350 research outputs found
Explorations into Appendicular Ontogeny using a Cross-Sectional, Contemporary U.S. Sample
Investigations into the subadult skeleton have been restricted by sample availability in biological anthropology. Alternatively, the same source of longitudinal data has been repeatedly used, which does not reflect the variability of growth and development (i.e., ontogeny) or the United States (U.S.) population. Small and/or homogenous samples have often resulted in limited or inappropriate modeling choices to investigate the growth and development and variation of the subadult skeleton. Recent technological advancements have made virtual anthropology possible. The use of computed tomography (CT) scans has opened the doors to increasing sample sizes of minority groups and in turn increasing the variation of skeletal information. One repository, the Subadult Virtual Anthropology Database (SVAD), has focused on increasing and diversifying subadult skeletal data to increase the possibilities of subadult research in biological anthropology. The articles in this (non)dissertation collection use the SVAD (M=610, F=416) and the Forensic Anthropology Data Bank (FDB; M=285, F=161) to evaluate three different perspectives of appendicular (i.e., long bone) ontogeny: absolute, relative, and index. First, relative long bone lengths and nonlinear modeling are used as the first-ever evaluation of long bone growth through adult stabilization. Second, the brachial and crural indices are used to explore the chronological ontogenetic trajectories of each index and their ecogeographic patterns. Third, absolute long bone breadth and length measurements are used to create linear and nonlinear equations for estimating subadult stature for forensic application. In doing so, this is the first comprehensive collection of studies that explore three distinct perspectives of long bone ontogeny and variation from the same source of subadult skeletal data, demonstrating the need for additional contemporary subadult samples and novel modeling approaches
Differentially Oblivious Database Joins: Overcoming the Worst-Case Curse of Fully Oblivious Algorithms
Numerous high-profile works have shown that access patterns to even encrypted databases can leak secret information and sometimes even lead to reconstruction of the entire database. To thwart access pattern leakage, the literature has focused on oblivious algorithms, where obliviousness requires that the access patterns leak nothing about the input data.
In this paper, we consider the Join operator, an important database primitive that has been extensively studied and optimized. Unfortunately, any fully oblivious Join algorithm would require always padding the result to the worst-case length which is quadratic in the data size N. In comparison, an insecure baseline incurs only O(R + N) cost where R is the true result length, and in the common case in practice, R is relatively short. As a typical example, when R = O(N), any fully oblivious algorithm must inherently incur a prohibitive, N-fold slowdown relative to the insecure baseline. Indeed, the (non-private) database and algorithms literature invariably focuses on studying the instance-specific rather than worst-case performance of database algorithms. Unfortunately, the stringent notion of full obliviousness precludes the design of efficient algorithms with non-trivial instance-specific performance.
To overcome this worst-case performance barrier of full obliviousness and enable algorithms with good instance-specific performance, we consider a relaxed notion of access pattern privacy called (?, ?)-differential obliviousness (DO), originally proposed in the seminal work of Chan et al. (SODA\u2719). Rather than insisting that the access patterns leak no information whatsoever, the relaxed DO notion requires that the access patterns satisfy (?, ?)-differential privacy. We show that by adopting the relaxed DO notion, we can obtain efficient database Join mechanisms whose instance-specific performance approximately matches the insecure baseline, while still offering a meaningful notion of privacy to individual users. Complementing our upper bound results, we also prove new lower bounds regarding the performance of any DO Join algorithm.
