Phase II evaluation of VDC-1101 in canine cutaneous T-cell lymphoma.

BackgroundCanine cutaneous T-cell lymphoma (CTCL) is an uncommon disease for which efficacious therapies are lacking. The novel anticancer nucleotide prodrug VDC-1101 (formerly known as GS-9219) has shown efficacy in dogs with multicentric lymphoma. One of the observed adverse effects with this drug was a skin change characterized by hair loss, erythema, and pruritus, implying delivery of VDC-1101 to the skin.Hypothesis/objectivesThe primary study objective was to identify the objective response rate (ORR) to VDC-1101 in canine CTCL; secondary objectives included characterization of progression-free survival (PFS) and adverse events (AEs).AnimalsTwelve dogs with chemotherapy-naïve or relapsed, histologically and immunohistochemically confirmed CTCL.MethodsDogs received VDC-1101 as a 30-minute IV infusion once every 21 days. Prednisone (1 mg/kg PO q48h) was administered concurrently.ResultsIn 11 evaluable patients, responses included 1 complete response (CR), 4 partial responses (PR), 2 stable disease (SD), and 4 progressive disease for an ORR of 45% and biologic response rate (CR/PR/SD) of 64%. The median PFS was 37.5 days (26 to >399 days), which includes 1 durable and ongoing CR (>1 year). Gastrointestinal and hematologic AEs were mild; no dogs developed grade 3 or 4 AEs. Three dogs developed dermatopathies and 1 of these dogs was removed from the study as a result of this AE.Conclusions and clinical importanceVDC-1101 has activity against canine CTCL and could provide another treatment option in a disease process with a poor prognosis

Uso de fontes em aulas de História e conciência histórica: encaminhamentos e discussões teóricas

Anais do XVII Congresso Internacional das Jornadas de Educaão História - teoria, pesquisa e prática - I Encontro da AIPEDH - Associação Iber-Americana de Pesquisadores em Educação História, realizado pela Universidade Federal da Integração Latino-Americana, entre 02, 03 e 04 de agosto de 2017.Este trabalho apresenta os encaminhamentos de uma pesquisa iniciada no curso de graduação em História na Universidade Estadual de Londrina, e prossegue como parte das discussões que estão sendo realizadas no Mestrado do Programa de Pós-Graduação em Educação da mesma universidade, sob orientação da Professora Dra. Marlene Rosa Cainelli. A investigação realizada tem como objetivo principal o estudo do uso de fontes no ensino de história, mais especificamente sobre a literatura em aulas de história na perspectiva da Educação Histórica, tendo como tema adaptações do clássico “Os Miseráveis”, de Victor Hugo. A pesquisa atual trata do uso de uma versão em História em Quadrinhos (HQ) da obra, buscando verificar como HQs podem contribuir para o desenvolvimento da consciência histórica dos alunos. Para tanto, utilizamo-nos, entre outros, dos escritos de Rüsen (2011) sobre a consciência histórica e Fronza (2007, 2012) sobre o uso de quadrinhos relacionados a temáticas históricasCAPE

The history of the elephant seal industry at Macquarie Island and an estimate of the pre-sealing numbers

A comprehensive list was compiled of all sealing ships that visited Macquarie Island (54°30'S, 158°57'E) between 1810 and 1919 and, where possible, their cargoes. Approximately 207 sealing visits were made to Macquarie Island in 109 years and an estimated 8380 tuns of elephant seal oil removed. The major sealing effort seems to have been in the first 20 years, between 1810 and 1829, when almost half of the voyages occurred and over half of the oil was collected. For the present study, a mathematical model was devised to examine the responses of the population to the estimated annual harvest of seals from 1810-29. Given the often incomplete nature of the sealing records, accurate estimates of the pre-sealing elephant seal population were impossible to obtain, but the model suggests that it may have been in the region of 93 000 to 110000 animals. The major impact of sealing activity was between 1820 and 1830, when the population was reduced by approximately 70%. Numbers are thought to have recovered to near pre-sealing levels by the 1900's, when the level of sealing was within the sustainable yield of the population. Key Words: elephant seal, sealing industry, sealing ships, Macquarie Islan

