Multi-purpose utility of circulating plasma DNA testing in patients with advanced cancers.

Tumor genomic instability and selective treatment pressures result in clonal disease evolution; molecular stratification for molecularly targeted drug administration requires repeated access to tumor DNA. We hypothesized that circulating plasma DNA (cpDNA) in advanced cancer patients is largely derived from tumor, has prognostic utility, and can be utilized for multiplex tumor mutation sequencing when repeat biopsy is not feasible. We utilized the Sequenom MassArray System and OncoCarta panel for somatic mutation profiling. Matched samples, acquired from the same patient but at different time points were evaluated; these comprised formalin-fixed paraffin-embedded (FFPE) archival tumor tissue (primary and/or metastatic) and cpDNA. The feasibility, sensitivity, and specificity of this high-throughput, multiplex mutation detection approach was tested utilizing specimens acquired from 105 patients with solid tumors referred for participation in Phase I trials of molecularly targeted drugs. The median cpDNA concentration was 17 ng/ml (range: 0.5-1600); this was 3-fold higher than in healthy volunteers. Moreover, higher cpDNA concentrations associated with worse overall survival; there was an overall survival (OS) hazard ratio of 2.4 (95% CI 1.4, 4.2) for each 10-fold increase in cpDNA concentration and in multivariate analyses, cpDNA concentration, albumin, and performance status remained independent predictors of OS. These data suggest that plasma DNA in these cancer patients is largely derived from tumor. We also observed high detection concordance for critical 'hot-spot' mutations (KRAS, BRAF, PIK3CA) in matched cpDNA and archival tumor tissue, and important differences between archival tumor and cpDNA. This multiplex sequencing assay can be utilized to detect somatic mutations from plasma in advanced cancer patients, when safe repeat tumor biopsy is not feasible and genomic analysis of archival tumor is deemed insufficient. Overall, circulating nucleic acid biomarker studies have clinically important multi-purpose utility in advanced cancer patients and further studies to pursue their incorporation into the standard of care are warranted.

Networking for conservation: social capital and perceptions of organizational success among land trust boards

As an important component in collaborative natural resource management and nonprofit governance, social capital is expected to be related to variations in the performance of land trusts. Land trusts are charitable organizations that work to conserve private land locally, regionally, or nationally. The purpose of this paper is to identify the level of structural and cognitive social capital among local land trusts, and how these two types of social capital relate to the perceived success of land trusts. The analysis integrates data for land trusts operating in the U.S. south-central Appalachian region, which includes western North Carolina, southwest Virginia, and east Tennessee. We use factor analysis to elicit different dimensions of cognitive social capital, including cooperation among board members, shared values, common norms, and communication effectiveness. Measures of structural social capital include the size and diversity of organizational networks of both land trusts and their board members. Finally, a hierarchical linear regression model is employed to estimate how cognitive and structural social capital measures, along with other organizational and individual-level attributes, relate to perceptions of land trust success, defined here as achievement of the land trusts’ mission, conservation, and financial goals. Results show that the diversity of organizational partnerships, cooperation, and shared values among land trust board members are associated with higher levels of perceived success. Organizational capacity, land trust accreditation, volunteerism, and financial support are also important factors influencing perceptions of success among local, nonprofit land trusts.

WFF-WFFP-ICSF-CIC: national workshop on capacity-building for the implementation of the voluntary guidelines for securing sustainable small-scale fisheries (SSF guidelines) - report, 21 and 22 March 2016 Multi-Purpose Hall, India International Centre, New Delhi, India

The report of the proceedings of the New Delhi workshop on the SSF Guidelines (Voluntary Guidelines for Securing Sustainable Small-scale Fisheries in the Context of Food Security and Poverty Eradication). The workshop brought together 95 participants from 13 states representing civil society organizations. governments, FAO, and fishworker organizations from both the marine and inland fisheries sectors. This report will be found useful for fishworker organizations, researchers, policy makers, members of civil society and anyone interested in small-scale fisheries, tenure rights, social development, livelihoods, post harvest and trade and disasters and climate change.

