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When the United Nations Universal Periodic Review was established in 2007, it was stressed that it should complement the work of the United Nations treaty bodies. At the same time, fears were expressed that similarities between the two procedures might lead to potentially problematic duplications or contradictions among them. To shed light on whether this is the case, this article devises a framework to assess the degree to which human rights bodies provide duplicating or contradicting recommendations to States. Focusing on the case of torture, it creates an original database of recommendations delivered to 14 countries in the years 2012–2016. Results show that duplications are frequent and provide opportunities to States to use the Universal Periodic Review to contest the implementation of treaty bodies’ recommendations. Contradictions are limited, although when they occur, they create room for States to selectively choose which recommendations to implement.

I read Rossetto and Lo Presti's article, ‘Reimagining the National Map’, as an invitation to develop what I call, following Eve Sedgwick, a reparative study of national cartographies. In this commentary, I enthusiastically support their call but also argue for the need to move from an appreciation of maps’ fundamental instability to a more daring engagement with the normative dimension of national mapping. Like many scholars working from a post-representational perspective, Rossetto and Lo Presti associate the fundamental dynamism and contingency of maps with (potential) positive social change and, more specifically, the development of multicultural national imaginaries. I suggest that these associations deserve further scrutiny and argue that change and ‘everydayness’ may offer a starting point, but not a basis for progressive national mappings. Finally, drawing on the thought-provoking examples presented by Rossetto and Lo Presti, I reflect on what principles and practices could guide a progressive national cartography of Italy in 2021.

PurposeThe authors use media research and crowdsourced mapping to document how the first wave of the pandemic (April–August 2020) affected the Mapuche, focussing on seven categories of events: territorial control, spiritual defence, food sovereignty, traditional health practices, political violence, territorial needs and solidarity, and extractivist expansion.Design/methodology/approachResearch on the effects of the pandemic on the Mapuche and their territories is lacking; the few existing studies focus on death and infection rates but overlook how the pandemic interacts with ongoing processes of extractivism, state violence and community resistance. The authors’ pilot study addresses this gap through a map developed collaboratively by disaster scholars and Mapuche journalists.FindingsThe map provides a spatial and chronological overview of this period, highlighting the interconnections between the pandemic and neocolonialism. As examples, the authors focus on two phenomena: the creation of “health barriers” to ensure local territorial control and the state-supported expansion of extractive industries during the first months of the lockdown.Research limitations/implicationsThe authors intersperse our account of the project with reflections on its limitations and, specifically, on how colonial formations shape the research. Decolonising disaster studies and disaster risk reduction practice, the authors argue, is an ongoing process, bound to be flawed and incomplete but nevertheless an urgent pursuit.Originality/valueIn making this argument, the paper responds to the Disaster Studies Manifesto that inspires this special issue, taking up its invitation to scholars to be more reflexive about their research practice and to frame their investigations through grounded perspectives.

ObjectiveTo date, no useful prognostic biomarker exists for patients with oral squamous cell carcinoma (OCSCC), a tumour with uncertain biological behaviour and subsequent unpredictable clinical course. We aim to investigate the prognostic significance of two recurrent somatic mutations (-124 C>T and -146 C>T) within the promoter of telomerase reverse transcriptase (TERT) gene and the impact of TERT single nucleotide polymorphism (SNP) rs2853669 in patients surgically treated for OCSCC.MethodsThe genetic frequencies of rs2853669, -124 C>T and -146 C>T as well as the telomere length were investigated in 144 tumours and 57 normal adjacent mucosal (AM) specimens from OCSCC patients.ResultsForty-five tumours harboured TERT promoter mutations (31.3%), with -124 C>T and -146 C>T accounting for 64.4% and 35.6% of the alterations respectively. Patients with -124 C>T TERT promoter mutated tumours had the shortest telomeres in the AM (p=0.016) and showed higher risk of local recurrence (hazard ratio [HR]:2.75, p=0.0143), death (HR:2.71, p=0.0079) and disease progression (HR:2.71, p=0.0024) with the effect being potentiated by the co-occurrence of T/T genotype of rs2853669.Conclusion-124 C>T TERT promoter mutation as well as the T/T genotype of the rs2853669 SNP are attractive independent prognostic biomarkers in patients surgically treated for OCSCC, with the coexistence of these genetic variants showing a synergistic impact on the aggressiveness of the disease.

This paper presents a comparative study of the Waze avoid areas (WADA) feature in Jerusalem, Rio de Janeiro, and the US. I argue that, through comparative approaches, geographers can ‘ground’ the digital, developing situated accounts of how emerging technologies work at different sites. Taking as a starting point the controversies raised by WADA, I address the following research questions: How does the feature work in the three research sites? What political problems does it raise? What are its effects? Drawing on 124 news articles, blog posts and forum threads in English, Arabic, Hebrew and Portuguese, the analysis complicates existing characterisations of similar apps as emblematic of the smart city’s most oppressive characteristics, pointing at three themes: the relevance of local settings in the enactment of WADA, the interplay of different logics in its definition of danger, and the heterogeneity of public reactions to the app. More broadly, the study demonstrates that grounded comparative studies can decentre and enrich the scholarship on digital geographies, underscoring the contingency and ambivalence of digital technologies.