Dissecting the genetic basis for seed coat mucilage heteroxylan biosynthesis in plantago ovata using gamma irradiation and infrared spectroscopy

Seeds from the myxospermous species Plantago ovata release a polysaccharide-rich mucilage upon contact with water. This seed coat derived mucilage is composed predominantly of heteroxylan (HX) and is utilized as a gluten-free dietary fiber supplement to promote human colorectal health. In this study, a gamma-irradiated P. ovata population was generated and screened using histological stains and Fourier Transform Mid Infrared (FTMIR) spectroscopy to identify putative mutants showing defects in seed coat mucilage HX composition and/or structure. FTMIR analysis of dry seed revealed variation in regions of the IR spectra previously linked to xylan structure in Secale cereale (rye). Subsequent absorbance ratio and PCA multivariate analysis identified 22 putative mutant families with differences in the HX IR fingerprint region. Many of these showed distinct changes in the amount and subtle changes in structure of HX after mucilage extrusion, while 20% of the putative HX mutants identified by FTMIR showed no difference in staining patterns of extruded mucilage compared to wild-type. Transcriptional screening analysis of two putative reduced xylan in mucilage (rxm) mutants, rxm1 and rxm3, revealed that changes in HX levels in rxm1 correlate with reduced transcription of known and novel genes associated with xylan synthesis, possibly indicative of specific co-regulatory units within the xylan biosynthetic pathway. These results confirm that FTMIR is a suitable method for identifying putative mutants with altered mucilage HX composition in P. ovata, and therefore forms a resource to identify novel genes involved in xylan biosynthesis.Matthew R. Tucker, Chao Ma, Jana Phan, Kylie Neumann, Neil J. Shirley, Michael G. Hahn, Daniel Cozzolino and Rachel A. Burto

Shifting of wrapped phase maps in the frequency domain using a rational number

The number of phase wraps in an image can be either reduced, or completely eliminated, by transforming the image into the frequency domain using a Fourier transform, and then shifting the spectrum towards the origin. After this, the spectrum is transformed back to the spatial domain using the inverse Fourier transform and finally the phase is extracted using the arctangent function. However, it is a common concern that the spectrum can be shifted only by an integer number, meaning that the phase wrap reduction is often not optimal. In this paper we propose an algorithm than enables the spectrum to be frequency shifted by a rational number. The principle of the proposed method is confirmed both by using an initial computer simulation and is subsequently validated experimentally on real fringe patterns. The technique may offer in some cases the prospects of removing the necessity for a phase unwrapping process altogether and/or speeding up the phase unwrapping process. This may be beneficial in terms of potential increases in signal recovery robustness and also for use in time-critical applications

Quantitative determination by real-time PCR of four vaginal Lactobacillus species, Gardnerella vaginalis and Atopobium vaginae indicates an inverse relationship between L. gasseri and L. iners

