Search results for: early recurrence
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 3823

Search results for: early recurrence

3463 Leading People in a Digital Era: A Theoretical Study of Challenges and Opportunities of Online Networking Platforms

Authors: Pawel Korzynski

Abstract:

Times where leaders communicate mainly while walking along the hallways have passed away. Currently, millennials, people that were born between the early 1980s and the early 2000s, extensively use applications based on Web 2.0 model that assumes content creation and edition by all Internet users in a collaborative fashion. Leaders who are willing to engage their subordinates in a digital era, increasingly often use above-mentioned applications. This paper discusses challenges and opportunities that are related to leaders’ online networking. First, online networking-related terms that appeared in literature are analyzed. Then, types of online networking platforms for leaders and ways how these platforms can be used are discussed. Finally, several trends in online networking studies and extrapolation of some findings to leadership are explained.

Keywords: social media, digital era, leadership, online networking

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3462 Generic Early Warning Signals for Program Student Withdrawals: A Complexity Perspective Based on Critical Transitions and Fractals

Authors: Sami Houry

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Complex systems exhibit universal characteristics as they near a tipping point. Among them are common generic early warning signals which precede critical transitions. These signals include: critical slowing down in which the rate of recovery from perturbations decreases over time; an increase in the variance of the state variable; an increase in the skewness of the state variable; an increase in the autocorrelations of the state variable; flickering between different states; and an increase in spatial correlations over time. The presence of the signals has management implications, as the identification of the signals near the tipping point could allow management to identify intervention points. Despite the applications of the generic early warning signals in various scientific fields, such as fisheries, ecology and finance, a review of literature did not identify any applications that address the program student withdrawal problem at the undergraduate distance universities. This area could benefit from the application of generic early warning signals as the program withdrawal rate amongst distance students is higher than the program withdrawal rate at face-to-face conventional universities. This research specifically assessed the generic early warning signals through an intensive case study of undergraduate program student withdrawal at a Canadian distance university. The university is non-cohort based due to its system of continuous course enrollment where students can enroll in a course at the beginning of every month. The assessment of the signals was achieved through the comparison of the incidences of generic early warning signals among students who withdrew or simply became inactive in their undergraduate program of study, the true positives, to the incidences of the generic early warning signals among graduates, the false positives. This was achieved through significance testing. Research findings showed support for the signal pertaining to the rise in flickering which is represented in the increase in the student’s non-pass rates prior to withdrawing from a program; moderate support for the signals of critical slowing down as reflected in the increase in the time a student spends in a course; and moderate support for the signals on increase in autocorrelation and increase in variance in the grade variable. The findings did not support the signal on the increase in skewness of the grade variable. The research also proposes a new signal based on the fractal-like characteristic of student behavior. The research also sought to extend knowledge by investigating whether the emergence of a program withdrawal status is self-similar or fractal-like at multiple levels of observation, specifically the program level and the course level. In other words, whether the act of withdrawal at the program level is also present at the course level. The findings moderately supported self-similarity as a potential signal. Overall, the assessment of the signals suggests that the signals, with the exception with the increase of skewness, could be utilized as a predictive management tool and potentially add one more tool, the fractal-like characteristic of withdrawal, as an additional signal in addressing the student program withdrawal problem.

Keywords: critical transitions, fractals, generic early warning signals, program student withdrawal

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3461 A Dialectical Behavioral Therapy Adaptation in Reducing Depression, Anxiety, and Self-Harm in Older Adults

Authors: Valerie Alexander, Amanda Gutierrez, Veronica Campbell, Dara Schwartz, B. Charles Tatum

Abstract:

