Miracle-dz/UniFAR-FTUs huggingface dataset:
Interpreting Clinical Trials in Lung Cancer: Impact of Methodology and Endpoints

The design and analysis of clinical trials are crucial if we are confidently to answer important questions regarding the treatment of patients with non-small cell lung cancer. Survival, response, and quality of life (QoL) are considered the key endpoints of oncology clinical trials. Survival is the primary endpoint of most randomized, phase III clinical trials, but small improvements in survival are difficult to detect without a sufficiently large sample size. Meta-analysis is a useful technique to increase statistical precision and better estimate the magnitude of a treatment effect. Although survival data guide treatment choice, the objective response is generally the parameter used to evaluate treatment in the clinic, despite its inherent unreliability. The objective response rate remains an important outcome for early phase clinical trials. QoL, which is a particularly important trial endpoint if survival differences are unlikely may, however, be a more relevant outcome in the clinic. Several validated QoL tools are available for use both in trials and in daily practice, but many clinicians do not routinely assess QoL when evaluating an individual patient's response to treatment. Recent advances in electronic technology make capturing QoL data at each office visit not only possible but practical, reliable, and useful for both patients and clinicians. Therefore, although survival, response, and QoL can all be relevant clinical trial endpoints, QoL may be the most relevant endpoint to assess in the clinic.
Living Mathematx: Towards a Vision for the Future.

This paper offers specific implications for teaching and learning and brings into conversation ideas from ethnomathematics (including Western mathematics), postcolonial theory, aesthetics, biology, and Indigenous knowledge in order to propose a new vision for practicing mathematics, what I call mathematx. I build upon the work of sustainability in mathematics education and suggest we need to think not only about more ethical ways of applying mathematics in teaching and learning but question the very nature of mathematics, who does it, and how we are affected by that practice.
Analysis of Immune Responses Directed toward a Recombinant Early Secretory Antigenic Target Six-Kilodalton Protein-Culture Filtrate Protein 10 Fusion Protein in Mycobacterium bovis-Infected Cattle

ABSTRACT Cell-mediated immune responses are critical for protective immunity to mycobacterial infections. Recent progress in defining mycobacterial antigens has determined that region of difference 1 (RD1) gene products induce strong T-cell responses, particularly the early secretory antigenic target 6-kDa (ESAT-6) protein and culture filtrate protein 10 (CFP10). However, comprehensive analysis of the immune response towards these antigens is incompletely characterized. To evaluate recall responses to ESAT-6 and CFP10, peripheral blood mononuclear cells from M. bovis-infected cattle were stimulated in vitro with a recombinant ESAT-6 (rESAT-6)-CFP10 fusion protein and compared to responses induced by M. bovis-derived purified protein derivative. Following antigenic stimulation, activation marker expression was evaluated. Significant proliferative responses (P < 0.05) were evident in CD4+, CD8+, immunoglobulin M-positive, and CD172a+ cell fractions after 6 days of culture. Expression of CD25 and CD26 was increased (P < 0.05) on CD4+, CD8+, and γδ T-cell-receptor-positive cells. CD4+ and CD8+ cells also exhibited significant changes (P < 0.05) in expression of CD45 isoforms. Using a flow cytometry-based proliferation assay, it was determined that CD45R expression is downregulated (P < 0.05) and that CD45RO expression is upregulated (P < 0.05) on proliferating (i.e., activated) CD4+ cells. Collectively, data indicate that recall immune responses directed toward the rESAT-6-CFP10 fusion protein or purified protein derivative are comparable and that recall to mycobacterial antigens correlates with a CD45RO+ phenotype.
Does time stop when we blink?