Carcinosarcomas are rare, highly aggressive neoplasms composed of a combination of carcinomatous and sarcomatous elements. These tumors represent a paradigmatic field for the study of intratumor heterogeneity. A series of 8 tubo-ovarian carcinosarcomas was characterized for the following: (i) immunohistochemical expression of MNF116, epithelial membrane antigen, vimentin, S100, chromogranin, synaptophysin, desmin, myogenin (MYF4), and p53; (ii) mutational profiling of KRAS, BRAF, PIK3CA, NRAS, TP53, and DICER1 genes. Heterologous differentiation was present in 6 of 8 tumors. Cytokeratin MNF116 and epithelial membrane antigen were positive in all the carcinomatous components and in 87.5% and 50.0% of the sarcomatous components, respectively. The sarcomatous components showed positive staining for vimentin in all cases. Two cases demonstrated positivity for neuroendocrine markers in their carcinomatous components. All rhabdomyosarcomas were positive for desmin and MYF-4. Chondrosarcomas were positive for S100. All but one tumor showed similar p53 immunoreactivity in both the carcinomatous and sarcomatous components, and one case showed cytoplasmic p53 expression. Three of 8 cases (37.5%) showed TP53 mutations, and, in 2 cases, the TP53 mutation was shared by both epithelial and mesenchymal components. DICER1 mutation was found in all components of one case. Mutations in KRAS, NRAS, BRAF, and PIK3CA genes were not found in the study cohort. Our results highlight the heterogeneity of ovarian carcinosarcomas at the phenotypic level. A common mutational signature was observed in both components in 3 of 4 informative tumors. More studies are required to dissect different levels of ovarian carcinosarcomas' heterogeneity in order to define the best therapeutic approaches to these aggressive neoplasms.

AIMS In chronic rhinosinusitis with nasal polyps (CRSwNP), tools based on objective evidence, such as histopathology, are needed to assist clinical decision-making. The main aim of this exploratory investigation was to determine whether structured histopathology could be used to classify CRSwNP in homogeneous histological clusters. METHODS AND RESULTS A cohort of 135 CRSwNP patients was assessed, on the basis of clinicopathological features: allergic fungal rhinosinusitis (17 patients); non-steroidal anti-inflammatory drug-exacerbated respiratory disease (19 patients); intrinsic asthma (18 patients); extrinsic asthma (21 patients); allergy (21 patients); histologically eosinophilic (22 patients); and histologically non-eosinophilic (17 patients). For structured histopathology, we considered: the degree of inflammation; eosinophil count; eosinophil aggregates; neutrophil infiltration; goblet cell hyperplasia; basement membrane thickening; fibrosis; hyperplastic/papillary changes; squamous metaplasia; mucosal ulceration; and subepithelial oedema. Cluster analysis identified four distinct sets of cases. On discriminant analysis, the global error rate was 1.48%, and the stratified error rates were 4.34%, 0%, 0%, and 0% for clusters 1, 2, 3 and 4, respectively. Cluster 1 was characterised by infrequent fibrosis (

Independent experts are employed in international organizations to carry out a variety of functions, including conducting independent evaluations of state performance in a given policy area. In the field of human rights, a well-known example of the use of independent expertise in public organizations is that of the United Nations treaty bodies, committees of independent experts in charge of monitoring state compliance with the major United Nations human rights treaties. Considering the sensitive tasks that these experts perform, and the fact that they are elected by states, the question of whether they actually possess the required levels of independence and expertise to fulfil their role arises. This article proposes and applies a framework to study the formal and informal processes leading to the appointment of expert committees in international bodies, and to assess their level of expertise and independence. Data were collected by means of an original survey and 40 semi-structured interviews. The article shows that the overall level of independent expertise possessed by committees is surprisingly high when considering the highly political electoral process. Therefore, it argues that to study the expertise and independence of expert committees, one should conceive of them as groups that might be able to maintain a certain independence from the states that have elected them.

The consumption of fresh or RTE fruits is increasing every year and Listeria monocytogenes has been identified on raw or minimally processed fruits. A food product can become contaminated with L. monocytogenes anywhere along the pathway of food production during planting, harvesting, packaging, distribution and serving. The aim of this work was to assess the microbiological risks associated with consumption of ready- to- eat fruit such as melon, pineapple, coconut and fruit salad. The presence of Escherichia coli, Salmonella spp. and L. monocytogenes was also evaluated. Microbiological challenge tests were carried out for the evaluation of the L. monocytogenes growth potential in RTE fruit stored at 4 and 8°C. E. coli counts resulted under the detection limit of 10 CFU g-1, Salmonella and L. monocytogenes were not detected (absence in 25g). The growth potential values in coconut and melon (δ>0.5) showed the growth capacity of Listeria at the temperatures considered. A low initial load, also derived from good hygiene practices, and correct storage temperatures are essential to reduce bacterial growth in RTE fruit. The challenge test showed how each type of RTE fruit has a different commercial life based on its specific growth potential and that food should be stored at temperatures not higher than 4°C for a short period.

