Results of a randomized, double-blind phase II clinical trial of NY-ESO-1 vaccine with ISCOMATRIX adjuvant versus ISCOMATRIX alone in participants with high-risk resected melanoma.

BACKGROUND: To compare the clinical efficacy of New York Esophageal squamous cell carcinoma-1 (NY-ESO-1) vaccine with ISCOMATRIX adjuvant versus ISCOMATRIX alone in a randomized, double-blind phase II study in participants with fully resected melanoma at high risk of recurrence. METHODS: Participants with resected stage IIc, IIIb, IIIc and IV melanoma expressing NY-ESO-1 were randomized to treatment with three doses of NY-ESO-1/ISCOMATRIX or ISCOMATRIX adjuvant administered intramuscularly at 4-week intervals, followed by a further dose at 6 months. Primary endpoint was the proportion free of relapse at 18 months in the intention-to-treat (ITT) population and two per-protocol populations. Secondary endpoints included relapse-free survival (RFS) and overall survival (OS), safety and NY-ESO-1 immunity. RESULTS: The ITT population comprised 110 participants, with 56 randomized to NY-ESO-1/ISCOMATRIX and 54 to ISCOMATRIX alone. No significant toxicities were observed. There were no differences between the study arms in relapses at 18 months or for median time to relapse; 139 vs 176 days (p=0.296), or relapse rate, 27 (48.2%) vs 26 (48.1%) (HR 0.913; 95% CI 0.402 to 2.231), respectively. RFS and OS were similar between the study arms. Vaccine recipients developed strong positive antibody responses to NY-ESO-1 (p≤0.0001) and NY-ESO-1-specific CD4+ and CD8+ responses. Biopsies following relapse did not demonstrate differences in NY-ESO-1 expression between the study populations although an exploratory study demonstrated reduced (NY-ESO-1)+/Human Leukocyte Antigen (HLA) class I+ double-positive cells in biopsies from vaccine recipients performed on relapse in 19 participants. CONCLUSIONS: The vaccine was well tolerated, however, despite inducing antigen-specific immunity, it did not affect survival endpoints. Immune escape through the downregulation of NY-ESO-1 and/or HLA class I molecules on tumor may have contributed to relapse

Vitamin D Receptor Gene Polymorphisms Modify Cardiometabolic Response to Vitamin D Supplementation in T2DM Patients

There is conflicting evidence on the favorable effects of vitamin D supplementation on metabolic profile in Type 2 diabetes mellitus (T2DM) patients and this might be due to genetic variations in vitamin D receptors (VDRs). Thus, we studied the metabolic effects of a 12-month vitamin D supplementation in T2DM patients according to VDR polymorphisms. A total of 204 T2DM subjects received 2000 IU vitamin D3 daily for 12 months. Serum 25(OH)D and metabolic profiles were measured at baseline and after 12 months. VDR polymorphisms (Taq-I, Bsm-I, Apa-I and Fok-I) were identified using TaqMan genotyping assays. Vitamin D supplementation significantly increased HOMA β-cell function (p = 0.003) as well as significantly decreased triglycerides, total and LDL-cholesterol (p < 0.001). The lowest increment in 25(OH)D levels was detected in patients with Fok-I CC genotypes (p < 0.0001). With vitamin D supplementation, Taq-I GG genotype carriers showed significant improvements in triglycerides, LDL- and total cholesterol, insulin, HbA1c and HOMA-IR (p < 0.005, 0.01, < 0.001, < 0.005, 0.03 and 0.01, respectively). Similarly, Bsm-I TT genotype carriers showed significant improvements in triglycerides (p = 0.01), insulin and HOMA-IR (p-values < 0.05). In conclusion, improvements in metabolic profile due to vitamin D supplementation is influenced by VDR polymorphisms, specifically for carriers of Taq-I GG and Bsm-I TT genotypes

Hubble PanCET: An isothermal day-side atmosphere for the bloated gas-giant HAT-P-32Ab

