's total number of family members with colon cancer increased (multivariate odds ratio, 1.7 for each increase in the total number of family members with cancer; 95% confidence interval, 1.1-2.8). CONCLUSIONS: The results suggest that cotton-top tamarins with ulcerative colitis are at significant increased risk for developing colon cancer if they have a family history of colon cancer. Further investigation of this relationship in both tamarins and humans is warranted.

The association between lactation and breast cancer in an international case-control study: a re-analysis by menopausal status.

In the large, hospital-based, international case-control study of breast cancer conducted by MacMahon and colleagues in the 1960s, no protective effect of lactation was observed. However, more recent reports have suggested that such an association may be limited to pre-menopausal women. Therefore, a re-analysis of the data from that original study was performed by menopausal status and with control for additional breast-cancer risk factors since identified. Overall, data from 4,671 parous pre-menopausal and 7,200 parous post-menopausal women were analyzed, from 7 different sites representing areas of high risk (Glamorgan, Wales; Boston, USA), moderate risk (Athens, Greece; Slovenia, ex-Yugoslavia; São Paolo, Brazil), and low risk (Tokyo, Japan; Taipei, Taiwan) of breast cancer. No significant effect of lactation was found for pre-menopausal or post-menopausal women from the high-, moderate-, or low-risk areas; the center-adjusted, combined odds ratio (OR) for having breast-fed was 1.05 (95% confidence interval, 0.86-1.29) among pre-menopausal and 1.04 (0.88-1.24) among post-menopausal women. Moreover, examination of cumulative duration of lactation did not support an inverse association between breast cancer and increased length of total breast-feeding. In conclusion, re-analysis of these data, by menopausal status and adjusting for age at first parity, age at menarche, age at menopause, body-mass index and years of schooling, did not reveal a protective effect of lactation or duration of lactation against breast-cancer occurrence among the pre-menopausal, parous women.

[Comments relating to the psychosexual characteristics of the male transsexual. A clinical study]. / Alcune considerazioni relative alle caratteristiche psicosessuologiche del transessuale maschio. Una ricerca clinica.

In this paper the authors analyse transexualism from a psychopathological, nosographic and clinical point of view. The re-examine the theories on the subjects elaborated by a number of authors and describe the clinical characteristics of the syndrome, paying special attention to problems relating to differential diagnosis. Moreover, they present the results ofa study carried out in a personal series of cases. The sample studied included 11 male transsexual subjects. The latter were evaluated through psychiatric interview and a questionnaire aimed at obtaining information on the following topics: the subjects' social and affective relations; their childhood experience; their perception and acceptance of themselves; the meaning, characteristics, localisation and experience of sexual pleasure. The results are discussed and compared with those of national and international literature on this subjects.