The consumption of fresh or RTE fruits is increasing every year and Listeria monocytogenes has been identified on raw or minimally processed fruits. A food product can become contaminated with L. monocytogenes anywhere along the pathway of food production during planting, harvesting, packaging, distribution and serving. The aim of this work was to assess the microbiological risks associated with consumption of ready- to- eat fruit such as melon, pineapple, coconut and fruit salad. The presence of Escherichia coli, Salmonella spp. and L. monocytogenes was also evaluated. Microbiological challenge tests were carried out for the evaluation of the L. monocytogenes growth potential in RTE fruit stored at 4 and 8°C. E. coli counts resulted under the detection limit of 10 CFU g-1, Salmonella and L. monocytogenes were not detected (absence in 25g). The growth potential values in coconut and melon (δ>0.5) showed the growth capacity of Listeria at the temperatures considered. A low initial load, also derived from good hygiene practices, and correct storage temperatures are essential to reduce bacterial growth in RTE fruit. The challenge test showed how each type of RTE fruit has a different commercial life based on its specific growth potential and that food should be stored at temperatures not higher than 4°C for a short period.

In this chapter, I consider how Google assembles its maps from many sources, using algorithms and, occasionally, a set of loose norms, to decide which information to foreground for which users. This process goes largely unnoticed, but glitches such as the 2016 erasure of Palestine from Google Maps can cause users to notice and question Google’s cartographic choices. Furthermore, in this case, the ‘gap in the map’ was taken up on Twitter by Palestinians abroad, allowing the performance of a national public outside the Israel/Palestine territory, in a curious twist of the historical relation between cartography and state-building. This episode demonstrates that maps continue to play an important role in supporting national imaginaries, albeit in distinctively postmodern ways.

El marco normativo de planificación urbana exige la presentación de un estudio de riesgo en apoyo a la elaboración de los instrumentos de planificación territorial (IPT), pero no establecen su contenido ni su metodología. Estos estudios, generalmente elaborados por consultoras convocadas a través de procesos de licitación, tienden a centrarse en acontecimientos pasados y en las características geomorfológicas locales, prestando escasa atención al entorno construido y a las dinámicas sociales. A pesar de la incorporación de mecanismos de participación ciudadana a lo largo de elaboración de los IPT, y específicamente en lo relativo a los estudios de riesgo, la participación ciudadana es superficial y se relaciona directamente a información y consulta pública, dejando de lado aspectos ligados a la incorporación del conocimiento local y la co-construcción de saberes, limitando una planificación territorial y gobernanza para la reducción del riesgo de desastres (RRD) basada en el lugar. En este contexto, y sobre la base de la experiencia de CIGIDEN, planteamos tres recomendaciones metodológicas: 1) la definición normativa de riesgo debería modificarse para reconocer la importancia de las dinámicas sociales y del entorno construido 2) la ciudadanía debería participar directamente en la elaboración de los estudios del riesgo, específicamente en lo relativo a la evaluación de la vulnerabilidad 3) las autoridades nacionales encargadas de la planificación territorial (MINVU) y de la reducción del riesgo de desastres (ONEMI) deberían proporcionar directrices metodológicas claras y vinculantes para los estudios de riesgo, además de capacitación a los funcionarios municipales y a los profesionales de la planificación territorial. Sugerimos que el mapeo colectivo puede facilitar significativamente estos objetivos.

Dynamic, multidirectional and data-driven, digital mappings blur the distinction between maps and mapped worlds. A critical cartography for the digital age should approach maps as lively matters that change as they interact with users and non-users, other (digital) media, places and events. It should also attend, however, to the durable processes of symbolic and material differentiation enacted through mapping, questioning who benefits and who loses from current arrangements. To this end, I approach maps as matters of care that need to be assembled. Empirically, I take as a starting point the mapping controversies surrounding three major map providers (Waze, Google Maps and OpenStreetMap) and connect them to produce an alternative account of mapping politics in Jerusalem.

Waze is a navigation app that provides routing, as well as information about traffic, road closures and fuel prices, among other things. In Israel/Palestine, it also offers an ‘avoid dangerous areas’ feature that allows users to avoid Palestinian areas. In this chapter, I examine the debates and controversies generated by this function. While critics from the US have accused similar apps of reproducing spatial segregation based on race and class, I argue that, in Jerusalem, ‘social mixing’ is ruled out by the political situation and, above all, by a pervasive bordering system made up of differentiated IDs, segregated roads, road closures and checkpoints. In this context, Waze’s main effect is to highlight the crucial discrepancy that exists between a spatial and ethnic definition of Israel.