It has long been assumed that personality disorders (PD) originate in adolescence or early adulthood and that the maladaptive behaviors significantly attenuate over time. The Diagnostic and Statistical Manual of Mental Disorders-5 supports early onset of PD and views the pattern of behaviors as enduring and stable. The premise of this study is that PD may not always begin early in life, that behaviors may change over the lifespan, and that current treatment modalities may be beneficial in seniors. Self-injurious behaviors (SIB) exhibited earlier in life may, in older adults, be manifested in less overt high-risk behaviors but by refusal to take medication and get necessary medical treatment. Dialectical Behavioral Therapy is a well-known treatment modality for teaching emotional regulation and distress tolerance and thus reducing self-injurious behaviors yet very little has been studied about SIB and treatment in older adults. The population for this study was older adults, with a history of SIB, a PD, and depression and/or anxiety. Participants learned an adapted version of Dialectical Behavioral Therapy (DBT) as developed by DBT trained therapists. The results provided clinical potentials for the efficacy of DBT to reduce SIB, decrease depression and anxiety in the older adult population.

Keywords: anxiety, depression, dialectical behavioral therapy, personality disorders, self-harm behavior, treatment in older adults

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3460 Early Marriage and Women's Empowerment: The Case of Chil-bride in East Hararghe Zone of Oromia National Regional State, Ethiopia

Authors: Emad Mohammed Sani

Abstract:

Women encounter exclusion and discrimination in varying degrees, particularly those who marry as minors. The detrimental custom of getting married young is still prevalent worldwide and affects millions of people. It has been less common over time, although it is still widespread in underdeveloped nations. Oromia Regional State is the region in Ethiopia with the highest proportion of child brides. This study aimed at evaluating the effects of early marriage on its survivors’ life conditions – specifically, empowerment and household decision-making – in Eastern Hararghe Zone of Oromia Region. This study employed community-based cross-sectional study design. It adopted mixed method approach – survey, in-depth interview and focus group discussion (FGD) – to collect, analyses and interpret data on early marriage and its effects on household decision-making processes. Narratives and analytical descriptions were integrated to substantiate and/or explain observed quantitative results, or generate contextual themes. According to this study, married women who were married at or after the age of eighteen participated more in household decision-making than child brides. Child brides were more likely to be victims of violence and other types of spousal abuse in their marriages. These changes are mostly caused by an individual's age at first marriage. Delaying marriage had a large positive impact on women's empowerment at the household level, and age at first marriage had a considerable negative impact. In order to advance women's welfare and emancipation, we advise more research to concentrate on the relationship between the home and the social-structural forms that appear at the individual and communal levels.

Keywords: child-bride, early marriage, women, ethiopia

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3459 Time Optimal Control Mode Switching between Detumbling and Pointing in the Early Orbit Phase

Authors: W. M. Ng, O. B. Iskender, L. Simonini, J. M. Gonzalez

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A multitude of factors, including mechanical imperfections of the deployment system and separation instance of satellites from launchers, oftentimes results in highly uncontrolled initial tumbling motion immediately after deployment. In particular, small satellites which are characteristically launched as a piggyback to a large rocket, are generally allocated a large time window to complete detumbling within the early orbit phase. Because of the saturation risk of the actuators, current algorithms are conservative to avoid draining excessive power in the detumbling phase. This work aims to enable time-optimal switching of control modes during the early phase, reducing the time required to transit from launch to sun-pointing mode for power budget conscious satellites. This assumes the usage of B-dot controller for detumbling and PD controller for pointing. Nonlinear Euler's rotation equations are used to represent the attitude dynamics of satellites and Commercial-off-the-shelf (COTS) reaction wheels and magnetorquers are used to perform the manoeuver. Simulation results will be based on a spacecraft attitude simulator and the use case will be for multiple orbits of launch deployment general to Low Earth Orbit (LEO) satellites.