Differential obliviousness (DO) is a new notion and is a relatively unexplored territory. Following the pioneering investigations by Chan et al. and others, our work is among the very first to formally explore how DO can help overcome the worst-case performance curse of full obliviousness; moreover, we motivate our work with database applications. Our work shows new evidence why DO might be a promising notion, and opens up several exciting future directions
Adore: Differentially Oblivious Relational Database Operators
There has been a recent effort in applying differential privacy on memory
access patterns to enhance data privacy. This is called differential
obliviousness. Differential obliviousness is a promising direction because it
provides a principled trade-off between performance and desired level of
privacy. To date, it is still an open question whether differential
obliviousness can speed up database processing with respect to full
obliviousness. In this paper, we present the design and implementation of three
new major database operators: selection with projection, grouping with
aggregation, and foreign key join. We prove that they satisfy the notion of
differential obliviousness. Our differentially oblivious operators have reduced
cache complexity, runtime complexity, and output size compared to their
state-of-the-art fully oblivious counterparts. We also demonstrate that our
implementation of these differentially oblivious operators can outperform their
state-of-the-art fully oblivious counterparts by up to .Comment: VLDB 202
Randomized phase 2 trial of regadenoson for treatment of acute vaso-occlusive crises in sickle cell disease
Examining Intercultural Interaction in Hong Kong Residential Halls
The integration of non-local students into their host environments and their ability to develop meaningful local relationships are concerns for researchers, educators, and policymakers. Given the increased diversity of higher educational settings, a deeper understanding of these topics can help residential halls better accommodate students from various cultures, improve students’ residential experiences, and enhance their relationships with their peers. Research on these issues has focused mainly on Western universities; this study aims to explore the acculturation dynamics of residential education through focus-group interviews with 14 Mainland Chinese undergraduates living in residential halls in Hong Kong. The findings reveal that although the residential experience can engender interpersonal conflict, it can also foster intercultural interaction, help build a sense of belonging, and create the conditions for overcoming barriers and difficulties. The findings indicate that future programmes can improve adjustment outcomes in residential halls by creating a more welcoming environment for non-local students
Mixed cumulative probit : a multivariate generalization of transition analysis that accommodates variation in the shape, spread and structure of data
DATA AVAILABITY STATEMENT: The data and analyses are all freely available. The data used in the current study are available in the Zenodo Subadult Virtual Anthropology Database Community: https://doi.org/10.5281/zenodo.5193208 [71]. The vignette is freely available here: https://rpubs.com/elainechu/mcp_vignette. The relevant code for this work is stored in GitHub: https://github.com/michaelholtonprice/rsos_mcp_intro and has been archived within the Zenodo repository: https://doi.org/10.5281/zenodo.7603754 [72].SUPPORTING INFORMATION: FILE S1: Supplemental material is hosted by figshare.Biological data are frequently nonlinear, heteroscedastic and conditionally dependent, and often researchers deal with missing data. To account for characteristics common in biological data in one algorithm, we developed the mixed cumulative probit (MCP), a novel latent trait model that is a formal generalization of the cumulative probit model usually used in transition analysis. Specifically, the MCP accommodates heteroscedasticity, mixtures of ordinal and continuous variables, missing values, conditional dependence and alternative specifications of the mean response and noise response. Cross-validation selects the best model parameters (mean response and the noise response for simple models, as well as conditional dependence for multivariate models), and the Kullback–Leibler divergence evaluates information gain during posterior inference to quantify mis-specified models (conditionally dependent versus conditionally independent). Two continuous and four ordinal skeletal and dental variables collected from 1296 individuals (aged birth to 22 years) from the Subadult Virtual Anthropology Database are used to introduce and demonstrate the algorithm. In addition to describing the features of the MCP, we provide material to help fit novel datasets using the MCP. The flexible, general formulation with model selection provides a process to robustly identify the modelling assumptions that are best suited for the data at hand.The National Institute of Justice and the National Science Foundation.https://royalsocietypublishing.org/journal/rsosAnatomySDG-03:Good heatlh and well-bein
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Replication and Meta-analysis of the Association between BDNF Val66Met Polymorphism and Cognitive Impairment in Patients Receiving Chemotherapy.