An introduction to the recent history of Jerusalem, underscoring the role of cartography. Here, I explore how maps have been used to support the Zionist project, both symbolically (by presenting Palestine as a land without a people) and materially (by facilitating military expansion and civic administration). I also highlight key technological and social transformations undergone by cartography in recent decades. While it would be naive to think new technologies make maps any less political, my argument is that—in Jerusalem as elsewhere—there is a need to investigate their characteristics and effects. Do web maps ‘repackage’ the same substance in a new form, or do they bring about genuine change, for better (more democratic) or for worse (less transparent)?

This paper examines the links between neoliberal urbanism and disaster vulnerability in Cartagena, a town on the Chilean central coast. In recent decades, this area has been transformed by speculative urban development, resulting in environmental damage and increased socio-economic segregation. We adopt a political ecology perspective to consider how these changes interact with disaster risk, drawing on ten interviews with representatives of local community organisations, a collaborative mapping exercise and census data. We find that mass tourism and informal urban expansion contribute to environmental degradation, as well as infrastructural and economic fragility, leading to increased risks for residents and tourists alike. We position our case study against the critiques of vulnerability leveraged by several critical geographers, who have come to see the term as depoliticising. While sympathising with these critiques, we argue for the usefulness of vulnerability analyses combining political ecology approaches to the study of human-nature relations and insight from critical urban studies on issues such as neoliberal planning policies, extractivism, urban informality and touristification. Articulated in these terms, vulnerability can be usefully mobilised to push for substantive policy change.

In this chapter, I discuss the politics of toponomy in Jerusalem on OpenStreetMap, a collaborative mapping platform that, despite being ostensibly open to contributions from everyone, offers a surprisingly one-sided representation of Jerusalem. The absence of Palestinian names from the map could be interpreted as an objective reflection of reality ‘on the ground’, or a sign that Palestinian views continue to be excluded and erased. Instead, drawing on my experience working for Grassroots Jerusalem and on an analysis of historical sources, I argue that they point to ongoing confrontations over both the purpose of mapping and the city’s identity. Through its mapping standards, OpenStreetMap intervenes on these confrontations in ways that tend to consolidate the municipality’s naming power, but also to show its limits.

Breast cancer evolves thanks to a dense and close interaction with the surrounding tumor microenvironment (TME). Fibroblasts, leukocytes, blood and lymphatic endothelial cells and extracellular matrix are the constituents of this entity, and they synergistically play a pivotal role in all of the stages of breast cancer development, from its onset to its metastatic spread. Moreover, it has been widely demonstrated that variations to the TME can correspond to prognosis variations. Breast cancer not only modulates the transformation of the environment within the mammary gland, but the same process is observed in metastases as well. In this minireview, we describe the features of TME within the primitive breast cancer, throughout its evolution and spread into the main metastatic sites.

The consumption of fresh or RTE fruits is increasing every year and Listeria monocytogenes has been identified on raw or minimally processed fruits. A food product can become contaminated with L. monocytogenes anywhere along the pathway of food production during planting, harvesting, packaging, distribution and serving. The aim of this work was to assess the microbiological risks associated with consumption of ready- to- eat fruit such as melon, pineapple, coconut and fruit salad. The presence of Escherichia coli, Salmonella spp. and L. monocytogenes was also evaluated. Microbiological challenge tests were carried out for the evaluation of the L. monocytogenes growth potential in RTE fruit stored at 4 and 8°C. E. coli counts resulted under the detection limit of 10 CFU g-1, Salmonella and L. monocytogenes were not detected (absence in 25g). The growth potential values in coconut and melon (δ>0.5) showed the growth capacity of Listeria at the temperatures considered. A low initial load, also derived from good hygiene practices, and correct storage temperatures are essential to reduce bacterial growth in RTE fruit. The challenge test showed how each type of RTE fruit has a different commercial life based on its specific growth potential and that food should be stored at temperatures not higher than 4°C for a short period.

Background paper commissioned by the United Nations High-Level Panel on Financial Accountability, Transparency and Integrity for Achieving the 2030 Agenda.

Ensuring the microbiological quality of textiles is an important requirement for health care facilities. The present study examines the way transport times and temperatures influence microbial growth in textiles. Therefore, the effectiveness of washing and disinfection processes has also been studied.Microbial Challenge Tests were set up through the artificial contamination of different dry and wet textiles which were stored at different temperatures. The bacterial concentration was evaluated in well-defined time phases aimed at simulating the time it took for the textiles to be transported from the hospital facilities to the reconditioning unit. Three times were therefore considered from T = 0 inoculation moment to T = 72 h post inoculation. At the end of each time, the increase in bacterial concentration was assessed by means of microbiological cultures, using selective media for the enumeration of each type of inoculated microorganism.In all the contaminated textiles the bacterial concentration remained unchanged at a temperature of 4 °C, while at 22 °C and 37 °C there was a significant increase (p 0.05) starting from 8 h of storage. In these textiles, the microorganism that showed the greatest growth capacity was P. aeruginosa with average initial concentration values of 10The data highlights the fact that the degree of contamination in textiles does not undergo an increase when transport takes place at a controlled temperature. Refrigerated transport of hospital textiles is thus a desirable preventive measure to keep microbiological risk under control.