Commissioning for purpose: investigating commissioning as a collecting strategy for municipal museums and galleries 2000-present

The use of the ‘commission-accession’ principle as a mechanism for sustainable collecting in public museums and galleries has been significantly under-researched, only recently soliciting attention from national funding bodies in the United Kingdom (UK). This research has assessed an unfolding situation and provided a body of current evaluative evidence for commission-based acquisitions and a model for curators to use in future contemporary art purchases. ‘Commission-accession’ is a practice increasingly used by European and American museums yet has seen little uptake in the UK. Very recent examples demonstrate that new works produced via commissioning which then enter permanent collections, have significant financial and audience benefits that UK museums could harness, by drawing on the expertise of local and national commissioning organisations. Very little evaluative information is available on inter-institutional precedents in the United States (US) or ‘achat par commande’ in France. Neither is there yet literature that investigates the ambition for and viability of such models in the UK. This thesis addresses both of these areas, and provides evaluative case studies that will be of particular value to curators who seek sustainable ways to build their contemporary art collections. It draws on a survey of 82 museums and galleries across the UK conducted for this research, which provide a picture of where and how ‘commission-accession’ has been applied, and demonstrates its impacts as a strategy. In addition interviews with artists and curators in the UK, US and France on the social, economic and cultural implications of ‘commission-accession’ processes were undertaken. These have shed new light on issues inherent to the commissioning of contemporary art such as communication, trust, and risk as well as drawing attention to the benefits and challenges involved in commissioning as of yet unmade works of art.

Multi-purpose adaptable business tier components based on Call Level Interfaces

Call Level Interfaces (CLI) play a key role in business tiers of relational and on some NoSQL database applications whenever a fine tune control between application tiers and the host databases is a key requirement. Unfortunately, in spite of this significant advantage, CLI are low level API, this way not addressing high level architectural requirements. Among the examples we emphasize two situations: a) the need to decouple or not to decouple the development process of business tiers from the development process of application tiers and b) the need to automatically adapt business tiers to new business and/or security needs at runtime. To tackle these CLI drawbacks, and simultaneously keep their advantages, this paper proposes an architecture relying on CLI from which multi-purpose business tiers components are built, herein referred to as Adaptable Business Tier Components (ABTC). Beyond the reference architecture, this paper presents a proof of concept based on Java and Java Database Connectivity (an example of CLI).

ABTC: multi-purpose adaptable business tier components based on Call Level Interfaces

Call Level Interfaces (CLI) are low level API that play a key role in database applications whenever a fine tune control between application tiers and the host databases is a key requirement. Unfortunately, in spite of this significant advantage, CLI were not designed to address organizational requirements and contextual runtime requirements. Among the examples we emphasize the need to decouple or not to decouple the development process of business tiers from the development process of application tiers and also the need to automatically adapt to new business and/or security needs at runtime. To tackle these CLI drawbacks, and simultaneously keep their advantages, this paper proposes an architecture relying on CLI from which multi-purpose business tiers components are built, herein referred to as Adaptable Business Tier Components (ABTC). This paper presents the reference architecture for those components and a proof of concept based on Java and Java Database Connectivity (an example of CLI).

How to observe : architecture : or, questions upon various subjects connected therewith, suggested for the direction of correspondents and travellers, and for the purpose of eliciting uniformity of observation and intelligence in their communications to the Institute /

Mode of access: Internet.

Serious games applied to attention deficithyperactivity disorder: development of two games for therapeutic purpose

Attention Deficit-Hyperactivity Disorder is a disease that affects 3 to 5 percent of children globally. Many of those live in areas with very few or no medical professionals qualified to help them. To help assuage this problem a system was developed that allows physicians to accompany their patient’s progress and prescribe treatments. These treatments can be drugs or behavioral exercises. The behavioral exercises were designed in the form of games in order to motivate the patients, children, for the treatment. The system allows the patients to play the prescribed games, under the supervision of their tutors. Each game is designed to improve the patient’s handling of their disease through training in a specific mental component. The objective of this approach is to complement the traditional form of treatment by allowing a physician to prescribe therapeutic games and maintaining the patients under supervision between their regular consultations. The main goal of this project is to provide the patients with a better control of their symptoms that with just traditional therapy. Experimental field tests with children and clinical staff, offer promising results. This research is developed in the context of a financed project involving INESC C (Polytechnic Institute of Leiria delegation), the Santo André Hospital of Leiria, and the start-up company PlusrootOne (that owns the project).