Keywords: attitude control, detumbling, small satellites, spacecraft autonomy, time optimal control

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3458 Combined Treatment of Estrogen-Receptor Positive Breast Microtumors with 4-Hydroxytamoxifen and Novel Non-Steroidal Diethyl Stilbestrol-Like Analog Produces Enhanced Preclinical Treatment Response and Decreased Drug Resistance

Authors: Sarah Crawford, Gerry Lesley

Abstract:

This research is a pre-clinical assessment of anti-cancer effects of novel non-steroidal diethyl stilbestrol-like estrogen analogs in estrogen-receptor positive/ progesterone-receptor positive human breast cancer microtumors of MCF 7 cell line. Tamoxifen analog formulation (Tam A1) was used as a single agent or in combination with therapeutic concentrations of 4-hydroxytamoxifen, currently used as a long-term treatment for the prevention of breast cancer recurrence in women with estrogen receptor positive/ progesterone receptor positive malignancies. At concentrations ranging from 30-50 microM, Tam A1 induced microtumor disaggregation and cell death. Incremental cytotoxic effects correlated with increasing concentrations of Tam A1. Live tumor microscopy showed that microtumos displayed diffuse borders and substrate-attached cells were rounded-up and poorly adherent. A complete cytotoxic effect was observed using 40-50 microM Tam A1 with time course kinetics similar to 4-hydroxytamoxifen. Combined treatment with TamA1 (30-50 microM) and 4-hydroxytamoxifen (10-15 microM) induced a highly cytotoxic, synergistic combined treatment response that was more rapid and complete than using 4-hydroxytamoxifen as a single agent therapeutic. Microtumors completely dispersed or formed necrotic foci indicating a highly cytotoxic combined treatment response. Moreover, breast cancer microtumors treated with both 4-hydroxytamoxifen and Tam A1 displayed lower levels of long-term post-treatment regrowth, a critical parameter of primary drug resistance, than observed for 4-hydroxytamoxifen when used as a single agent therapeutic. Tumor regrowth at 6 weeks post-treatment with either single agent 4-hydroxy tamoxifen, Tam A1 or a combined treatment was assessed for the development of drug resistance. Breast cancer cells treated with both 4-hydroxytamoxifen and Tam A1 displayed significantly lower levels of post-treatment regrowth, indicative of decreased drug resistance, than observed for either single treatment modality. The preclinical data suggest that combined treatment involving the use of tamoxifen analogs may be a novel clinical approach for long-term maintenance therapy in patients with estrogen-receptor positive/progesterone-receptor positive breast cancer receiving hormonal therapy to prevent disease recurrence. Detailed data on time-course, IC50 and tumor regrowth assays post- treatment as well as a proposed mechanism of action to account for observed synergistic drug effects will be presented.

Keywords: 4-hydroxytamoxifen, tamoxifen analog, drug-resistance, microtumors

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3457 Tumour-Associated Tissue Eosinophilia as a Prognosticator in Oral Squamous Cell Carcinoma

Authors: Karen Boaz, C. R. Charan

Abstract:

Background: The infiltration of tumour stroma by eosinophils, Tumor-Associated Tissue Eosinophilia (TATE), is known to modulate the progression of Oral Squamous Cell Carcinoma (OSCC). Eosinophils have direct tumoricidal activity by release of cytotoxic proteins and indirectly they enhance permeability into tumor cells enabling penetration of tumoricidal cytokines. Also, eosinophils may promote tumor angiogenesis by production of several angiogenic factors. Identification of eosinophils in the inflammatory stroma has been proven to be an important prognosticator in cancers of mouth, oesophagus, larynx, pharynx, breast, lung, and intestine. Therefore, the study aimed to correlate TATE with clinical and histopathological variables, and blood eosinophil count to assess the role of TATE as a prognosticator in Oral Squamous Cell Carcinoma (OSCC). Methods: Seventy two biopsy-proven cases of OSCC formed the study cohort. Blood eosinophil counts and TNM stage were obtained from the medical records. Tissue sections (5µm thick) were stained with Haematoxylin and Eosin. The eosinophils were quantified at invasive tumour front (ITF) in 10HPF (40x magnification) with an ocular grid. Bryne’s grading of ITF was also performed. A subset of thirty cases was also assessed for association of TATE with recurrence, involvement of lymph nodes and surgical margins. Results: 1) No statistically significant correlation was found between TATE and TNM stage, blood eosinophil counts and most parameters of Bryne’s grading system. 2) Statistically significant relation of intense degree of TATE was associated with the absence of distant metastasis, increased lympho-plasmacytic response and increased survival (diseasefree and overall) of OSCC patients. 3) In the subset of 30 cases, tissue eosinophil counts were higher in cases with lymph node involvement, decreased survival, without margin involvement and in cases that did not recur. Conclusion: While the role of eosinophils in mediating immune responses seems ambiguous as eosinophils support cell-mediated tumour immunity in early stages while inhibiting the same in advanced stages, TATE may be used as a surrogate marker for determination of prognosis in oral squamous cell carcinoma.