Cancer-related cognitive impairment (CRCI) adversely affects cancer patients. We had previously demonstrated that the BDNF Val66Met genetic polymorphism is associated with lower odds of subjective CRCI in the multitasking and verbal ability domains among breast cancer patients receiving chemotherapy. To further assess our previous findings, we evaluated the association of BDNF Val66Met polymorphism with subjective and objective CRCI in a temporally separate cohort of patients and pooled findings from both the original (n = 145) and current (n = 193) cohorts in a meta-analysis. Subjective CRCI was assessed using FACT-Cog. Objective CRCI was evaluated using computerized neuropsychological tests. Genotyping was carried out using Sanger sequencing. The association of BDNF Val66Met genotypes and CRCI was examined with logistic regression. A fixed-effect meta-analysis was conducted using the inverse variance method. In the meta-analysis (n = 338), significantly lower odds of CRCI were associated with Met allele carriers based on the global FACT-Cog score (OR = 0.52, 95% CI 0.29-0.94). Furthermore, Met allele carriers were at lower odds of developing impairment in the domains of memory (OR = 0.34, 95% CI: 0.17-0.70), multitasking (OR = 0.33, 95% CI: 0.18-0.59), and verbal ability (OR = 0.46, 95% CI: 0.24-0.88). Consistent with the previous study, lower odds of subjective CRCI among patients with the BDNF Met allele was observed after adjusting for potential confounders in the multitasking (OR = 0.30, 95% CI: 0.14-0.67) domain. In conclusion, carriers of the BDNF Met allele were protected against global subjective CRCI, particularly in the domains of memory, multitasking, and verbal ability. Our findings further contribute to the understanding of CRCI pathophysiology
Autocrine TNF-α production supports CML stem and progenitor cell survival and enhances their proliferation.
Chronic myeloid leukemia (CML) stem cells are not dependent on BCR-ABL kinase for their survival, suggesting that kinase-independent mechanisms must contribute to their persistence. We observed that CML stem/progenitor cells (SPCs) produce tumor necrosis factor-α (TNF-α) in a kinase-independent fashion and at higher levels relative to their normal counterparts. We therefore investigated the role of TNF-α and found that it supports survival of CML SPCs by promoting nuclear factor κB/p65 pathway activity and expression of the interleukin 3 and granulocyte/macrophage-colony stimulating factor common β-chain receptor. Furthermore, we demonstrate that in CML SPCs, inhibition of autocrine TNF-α signaling via a small-molecule TNF-α inhibitor induces apoptosis. Moreover TNF-α inhibition combined with nilotinib induces significantly more apoptosis relative to either treatment alone and a reduction in the absolute number of primitive quiescent CML stem cells. These results highlight a novel survival mechanism of CML SPCs and suggest a new putative therapeutic target for their eradication.This study was supported by the Glasgow
Experimental Cancer Medicine Centre , which is funded by Cancer
Research UK and by the Chief Scientist’s Office, Scotland. Cell
sorting facilities were funded by the Kay Kendall Leukaemia Fund
(KKL501) and the Howat Foundation. Funding was provided by
Medical Research Council UK clinical research training fellowship
grant G1000288 (P.G.), Cancer Research UK Programme grant
C11074/A11008 and the Elimination of Leukaemia Fund (ELF/6/
29/1) (F.P.), National Institutes of Health, National Cancer Institute
research grant R01 CA095684 (R.B.), by the Friends of Paul
O’Gorman Leukaemia Research Centre (H.G.J.), and Cancer Research
UK Programme grant C11074/A11008 (T.L.H.)
Chronic myeloid leukemia stem cells are not dependent on Bcr-Abl kinase activity for their survival
Recent evidence suggests CML stem cells are insensitive to kinase inhibitors and responsible for minimal residual disease in treated patients. We investigated whether CML stem cells, in a transgenic mouse model of CML-like disease or derived from patients, are dependent on Bcr-Abl. In the transgenic model, following re-transplantation, donor-derived CML stem cells in which Bcr-Abl expression had been induced and subsequently shut off, were able to persist in vivo and re-initiate leukemia in secondary recipients upon Bcr-Abl re-expression. Bcr-Abl knockdown in human CD34+ CML cells cultured for 12 days in physiological growth factors achieved partial inhibition of Bcr-Abl and downstream targets p-CrkL and p-STAT5, inhibition of proliferation and colony forming cells, but no reduction of input cells. The addition of dasatinib further inhibited p-CrkL and p-STAT5, yet only reduced input cells by 50%. Complete growth factor withdrawal plus dasatinib further reduced input cells to 10%, however the surviving fraction was enriched for primitive leukemic cells capable of growth in long-term culture initiating cell assay and expansion upon removal of dasatinib and addition of growth factors. Together these data suggest that CML stem cell survival is Bcr-Abl kinase independent and suggest curative approaches in CML must focus on kinase-independent mechanisms of resistance
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