Reflections on fieldwork: A view from Amazonia

Amazonia is both a place of exceptional linguistic, sociocultural, and ecological diversity and a place where the documentation of this diversity is limited and ever-increasingly urgent. While recent decades have shown considerable progress in this area, our understanding of Amazonian languages is still challenged by a low proportion of researchers relative to its many distinct language contexts. In light of Himmelmann's framing of language documentation as a 'fairly independent field of linguistic inquiry and practice', we discuss key facets of what we consider the single most important unifying question that underlies language documentation work in Amazonia: Just how much description and analysis is necessary for Amazonian language documentation to be coherent, useful, and interpretable by others? We argue that the social and cultural diversity of this vast region calls into question the actual separability of 'documentation' from `description and analysis' of Amazonian language data; and we advocate for taking Himmelmann's proposals as an invitation to finer-grained, broader-minded thinking about the kinds of research questions, methods, and focused training that best serve linguists working in Amazonian speech communities, rather than as a guide to defining an appropriate scope for fieldwork with an Amazonian language.National Foreign Language Resource Cente

A Comprehensive Molecular Interaction Map for Rheumatoid Arthritis

Computational biology contributes to a variety of areas related to life sciences and, due to the growing impact of translational medicine - the scientific approach to medicine in tight relation with basic science -, it is becoming an important player in clinical-related areas. In this study, we use computation methods in order to improve our understanding of the complex interactions that occur between molecules related to Rheumatoid Arthritis (RA).Due to the complexity of the disease and the numerous molecular players involved, we devised a method to construct a systemic network of interactions of the processes ongoing in patients affected by RA. The network is based on high-throughput data, refined semi-automatically with carefully curated literature-based information. This global network has then been topologically analysed, as a whole and tissue-specifically, in order to translate the experimental molecular connections into topological motifs meaningful in the identification of tissue-specific markers and targets in the diagnosis, and possibly in the therapy, of RA.’

Iquito-English Dictionary

This dictionary documents the lexicon of Iquito, an indigenous language of northern Peruvian Amazonia. Iquito is a member of the Zaparoan language family, whose other members include Andoa, Arabela, and Sápara (also known as Záparo). Formerly spoken in a large region between the Tigre and Napo Rivers in what is now the departamento of Loreto, Peru, Iquito is currently spoken by a small number of elders in communities on or near the Pintuyacu River, four of whom, Jaime Pacaya Inuma, Ema Llona Yareja, Hermenegildo Díaz Cuyasa, and Ligia Inuma Inuma, contributed the broad linguistic, cultural, and historical knowledge documented in this dictionary. This dictionary serves not only as a comprehensive record of the Iquito lexicon; it also documents the unpredictable allomorphy and grammatical features of Iquito lexemes, and describes aspects of Iquito culture relevant to understanding their use and meanings. A glossary of Loretano Spanish terms used in the definitions is also provided

RNOP-09: Pegylated liposomal doxorubicine and prolonged temozolomide in addition to radiotherapy in newly diagnosed glioblastoma - a phase II study

BACKGROUND: Although Temozolomide is effective against glioblastoma, the prognosis remains dismal and new regimens with synergistic activity are sought for. METHODS: In this phase-I/II trial, pegylated liposomal doxorubicin (Caelyx, PEG-Dox) and prolonged administration of Temozolomide in addition to radiotherapy was investigated in 63 patients with newly diagnosed glioblastoma. In phase-I, PEG-Dox was administered in a 3-by-3 dose-escalation regimen. In phase-II, 20 mg/m2 PEG-Dox was given once prior to radiotherapy and on days 1 and 15 of each 28-day cycle starting 4 weeks after radiotherapy. Temozolomide was given in a dose of 75 mg/m2 daily during radiotherapy (60 Gy) and 150-200 mg/m2 on days 1-5 of each 28-day cycle for 12 cycles or until disease progression. RESULTS: The toxicity of the combination of PEG-Dox, prolonged administration of Temozolomide, and radiotherapy was tolerable. The progression free survival after 12 months (PFS-12) was 30.2%, the median overall survival was 17.6 months in all patients including the ones from Phase-I. None of the endpoints differed significantly from the EORTC26981/NCIC-CE.3 data in a post-hoc statistical comparison. CONCLUSION: Together, the investigated combination is tolerable and feasible. Neither the addition of PEG-Dox nor the prolonged administration of Temozolomide resulted in a meaningful improvement of the patient's outcome as compared to the EORTC26981/NCIC-CE.3 data

Evolution of antithrombotic therapy for patients with atrial fibrillation:The prospective global GLORIA-AF registry program

OBJECTIVE: To assess baseline characteristics and antithrombotic treatment (ATT) prescription patterns in patients enrolled in the third phase of the GLORIA-AF Registry Program, evaluate predictors of treatment prescription, and compare results with phase II. METHODS: GLORIA-AF is a large, global, prospective registry program, enrolling patients with newly diagnosed nonvalvular atrial fibrillation (AF) at risk of stroke. Patients receiving dabigatran were followed for two years in phase II, and all patients were followed for 3 years in phase III. Phase II started when dabigatran became available; phase III started when the characteristics of patients receiving dabigatran became roughly comparable with those receiving vitamin K antagonists (VKAs). RESULTS: Between 2014 and 2016, 21,241 patients were enrolled in phase III. In total, 82% of patients were prescribed oral anticoagulation ([OAC]; 59.5% novel/nonvitamin K oral anticoagulants [NOACs], 22.7% VKAs). A further 11% of patients were prescribed antiplatelets without OAC and 7% were prescribed no ATT. A high stroke risk was the main driver of OAC prescription. Factors associated with prescription of VKA over NOAC included type of site, region, physician specialty, and impaired kidney function. CONCLUSION: Over the past few years, data from phase III of GLORIA-AF show that OACs have become the standard treatment option, with most newly diagnosed AF patients prescribed a NOAC. However, in some regions a remarkable proportion of patients remain undertreated. In comparison with phase II, more patients received NOACs in phase III while the prescription of VKA decreased. VKAs were preferred over NOACs in patients with impaired kidney function