Background: Most studies of the vaginal microflora have been based on culture or on qualitative molecular techniques. Here we applied existing real-time PCR formats for Lactobacillus crispatus, L. gasseri and Gardnerella vaginalis and developed new formats for Atopobium vaginae, L. iners and L. jensenii to obtain a quantitative non culture-based determination of these species in 71 vaginal samples from 32 pregnant and 28 non-pregnant women aged between 18 and 45 years. Results: The 71 vaginal microflora samples of these women were categorized, using the Ison and Hay criteria, as refined by Verhelst et al. (2005), as follows: grade la: 8 samples, grade lab: 10, grade lb: 13, grade I-like: 10, grade II: 11, grade III: 12 and grade IV: 7. L. crispatus was found in all but 5 samples and was the most frequent Lactobacillus species detected. A significantly lower concentration of L. crispatus was found in grades II (p < 0.0001) and III (p = 0.002) compared to grade I. L. jensenii was found in all grades but showed higher concentration in grade lab than in grade la (p = 0.024). A. vaginae and G. vaginalis were present in high concentrations in grade III, with log(10) median concentrations (log(10) MC), respectively of 9.0 and 9.2 cells/ml. Twenty (38.5%) of the 52 G. vaginalis positive samples were also positive for A. vaginae. In grade II we found almost no L. iners (log(10) MC: 0/ml) but a high concentration of L. gasseri (log(10) MC: 8.7/ml). By contrast, in grade III we found a high concentration of L. iners (log(10) MC: 8.3/ml) and a low concentration of L. gasseri (log(10) MC: 0/ml). These results show a negative association between L. gasseri and L. iners (r = -0.397, p = 0.001) and between L. gasseri and A. vaginae (r = -0.408, p < 0.0001). Conclusion: In our study we found a clear negative association between L. iners and L. gasseri and between A. vaginae and L. gasseri. Our results do not provide support for the generally held proposition that grade II is an intermediate stage between grades I and III, because L. gasseri, abundant in grade II is not predominant in grade III, whereas L. iners, abundant in grade III is present only in low numbers in grade II samples

New generalized fuzzy metrics and fixed point theorem in fuzzy metric space

In this paper, in fuzzy metric spaces (in the sense of Kramosil and Michalek (Kibernetika 11:336-344, 1957)) we introduce the concept of a generalized fuzzy metric which is the extension of a fuzzy metric. First, inspired by the ideas of Grabiec (Fuzzy Sets Syst. 125:385-389, 1989), we define a new G-contraction of Banach type with respect to this generalized fuzzy metric, which is a generalization of the contraction of Banach type (introduced by M Grabiec). Next, inspired by the ideas of Gregori and Sapena (Fuzzy Sets Syst. 125:245-252, 2002), we define a new GV-contraction of Banach type with respect to this generalized fuzzy metric, which is a generalization of the contraction of Banach type (introduced by V Gregori and A Sapena). Moreover, we provide the condition guaranteeing the existence of a fixed point for these single-valued contractions. Next, we show that the generalized pseudodistance J:X×X→[0,∞) (introduced by Włodarczyk and Plebaniak (Appl. Math. Lett. 24:325-328, 2011)) may generate some generalized fuzzy metric NJ on X. The paper includes also the comparison of our results with those existing in the literature

Jumping towards field-based ground reaction force estimation and assessment with OpenCap

Low-cost and field-viable methods that can simultaneously assess external kinetics and kinematics are necessary to enhance field-based biomechanical monitoring. The aim of this study was to determine the accuracy and usability of ground reaction force (GRF) profiles estimated from segmental kinematics, measured with OpenCap (a low-cost markerless motion-capture system), during common jumping movements. Full-body segmental kinematics were recorded for fifteen recreational athletes performing countermovement, squat, bilateral drop, and unilateral drop jumps, and used to estimate vertical GRFs with a mechanics-based method. Eleven distinct performance-, fatigue-, or injury-related GRF variables were then validated against a gold-standard force platform. Across jumping movements, a total of six and three GRF variables were estimated with a bias or limits of agreement <5 % respectively. Bias and limits of agreement were between 5 and 15 % for seventeen and nineteen variables respectively. Moreover, we show that estimated force variables with a bias <15 % can adequately assess the within-athlete changes in GRF variables between jumping conditions (arm swing or leg dominance). These findings indicate that using a low-cost and field-viable markerless motion capture system (OpenCap) to estimate and assess GRF profiles during common jumping movements is approaching acceptable limits of accuracy. The presented method can be used to monitor force variables of interest and examine underlying segmental kinematics. This application is a jump towards researchers and sports practitioners performing biomechanical monitoring of jumping efficiently, regularly, and extensively in field settings