691 research outputs found
Natural Disasters, Climate Change, and Tourism Panel Discussion
Tourism, an economic sector of great global importance, faces a âtrifectaâ of challenges given its propensity towards locations that are densely populated and susceptible to extreme weather events that will be exacerbated by climate change. While climate change is a global problem, its impacts will manifest differently at the local scale and will likely necessitate responses that are specific to individual tourism communities. Subsequently, efforts to increase resilience for tourism destinations should be strongly tied to efforts to build their communitiesâ resilience, as some of the factors that increase community resilience have also been shown to increase the resilience of the tourism sector
NRF2 activation in Trp53;p16-deficient mice drives oral squamous cell carcinoma
UNLABELLED: Aberrant activation of the NRF2/NFE2L2 transcription factor commonly occurs in head and neck squamous cell carcinomas (HNSCC). Mouse model studies have shown that NRF2 activation alone does not result in cancer. When combined with classic oncogenes and at the right dose, NRF2 activation promotes tumor initiation and progression. Here we deleted the tumor suppressor genes p16INK4A and p53 (referred to as CP mice), which are commonly lost in human HNSCC, in the presence of a constitutively active NRF2E79Q mutant (CPN mice). NRF2E79Q expression in CPN mice resulted in squamous cell hyperplasia or dysplasia with hyperkeratosis in the esophagus, oropharynx, and forestomach. In addition, CPN mice displayed oral cavity squamous cell carcinoma (OSCC); CP mice bearing wild-type NRF2 expression did not develop oral cavity hyperplasia, dysplasia or OSCC. In both CP and CPN mice, we also observed predominantly abdominal sarcomas and carcinomas. Our data show that in the context of p53 and p16 tumor suppressor loss, NRF2 activation serves oncogenic functions to drive OSCC. CPN mice represent a new model for OSCC that closely reflects the genetics of human HNSCC.
SIGNIFICANCE: Human squamous cancers frequently show constitutive NRF2 activation, associated with poorer outcomes and resistance to multiple therapies. Here, we report the first activated NRF2-driven and human-relevant mouse model of squamous cell carcinoma that develops in the background of p16 and p53 loss. The availability of this model will lead to a clearer understanding of how NRF2 contributes to the initiation, progression, and therapeutic response of OSCC
Photonics and electronics integration in the HELIOS project
The objective of the European project HELIOS is to combine a photonic layer with a CMOS circuit by different innovative means, using microelectronics processes. Bonding of AWG + Ge Photodiodes on CMOS wafer is achieved
Expression of CD13 and CD26 on extracellular vesicles in canine seminal plasma: preliminary results
Canine seminal plasma is a complex fluid containing proteins, peptides, enzymes, hormones as well as extracellular vesicles that are involved in many physiological and pathological processes including reproduction. We examined the expression of the extracellular vesicles surface antigens Aminopeptidase-N (CD13) and Dipeptidyl peptidase IV (CD26) by flow cytometry. For this study, third fraction of the ejaculate, from fertile adult male German Shepherd dogs, was manually collected twice, two days apart. FACS analyses revealed that CD13 and CD26 are co-expressed on the 69.3 & PLUSMN; 3.7% of extracellular vesicles and only a 2.0 & PLUSMN; 0.5% of extracellular vesicles express CD26 alone. On the other hand, 28.6 & PLUSMN; 3.6% of seminal EVs express CD13 alone. Our results agree with the hypothesis that CD26 needs to be co-expressed with other signal-transducing molecules, while CD13, can perform functions independently of the presence or co-expression of CD26. The results obtained in normal fertile dogs could represent physiological expression of these enzymes. Therefore, it would be interesting to carry out further studies to evaluate the expression of CD13 and CD26 on extracellular vesicles as biomarker for prostate pathological condition in dogs
Direct Comparison of HPV16 Viral Genomic Integration, Copy Loss, and Structural Variants in Oropharyngeal and Uterine Cervical Cancers Reveal Distinct Relationships to E2 Disruption and Somatic Alteration