Visual perception appears nearly continuous despite frequent disruptions of the input caused by saccades and blinks. While research has focused on perception around saccades, blinks also constitute a drastic perturbation of vision, leading to a complete interruption of the visual input that lasts about 100ms but that we barely notice. Does the visual system actively fill in the missing information or does it simply ignore it? We addressed this question in two experiments in which observers judged the durations of brief visual stimuli in different temporal relations to blinks, using the method of single stimuli. In the first experiment stimuli either straddled the entire blink (onset before the start and offset after the end of the blink), or onset 200ms after the end of the blink. An analysis of the relative biases in the two conditions revealed that stimuli that straddled the blink appeared as 90ms briefer than those that followed the blink-a difference equal to about 77% of the mean blink duration. In a second experiment, the stimulus straddled the end of the blink (onset during the blink, offset after the end), or onset either just after or 200ms following the end of the blink. The optically visible durations of the stimuli that straddled the end of the blink were overestimated by about 20ms in comparison to stimuli that appeared long after. Significantly, we found that in both experiments the duration errors were correlated with trial-by-trial variations in blink durations. Thus, our results suggest that the default mode of the visual system is to ignore the absence of information during blinks. However, in the case of unexpected events, vision partially fills in the blink. Meeting abstract presented at VSS 2015.
Surveillance of Childhood Influenza Virus Infection: What Is the Best Diagnostic Method To Use for Archival Samples?

ABSTRACT Despite the clinical importance of influenza virus in pediatric respiratory infections, the optimal set of diagnostic tests to use when conducting studies using archival samples is not clear. In this study, we compared diagnostic tests for influenza virus in 75 children younger than 5 years of age who presented with symptomatic respiratory infection during one of four influenza seasons, had negative viral cultures for other respiratory pathogens, and had both an archival nasal aspirate obtained at the time of illness and serology spanning that influenza season. For all eligible children, we compared the results of viral culture performed at the time of collection with serology and PCR of archival nasal aspirates. Using real-time viral culture as the “gold standard,” the test characteristics of PCR of archival nasal aspirates (sensitivity, 82%; specificity, 100%) and serology (sensitivity, 82%; specificity, 87%) were similar. The relatively low sensitivity of PCR of archival nasal samples in this study compared to that of PCR of fresh samples in a previous study suggests that RNA degradation occurred despite storage of the specimens at −70°C. RNA degradation would also explain why only 11 (52%) of 21 archival nasal samples that had positive influenza virus cultures at the time of collection had positive repeat cultures in the summer of 2000. Thus, in archival specimens stored at −70°C, PCR was more sensitive than viral culture. However, testing of fresh specimens had the highest yield in this study. Studies of optimal methods for specimen storage are needed.
Resuscitating real interest rate parity: new evidence from panels

ABSTRACT This paper considers the real interest rate parity (RIRP) in OECD countries applying a sequential panel selection (SPS) method on alternative panel unit-root tests. Our approach exploits the enhanced power of panels to uncover evidence of stationarity, but also identifies the exact countries for which the RIRP holds in a panel. Moreover, we construct real interest rate measures using alternative approaches, including a Markov regime-switching procedure, which is consistent with the forward-looking nature of inflation expectations formation. Considering US as the benchmark economy, we produce strong evidence of stationarity in real interest rate differentials, which resuscitates RIRP, especially given the inconclusive results in the related literature. Our results are robust to different panel unit-root tests, measures of inflation expectations, and interest rate maturities. The RIRP appears quite resilient in the face of the global financial crisis and the low real interest rate environment after the great recession. The SPS allows to calculate half-lives, which avoid the pitfalls of over/underestimating the speed of adjustment and are lower as compared to the typical estimates in the literature.
Selection of immunostimulant AS15 for active immunization with MAGE-A3 protein: results of a randomized phase II study of the European Organisation for Research and Treatment of Cancer Melanoma Group in Metastatic Melanoma.