This is the author accepted manuscript. The final version is available from OUP via the DOI in this recordWe present a thermal emission spectrum of the bloated hot Jupiter HAT-P-32Ab from a single eclipse observation made in spatial scan mode with the Wide Field Camera 3 (WFC3) aboard the Hubble Space Telescope (HST). The spectrum covers the wavelength regime from 1.123 to 1.644 microns which is binned into 14 eclipse depths measured to an averaged precision of 104 parts-per million. The spectrum is unaffected by a dilution from the close M-dwarf companion HAT-P-32B, which was fully resolved. We complemented our spectrum with literature results and performed a comparative forward and retrieval analysis with the 1D radiative-convective ATMO model. Assuming solar abundance of the planet atmosphere, we find that the measured spectrum can best be explained by the spectrum of a blackbody isothermal atmosphere with Tp = 1995 +/- 17K, but can equally-well be described by a spectrum with modest thermal inversion. The retrieved spectrum suggests emission from VO at the WFC3 wavelengths and no evidence of the 1.4 micron water feature. The emission models with temperature profiles decreasing with height are rejected at a high confidence. An isothermal or inverted spectrum can imply a clear atmosphere with an absorber, a dusty cloud deck or a combination of both. We find that the planet can have continuum of values for the albedo and recirculation, ranging from high albedo and poor recirculation to low albedo and efficient recirculation. Optical spectroscopy of the planet's day-side or thermal emission phase curves can potentially resolve the current albedo with recirculation degeneracy.NN, DKS and TME acknowledge funding from the European Research Council under the European Unions Seventh Framework Programme (FP7/2007-2013)/ERC grant agreement no. 336792. JG acknowledges support from a Leverhulme Trust Research Project Grant. G.W.H. and M.H.W. acknowledge long-term support from Tennessee State University and the State of Tennessee through its Centers of Excellence program and from the Space Telescope Science Institue under HST-GO-14767. This work has been carried out in the frame of the National Centre for Competence in Research PlanetS supported by the Swiss National Science Foundation (SNSF). DE and VB acknowledge the financial support of the SNSF. This project has received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (project FOUR ACES; grant agreement No 724427)

Improving the Deaf community's access to prostate and testicular cancer information: a survey study

BACKGROUND: Members of the Deaf community face communication barriers to accessing health information. To resolve these inequalities, educational programs must be designed in the appropriate format and language to meet their needs. METHODS: Deaf men (102) were surveyed before, immediately following, and two months after viewing a 52-minute prostate and testicular cancer video in American Sign Language (ASL) with open text captioning and voice overlay. To provide the Deaf community with information equivalent to that available to the hearing community, the video addressed two cancer topics in depth. While the inclusion of two cancer topics lengthened the video, it was anticipated to reduce redundancy and encourage men of diverse ages to learn in a supportive, culturally aligned environment while also covering more topics within the partnership's limited budget. Survey data were analyzed to evaluate the video's impact on viewers' pre- and post-intervention understanding of prostate and testicular cancers, as well as respondents' satisfaction with the video, exposure to and use of early detection services, and sources of cancer information. RESULTS: From baseline to immediately post-intervention, participants' overall knowledge increased significantly, and this gain was maintained at the two-month follow-up. Men of diverse ages were successfully recruited, and this worked effectively as a support group. However, combining two complex cancer topics, in depth, in one video appeared to make it more difficult for participants to retain as many relevant details specific to each cancer. Participants related that there was so much information that they would need to watch the video more than once to understand each topic fully. When surveyed about their best sources of health information, participants ranked doctors first and showed a preference for active rather than passive methods of learning. CONCLUSION: After viewing this ASL video, participants showed significant increases in cancer understanding, and the effects remained significant at the two-month follow-up. However, to achieve maximum learning in a single training session, only one topic should be covered in future educational videos

Health Locus of Control and Assimilation of Cervical Cancer Information in Deaf Women