Although transparency is frequently employed to enhance the legitimacy of public organizations, several scholars point to its potentially negative implications. This study analyzes the impact of transparency on the authority of peer reviews in international organizations. Authority, here conceived as rooted in legitimacy beliefs, is crucial for peer reviews to produce effects. This research is based on results from an online survey and forty-three interviews with actors involved in two United Nations peer reviews: the Universal Periodic Review in human rights and the Implementation Review Mechanism in the fight against corruption. The article shows that transparency positively affects the perceived development of pressure, yet negatively influences mutual learning and appears to be unable to ensure equal treatment of states.

This paper contributes to the literature on participation and marginality on the geoweb by exploring the politics of non-mapping on OpenStreetMap (OSM). To this end, we reflect on our collaboration with Grassroots Jerusalem (GJ) – a Jerusalem-based Palestinian non-governmental organization (NGO) – and their engagement with OSM. Specifically, we draw on observations from mapping workshops with Palestinian youth, and on the analysis of GJ’s involvement in the dispute about the name ‘Jerusalem’ on OSM. We address the following research questions: How should we understand Palestinian underrepresentation on OpenStreetMap? What does this imply for the conceptualisation of participation and marginality in the geoweb literature? We suggest that the underrepresentation of Palestinian mappers stems in part from the project's technical and linguistic barriers, and in part from a deliberate 'exit' tactic linked to Palestinian anti-normalisation efforts. These findings challenge prevailing understandings of (non)participation as the product of exclusion alone, and indicate that geoweb scholars should pay greater attention to non-users, and their engagements with crowdsourced projects from an outsider position.

Trihalomethanes (THMs) – CHCl3, CHCl2Br, CHClBr2 and CHBr3 – are drinking water disinfection by-products (DBPs). These compounds can also be absorbed by different types of foods, including ready-to...

Spindle cell oncocytoma (SCO) is a rare pituitary tumor, classified as a WHO grade I neoplasm. Due to its rarity, SCO is often preoperatively misdiagnosed as a pituitary macroadenoma. In the present study we report two recent cases of SCO, a 61-year-old male and a 65-year-old female presenting at Treviso General Hospital between March 2014 and April 2015. Tumor resection was achieved by endoscopic transsphenoidal approach but massive hemorrhagic events hampered surgery, endangering the patient's life in both cases. Both tumors featured fascicles of spindle cells with eosiniphilic cytoplasm expressing vimentin, S-100 and thyroid transcription factor-1 (TTF-1). The diagnosis of SCO was confirmed by second opinion in both cases. Extensive review of available literature, about 30 cases from 2002 to 2015, provided valuable clinical data for preoperative diagnosis and surgical removal of SCO tumors.

Well water requires chemical, physical-chemical, and microbiological analysis to ensure that the water used for irrigation or for human consumption presents no specific risks. The aim of the present work was to determine the microbiological risk of samples taken from wells in south-central Sardinia. In this survey, 55 water samples were taken from private wells in the period from 2014 to 2018. Quality was assessed through the detection of the parameters required by national law. The analysis of the data showed that only 36.4% of the samples (20 wells) complied with legal limits for water for human consumption. The most isolated species was P. aeruginosa, present in 29.1%; its high concentration and recorded Coliforms suggest that the disinfection of the wells was insufficient or not performed properly if implemented. Such data suggest the need to pay more attention to the waters used not only for human consumption but also for irrigation, since the cultivated vegetables could become a vehicle for potentially pathogenic microorganisms. National legislation sets contamination limits only for water intended for human consumption and not for irrigation water. However, based on these considerations, it appears necessary to develop reference standards for irrigation water.

BACKGROUND The aim of this investigation was to see if a panel of biomarkers (maspin, CD105, and nm23-H1) could be used to stratify patients with laryngeal squamous cell carcinoma (LSCC) in homogeneous disease recurrence risk clusters. METHODS Cluster analysis was used to classify 89 patients based on their immunohistochemical expression of nm23-H1, CD105, and maspin. RESULTS Our analysis identified seven homogeneous clusters: the LSCC recurrence rate was lowest in cluster 6 (non-nuclear maspin pattern, nuclear nm23-H1 expression ≥10%, endothelial CD105 expression

This article conducts a comparative analysis of peer and public pressure in peer reviews among states. Arguing that such pressure is one increasingly important form of shaming in global politics, we seek to understand the extent to which five different peer reviews exert peer and public pressure and how possible variation among them can be explained. Our findings are based on responses to an original survey and semi-structured interviews among participants in the reviews. We find that peer and public pressure exist to different degrees in the peer reviews under study. Such differences cannot be explained by the policy area under review or the international organization in which peer reviews are organized. Likewise, the expertise of the actors involved in a peer review or perceptions of the legitimacy of peer review as a monitoring instrument do not explain the variation. Instead, we find that institutional factors and the acceptance of peer and public pressure among the participants in a peer review offer the best explanations.