Squamous cell carcinoma of the oropharynx caused by HPV type 16 (HPV16+ OPSCC) is the most common HPV-associated malignancy in the USA and has many molecular differences from uterine cervical squamous cell carcinoma (UCSCC). Our understanding of HPV oncogenesis relied on studies of UCSCC revealing a consensus model reliant on HPV integration with a loss of E2. Here, we compare patterns of HPV integration in UCSCC and OPSCC by analysis of affinity capture sequencing of the HPV16 genome in 104 OPSCC and 44 UCSCC tumors. These cohorts were contemporaneously sequenced using an identical strategy. Integration was identified using discordant read pair clustering and assembly-based approaches. Viral integration sites, structural variants, and copy losses were examined. While large-scale deep losses of HPV16 genes were common in UCSCC and were associated with E2 loss, deep copy losses of the HPV16 genome were infrequent in HPV16+ OPSCC. Similarly, structural variants within HPV16 favored E2 loss in UCSCC but not OPSCC. HPV16 integration sites were non-random, with recurrent integration hot-spots identified. OPSCC tumors had many more integration sites per tumor when compared to UCSCC and had more integration sites in genomic regions with high gene density. These data show that viral integration and E2 disruption are distinct in UCSCC and OPSCC. Our findings also add to growing literature suggesting that HPV tumorigenesis in OPSCC does not follow the model developed based on UCSCC
WELLFOCUS PPT â modified positive psychotherapy to improve well-being in psychosis: study protocol for a pilot randomised controlled trial
BACKGROUND: The promotion of well-being is an important goal of recovery oriented mental health services. No structured, evidence-based intervention exists that aims to increase the well-being in people with severe mental illness such as psychosis. Positive psychotherapy (PPT) is a promising intervention for this goal. Standard PPT was adapted for use with people with psychosis in the UK following the Medical Research Council framework for developing and testing complex interventions, resulting in the WELLFOCUS Model describing the intended impact of WELLFOCUS PPT. This study aims to test the WELLFOCUS Model, by piloting the intervention, trial processes, and evaluation strategy. METHODS/DESIGN: This study is a non-blinded pragmatic pilot RCT comparing WELLFOCUS PPT provided as an 11-session group therapy in addition to treatment as usual to treatment as usual alone. Inclusion criteria are adults (aged 18â65 years) with a main diagnosis of psychosis who use mental health services. A target sample of 80 service users with psychosis are recruited from mental health services across the South London and Maudsley NHS Foundation Trust. Participants are randomised in blocks to the intervention and control group. WELLFOCUS PPT is provided to groups by specifically trained and supervised local therapists and members of the research team. Assessments are conducted before randomisation and after the group intervention. The primary outcome measure is well-being assessed by the Warwick-Edinburgh Mental Well-being Scale. Secondary outcomes include good feelings, symptom relief, connectedness, hope, self-worth, empowerment, and meaning. Process evaluation using data collected during the group intervention, post-intervention individual interviews and focus groups with participants, and interviews with trial therapists will complement quantitative outcome data. DISCUSSION: This study will provide data on the feasibility of the intervention and identify necessary adaptations. It will allow optimisation of trial processes and inform the evaluation strategy, including sample size calculation, for a future definitive RCT. TRIAL REGISTRATION: Current Controlled Trials ISRCTN04199273 â WELLFOCUS study: an intervention to improve well-being in people with psychosis, Date registered: 27 March 2013, first participant randomised on 26 April 2013
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The impact of mental health recovery narratives on recipients experiencing mental health problems: Qualitative analysis and change model.