Urban Agriculture Oriented towards Self-Supply, Social and Commercial Purpose: A Typology

Urban agriculture, a dynamic multifunctional phenomenon, affects the spatial diversification of urban land use, its valorization and its governance. Literature acknowledges its contribution to the development of sustainable cities. The dimension and extent of this contribution depends significantly on the particular form and function of urban agriculture. However, the complexity of interests and dimensions is insufficiently covered by theory. This paper proposes a typology for urban agriculture, supporting both theory building and practical decision processes. We reviewed and mapped the diversity of the types of agriculture found along three beneficial dimensions (self-supply, socio-cultural, commercial) for product distribution scale and actors. We distinguish between ideal types, subtypes and mixed types. Our intention is to include a dynamic perspective in the typology of urban agricultural land use because transition processes between types are observable due to the existence of complex motivations and influences. In a pilot study of 52 urban agriculture initiatives in Germany, we tested the validity of the typology and discussed it with stakeholders, proving novelty and relevance for profiling discussions.

Function, Purpose, Predication, and Context of Information Organization Frameworks

This paper outlines the purposes, predications, functions, and contexts of information organization frameworks; including: bibliographic control, information retrieval, resource discovery, resource description, open access scholarly indexing, personal information management protocols, and social tagging in order to compare and contrast those purposes, predications, functions, and contexts. Information organization frameworks, for the purpose of this paper, consist of information organization systems (classification schemes, taxonomies, ontologies, bibliographic descriptions, etc.), methods of conceiving of and creating the systems, and the work processes involved in maintaining these systems. The paper first outlines the theoretical literature of these information organization frameworks. In conclusion, this paper establishes the first part of an evaluation rubric for a function, predication, purpose, and context analysis.

Progettare l'inserimento di General Purpose Technologies nelle Organizzazioni con il Design Thinking: evidenze dal campo e metodologia proposta

Vista la crescente necessità di svolgere progetti d'innovazione guidati dalle nuove tecnologie, la presente ricerca risponde all'esigenza di trovare una metodologia efficace per poterli affrontare proficuamente. In un primo momento, l'elaborato propone una metodologia che permette di elaborare una classificazione dei progetti d'innovazione technology-driven in classi ed un pacchetto di tools funzionali al riconoscimento dell'appartenenza alle stesse. In un secondo momento, giunti a comprensione del fatto che ad ognuna delle classi corrisponde uno specifico fine raggiungibile con una specifica metodologia, lo studio descrive la metodologia seguita per raggiungere una efficace e ripetibile elaborazione di principi progettuali, buone pratiche e strumenti che permettano ad una Organizzazione di appropriarsi del valore di una tecnologia General Purpose (GPT) attraverso l'ideazione di soluzioni innovativa. La progettazione è figlia di un approccio di Design Thinking (DT), sia poichè esso è stato usato nello svolgimento stesso della ricerca, sia perchè la metodologia DT è alla base della modellazione del processo proposto per la classe.

Stayability in Italian Simmental dual-purpose cows: phenotypic and genetic associations

In recent years, dairy farmers have observed a substantial decrease in cows’ survival, with a direct negative consequence on the profitability. Shorter lifespan raises questions about animal welfare and farming conditions at which cows are exposed to. However, the length of productive life depends also on voluntary culling due to low productivity and, in dual-purpose breed, to low price of carcasses (meat). The general aim of the thesis was to investigate the genetic and phenotypic relationship of functional longevity with morphological features like muscularity and body condition score (BCS) and productive traits within Italian Simmental dual-purpose dairy cattle raised in Emilia-Romagna herds.

Toxic cyanobacteria in water intended for drinking purpose: improvement of cells and toxins’ analyses and of treatments for their removal

