Label-free, live optical imaging of reprogrammed bipolar disorder patient-derived cells reveals a functional correlate of lithium responsiveness

Development of novel treatments and diagnostic tools for psychiatric illness has been hindered by the absence of cellular models of disease. With the advent of cellular reprogramming, it may be possible to recapitulate the disease biology of psychiatric disorders using patient skin cells transdifferentiated to neurons. However, efficiently identifying and characterizing relevant neuronal phenotypes in the absence of well-defined pathophysiology remains a challenge. In this study, we collected fibroblast samples from patients with bipolar 1 disorder, characterized by their lithium response (n=12), and healthy control subjects (n=6). We identified a cellular phenotype in reprogrammed neurons using a label-free imaging assay based on a nanostructured photonic crystal biosensor and found that an optical measure of cell adhesion was associated with clinical response to lithium treatment. This cellular phenotype may represent a useful biomarker to evaluate drug response and screen for novel therapeutics

Password Theft: Rethinking an Old Crime in a New Era

By putting themselves out in front as the victims, the Recording Industry Association of America (RIAA) helped reshape the governing norms of the times, and as a result, people viewed the act of file-sharing differently. By forcing people to see music downloading as a form of theft, the RIAA was quite successful in deterring it. In the process, they also proposed a radical view of theft that changes our basic economic understandings of the action[...] This paper argues that the RIAA\u27s model for deterring music theft could be successfully used to deter many other forms of computer theft, and, specifically, stealing passwords. By focusing on the victim, content-providers can alter people\u27s views of their own actions, thereby properly bringing what was once an innocuous activity into the realm of the criminal where it belongs. To accomplish this task, however, we have to comport our traditional views of theft to the realities of the Internet. First, economic notions of rivalry and non-rivalry are undermined in a digital world where data is infinitely copyable, and these notions need to be updated appropriately. Secondly, finding real space analogues to password theft is important when locating an existing legal framework in which to work. This Note attempts to do both. Part I of this Note gives a brief background and explication of rivalrous and non-rivalrous theft, and the problems that the Internet poses, specifically in the music downloading area. In so doing, I propose a new way of conceiving of rivalry that fits into the realities of digital networks. Part II is an analysis of password theft, in particular the distinction between first-party and second-party password theft. First-party password theft concerns actions--stealing personal identification numbers and the like--that are probably familiar to most readers. Second-party password theft, however, is a far more radical notion that is crucial for understanding why password theft in general is criminal, and why it can be so damaging. I analogize first and second-party password theft to larceny and embezzlement, respectively; the purpose of this is to provide a legal framework for analyzing password theft as a criminal activity. Additionally, I show how the updated views of rivalry proposed in Part I allow us to evaluate properly the harm that password theft causes. Finally, Part III argues that by following the model of the RIAA, the government, content-providers, and law enforcement can effectively deter password theft in a variety of ways

Password Theft: Rethinking an Old Crime in a New Era

By putting themselves out in front as the victims, the Recording Industry Association of America (RIAA) helped reshape the governing norms of the times, and as a result, people viewed the act of file-sharing differently. By forcing people to see music downloading as a form of theft, the RIAA was quite successful in deterring it. In the process, they also proposed a radical view of theft that changes our basic economic understandings of the action[...] This paper argues that the RIAA\u27s model for deterring music theft could be successfully used to deter many other forms of computer theft, and, specifically, stealing passwords. By focusing on the victim, content-providers can alter people\u27s views of their own actions, thereby properly bringing what was once an innocuous activity into the realm of the criminal where it belongs. To accomplish this task, however, we have to comport our traditional views of theft to the realities of the Internet. First, economic notions of rivalry and non-rivalry are undermined in a digital world where data is infinitely copyable, and these notions need to be updated appropriately. Secondly, finding real space analogues to password theft is important when locating an existing legal framework in which to work. This Note attempts to do both. Part I of this Note gives a brief background and explication of rivalrous and non-rivalrous theft, and the problems that the Internet poses, specifically in the music downloading area. In so doing, I propose a new way of conceiving of rivalry that fits into the realities of digital networks. Part II is an analysis of password theft, in particular the distinction between first-party and second-party password theft. First-party password theft concerns actions--stealing personal identification numbers and the like--that are probably familiar to most readers. Second-party password theft, however, is a far more radical notion that is crucial for understanding why password theft in general is criminal, and why it can be so damaging. I analogize first and second-party password theft to larceny and embezzlement, respectively; the purpose of this is to provide a legal framework for analyzing password theft as a criminal activity. Additionally, I show how the updated views of rivalry proposed in Part I allow us to evaluate properly the harm that password theft causes. Finally, Part III argues that by following the model of the RIAA, the government, content-providers, and law enforcement can effectively deter password theft in a variety of ways

