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Efficacy of a Smart Toothbrush on Glycemic Control in Patients with Type 2 Diabetes Mellitus and Chronic Periodontitis. A Prospective Randomized Controlled Clinical trial.
No full textBackground: Periodontitis is the 11th most prevalent chronic disease globally, with a disease burden of approximately 1.1 billion people. Similarly, type 2 diabetes mellitus (T2DM) is a global health concern affecting 537 million adults worldwide. The bidirectional relationship between periodontal diseases and diabetes is well-established. Treatment and control of periodontal diseases improves diabetes outcomes. This study aims to investigate the efficacy of an electric toothbrush with mobile smart application as an adjunct to periodontal therapy on the improvement of glycemic control and oral health parameters in moderate to severe periodontitis patients with uncontrolled type 2 diabetes (T2DM). Methods: Forty (40) individuals diagnosed with uncontrolled type 2 diabetes mellitus (T2DM) and moderate to severe periodontal disease were included in this prospective randomized control clinical trial. Baseline periodontal parameters were measured (probing depths, bleeding on probing and plaque index), and gingival crevicular fluid and fasting blood were collected. Non-surgical periodontal therapy was performed on all enrolled patients. Twenty (20) patients were randomized into the control group and received oral hygiene instructions (OHI) with a standard manual toothbrush, while the other twenty (20) were randomized into the test group and received OHI with an electric smart toothbrush linked to a mobile device application. Clinical measurements were re- evaluated at eight weeks and at three, six, nine, and twelve months post non-surgical therapy. Results: HbA1c for the test group decreased from 8.6% at baseline to 7.6% at 12 months and for the control group from 7.9% to 7.7%; the difference was not statistically significant for either of the treatment groups. Both treatment groups demonstrated a 63% decrease in plaque accumulation which was significant when compared to baseline, but not significant between the groups at any time point. There was statistically significant reduction in the mean PPD (3.04 mm) for the test group between baseline and 12 months compared to the control group (1.89 mm). Additionally, 14.2% of controls and 16.7% of the test group achieved a clinical endpoint of £ 4 clinical sites with PPD £ 5mm. Conclusions: The preliminary results from the present RCT study suggest that a smart toothbrush with a mobile application to guide self-efficacy in oral home care is a valuable adjunct to non-surgical therapy in patients with periodontitis and poorly or uncontrolled diabetes. Completion of the study is required to drawn definitive conclusions
Cold War Futurity on Display: New Techno-Environment Staged in South Korea and Japan through Models and Miniatures
No full textThis dissertation traces how new techno-environments were displayed in cold war Japan and South Korea, especially concerning the intricate temporal senses of futurity in them. It aims to demonstrate the ways in which emerging, publicly exhibited techno-things and novel environments were associated with certain dreams and imagination for futures that were, in turn, molded in the historical context of cold war geopolitics. My argument is that the cold war was the era of display since this period witnessed not only various processes of each nation or region becoming a showcase in the context of global confrontation, but also a great number of global and local expositions and exhibitions, which became a visible stage for advanced science and technology, new materials, and eye-opening attractions. Specifically, I explore things new displayed mostly in exhibitions, including new science and technology, new media, and new life environment, which were seen as soon-to-be actualized in people’s everyday lives. In so doing, I argue that publicly displayed models and miniatures played a role in persistently (re)producing collective dreams for the futures in cold war South Korea and Japan. The three-dimensional physicality of these displayed things functioned as a training medium for the audience, and people were able to learn about new goods, technological products, and novel circumstances in concrete and tangible ways using their corporeal senses. Moreover, I attempt to show how futuristic dreams were envisioned and (re)created in Japan and South Korea unevenly and disparately, even though the two nations appear to have shared the allegedly indistinguishable temporal senses of the cold war. I argue that this was because the cold wars were heterogeneously and vernacularly experienced in accordance with the entangled geopolitics and histories of each society in East Asia, which I will unveil in my dissertation through these two countries’ presentations of models and miniatures
Contradizendo os arquivos da nação: revisões da “mãe preta” na arte brasileira
