Free versus purchased mosquito net ownership and use in Budondo sub-county, Uganda.

BACKGROUND: While the distribution of mosquito bed nets is a widely adopted approach for malaria prevention, studies exploring how the usage of a net may be influenced by its source and other factors remain sparse. METHODS: A standardized questionnaire and home-visit observations were used to collect data from 9 villages in Budondo sub-county, Uganda in 2016. Household- and individual-level data were collected, such as bed net ownership (at least one net versus none), acquirement source (free versus purchased), demographics, as well as knowledge of malaria and preventative measures. Net-level data, including alternative uses, and bed net quantity and integrity, were also collected. Mixed effects logistic regression models were performed to identify the key determinants of bed net use. RESULTS: Overall, the proportion of households with at least one bed net was 40%, while bed net availability was only reported among 27% of all household members. Awareness of the benefits of bed net use was statistically significantly associated with ownership of at least one net (OR = 1.72, 95% CI 1.11-2.68, p = 0.02). Among those who own net(s), the odds of a bed net being correctly used (i.e., to sleep under) after adjusting for potential confounders were significantly lower for nets that were obtained free compared to nets that were purchased by the owners themselves (OR = 0.33, 95% CI 0.21-0.51, p < 0.01), resulting in an alternative use of the net. Other factors such as female gender, children ≤ 5 years old, and pregnancy status were also significantly associated with having a net to sleep under (all p < 0.01). CONCLUSION: Understanding inter- and intra-household net-use factors will help malaria control programmes more effectively direct their efforts to increase public health impact. Future studies may additionally consider socioeconomic status and track the lifetime of the net

How an early learning and child care program embraced outdoor play: A case study

Research indicates outdoor play influences children’s physical, cognitive and social-emotional well-being, but there are barriers to implementation in early learning settings. This study explores an early learning and child care (ELCC) program achieving success with outdoor play to identify strategies that may help overcome barriers and support outdoor play in similar contexts. Focus groups and interviews were conducted with ELCC program Early Childhood Educators (ECEs) and facilitators, school teachers and principal, and government staff. Data also included relevant documentation and photographs of the outdoor play spaces. Thematic analysis of all data was completed, resulting in a description of the ELCC program’s outdoor play space and practices and factors that may be influencing these identified practices. Six themes or influencing factors were identified: 1) outdoor play, including loose parts and risky play, is valued; 2) outdoor play is promoted and engaged in by others; 3) space and resources are available; 4) communication and engagement happens; 5) leaders are integral; and 6) partnerships and collaboration are essential. Using Bronfenbrenner’s ecological systems model, this research identifies outdoor play implementation strategies that may provide guidance to ELCC stakeholders such as ECEs and policymakers. To overcome outdoor play challenges, considerations should be made to purposefully target and engage multiple subsystems and stakeholders as described in this study for greatest impact

A Machine Learning Approach to Customer Needs Analysis for Product Ecosystems

Creating product ecosystems has been one of the strategic ways to enhance user experience and business advantages. Among many, customer needs analysis for product ecosystems is one of the most challenging tasks in creating a successful product ecosystem from both the perspectives of marketing research and product development. In this paper, we propose a machine-learning approach to customer needs analysis for product ecosystems by examining a large amount of online user-generated product reviews within a product ecosystem. First, we filtered out uninformative reviews from the informative reviews using a fastText technique. Then, we extract a variety of topics with regard to customer needs using a topic modeling technique named latent Dirichlet allocation. In addition, we applied a rule-based sentiment analysis method to predict not only the sentiment of the reviews but also their sentiment intensity values. Finally, we categorized customer needs related to different topics extracted using an analytic Kano model based on the dissatisfaction-satisfaction pair from the sentiment analysis. A case example of the Amazon product ecosystem was used to illustrate the potential and feasibility of the proposed method.https://deepblue.lib.umich.edu/bitstream/2027.42/153965/1/A Machine Learning Approach to Customer Needs Analysis for Product Ecosystems.pd