// Sabrina Rossi 1 , Marta Sbaraglia 1 , Marta Campo Dell’Orto 1 , Daniela Gasparotto 2 , Matilde Cacciatore 1 , Elena Boscato 1 , Valentina Carraro 1 , Luisa Toffolatti 1 , Giovanna Gallina 1 , Monia Niero 1 , Emanuela Pilozzi 3 , Alessandra Mandolesi 4 , Fausto Sessa 5 , Aurelio Sonzogni 6 , Cristina Mancini 7 , Guido Mazzoleni 8 , Salvatore Romeo 1 , Roberta Maestro 2,* and Angelo P. Dei Tos 1,* 1 Department of Pathology and Molecular Genetics, Treviso General Hospital, Treviso, Italy 2 Department of Experimental Oncology, CRO, Aviano, Italy 3 Department of Clinical and Molecular Medicine, University of Rome “La Sapienza”, Rome, Italy 4 Department of Pathology, University of Marche, Ancona School of Medicine, Ancona, Italy 5 Department of Pathology, Macchi Fondation, Varese, Italy 6 Department of Pathology, General Hospital, Bergamo, Italy 7 Department of Pathology, Azienda Ospedaliera-Universitaria, Parma, Italy 8 Department of Pathology, General Hospital, Bolzano, Italy * These authors have contributed equally to the work Correspondence to: Angelo P. Dei Tos, email: // Keywords : GIST, BRAF-mutated GIST, KIT/BRAF concomitant mutations, Imatinib resistance, BRAF VE1 antibody, Pathology Section Received : December 30, 2015 Accepted : April 04, 2016 Published : April 16, 2016 Abstract AIM: The BRAF mutation is a rare pathogenetic alternative to KIT/PDGFRA mutation in GIST and causes Imatinib resistance. A recent description of KIT and BRAF mutations co-occurring in an untreated GIST has challenged the concept of their being mutually exclusive and may account for ab initio resistance to Imatinib, even in the presence of Imatinib-sensitive KIT mutations. BRAF sequencing is generally limited to KIT/PDGFRA wild-type cases. Hence, the frequency of concomitant mutations may be underestimated. METHODS: We screened for KIT (exon 9, 11 ,13 ,17), PDGFRA (exon 12,14, 18) and BRAF (exon 15) mutations a series of 407 GIST. Additionally, we evaluated the BRAF V600E mutation-specific antibody, VE1, as a surrogate for V600E mutation, on a series of 313 GIST (24 on whole sections, 288 cases on tissue array), including 6 cases molecularly ascertained to carry the BRAF V600E mutation. RESULTS: No concomitant KIT / BRAF or PDGFRA / BRAF mutations were detected. BRAF mutation was detected only in one case, wild-type for KIT/PDGFRA. All the 6 BRAF -mutant cases stained positive with the VE1 antibody. A weak VE1 expression was observed in 14/287 (4.9%) BRAF wild-type cases, as observed also in 2/6 BRAF -mutant cases. Overall in our series, sensitivity and specificity of the VE1 antobody were 100% and 95.1%, respectively. CONCLUSION: The concomitance of BRAF mutation with either KIT or PDGFRA mutation is rare in GIST. In these tumors, moderate/strong VE1 immunoreactivity is a valuable surrogate for molecular analysis. Instead, genotyping is warranted in the presence of weak VE1 staining.

What mechanisms facilitate state compliance with human rights? This article proposes and applies a model to assess the extent to which two United Nations human rights mechanisms—the Universal Periodic Review (UPR) and the state reporting procedure of the treaty bodies—are perceived as capable of stimulating compliance with human rights, and why. It does so by identifying a set of goals potentially achieved by these organizations—generating pressure, stimulating learning, providing an accurate overview of states’ performance, and delivering practically feasible recommendations—and testing the extent to which reaching these goals is seen to facilitate compliance with human rights. It concludes that the treaty bodies’ perceived strength lies in providing states with learning opportunities and an accurate overview of their internal situations. In contrast, the UPR is deemed particularly strong in generating peer and public pressure on states. From a theoretical point of view, this article shows that, under certain conditions, the three main theoretical schools on compliance—enforcement, management, and constructivist—offer credible explanations for states’ performance in implementing human rights recommendations, with the enforcement school faring relatively better than the other two. Data were collected by means of forty semi-structured interviews and an online survey.

