Impact of pretransplant minimal residual disease after cord blood transplantation for childhood acute lymphoblastic leukemia in remission: an Eurocord, PDWP-EBMT analysis

To address the prognostic value of minimal residual disease (MRD) before unrelated cord blood transplantation (UCBT) in children with acute lymphoblastic leukemia (ALL), we analyzed 170 ALL children transplanted in complete remission (CR) after myeloablative conditioning regimen. In all, 72 (43%) were in first CR (CR1), 77 (45%) in second CR (CR2) and 21 (12%) in third CR (CR3). The median interval from MRD quantification to UCBT was 18 days. All patients received single-unit UCBT. Median follow-up was 4 years. Cumulative incidence (CI) of day-60 neutrophil engraftment was 85%. CI of 4 years relapse was 30%, incidence being lower in patients with negative MRD before UCBT (hazard ratio (HR) = 0.4, P = 0.01) and for those transplanted in CR1 and CR2 (HR = 0.3, P = 0.002). Probability of 4 years leukemia-free survival (LFS) was 44%, (56, 44 and 14% for patients transplanted in CR1, CR2 and CR3, respectively (P = 0.0001)). Patients with negative MRD before UCBT had better LFS after UCBT compared with those with positive MRD (54% vs 29%; HR = 2, P = 0.003). MRD assessment before UCBT for children with ALL in remission allows identifying patients at higher risk of relapse after transplantation. Approaches that may decrease relapse incidence in children given UCBT with positive MRD should be investigated to improve final outcomes. Leukemia (2012) 26, 2455-2461; doi:10.1038/leu.2012.123

Farm tourism: a cross-country empirical study in Germany and Italy

PROBLEM In the last few years farm tourism or agritourism as it is also referred to has enjoyed increasing success because of its generally acknowledged role as a promoter of economic and social development of rural areas. As a consequence, a plethora of studies have been dedicated to this tourist sector, focusing on a variety of issues. Nevertheless, despite the difficulties of many farmers to orient their business towards potential customers, the contribution of the marketing literature has been moderate. PURPOSE This dissertation builds upon studies which advocate the necessity of farm tourism to innovate itself according to the increasingly demanding needs of customers. Henceforth, the purpose of this dissertation is to critically evaluate the level of professionalism reached in the farm tourism market within a marketing approach. METHODOLOGY This dissertation is a cross-country perspective incorporating the marketing of farm tourism studied in Germany and Italy. Hence, the marketing channels of this tourist sector are examined both from the supply and the demand side by means of five exploratory studies. The data collection has been conducted in the timeframe of 2006 to 2009 in manifold ways (online survey, catalogues of industry associations, face-to-face interviews, etc.) according to the purpose of the research of each study project. The data have been analyzed using multivariate statistical analysis. FINDINGS A comprehensive literature review provides the state of the art of the main differences and similarities of farm tourism in the two countries of study. The main findings contained in the empirical chapters provide insights on many aspects of agritourism including how the expectations of farm operators and customers differ, which development scenarios of farm tourism are more likely to meet individuals’ needs, how new technologies can impact the demand for farm tourism, etc. ORIGINALITY/VALUE The value of this study is in the investigation of the process by which farmers’ participation in the development of this sector intersects with consumer consumption patterns. Focusing on this process should allow farm operators and others including related businesses to more efficiently allocate resources.

Analysis of the Slow Food movement impact on the farmers and rural areas’ sustainable development

The evaluation of the farmers’ communities’ approach to the Slow Food vision, their perception of the Slow Food role in supporting their activity and their appreciation and expectations from participating in the event of Mother Earth were studied. The Unified Theory of Acceptance and Use of Technology (UTAUT) model was adopted in an agro-food sector context. A survey was conducted, 120 questionnaires from farmers attending the Mother Earth in Turin in 2010 were collected. The descriptive statistical analysis showed that both Slow Food membership and participation to Mother Earth Meeting were much appreciated for the support provided to their business and the contribution to a more sustainable and fair development. A positive social, environmental and psychological impact on farmers also resulted. Results showed also an interesting perspective on the possible universality of the Slow Food and Mother Earth values. Farmers declared that Slow Food is supporting them by preserving the biodiversity and orienting them to the use of local resources and reducing the chemical inputs. Many farmers mentioned the language/culture and administration/bureaucratic issues as an obstacle to be a member in the movement and to participate to the event. Participation to Mother Earth gives an opportunity to exchange information with other farmers’ communities and to participate to seminars and debates, helpful for their business development. The absolute majority of positive answers associated to the farmers’ willingness to relate to Slow Food and participate to the next Mother Earth editions negatively influenced the UTAUT model results. A factor analysis showed that the variables associated to the UTAUT model constructs Performance Expectancy and Effort Expectancy were consistent, able to explain the construct variability, and their measurement reliable. Their inclusion in a simplest Technology Acceptance Model could be considered in future researches.