PURPOSE Active immunization against the tumor-specific MAGE-A3 antigen is followed by a few but impressive and durable clinical responses. This randomized phase II trial evaluated two different immunostimulants combined with the MAGE-A3 protein to investigate whether a more robust and persistent immune response could be associated with increased clinical benefit. PATIENTS AND METHODS Patients with MAGE-A3-positive stage III or IV M1a melanoma were randomly assigned to receive the MAGE-A3 protein combined either with AS02B or with AS15 immunostimulant. Clinical end points were toxicity and rates of objective clinical responses, progression-free survival (PFS), and overall survival (OS). RESULTS Seventy-five patients were treated, with 36 eligible patients per arm. Both treatments were well tolerated. In the AS15 arm, four objective responses were observed (three complete responses and one partial response) versus one partial response in the AS02B arm. In the AS15 and AS02B arms, the PFS rates after 6 months were 25% and 14%, respectively; and the median OS times were 33 months and 19.9 months, respectively, with a median observation period of 48 months. Antibodies against MAGE-A3, found in all patients, showed three-fold higher titers in the AS15 arm. The anti-MAGE-A3 cellular response was also more pronounced in the AS15 arm. CONCLUSION In the MAGE-A3+AS15 arm, clinical activity was higher and the immune response more robust. Therefore, the AS15 immunostimulant was selected for combination with the MAGE-A3 protein in phase III trials.
Tumor Burden Modeling Versus Progression-Free Survival for Phase II Decision Making

Randomized Phase II oncology trial endpoints for decision making include both progression-free survival (PFS) and change in tumor burden as measured by the sum of longest diameters (SLD) of the target lesions. In addition to observed SLD changes, tumor shrinkage and growth parameters can be estimated from the patient-specific SLD profile over time. The ability of these SLD analyses to identify an active drug is contrasted with that of a PFS analysis through the simulation of Phase II trials via resampling from each of 6 large, Phase II and III trials, 5 of which were positive and one negative. From each simulated Phase II trial, a P value was obtained from 4 analyses—a log-rank test on PFS, a Wilcoxon rank-sum test on the minimum observed percentage change from baseline in SLD, and 2 nonlinear, mixed-effects model analyses of the SLD profiles. All 4 analyses led to approximately uniformly distributed P values in the negative trial. The PFS analysis was the best or nearly the best analysis in the other 5 trials. In only one of the positive studies did the modeling analysis outperform the analysis of the minimum SLD. In conclusion, for the decision to start a Phase III trial based on the results of a randomized Phase II trial of an oncology drug, PFS appears to be a better endpoint than does SLD, whether analyzed through simple SLD endpoints, such as the minimum percentage change from baseline, or through the modeling of the SLD time course to estimate tumor dynamics. Clin Cancer Res; 19(2); 314–9. ©2012 AACR.
Characteristics of effective nutrition-agricultural extension interventions: Lessons from civil society extension organizations in Uganda

Conventional agricultural extension interventions have focused on production objectives with limited attention on nutrition. Recently, there has been a new thrust by the international and regional organizations as well as national governments to adopt extension interventions that engage farmers to improve their dietary practices and achieve nutrition outcomes. However, little has been documented on how these extension interventions can effectively facilitate the desired changes. The objective of the study was to identify characteristics of extension interventions that facilitate changes in farmers’ dietary practices. The study was conducted in Kihihi and Nyamirama subcounties of Kanungu District in South-western, Uganda. These communities are served by two civil society extension organizations; Africa2000Network (A2N) and Community Connector (CC). Nine in-depth Focus Group Discussions (FGDs) with 98 farmers were conducted to collect qualitative data about the interventions and their effect on farmers’ dietary practices. Two FGDs were conducted with extension workers to complement the farmers’ opinions. Results show that interventions that involve both men and women for trainings facilitated positive changes in dietary practices. Messages that go beyond food production and intake to include hygiene fostered positive change in the dietary practices. Furthermore, methods that were considered effective engaged farmers beyond formal training settings and included entertainment by incorporating drama, songs, and radio talk shows during their leisure time. Drama was pointed out as the most effective method. Conversely, individual methods mainly farmer-to-farmer visits and individual-learning through reading nutrition books were not well rated by farmers. Thus, the extension interventions that mix a variety of methods, more especially those that target men and women; reach farmers during their leisure time; train farmers on food production, food in-take, household hygiene and savings; conduct activities in accessible venues; and partner with universities to incorporate research findings to inform their design; facilitate positive changes in farmers’ dietary practices.
Essays on liquidity commonality in equity markets