Demographic and spatial predictors of anemia in women of reproductive age in Timor-Leste: Implications for health program prioritization

10.1371/journal.pone.0091252PLoS ONE93-POLN

Association of food security status with overweight and dietary intake: exploration of White British and Pakistani-origin families in the Born in Bradford cohort.

BACKGROUND: Food insecurity has been associated with dietary intake and weight status in UK adults and children although results have been mixed and ethnicity has not been explored. We aimed to compare prevalence and trajectories of weight and dietary intakes among food secure and insecure White British and Pakistani-origin families. METHODS: At 12 months postpartum, mothers in the Born in Bradford cohort completed a questionnaire on food security status and a food frequency questionnaire (FFQ) assessing their child's intake in the previous month; at 18 months postpartum, mothers completed a short-form FFQ assessing dietary intake in the previous 12 months. Weights and heights of mothers and infants were assessed at 12-, 24-, and 36-months postpartum, with an additional measurement of children taken at 4-5 years. Associations between food security status and dietary intakes were assessed using Wilcoxon-Mann-Whitney for continuous variables and χ2 or Fisher's exact tests for categorical variables. Quantile and logistic regression were used to determine dietary intakes adjusting for mother's age. Linear mixed effects models were used to assess longitudinal changes in body mass index (BMI) in mothers and BMI z-scores in children. RESULTS: At 12 months postpartum, White British mothers reported more food insecurity than Pakistani-origin mothers (11% vs 7%; p < 0.01) and more food insecure mothers were overweight. Between 12 and 36 months postpartum, BMI increased more among food insecure Pakistani-origin mothers (β = 0.77 units, [95% Confidence Interval [CI]: 0.40, 1.10]) than food secure (β = 0.44 units, 95% CI: 0.33, 0.55). This was also found in Pakistani-origin children (BMI z-score: food insecure β = 0.40 units, 95% CI: 0.22, 0.59; food secure β = 0.25 units, 95% CI: 0.20, 0.29). No significant increases in BMI were observed for food secure or insecure White British mothers while BMI z-score increased by 0.17 (95% CI: 0.13, 0.21) for food secure White British children. Food insecure mothers and children had dietary intakes of poorer quality, with fewer vegetables and higher consumption of sugar-sweetened drinks. CONCLUSIONS: Food security status is associated with body weight and dietary intakes differentially by ethnicity. These are important considerations for developing targeted interventions

Dependence of cancer cell adhesion kinetics on integrin ligand surface density measured by a high-throughput label-free resonant waveguide grating biosensor

A novel high-throughput label-free resonant waveguide grating (RWG) imager biosensor, the Epic® BenchTop (BT), was utilized to determine the dependence of cell spreading kinetics on the average surface density (vRGD) of integrin ligand RGD-motifs. vRGD was tuned over four orders of magnitude by co-adsorbing the biologically inactive PLL-g-PEG and the RGD-functionalized PLL-g-PEG-RGD synthetic copolymers from their mixed solutions onto the sensor surface. Using highly adherent human cervical tumor (HeLa) cells as a model system, cell adhesion kinetic data of unprecedented quality were obtained. Spreading kinetics were fitted with the logistic equation to obtain the spreading rate constant (r) and the maximum biosensor response (Δλmax), which is assumed to be directly proportional to the maximum spread contact area (Amax). r was found to be independent of the surface density of integrin ligands. In contrast, Δλmax increased with increasing RGD surface density until saturation at high densities. Interpreting the latter behavior with a simple kinetic mass action model, a 2D dissociation constant of 1753 ± 243 μm−2 (corresponding to a 3D dissociation constant of ~30 μM) was obtained for the binding between RGD-specific integrins embedded in the cell membrane and PLL-g-PEG-RGD. All of these results were obtained completely noninvasively without using any labels