Entrepreneurship influential factors in development of rural tourism as diversified rural activity in Republic of Macedonia

Rural tourism is relatively new product in the process of diversification of the rural economy in Republic of Macedonia. This study used desk research and life story interviews of rural tourism entrepreneurs as qualitative research method to identify prevalent success influential factors. Further quantitative analysis was applied in order to measure the strength of influence of identified success factors. The primary data for the quantitative research was gathered using telephone questionnaire composed of 37 questions with 5-points Likert scale. The data was analyzed using Partial Least Squares Structural Equation Modeling (PLS-SEM) by SmartPLS 3.1.6. Results indicated that human capital, social capital, entrepreneurial personality and external business environment are predominant influential success factors. However, human capital has non-significant direct effect on success (p 0.493) nonetheless the effect was indirect with high level of partial mediation through entrepreneurial personality as mediator (VAF 73%). Personality of the entrepreneur, social capital and business environment have direct positive affect on entrepreneurial success (p 0.001, 0.003 and 0.045 respectably). Personality also mediates the positive effect of social capital on entrepreneurial success (VAF 28%). Opposite to the theory the data showed no interaction between social and human capital on the entrepreneurial success. This research suggests that rural tourism accommodation entrepreneurs could be more successful if there is increased support in development of social capital in form of conservation of cultural heritage and natural attractions. Priority should be finding the form to encourage and support the establishment of formal and informal associations of entrepreneurs in order to improve the conditions for management and marketing of the sector. Special support of family businesses in the early stages of the operation would have a particularly positive impact on the success of rural tourism. Local infrastructure, access to financial instruments, destination marketing and entrepreneurial personality have positive effect on success.

The role of language in tv shows and its impact on the audience: A linguistic analysis of Game of Thrones

Through the analysis of American TV show Game of Thrones, this dissertation will focus on the linguistic issues concerning the adaptation from books to television, the power of language over the audience, and the creation of two languages, with all the linguistic and cultural implications related to this phenomenon.

Desmosomal gene analysis in arrhythmogenic right ventricular dysplasia/cardiomyopathy: spectrum of mutations and clinical impact in practice

Five desmosomal genes have been recently implicated in arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) but the clinical impact of genetics remains poorly understood. We wanted to address the potential impact of genotyping.

Impact of treatment characteristics on response of different breast cancer phenotypes: pooled analysis of the German neo-adjuvant chemotherapy trials

Pathological complete response (pCR) to neoadjuvant treatment correlates with outcome in breast cancer. We determined whether characteristics of neoadjuvant therapy are associated with pCR. We used multi-level models, which accounted for heterogeneity in pCR across trials and trial arms, to analyze individual patient data from 3332 women included in 7 German neoadjuvant trials with uniform protocols. PCR was associated with an increase in number of chemotherapy cycles (odds ratio [OR] 1.2 for every two additional cycles; P = 0.009), with higher cumulative anthracycline doses (OR 1.6; P = 0.002), higher cumulative taxane doses (OR 1.6; P = 0.009), and with capecitabine containing regimens (OR 1.62; P = 0.022). Association of pCR with increase in number of cycles appeared more pronounced in hormone receptor (HR)-positive tumors (OR 1.35) than in HR-negative tumors (OR 1.04; P for interaction = 0.046). Effect of anthracycline dose was particularly pronounced in HER2-negative tumors (OR 1.61), compared to HER2-positive tumors (OR 0.83; P for interaction = 0.14). Simultaneous trastuzumab treatment in HER2-positive tumors increased odds of pCR 3.2-fold (P < 0.001). No association of pCR and number of trastuzumab cycles was found (OR 1.20, P = 0.39). Dosing characteristics appear important for successful treatment of breast cancer. Longer treatment, higher cumulative doses of anthracyclines and taxanes, and the addition of capecitabine and trastuzumab are associated with better response. Tailoring according to breast cancer phenotype might be possible: longer treatment in HR-positive tumors, higher cumulative anthracycline doses for HER2-negative tumors, shorter treatment at higher cumulative doses for triple-negative tumors, and limited number of preoperative trastuzumab cycles in HER2-positive tumors.

The impact of frozen sections on final surgical margins in squamous cell carcinoma of the oral cavity and lips: a retrospective analysis over an 11 years period

Taking intraoperative frozen sections (FS) is a widely used procedure in oncologic surgery. However so far no evidence of an association of FS analysis and premalignant changes in the surgical margin exists. Therefore, the aim of this study was to evaluate the impact of FS on different categories of the final margins of squamous cell carcinoma (SCC) of the oral cavity and lips.