No full textNos processos históricos da disputa do que significa raça ou a raça brasileira, as representações da “mãe preta” apareceram com uma frequência significativa. Esta tese investiga por que e como artistas negras contemporâneas reivindicam uma revisão das imagens de “mães pretas” nos seus trabalhos artísticos visuais e literários. O trabalho aborda como Rosana Paulino, Renata Felinto e Carolina Maria de Jesus recorrem aos arquivos da escravidão, como é o caso das fotografias das amas de leite, e aos arquivos da arte brasileira, tais como as representações modernistas da “mãe preta”. A análise de obras selecionadas dessas artistas mostra que as representações das “mães pretas” têm sido tanto um produto como produtoras da história, particularmente durante períodos de mudanças nas ideologias raciais predominantes: o abolicionismo do final do século XIX; a construção do mito da democracia racial no Brasil nas décadas de 1920-1930; e o reconhecimento estatal do início do século XXI do legado e da persistência das desigualdades raciais no Brasil. Em todos esses períodos, as representações das “mães pretas”, cujo trabalho de cuidado infantil e/ou cuidado doméstico permaneceu central na sociedade brasileira, oscilaram entre símbolos de afeto ou violência dependendo da ideologia racial predominante e do contexto de produção da imagem. O que essas artistas negras contemporâneas apontam é que as imagens estereotipadas da mãe negra contribuem ativamente com a manutenção das desigualdades sociais, raciais e de gênero na sociedade. Ao mesmo tempo, esses trabalhos artísticos mostram a constante agência das mulheres negras e do povo negro na resistência a essas imagens de controle. A autorrepresentação da mulher negra nas artes visuais, literatura e poesia torna-se um caminho de recuperar e recriar imagens da mulher negra vinculada a uma reterritorialização no espaço e no tempo orientada pela ancestralidade, portanto por uma cosmovisão afrodiaspórica. Desse modo, esta investigação contribui com discussões que privilegiam a interseção de raça, gênero, classe, maternidade e a construção de uma identidade nacional no campo da arte, da cultura e da história. Ressaltar a resistência histórica das mulheres negras às imagens de controle através de modos de reconexão com memória ancestral é matéria fundamental para uma mais ampla reflexão sobre a sociedade, no campo do Feminismo Decolonial, da Psicanálise, das Artes Visuais Brasileiras e da Literatura Brasileira
Neural circuit mechanisms underlying contingency learning
No full textStudies on animal learning have shown that the efficacy of both associative learning and responding depends on contingency, the extent to which the likelihood of an outcome changes by a presentation of a stimulus. However, how neural representations in the mesolimbic dopamine system and ventral striatum are modulated by contingency remain unclear. Chapter I of my dissertation focuses on this by examining mice trained in a Pavlovian conditioning degradation task. I observed that anticipatory licking for odors previously associated with rewards significantly diminished when unpredicted rewards were introduced but remained stable with predicted additional rewards. Furthermore, dopamine (DA) axonal signals in the Olfactory Tubercle (OT) and Nucleus Accumbens (NAc), measured using photometry, mirrored these behavioral changes. While dopamine signals are commonly thought to resemble the temporal difference (TD) error in TD learning models, previous studies suggested these models couldn't explain the contingency degradation phenomenon. However, our findings indicated that DA responses in various experimental conditions align closely with a TD learning model incorporating state transitions reflective of task structure. Furthermore, we showed that recurrent neural networks (RNNs) trained in the task using a TD learning framework recapitulate dopamine responses and develop state representations consistent with the task states, merely from observations. Based on these results, we provided a theoretical framework linking TD errors to contingency and causal learning
Many studies of reinforcement learning in rodents have involved the olfactory system. Previous studies have indicated that neural activity related to the odor valence have been observed in the OT, a relatively understudied structure situated in both the olfactory pathway and the ventral striatum. In Chapter II, I examined how valence representations of odor cues evolve over time in the two distinct neuronal populations in the OT, and how stable these representations are under different conditions in contingency learning using 2-photon microscopy. As the idea of representational stability and drift are vigorously debated, this study will add valuable biological data to inform conceptual ideas of neural representations in the brain.
Together, these results provided new insights into the neural circuits involved in the representation of contingency in the mammalian brain
Measuring and modeling the dynamics of mitotic error correction
No full textAccurate chromosome segregation is essential to human health. Chromosome segregation is mediated by the spindle, a bipolar structure of microtubules that aligns chromosomes and separates sister chromatids to opposite daughter cells. Issues with chromosome segregation can arise from the initial configuration of chromosomes and microtubules, perturbed correction of erroneous attachments, and reduced functionality of the spindle assembly checkpoint. The relative contributions of these factors to the overall result of chromosome segregation, and how these factors are impacted by various mitotic proteins, is not well understood.