Surveillance of vector populations and malaria transmission during the 2009/10 El Niño event in the western Kenya highlands: opportunities for early detection of malaria hyper-transmission

<p>Abstract</p> <p>Background</p> <p>Vector control in the highlands of western Kenya has resulted in a significant reduction of malaria transmission and a change in the vectorial system. Climate variability as a result of events such as El Niño increases the highlands suitability for malaria transmission. Surveillance and monitoring is an important component of early transmission risk identification and management. However, below certain disease transmission thresholds, traditional tools for surveillance such as entomological inoculation rates may become insensitive. A rapid diagnostic kit comprising <it>Plasmodium falciparum </it>circumsporozoite surface protein and merozoite surface protein antibodies in humans was tested for early detection of transmission surges in the western Kenya highlands during an El Niño event (October 2009-February 2010).</p> <p>Methods</p> <p>Indoor resting female adult malaria vectors were collected in western Kenya highlands in four selected villages categorized into two valley systems, the U-shaped (Iguhu and Emutete) and the V-shaped valleys (Marani and Fort Ternan) for eight months. Members of the <it>Anopheles gambiae </it>complex were identified by PCR. Blood samples were collected from children 6-15 years old and exposure to malaria was tested using a circum-sporozoite protein and merozoite surface protein immunchromatographic rapid diagnostic test kit. Sporozoite ELISA was conducted to detect circum-sporozoite protein, later used for estimation of entomological inoculation rates.</p> <p>Results</p> <p>Among the four villages studied, an upsurge in antibody levels was first observed in October 2009. <it>Plasmodium falciparum </it>sporozoites were then first observed in December 2009 at Iguhu village and February 2010 at Emutete. Despite the upsurge in Marani and Fort Ternan no sporozoites were detected throughout the eight month study period. The antibody-based assay had much earlier transmission detection ability than the sporozoite-based assay. The proportion of <it>An. arabiensis </it>among <it>An. gambiae s.l</it>. ranged from 2.9-66.7% indicating a rearrangement of the sibling species of the <it>An. gambiae s.l </it>complex. This is possibly an adaptation to insecticide interventions and climate change.</p> <p>Conclusion</p> <p>The changing malaria transmission rates in the western Kenya highlands will lead to more unstable transmission, decreased immunity and a high vulnerability to epidemics unless surveillance tools are improved and effective vector control is sustained.</p

CD133 expression in chemo-resistant Ewing sarcoma cells

<p>Abstract</p> <p>Background</p> <p>Some human cancers demonstrate cellular hierarchies in which tumor-initiating cancer stem cells generate progeny cells with reduced tumorigenic potential. This cancer stem cell population is proposed to be a source of therapy-resistant and recurrent disease. Ewing sarcoma family tumors (ESFT) are highly aggressive cancers in which drug-resistant, relapsed disease remains a significant clinical problem. Recently, the cell surface protein CD133 was identified as a putative marker of tumor-initiating cells in ESFT. We evaluated ESFT tumors and cell lines to determine if high levels of CD133 are associated with drug resistance.</p> <p>Methods</p> <p>Expression of the CD133-encoding <it>PROM1 </it>gene was determined by RT-PCR in ESFT tumors and cell lines. CD133 protein expression was assessed by western blot, FACS and/or immunostaining. Cell lines were FACS-sorted into CD133+ and CD133- fractions and proliferation, colony formation in soft agar, and <it>in vivo </it>tumorigenicity compared. Chemosensitivity was measured using MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxy-methoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) assays.</p> <p>Results</p> <p><it>PROM1 </it>expression was either absent or extremely low in most tumors. However, <it>PROM1 </it>was highly over-expressed in 4 of 48 cases. Two of the 4 patients with <it>PROM1 </it>over-expressing tumors rapidly succumbed to primary drug-resistant disease and two are long-term, event-free survivors. The expression of <it>PROM1 </it>in ESFT cell lines was similarly heterogeneous. The frequency of CD133+ cells ranged from 2-99% and, with one exception, no differences in the chemoresistance or tumorigenicity of CD133+ and CD133- cell fractions were detected. Importantly, however, the STA-ET-8.2 cell line was found to retain a cellular hierarchy in which relatively chemo-resistant, tumorigenic CD133+ cells gave rise to relatively chemo-sensitive, less tumorigenic, CD133- progeny.</p> <p>Conclusions</p> <p>Up to 10% of ESFT express high levels of <it>PROM1</it>. In some tumors and cell lines the CD133+ fraction is relatively more drug-resistant, while in others there is no apparent difference between CD133+ and CD133- cells. These studies reveal heterogeneity in <it>PROM1</it>/CD133 expression in ESFT tumors and cell lines and confirm that high levels of <it>PROM1 </it>expression are, in at least some cases, associated with chemo-resistant disease. Further studies are required to elucidate the contribution of <it>PROM1/</it>CD133 expressing cells to therapeutic resistance in a large, prospective cohort of primary ESFT.</p

Targeting A20 Decreases Glioma Stem Cell Survival and Tumor Growth

The A20 protein is a known inhibitor of apoptosis that here is shown to be a novel cancer stem cell-promoting factor associated with poor glioma patient survival