The Challenges of Pain Assessment in Geriatric Patients With Dementia: A Review

: Pain in dementia patients is common, poorly measured, and undertreated. It is important to discuss the challenges in the pain assessment and management to find a possible solution for adequate pain management. The aim of this article is to discuss the challenges in the assessment of pain in geriatric patients with dementia. An extensive online database search was conducted via multiple websites using the following keywords: "dementia," "pain assessments," "pain assessment with dementia," "causes of pain with dementia," "pain assessments using recent technology," "geriatric," and "old age" to identify the relevant articles. Our inclusion criteria were articles that focused on pain in geriatric patients diagnosed with dementia, in English, published between January 2018 and January 2023, and available as free full text and those which were clinical trials, observational studies, review articles, systemic reviews, meta-analysis, or case series. The exclusion criteria were articles that did not have pain in geriatric patients diagnosed with dementia as their primary focus, involving geriatric or non-geriatric patients with major psychological distress, not in the English language, not published between January 2018 and January 2023, and not available as free full-text and those which were case reports and editorial articles. After manually excluding the articles that did not meet our inclusion criteria, we ended up with 38 articles. In conclusion, any instruments have been made for the pain assessment in patients with dementia. The two most common tools used to assess pain in this vulnerable population are the Pain Assessment in Advanced Dementia (PAINAD) and Pain Assessment Checklist for Seniors with Limited Ability to Communicate (PACSLAC) scales. The utilization of new technology may offer promising solutions for the pain assessment in patients with dementia

Observational approaches to chimpanzee behavior in an African sanctuary: Implications for research, welfare, and capacity‐building

Research in African ape sanctuaries has emerged as an important context for our understanding of comparative cognition and behavior. While much of this work has focused on experimental studies of cognition, these animals semi-free-range in forest habitats and therefore can also provide important information about the behavior of primates in socioecologically-relevant naturalistic contexts. In this “New Approaches” article, we describe a project where we implemented a synthetic program of observational data collection at Ngamba Island Chimpanzee Sanctuary in Uganda, directly modeled after long-term data collection protocols at the Kibale Chimpanzee Project in Uganda, a wild chimpanzee field site. The foundation for this project was a strong partnership between sanctuary staff, field site staff, and external researchers. We describe how we developed a data-collection protocol through discussion and collaboration among these groups, and trained sanctuary caregivers to collect novel observational data using these protocols. We use these data as a case study to examine: (1) how behavioral observations in sanctuaries can inform primate welfare and care practices, such as by understanding aggression within the group; (2) how matched observational protocols across sites can inform our understanding of primate behavior across different contexts, including sex differences in social relationships; and (3) how more robust collaborations between foreign researchers and local partners can support capacity-building in primate range countries, along with mentoring and training students more broadly

Reactivity-Dependent PCR: Direct, Solution-Phase in Vitro Selection for Bond Formation

In vitro selection is a key component of efforts to discover functional nucleic acids and small molecules from libraries of DNA, RNA, and DNA-encoded small molecules. Such selections have been widely used to evolve RNA and DNA catalysts and, more recently, to discover new reactions from DNA-encoded libraries of potential substrates. While effective, current strategies for selections of bond-forming and bond-cleaving reactivity are generally indirect, require the synthesis of biotin-linked substrates, and involve multiple solution-phase and solid-phase manipulations. In this work we report the successful development and validation of reactivity-dependent PCR (RDPCR), a new method that more directly links bond formation or bond cleavage with the amplification of desired sequences and that obviates the need for solid-phase capture, washing, and elution steps. We show that RDPCR can be used to select for bond formation in the context of reaction discovery and for bond cleavage in the context of protease activity profiling.Chemistry and Chemical Biolog