We developed an experimental method and coarse-grained model to measure the dynamics of mitotic error correction. We measured the rate of error correction in human tissue culture cells using distributions of divided kinetochore counts, and found that error correction can be well-described as a chromosome-autonomous process, in which errors are corrected at a constant rate over time. We measured an identical error correction rate using the distribution of anaphase timing, and found that anaphase timing can be well-described as a slowest first passage time problem. We showed that this coarse-grained model can also explain the perturbed dynamics of error correction when changing the initial configuration of chromosomes and when changing microtubule dynamics. This project is described in Chapter 1.
In Chapter 2, we explored how a faulty spindle assembly checkpoint can work in concert with perturbed error correction to cause errors in chromosome segregation. We incorporated the possibility of a faulty spindle assembly checkpoint in our model, in which a cell can only enter premature anaphase if every erroneous chromosome fails to block anaphase. This model can successfully explain the observed anaphase onset time distribution, spontaneous kinetochore count difference distribution, and error correction time course in multiple human tissue culture cell lines with genetic and small molecule perturbations of mitotic proteins. In Chapter 3, we tested what kind of information about underlying error rates and allocation bias can be extracted from kinetochore count data.
This work provides a quantitative method to distinguish between perturbations that affect the initial error state, error correction rate, and spindle assembly checkpoint function and can be used to measure these parameters across different cell types and conditions
Problems in Variable Selection: False Discovery Rate Control and Variational Inference
No full textVariable selection plays a key role in modern high-dimensional statistics. This dissertation provides a comprehensive survey of theory and methods developed by the author and collaborators, with a specific focus on two areas: false discovery rate (FDR) control and Bayesian variable selection. In the domain of FDR control, we introduce a data-splitting method to asymptotically control the FDR while maintaining a high power. Furthermore,
a Multiple Data Splitting (MDS) method is proposed to stabilize the selection result and boost the power. In Chapter 1, we apply both DS and MDS to the generalized linear models, which appear to be more robust in finite-sample cases compared to existing methods. Chapter 2 provides some following discussions regarding the proposed method and Chapter 3 compares the power of the proposed method with two existing methods: the model-X knockoff and Gaussian mirror. In terms of the Bayesian variable selection, the posterior is typically high-dimensional and analytically intractable. Exact inference methods based on sampling, such as Markov Chain Monte Carlo (MCMC), can encounter challenges related to mixing. Variational inference has emerged as an attractive alternative for approximating the posterior distribution. By recasting the sampling problem as an optimization problem, variational inference can significantly reduce computational time. In chapter 4, we apply the variational inference to group variable selection with spike-and-slab prior and propose an efficient parameter-expanded coordinate-ascent algorithm to obtain the optimal variational Bayes approximation. The proposed method has demonstrated good performance in both simulations and a real data example
The Truth in the Transformation: How Messages Are Portrayed in Character Arc
No full text"In Chronological Order" is a first-person, realistic literary fiction novella that unfolds over seven years in the life of Catherine Ciriani. The narrative revolves around the transformative encounters with two individuals who profoundly shape her perception of love. Initially guided by conventional ideals of romantic relationships, Catherine's optimistic outlook is shattered when she falls for Jess Moore, a person whose beliefs and actions contradict her own. Despite the dissonance between her romantic ideals and involvement with Jess, Catherine undergoes a moral descent as she is dragged into a world where love is perceived as temporary and partners as replaceable.
The novella explores her internal conflict between being a hopeless romantic and the harsh reality of her relationship with Jess. His perfect deception leads her to believe that her desires are the exception rather than the norm. Through Jess, the story conveys a powerful message about the complexities of love and the impact of conflicting beliefs on one's character.