Objectives Comprehension of the interplay of pro-apoptotic and anti-apoptotic stimuli in laryngeal squamous cell carcinoma (LSCC) is crucial to understand tumor development, biological behavior and treatment response. Bcl-2 family proteins mainly regulate the apoptotic signal cascade. In some cancers, maspin seems to influence the balance between pro-apoptosis and anti-apoptosis bcl-2 family proteins. The aim of this study was to investigate the potential relationship between bcl-2 anti-apoptotic factor and the tumor suppressor maspin in LSCC. Materials and methods 31 consecutive patients who underwent primary surgery and post-operative radiotherapy for LSCC were evaluated retrospectively. For each case, immunohistochemistry assays for bcl-2 and maspin were performed. Data were also collected on N-status, pT stage, grading, recurrence and disease-free survival (DFS). Results Patients with nuclear maspin pattern of expression showed a significantly lower recurrence rate (p = 0.04) and longer DFS (p = 0.0018). The expression of bcl-2 was not associated with recurrence rate or DFS either in the whole cohort or in cases with nuclear maspin pattern, while in patients with non-nuclear maspin pattern, a statistical trend was found toward a shorter DFS for bcl-2 positive cases (p = 0.062). In the multivariate model, only maspin expression pattern retained its independent prognostic significance (p = 0.006). Conclusions Nuclear maspin pattern seemed to be an independent positive prognostic factor, while bcl-2 prognostic value was related to maspin expression pattern. Further investigations are needed to support the use of bcl-2 inhibitors in multimodality or multitarget strategies against advanced LSCCs, also considering the role and expression of tumor suppressor genes.

Ricotta Salata is a traditional ripened and salted whey cheese made in Sardinia (Italy) from sheep's milk. This product is catalogued as ready-to-eat food (RTE) since it is not submitted to any further treatment before consumption. Thus, foodborne pathogens, such as Listeria monocytogenes, can represent a health risk for consumers. In September 2012, the FDA ordered the recall of several batches of Ricotta Salata imported from Italy linked to 22 cases of Listeriosis in the United States. This study was aimed at evaluating the presence and virulence properties of L. monocytogenes in 87 samples of Ricotta Salata produced in Sardinia. The ability of this product to support its growth under foreseen packing and storing conditions was also evaluated in 252 samples. Of the 87 samples 17.2% were positive for the presence of L. monocytogenes with an average concentration of 2.2 log10 cfu/g. All virulence-associated genes (prfA, rrn, hlyA, actA, inlA, inlB, iap, plcA, and plcB) were detected in only one isolated strain. The Ricotta Salata samples were artificially inoculated and growth potential (δ) was assessed over a period of 3 mo. The value of the growth potential was always >0.5 log10 cfu/g under foreseen packing and storing conditions. This study indicates that Ricotta Salata supports the L. monocytogenes growth to levels that may present a serious risk to public health, even while stored at refrigeration temperatures.

In the Mediterranean area, salted and dried roe from the gray Mugil cephalus “bottarga” represent a speciality food with great commercial value. Bottarga is currently produced by a traditional handmade process and, the risk of human bacterial contamination during its manufacturing is still unknown; in this perspective the foodborne pathogen Staphylococcus aureus could potentially contaminate this product due to poor sanitation or bad handling during processing. The aim of this work is: to evaluate the contamination level of foodborne pathogens at different product manufacturing stages and, in addition, to describe a fast and realizable method for the rapid detection of S. aureus in bottarga samples in the field. A cultural procedure was initially used to investigate the occurrence of S. aureus and the other main foodborne pathogens in bottarga samples at the different manufacturing stages (from roe to final product). In addition, a molecular approach was used to rapidly determine the presence of total bacteria, S. aureus, and its potential toxigenicity. Of the 194 specimens analyzed, we identified: Clostridium perfringens, Enterococcus spp. and Enterobacteriaceae. However, some samples resulted as being contaminated with S. aureus (4% in roe and 8.7% in the final product). During the bottarga manufacturing process, we observed an increase in pathogen levels (from 102 to 105 CFU/g) in contaminated samples, and entA and entB genotypes were identified. Reconstruction experiments suggest that the fresh roe and the bottarga (not completely dried) could represent a risk for the contamination and growth of pathogen bacteria. Pratical Application Salted and dried roe from Mugil cephalus can be contaminated with different bacteria species, especially on the farm during the manufacturing process. Among the possible contaminants, S. aureus could be a main cause of foodborne illness in this product. A molecular procedure by real-time PCR could be suitable for a rapid and complete analysis of S. aureus in bottarga or other fish roe products.

The absence of politicization is widely considered an essential feature in ensuring the credibility of international organizations concerned with human rights monitoring. Nonetheless, hardly any empirical research has been conducted to systematically assess its presence and identify its consequences. Therefore, this article investigates the extent to which the state reporting process of the Treaty Bodies and the Universal Periodic Review are perceived to be politicized, and what consequences politicization has on their credibility. It claims that whereas politicization carries exclusively negative consequences in the Treaty Bodies, it has some unexpected positive consequences in the case of the Universal Periodic Review.

Monitoring the extent to which states respect their human rights obligations is a difficult task. Within the United Nations, two major mechanisms exist to review states’ human rights performance, namely the Universal Periodic Review (UPR) and the Treaty Bodies. This study shows that both instruments have their strengths and weaknesses. The UPR is successful in pressuring states to comply with human rights recommendations, although the mechanism is often perceived as unfair towards certain groups of states. In contrast, Treaty Bodies provide states with learning opportunities and specific advice on how to improve their performance, yet their recommendations do not carry considerable political weight.