This thesis contributes to the emerging literature that investigates the drivers of liquidity commonality in equity markets. Our main contribution is three- fold. First, we propose a new method to estimate liquidity commonality in equity markets to explore both supply-side (funding liquidity of intermediaries) and demand-side (trading behaviour of investors) determinants of its dynamics. The empirical analysis uses weekly data on 1909 stocks from the US, Japan, the UK and Euro zone countries, from January 2000 to January 2017. Second, we propose high-frequency quoting (HFQ), an activity carried out by high-frequency traders (HFT), as a new supply-side explanation of high-frequency liquidity commonality. Using the upgrade of the London Stock Exchange (LSE) trading system as an exogenous shock, we find that an increase in HFQ leads to an increase in liquidity commonality. Furthermore, we analyse the intraday patterns in high-frequency liquidity provision in relation to other microstructure variables, using tick-by-tick data for the FTSE100 stocks listed on the LSE, from September 2010 to July 2011. Finally, motivated by the crucial role of factor models in our research, we propose a two-level factor model with time-varying loadings that captures financial, global and regional risk in stock returns. We use it to investigate the dynamics of systematic risk in a large portfolio of firms from 54 countries, from January 2006 to January 2016.
Phosphorylation by cdc2-CyclinB1 Kinase Releases Cytoplasmic Dynein from Membranes*

Movement of various cargoes toward microtubule minus ends is driven by the microtubule motor cytoplasmic dynein (CD). Many cargoes are motile only during certain cell cycle phases, suggesting that CD function may be under cell cycle control. Phosphorylation of the CD light intermediate chain (DLIC) has been suggested to play a crucial role in modulating CD function during theXenopus embryonic cell cycle, where CD-driven organelle movement is active in interphase but greatly reduced in metaphase. This down-regulation correlates with hyperphosphorylation of DLIC and release of CD from the membrane. Here we investigate the role of the key mitotic kinase, cdc2-cyclinB1, in this process. We show that DLIC within the native Xenopus CD complex is an excellent substrate for purified Xenopus cdc2-glutathioneS-transferase (GST) cyclinB1 (cdc2-GSTcyclinB1) kinase. Mass spectrometry of native DLIC revealed that a conserved cdc2 site (Ser-197) previously implicated in the metaphase modulation of CD remains phosphorylated in interphase and so is unlikely to be the key regulatory site. We also demonstrate that incubating interphase membranes with cdc2-GSTcyclinB1 kinase results in substantial release of CD from the membrane. These data suggest that phosphorylation of DLIC by cdc2 kinase leads directly to the loss of membrane-associated CD and an inhibition of organelle movement.
Assessment of the frequency of the 22q11 deletion in Afrikaner schizophrenic patients

A hemizygous deletion of the q11 band on chromosome 22 occurs in 1 of every 5,950 live births (0.017%). The deletion is mediated by low copy repeats (LCRs) flanking this locus. Presence of the deletion is associated with variable phenotypic expression, which can include distinctive facial dysmorphologies, congenital heart disease and learning disabilities. An unusually high percentage of individuals with this deletion (25–30%) have been described to develop schizophrenia or schizoaffective disorder. In previous studies, the prevalence of the 22q11 deletion in patients with schizophrenia was found to be approximately 2% in Caucasian adults and 6% in childhood‐onset cases. Both these frequencies represent a dramatic increase from the prevalence of the deletion in the general population. In this study, we investigate the occurrence of the 22q11 deletion in an independent sample of schizophrenic patients of Afrikaner origin. We first ascertained a sample of 85 patients who meet full diagnostic criteria for schizophrenia for presence of two or more of the clinical features associated with presence of the 22q11 deletion. A group of six patients (7%) met these criteria. This group was subjected to fluorescent in situ hybridization (FISH) and presence of the 22q11 deletion was confirmed for two subjects. Our study therefore confirms the previously reported rate of 2% frequency of the 22q11 deletion in adult schizophrenic patients and provides a two‐stage screening protocol to identify these patients. © 2004 Wiley‐Liss, Inc.
Crosstalk Evaluation in Stereoscopic Displays