Astrophysics with the Laser Interferometer Space Antenna

Laser Interferometer Space Antenna (LISA) will be a transformative experiment for gravitational wave astronomy as it will offer unique opportunities to address many key astrophysical questions in a completely novel way. The synergy with ground-based and other space-based instruments in the electromagnetic domain, by enabling multi-messenger observations, will add further to the discovery potential of LISA. The next decade is crucial to prepare the astrophysical community for LISA's first observations. This review outlines the extensive landscape of astrophysical theory, numerical simulations, and astronomical observations that are instrumental for modeling and interpreting the upcoming LISA datastream. To this aim, the current knowledge in three main source classes for LISA is reviewed: ultra-compact stellar-mass binaries, massive black hole binaries, and extreme or intermediate mass ratio inspirals. The relevant astrophysical processes and the established modeling techniques are summarized. Likewise, open issues and gaps in our understanding of these sources are highlighted, along with an indication of how LISA could help make progress in the different areas. New research avenues that LISA itself, or its joint exploitation with studies in the electromagnetic domain, will enable, are also illustrated. Improvements in modeling and analysis approaches, such as the combination of numerical simulations and modern data science techniques, are discussed. This review is intended to be a starting point for using LISA as a new discovery tool for understanding our Universe

The genomic landscape of balanced cytogenetic abnormalities associated with human congenital anomalies

Despite the clinical significance of balanced chromosomal abnormalities (BCAs), their characterization has largely been restricted to cytogenetic resolution. We explored the landscape of BCAs at nucleotide resolution in 273 subjects with a spectrum of congenital anomalies. Whole-genome sequencing revised 93% of karyotypes and demonstrated complexity that was cryptic to karyotyping in 21% of BCAs, highlighting the limitations of conventional cytogenetic approaches. At least 33.9% of BCAs resulted in gene disruption that likely contributed to the developmental phenotype, 5.2% were associated with pathogenic genomic imbalances, and 7.3% disrupted topologically associated domains (TADs) encompassing known syndromic loci. Remarkably, BCA breakpoints in eight subjects altered a single TAD encompassing MEF2C, a known driver of 5q14.3 microdeletion syndrome, resulting in decreased MEF2C expression. We propose that sequence-level resolution dramatically improves prediction of clinical outcomes for balanced rearrangements and provides insight into new pathogenic mechanisms, such as altered regulation due to changes in chromosome topology

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Structural Snapshots of an Engineered Cystathionine-γ-lyase Reveal the Critical Role of Electrostatic Interactions in the Active Site

Enzyme therapeutics that can degrade l-methionine (l-Met) are of great interest as numerous malignancies are exquisitely sensitive to l-Met depletion. To exhaust the pool of methionine in human serum, we previously engineered an l-Met-degrading enzyme based on the human cystathionine-γ-lyase scaffold (hCGL-NLV) to circumvent immunogenicity and stability issues observed in the preclinical application of bacterially derived methionine-γ-lyases. To gain further insights into the structure–activity relationships governing the chemistry of the hCGL-NLV lead molecule, we undertook a biophysical characterization campaign that captured crystal structures (2.2 Å) of hCGL-NLV with distinct reaction intermediates, including internal aldimine, substrate-bound, gem-diamine, and external aldimine forms. Curiously, an alternate form of hCGL-NLV that crystallized under higher-salt conditions revealed a locally unfolded active site, correlating with inhibition of activity as a function of ionic strength. Subsequent mutational and kinetic experiments pinpointed that a salt bridge between the phosphate of the essential cofactor pyridoxal 5′-phosphate (PLP) and residue R62 plays an important role in catalyzing β- and γ-eliminations. Our study suggests that solvent ions such as NaCl disrupt electrostatic interactions between R62 and PLP, decreasing catalytic efficiency

One and Done: Examining the Relationship Between Years of College Basketball Experience and Career Statistics in the National Basketball Association

Since 2006, the so-called one and done rule prevents American high school players from joining the National Basketball Association (NBA) without at least 1 year of college basketball experience. While there is debate about the pros and cons of the one and done rule, few studies have fully examined how minimal (or no) college experience relates to performance in the NBA. The current study used publicly available offensive and defensive statistics for all players in the NBA from 1995 to 2016, to examine the relationship between years of college experience and career success in the NBA. Results showed that players with less college experience had better offensive, defensive, and advanced metric (player efficiency rating [PER] and value over replacement player [VORP]) statistics than players with more college experience. However, players with less college experience also made more mistakes in game play, such as turnovers and fouls. The results suggest that college players may not need to attend college to succeed in the NBA.This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]