Ricotta Salata is a traditional ripened and salted whey cheese made in Sardinia (Italy) from sheep's milk. This product is catalogued as ready-to-eat food (RTE) since it is not submitted to any further treatment before consumption. Thus, foodborne pathogens, such as Listeria monocytogenes, can represent a health risk for consumers. In September 2012, the FDA ordered the recall of several batches of Ricotta Salata imported from Italy linked to 22 cases of Listeriosis in the United States. This study was aimed at evaluating the presence and virulence properties of L. monocytogenes in 87 samples of Ricotta Salata produced in Sardinia. The ability of this product to support its growth under foreseen packing and storing conditions was also evaluated in 252 samples. Of the 87 samples 17.2% were positive for the presence of L. monocytogenes with an average concentration of 2.2 log10 cfu/g. All virulence-associated genes (prfA, rrn, hlyA, actA, inlA, inlB, iap, plcA, and plcB) were detected in only one isolated strain. The Ricotta Salata samples were artificially inoculated and growth potential (δ) was assessed over a period of 3 mo. The value of the growth potential was always0.5 log10 cfu/g under foreseen packing and storing conditions. This study indicates that Ricotta Salata supports the L. monocytogenes growth to levels that may present a serious risk to public health, even while stored at refrigeration temperatures.

In the Mediterranean area, salted and dried roe from the gray Mugil cephalus "bottarga" represent a speciality food with great commercial value. Bottarga is currently produced by a traditional handmade process and, the risk of human bacterial contamination during its manufacturing is still unknown; in this perspective the foodborne pathogen Staphylococcus aureus could potentially contaminate this product due to poor sanitation or bad handling during processing. The aim of this work is: to evaluate the contamination level of foodborne pathogens at different product manufacturing stages and, in addition, to describe a fast and realizable method for the rapid detection of S. aureus in bottarga samples in the field. A cultural procedure was initially used to investigate the occurrence of S. aureus and the other main foodborne pathogens in bottarga samples at the different manufacturing stages (from roe to final product). In addition, a molecular approach was used to rapidly determine the presence of total bacteria, S. aureus, and its potential toxigenicity. Of the 194 specimens analyzed, we identified: Clostridium perfringens, Enterococcus spp. and Enterobacteriaceae. However, some samples resulted as being contaminated with S. aureus (4% in roe and 8.7% in the final product). During the bottarga manufacturing process, we observed an increase in pathogen levels (from 10(2) to 10(5) CFU/g) in contaminated samples, and entA and entB genotypes were identified. Reconstruction experiments suggest that the fresh roe and the bottarga (not completely dried) could represent a risk for the contamination and growth of pathogen bacteria.

Edible lamellibranch molluscs are frequently the cause of very serious outbreaks of food poisoning. Microbiological suitability for human consumption, according to EC Reg. n. 1441/2007, is only based on two faecal bacteriological contamination parameters (Escherichia coli and Salmonella) and does not consider other microorganisms which are naturally present within the marine environment and are potentially pathogenic such as those belonging to the genus Vibrio. In this study, a total of 540 samples of edible lamellibranch molluscs (mussels, clams and oysters) bred in Sardinia were analyzed for E. coli and Salmonella, according to EC Reg n. 1441/2005, and for the presence of Vibrios of major public health interest. Environmental parameters (seawater temperature and salinity) were also recorded. The 40% (n=216) of samples were positive for Vibrio while the levels of E. coli were above the legal European limit only in 6.4% of samples. A correlation between the presence of micro-organisms of faecal origin and potentially harmful Vibrios to human health was not observed. Vibrio alginolyticus was the most common in 68% of isolated species, followed by Vibrio parahaemolyticus in 22.6%, Vibrio cholerae in 6% and Vibrio vulnificus in 1.1%. Virulence gene (trh sequence) was present in 1.6% of the V. parahaemolyticus-positive samples. The V. cholerae, V. vulnificus and V. alginolyticus strains detected were non toxigenic. The absence of genes encoding major virulence factors in the studied strains does not exclude the possibility of exposure to pathogenic strains. This study indicates the potential health risk associated with the presence of pathogenic Vibrios in edible lamellibranch molluscs bred in Sardinia, where shellfish production is very important to the local economy.

This article presents the results of a single-case study done in order to probe a specific version of an information processing approach to the study of (public) organizations. The case used for this probe is the European Fundamental Rights Agency. The article demonstrates that the information processing approach to public organizations as sketched out in the first sections of this article provides a conceptual framework that enables a fine-grained descriptive analysis of bureaucratic processes and their essential structures. It is shown how the rather fierce (‘constitutive’) politics behind the Fundamental Rights Agency establishment resulted in specific organizational structures that, from a strictly formal point of view, seem to effectively put the agency in shackles. This article also shows that although seemingly weak, the Fundamental Rights Agency is able to circumvent its formal restrictions through the exploitation of the structural incoherencies and gaps that are inevitable concomitants of political compromise in its daily operations.