BACKGROUND: Mental health recovery narratives are stories of recovery from mental health problems. Narratives may impact in helpful and harmful ways on those who receive them. The objective of this paper is to develop a change model identifying the range of possible impacts and how they occur. METHOD: Semi-structured interviews were conducted with adults with experience of mental health problems and recovery (n = 77). Participants were asked to share a mental health recovery narrative and to describe the impact of other people's recovery narratives on their own recovery. A change model was generated through iterative thematic analysis of transcripts. RESULTS: Change is initiated when a recipient develops a connection to a narrator or to the events descripted in their narrative. Change is mediated by the recipient recognising experiences shared with the narrator, noticing the achievements or difficulties of the narrator, learning how recovery happens, or experiencing emotional release. Helpful outcomes of receiving recovery narratives are connectedness, validation, hope, empowerment, appreciation, reference shift and stigma reduction. Harmful outcomes are a sense of inadequacy, disconnection, pessimism and burden. Impact is positively moderated by the perceived authenticity of the narrative, and can be reduced if the recipient is experiencing a crisis. CONCLUSIONS: Interventions that incorporate the use of recovery narratives, such as peer support, anti-stigma campaigns and bibliotherapy, can use the change model to maximise benefit and minimise harms from narratives. Interventions should incorporate a diverse range of narratives available through different mediums to enable a range of recipients to connect with and benefit from this material. Service providers using recovery narratives should preserve authenticity so as to maximise impact, for example by avoiding excessive editing
Phylogenetic placement of environmental sequences using taxonomically reliable databases helps to rigorously assess dinophyte biodiversity in Bavarian lakes (Germany).
1. Reliable determination of organisms is a prerequisite to explore their spatial
and temporal occurrence and to study their evolution, ecology, and dispersal. In
Europe, Bavaria (Germany) provides an excellent study system for research on the
origin and diversification of freshwater organisms including dinophytes, due to
the presence of extensive lake districts and ice age river valleys. Bavarian freshwater
environments are ecologically diverse and range from deep nutrientâpoor
mountain lakes to shallow nutrientârich lakes and ponds.
2. We obtained amplicon sequence data (V4 region of small subunitârRNA, c. 410 bp
long) from environmental samples collected at 11 sites in Upper Bavaria. We
found 186 operational taxonomic units (OTUs) associated with Dinophyceae that
were further classified by means of a phylogenetic placement approach.
3. The maximum likelihood tree inferred from a wellâcurated reference alignment comprised
a systematically representative set of 251 dinophytes, covering the currently
known molecular diversity and OTUs linked to type material if possible. Environmental
OTUs were scattered across the reference tree, but accumulated mostly in freshwater
lineages, with 79% of OTUs placed in either Apocalathium, Ceratium, or Peridinium,
the most frequently encountered taxa in Bavaria based on morphology.
4. Twentyâone Bavarian OTUs showed identical sequences to already known and
vouchered accessions, two of which are linked to type material, namely Palatinus
apiculatus and Theleodinium calcisporum. Particularly within Peridiniaceae, delimitation
of Peridinium species was based on the intraspecific sequence variation.
5. Our approach indicates that highâthroughput sequencing of environmental samples
is effective for reliable determination of dinophyte species in Bavarian lakes.
We further discuss the importance of wellâcurated reference databases that remain
to be developed in the future
Lean and green in the transport and logistics sector â a case study of simultaneous deployment
© 2016 Informa UK Limited, trading as Taylor & Francis Group. The transport and logistics sector is of vital importance for the stimulation of trade and hence the economic development of nations. However, over the last few years, this sector has taken central stage in the green agenda due to the negative environmental effects derived from its operations. Several disciplines including operations research and sub-areas of supply chain management such as green supply chains, green logistics and reverse logistics have tried to address this problem. However, despite the work undertaken through these disciplines, theoretical or empirical research into the sequential or simultaneous deployment of the lean and green paradigms, particularly, in the road transport and logistics sector is limited. This paper presents a case study where both paradigms have been combined to improve the transport operations of a world leader logistics organisation in the metropolitan area of Monterrey, Mexico. To do this, a systematic methodology and a novel tool called Sustainable Transportation Value Stream Map (STVSM) were proposed. The results obtained from the case study indicate that the concurrent deployment of the green and lean paradigms through such methodology and the STVSM tool is an effective approach to improve both operational efficiency and environmental performance of road transport operations. The paper can be used as a guiding reference for transport and logistics organisations to undertake improvement projects similar to the one presented in this paper. Additionally, this research also intends to stimulate scholarly research into the application of lean and green paradigms in the transport and logistics sector to expand the limited research pursued in this area
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