This study assessed the relationship between Deaf women's internal health locus of control (IHLC) and their cervical cancer knowledge acquisition and retention. A blind, randomized trial evaluated Deaf women's (N = 130) baseline cancer knowledge and knowledge gained and retained from an educational intervention, in relation to their IHLC. The Multidimensional Health Locus of Control scales measured baseline IHLC, and a cervical cancer knowledge survey evaluated baseline to post-intervention knowledge change. Women's IHLC did not significantly predict greater cervical cancer knowledge at baseline or over time. IHLC does not appear to be a characteristic that must be considered when creating Deaf women's cancer education programs

Saccadic Eye Movement Abnormalities in Children with Epilepsy

Childhood onset epilepsy is associated with disrupted developmental integration of sensorimotor and cognitive functions that contribute to persistent neurobehavioural comorbidities. The role of epilepsy and its treatment on the development of functional integration of motor and cognitive domains is unclear. Oculomotor tasks can probe neurophysiological and neurocognitive mechanisms vulnerable to developmental disruptions by epilepsy-related factors. The study involved 26 patients and 48 typically developing children aged 8–18 years old who performed a prosaccade and an antisaccade task. Analyses compared medicated chronic epilepsy patients and unmedicated controlled epilepsy patients to healthy control children on saccade latency, accuracy and dynamics, errors and correction rate, and express saccades. Patients with medicated chronic epilepsy had impaired and more variable processing speed, reduced accuracy, increased peak velocity and a greater number of inhibitory errors, younger unmedicated patients also showed deficits in error monitoring. Deficits were related to reported behavioural problems in patients. Epilepsy factors were significant predictors of oculomotor functions. An earlier age at onset predicted reduced latency of prosaccades and increased express saccades, and the typical relationship between express saccades and inhibitory errors was absent in chronic patients, indicating a persistent reduction in tonic cortical inhibition and aberrant cortical connectivity. In contrast, onset in later childhood predicted altered antisaccade dynamics indicating disrupted neurotransmission in frontoparietal and oculomotor networks with greater demand on inhibitory control. The observed saccadic abnormalities are consistent with a dysmaturation of subcortical-cortical functional connectivity and aberrant neurotransmission. Eye movements could be used to monitor the impact of epilepsy on neurocognitive development and help assess the risk for poor neurobehavioural outcomes

Congenital Chagas Disease: Recommendations for Diagnosis, Treatment and Control of Newborns, Siblings and Pregnant Women

SCOPUS: ar.jinfo:eu-repo/semantics/publishe

An optical transmission spectrum for the ultra-hot Jupiter WASP-121b measured with the Hubble Space Telescope

This is the author accepted manuscript. The final version is available from American Astronomical Society / IOP Publishing via the DOI in this record.We present an atmospheric transmission spectrum for the ultra-hot Jupiter WASP-121b, measured using the Space Telescope Imaging Spectrograph (STIS) onboard the Hubble Space Telescope (HST). Across the 0.47-1 micron wavelength range, the data imply an atmospheric opacity comparable to - and in some spectroscopic channels exceeding - that previously measured at near-infrared wavelengths (1.15-1.65 micron). Wavelength-dependent variations in the opacity rule out a gray cloud deck at a confidence level of 3.8-sigma and may instead be explained by VO spectral bands. We find a cloud-free model assuming chemical equilibrium for a temperature of 1500K and metal enrichment of 10-30x solar matches these data well. Using a free-chemistry retrieval analysis, we estimate a VO abundance of -6.6(-0.3,+0.2) dex. We find no evidence for TiO and place a 3-sigma upper limit of -7.9 dex on its abundance, suggesting TiO may have condensed from the gas phase at the day-night limb. The opacity rises steeply at the shortest wavelengths, increasing by approximately five pressure scale heights from 0.47 to 0.3 micron in wavelength. If this feature is caused by Rayleigh scattering due to uniformly-distributed aerosols, it would imply an unphysically high temperature of 6810+/-1530K. One alternative explanation for the short-wavelength rise is absorption due to SH (mercapto radical), which has been predicted as an important product of non-equilibrium chemistry in hot Jupiter atmospheres. Irrespective of the identity of the NUV absorber, it likely captures a significant amount of incident stellar radiation at low pressures, thus playing a significant role in the overall energy budget, thermal structure, and circulation of the atmosphere.Support for program GO-14767 was provided by NASA through a grant from the Space Telescope Science Institute, which is operated by the Association of Universities for Research in Astronomy, Inc., under NASA contract NAS 5-26555. T.M.E., D.K.S., and N.N. acknowledge funding from the European Research Council under the European Unions Seventh Framework Programme (FP7/2007-2013)/ERC grant agreement no. 336792. G.W.H. and M.H.W. acknowledge support from Tennessee State University and the State of Tennessee through its Centers of Excellence program. J.S.F. acknowledges funding by the Spanish MINECO grant AYA2016-79425-C3-2-P. J.K.B. is supported by a Royal Astronomical Society Research Fellowship. This work has been carried out in the frame of the National Centre for Competence in Research PlanetS supported by the Swiss National Science Foundation (SNSF). V.B. and D.E. have received funding from the European Research Council (ERC) under the European Unions Horizon 2020 research and innovation programme (project Four Aces; grant agreement no. 724427)