Treatment failure in pneumonia: Impact of antibiotic treatment and cost analysis

The aim of this study was to investigate treatment failure (TF) in hospitalised community-acquired pneumonia (CAP) patients with regard to initial antibiotic treatment and economic impact. CAP patients were included in two open, prospective multicentre studies assessing the direct costs for in-patient treatment. Patients received treatment either with moxifloxacin (MFX) or a nonstandardised antibiotic therapy. Any change in antibiotic therapy after >72 h of treatment to a broadened antibiotic spectrum was considered as TF. Overall, 1,236 patients (mean ± SD age 69.6 ± 16.8 yrs, 691 (55.9%) male) were included. TF occurred in 197 (15.9%) subjects and led to longer hospital stay (15.4 ± 7.3 days versus 9.8 ± 4.2 days; p < 0.001) and increased median treatment costs (€2,206 versus €1,284; p<0.001). 596 (48.2%) patients received MFX and witnessed less TF (10.9% versus 20.6%; p < 0.001). After controlling for confounders in multivariate analysis, adjusted risk of TF was clearly reduced in MFX as compared with β-lactam monotherapy (adjusted OR for MFX 0.43, 95% CI 0.27-0.68) and was more comparable with a β-lactam plus macrolide combination (BLM) (OR 0.68, 95% CI 0.38-1.21). In hospitalised CAP, TF is frequent and leads to prolonged hospital stay and increased treatment costs. Initial treatment with MFX or BLM is a possible strategy to prevent TF, and may thus reduce treatment costs.

A patient-level pooled analysis assessing the impact of the SYNTAX (synergy between percutaneous coronary intervention with taxus and cardiac surgery) score on 1-year clinical outcomes in 6,508 patients enrolled in contemporary coronary stent trials

This study sought to assess the impact of the SYNTAX (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery) score (SXscore) on clinical outcomes in patients undergoing percutaneous coronary intervention.

Urban Expansion and its impact on urban agriculture - remote sensing based change analysis of Kizinga and Mzinga Valley - Dar Es Salaam, Tanzania

Urban agriculture is a phenomenon that can be observed world-wide, particularly in cities of devel- oping countries. It is contributing significantly to food security and food safety and has sustained livelihood of the urban and peri-urban low income dwe llers in developing countries for many years. Population increase due to rural-urban migration and natural - formal as well as informal - urbani- sation are competing with urban farming for available space and scarce water resources. A mul- titemporal and multisensoral urban change analysis over the period of 25 years (1982-2007) was performed in order to measure and visualise the urban expansion along the Kizinga and Mzinga valley in the south of Dar Es Salaam. Airphotos and VHR satellite data were analysed by using a combination of a composition of anisotropic textural measures and spectral information. The study revealed that unplanned built-up area is expanding continuously, and vegetation covers and agricultural lands decline at a fast rate. The validation showed that the overall classification accuracy varied depending on the database. The extracted built-up areas were used for visual in- terpretation mapping purposes and served as information source for another research project. The maps visualise an urban congestion and expansion of nearly 18% of the total analysed area that had taken place in the Kizinga valley between 1982 and 2007. The same development can be ob- served in the less developed and more remote Mzinga valley between 1981 and 2002. Both areas underwent fast changes where land prices still tend to go up and an influx of people both from rural and urban areas continuously increase the density with the consequence of increasing multiple land use interests.

Characterization of CDKN2A(p16) methylation and impact in colorectal cancer: systematic analysis using pyrosequencing

Background The aim of this study is to analyse CDKN2A methylation using pyrosequencing on a large cohort of colorectal cancers and corresponding non-neoplastic tissues. In a second step, the effect of methylation on clinical outcome is addressed. Methods Primary colorectal cancers and matched non-neoplastic tissues from 432 patients underwent CDKN2A methylation analysis by pyrosequencing (PyroMarkQ96). Methylation was then related to clinical outcome, microsatellite instability (MSI), and BRAF and KRAS mutation. Different amplification conditions (35 to 50 PCR cycles) using a range of 0-100% methylated DNA were tested. Results Background methylation was at most 10% with ≥35 PCR cycles. Correlation of observed and expected values was high, even at low methylation levels (0.02%, 0.6%, 2%). Accuracy of detection was optimal with 45 PCR cycles. Methylation in normal mucosa ranged from 0 to >90% in some cases. Based on the maximum value of 10% background, positivity was defined as a ≥20% difference in methylation between tumor and normal tissue, which occurred in 87 cases. CDKN2A methylation positivity was associated with MSI (p = 0.025), BRAF mutation (p < 0.0001), higher tumor grade (p < 0.0001), mucinous histology (p = 0.0209) but not with KRAS mutation. CDKN2A methylation had an independent adverse effect (p = 0.0058) on prognosis. Conclusion The non-negligible CDKN2A methylation of normal colorectal mucosa may confound the assessment of tumor-specific hypermethylation, suggesting that corresponding non-neoplastic tissue should be used as a control. CDKN2A methylation is robustly detected by pyrosequencing, even at low levels, suggesting that this unfavorable prognostic biomarker warrants investigation in prospective studies.

Impact of age and comorbidities on long-term survival of patients with high-risk prostate cancer treated with radical prostatectomy: a multi-institutional competing-risks analysis

Survival after surgical treatment using competing-risk analysis has been previously examined in patients with prostate cancer (PCa). However, the combined effect of age and comorbidities has not been assessed in patients with high-risk PCa who might have heterogeneous rates of competing mortality despite the presence of aggressive disease.