Massive proliferations of cyanobacteria in freshwaters have recently increased, causing ecological and economic losses. Their ever-increasing presence in water sources destined to potabilization has become a major threat for public health, since several species can produce harmful toxins (cyanotoxin). Therefore, additional specific measures to improve management and treatment of drinking water(s) are required. The PhD thesis investigates toxic cyanobacteria in drinking waters with a special focus on Emilia-Romagna (Italy), throughout three separated chapters, each with different specific objectives. The first chapter aims at improving the fast monitoring of cyanobacteria in drinking water, which was investigated by testing different models of multi-wavelength spectrofluorometers. Inter-laboratories calibrations were conducted using mono-specific cultures and field samples, and both the feasibility and the technical limitations of such tools were illustrated. The second chapter evaluates the effectiveness of drinking water treatments in removing cyanobacterial cells and toxins. Two chlorinated oxidants (sodium hypochlorite and chlorine dioxide) already in use for pre-oxidation during water potabilization, were tested on cultures of the toxic cyanobacterium Microcystis aeruginosa posing a specific focus on toxin removal and revealing that pre-oxidation can cause the release of toxins and unknown metabolites. Innovative treatments based on non-thermal plasma were also tested, observing an effective and rapid inactivation of cyanobacterial cells. The third chapter presents a study on a cyanobacterium isolated from a drinking water reservoir of Emilia-Romagna and investigated by combining biological, chemical, and genomic methods. Although the strain did not produce any known cyanotoxin, high toxicity of water-extract was observed in bioassays and potential implications for drinking water were discussed. Overall, the PhD thesis offers new insights into toxic cyanobacteria management in drinking water, highlighting best practices for drinking water managers regarding their detection and removal. Additionally, the thesis provides new contributions to the understanding of the freshwater cyanobacteria community in the Emilia-Romagna region.

Adapting The Sniffin' Sticks Olfactory Test To Diagnose Parkinson's Disease In Estonia.

The aim of the study was to develop a culturally adapted translation of the 12-item smell identification test from Sniffin' Sticks (SS-12) for the Estonian population in order to help diagnose Parkinson's disease (PD). A standard translation of the SS-12 was created and 150 healthy Estonians were questioned about the smells used as response options in the test. Unfamiliar smells were replaced by culturally familiar options. The adapted SS-12 was applied to 70 controls in all age groups, and thereafter to 50 PD patients and 50 age- and sex-matched controls. 14 response options from 48 used in the SS-12 were replaced with familiar smells in an adapted version, in which the mean rate of correct response was 87% (range 73-99) compared to 83% with the literal translation (range 50-98). In PD patients, the average adapted SS-12 score (5.4/12) was significantly lower than in controls (average score 8.9/12), p < 0.0001. A multiple linear regression using the score in the SS-12 as the outcome measure showed that diagnosis and age independently influenced the result of the SS-12. A logistic regression using the SS-12 and age as covariates showed that the SS-12 (but not age) correctly classified 79.0% of subjects into the PD and control category, using a cut-off of <7 gave a sensitivity of 76% and specificity of 86% for the diagnosis of PD. The developed SS-12 cultural adaption is appropriate for testing olfaction in Estonia for the purpose of PD diagnosis.

Solid Lipid Nanoparticles For Hydrophilic Biotech Drugs: Optimization And Cell Viability Studies (caco-2 & Hepg-2 Cell Lines).

Insulin was used as model protein to developed innovative Solid Lipid Nanoparticles (SLNs) for the delivery of hydrophilic biotech drugs, with potential use in medicinal chemistry. SLNs were prepared by double emulsion with the purpose of promoting stability and enhancing the protein bioavailability. Softisan(®)100 was selected as solid lipid matrix. The surfactants (Tween(®)80, Span(®)80 and Lipoid(®)S75) and insulin were chosen applying a 2(2) factorial design with triplicate of central point, evaluating the influence of dependents variables as polydispersity index (PI), mean particle size (z-AVE), zeta potential (ZP) and encapsulation efficiency (EE) by factorial design using the ANOVA test. Therefore, thermodynamic stability, polymorphism and matrix crystallinity were checked by Differential Scanning Calorimetry (DSC) and Wide Angle X-ray Diffraction (WAXD), whereas the effect of toxicity of SLNs was check in HepG2 and Caco-2 cells. Results showed a mean particle size (z-AVE) width between 294.6 nm and 627.0 nm, a PI in the range of 0.425-0.750, ZP about -3 mV, and the EE between 38.39% and 81.20%. After tempering the bulk lipid (mimicking the end process of production), the lipid showed amorphous characteristics, with a melting point of ca. 30 °C. The toxicity of SLNs was evaluated in two distinct cell lines (HEPG-2 and Caco-2), showing to be dependent on the concentration of particles in HEPG-2 cells, while no toxicity in was reported in Caco-2 cells. SLNs were stable for 24 h in in vitro human serum albumin (HSA) solution. The resulting SLNs fabricated by double emulsion may provide a promising approach for administration of protein therapeutics and antigens.