Drugs in early clinical development for the treatment of osteosarcoma

Introduction: Osteosarcomas are the main malignant primary bone tumours found in children and young adults. Conventional treatment is based on diagnosis and resection surgery, combined with polychemotherapy. This is a protocol that was established in the 1970s. Unfortunately, this therapeutic approach has reached a plateau of efficacy and the patient survival rate has not improved in the last four decades. New therapeutic approaches are thus required to improve the prognosis for osteosarcoma patients. Areas covered: From the databases available and published scientific literature, the present review gives an overview of the drugs currently in early clinical development for the treatment of osteosarcoma. For each drug, a short description is given of the relevant scientific data supporting its development. Expert opinion: Multidrug targeted approaches are set to emerge, given the heterogeneity of osteosarcoma subtypes and the multitude of therapeutic responses. The key role played by the microenvironment in the disease increases the number of therapeutic targets (such as macrophages or osteoclasts), as well as the master proteins that control cell proliferation or cell death. Ongoing phase I/II trials are important steps, not only for identifying new therapies with greater safety and efficacy, but also for better defining the role played by the microenvironment in the pathogenesis of osteosarcoma

Tracking of sport and exercise types from midlife to old age: a 20-year cohort study of British men.

Background: Previous physical activity (PA) tracking studies have examined the stability of overall PA and/or PA types, but few have investigated how specific types of sport/exercise track over the life course. The aim of this study was to determine how specific sports/exercises in midlife track and predict future sport/exercise and PA in men transitioning to old age. Methods: Seven thousand seven hundred thirty-five men (aged 40-59 years) recruited in 1978-80 were followed up after 12, 16 and 20 years. At each wave men self-reported participation in sport/exercise. Frequent sport/exercise participants (> 1/month) reported the types of sport/exercise they engaged in. Men also reported total PA, health status, lifestyle behaviours and socio-demographic characteristics. Stability of each sport/exercise was assessed using kappa statistics and intraclass correlation coefficients. Logistic regression estimated the odds of participating in sport/exercise and being active at 20-year follow up according to specific types of sport/exercise in midlife. Results: Three thousand three hundred eighty-four men with complete data at all waves were included in analyses. Tracking of specific sports/exercises ranged from fair to substantial, with golf being the most common and most stable. Bowls was the most frequently adopted. Odds of participating in sport/exercise and being active in old age varied according to sport/exercise types in midlife. Golf and bowls in midlife were the strongest predictors of sport/exercise participation in old age. Golf, cricket and running/jogging in midlife were among the strongest predictors of being active in old age. Compared to participating in just one sport/exercise in midlife, sampling multiple sports/exercises was more strongly associated with sport/exercise participation and being active in old age. Conclusion: The stability of sport/exercise participation from midlife to old age varies by type. Specific sports/exercises in midlife may be more likely to predict future PA than others. However, participating in a range of sports/exercises may be optimal for preserving PA into old age