In the latter half of the narrative, Catherine encounters Mark, a work peer who effortlessly establishes an unexpected bond with her. Their relationship embodies everything Catherine once deemed unattainable – genuine partnership, equality, and a profound friendship. That is until she must navigate betrayal once she discovers the secrets he has been hiding from her for years
Advancing Digital Health Applications: Priorities for Innovation in Real-World Evidence Generation
No full textIn 2019, Germany passed the Digital Healthcare Act, which, among other things, created a “Fast-Track” regulatory and reimbursement pathway for digital health applications in the German market. The pathway explicitly provides for flexibility in how researchers can present evidence for new digital products, including the use of real world data and real-world evidence. Against this backdrop, the Digital Medicine Society and the Health Innovation Hub of the German Federal Ministry of Health convened a set of roundtable discussions to bring together international experts in evidence generation for digital medicine products. This Viewpoint highlights findings from these discussions with the aims of (1) accelerating and stimulating innovative approaches to digital medical product evaluation, and (2) promoting international harmonisation of best evidentiary practices. Advancing these topics and fostering international agreement on evaluation approaches will be vital to the safe, effective, and evidence-based deployment and acceptance of digital health applications globally.Version of Recor
Developmental and evolutionary trade-offs with early-life disruption of the gut microbiota
No full textEnvironmental adversity during early life can cue developmental changes in young animals that promote metabolic diseases, such as obesity, in adults. The gut microbiota plays critical roles in the regulation of host energy balance, can undergo lasting changes in response to transient environmental influences, and is subject to vertical transmission from mother to offspring, raising the possibility that environmental influences on the microbiota can initiate developmental tradeoffs and adult metabolic disease. Notably, disruption of the gut microbiome in early life via exposure to antibiotics has been linked to increased adiposity in humans, mice, and other animals, but the physiological mechanisms (proximate) and evolutionary adaptations (ultimate) underlying this effect remain unclear. In this dissertation, we use an intergenerational mouse model to evaluate the general hypothesis that microbiota disruption during the critical period of early life is a signal of environmental adversity or volatile energy availability, necessitating energy allocation tradeoffs that promote adiposity in adulthood at the cost of fitness. First, we introduce a framework to understand the energetic, developmental, and evolutionary mechanisms of obesity associated with early-life antibiotic exposure (ELA). Second, we show that early-life exposure to both therapeutic and non-therapeutic antimicrobial compounds, including common dietary preservatives, can alter gut microbial composition in vitro and in vivo, with differing consequences for host metabolism. Third, we establish that pulsed therapeutic and chronic subtherapeutic doses of antibiotics in early life have variable effects on host energy status in the short-term, but nevertheless act through similar physiological mechanisms to promote obesity in the long-term, primarily by inducing metabolic thrift in males. Females proved resistant to the development of metabolic thrift and subsequently showed no evidence of obesity in response to ELA treatment. Last, we evaluate the fitness trade-offs involved in ELA-induced obesity, demonstrating that the development of metabolic thrift in males as a response to ELA treatment helps them better buffer against periods of food limitation in adulthood, while the lack of such metabolic thrift in ELA-treated females impairs their ability to produce high-quality offspring and maintain body mass in an energy- limited environment. Altogether, this work synthesizes perspectives from microbiology, developmental biology, clinical medicine, and evolutionary theory to advance our understanding of the physiological underpinnings and health implications of early-life disruption of the gut microbiome
Insights on Minimalistic Control Systems from in vivo Visualization of Plasmids
No full textPlasmids are under strong selective pressure to control fluctuations in their copy number to prevent extinction from plasmid loss or low host cell fitness. Under this pressure, plasmids have therefore evolved robust yet minimalistic copy number control systems to regulate their replication and segregation. To evaluate the ability of these control system mechanisms to control copy number fluctuations, plasmid copy number must be analyzed in single cells, but doing so reliably has been a challenging constraint for the field. Here, we present an improved, minimally perturbative labeling method for visualizing plasmids in vivo. We use this method to construct a copy number distribution of plasmid mini-R1 and find that the variability is unexpectedly low and even sub-Poissonian, surpassing theoretical predictions. Interestingly, we find that low copy number states, which are the most dangerous because of their disproportionate likelihoods of plasmid loss, are observed with sub-Poissonian frequency. We also evaluate copy number control mutants to determine whether their mechanisms contribute to the sub-Poissonian copy number distribution. Our findings suggest that the CopB-mediated and partitioning mechanisms aid the primary copA-mediated mechanism with steady-state copy number control. Finally, we use our technique for labeling plasmids in combination with HaloTag-labeled filaments to visualize the R1 partitioning system, which forms filaments between plasmid pairs to push them to the poles for equipartitioning. This work provides ample avenues for future work and has implications for the field of plasmid biology as well as biological control theory and synthetic biology