Substantial progress in liquid-crystal display and polarization film technology has enabled several types of stereoscopic displays. Despite all progress, some image distortions still exist in these 3-D displays, of which interocular crosstalk-light leakage of the image for one eye to the other eye-is probably the most annoying. The aim of the current research is to investigate how the two most important physical quantities, contrast and binocular disparity, influence crosstalk perception. Images consisting of a single character and varying in contrast and disparity were computer-generated to measure crosstalk visibility and acceptability thresholds for two stereoscopic displays; one display was based on active shutter glasses, and the other on passive glasses. Results show that, under the same experimental condition, there is no significant difference in crosstalk perception between both 3-D display technologies. Crosstalk annoyance increases with increasing contrast and disparity, i.e., less crosstalk is allowed for higher levels of contrast and disparity. Based on the experimental results, an analytical formula for predicting crosstalk perception is proposed.
Homocysteine and Alzheimer's Disease: Evidence for a Causal Link from Mendelian Randomization.

BACKGROUND/OBJECTIVE The relationship between plasma homocysteine (Hcy) levels and Alzheimer's disease (AD) has been studied for many years, but remains controversial. While a recent meta-analysis of epidemiological studies, which included observational studies, indicated that homocysteine may be a risk factor for AD, there remains a need to further demonstrate this link due to the large degree of heterogeneity between studies. Epidemiological studies have certain limitations, as their results can be affected by confounding factors and reverse causation. In this study, we evaluated the relationship between plasma homocysteine and AD by using a Mendelian randomization method to avoid problems of confounding bias and reverse causality. METHODS We searched the PubMed and EMBASE databases for reports regarding the MTHFR C677T polymorphism (rs1801133) from the time of their inception to September 2015. These reports were combined with related observational studies, and used to evaluate the effect of MTHFR C677T (rs1801133) on the risk for AD. A recent meta-analysis of genome-wide association studies had previously suggested a relationship between homocysteine and MTHFR C677T (rs 1801133). RESULTS Our met-analysis included 34 studies with 9397 subjects, and demonstrated a significant relationship between plasma total homocysteine levels and the risk for AD (OR = 3.37; 95% CI = 1.90-5.95; p = 2.9×10-5). CONCLUSION Our meta-analysis demonstrated a causal link between plasma total homocysteine and the risk for AD, and provides a new insight into the etiology and prevention of AD.
Pathologic changes associated with androgen deprivation therapy for prostate cancer

Prostate glands exposed to androgen deprivation with leuprolide ± flutamide were evaluated for pathologic changes which might be related to therapy. Comparing pretreatment and posttreatment tissue by visual discrimination using light microscopic study revealed treatment‐related alterations in the size and distribution of neoplastic glands in 60% of cases. Quantitative measurements documented glandular changes in an even greater percentage of cases. Although distinctive, the histologic pattern was not specific for leuprolide/flutamide. The absence of appreciable degeneration and necrosis in tumor cells suggests that this type of androgen deprivation may act through suppression rather than ablation of prostatic cancers. The relationship between treatment‐related histologic effects and initial tumor grade and clinical stage as well as expression of prostate‐specific antigen was studied. Accurate histologic assessment of leuprolide/flutamide‐treated prostate glands should not be a problem so long as specimens are thoroughly examined and drug‐related variations in tumor morphologic features are appreciated.