Keywords: tumour-associated tissue eosinophilia, oral squamous cell carcinoma, prognosticator, tumoral immunity

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3456 Gender Diversity in Early Years Education: An Exploratory Study Applied to Preschool Curriculum System in Romania

Authors: Emilia-Gheorghina Negru

Abstract:

As an EU goal, gender diversity in early year’s education aims and promotes equality of chances and respect for gender peculiarities of the pupils which are involved in formal educational activities. Early year’s education, as the first step to the Curriculum, prints to teachers the need to identify the role of the gender dimension on this stage, depending on the age level of preschool children through effective, complex, innovative and analytical awareness of gender diversity teaching and management strategies. Through gender educational work we, as teachers, will examine the effectiveness of the PATHS (Promoting Alternative Thinking Strategies) curriculum the gender development of school-aged children. PATHS and a school-based preventive intervention model are necessary to be designed to improve children's ability to discuss and understand equality and gender concepts. Our teachers must create an intervention model and provide PATHS lessons during the school year. Results of the intervention will be effective for both low- and high-risk children in improving their range of math’s skills for girls and vocabulary, fluency and emotional part for boys in discussing gender experiences, their efficacy beliefs regarding the management of equality in gender area, and their developmental understanding of some aspects of gender.

Keywords: gender, gender differences, gender equality, gender role, gender stereotypes

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3455 Improving Early Detection, Diagnosis And Intervention For Children With Autism Spectrum Disorder: A Cross-sectional Survey In China

Authors: Yushen Dai, Tao Deng, Miaoying Chen, Baoqin Huang, Yan Ji, Yongshen Feng, Shaofei Liu, Dongmei Zhong, Tao Zhang, Lifeng Zhang

Abstract:

Background: Detection and diagnosis are prerequisites for early interventions in the care of children with Autism Spectrum Disorder (ASD). However, few studies have focused on this topic. Aim: This study aims to characterize the timing from symptom detection to intervention in children with ASD and to identify the potential predictors of early detection, diagnosis, and intervention. Methods and procedures: A cross-sectional survey was conducted with 314 parents of children with ASD in Guangzhou, China. Outcomes and Results: This study found that most children (76.24%) were diagnosed within one year after detection, and 25.8% of them did not receive the intervention after diagnosis. Predictors to ASD diagnosis included ASD-related symptoms identified at a younger age, more serious symptoms, and initial symptoms with abnormal development and sensory anomalies. ASD-related symptoms observed at an older age, initial symptoms with the social deficit, sensory anomalies, and without language impairment, parents as the primary caregivers, family with lower income and less social support utilization increased the odds of the time lag between detection and diagnosis. Children whose fathers had a lower level of education were less likely to receive the intervention. Conclusions and Implications: The study described the time for detection, diagnosis, and interventions of children with ASD. Findings suggest that the ASD-related symptoms, the timing at which symptoms first become a concern, primary caregivers’ roles, father’s educational level, and the family economic status should be considered when offering support to improve early detection, diagnosis, and intervention. Helping children and their families take full advantage of support is also important.

Keywords: autism spectrum disorder, child, detection, diagnosis, intervention, social support

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3454 A Review on Predictive Sound Recognition System

Authors: Ajay Kadam, Ramesh Kagalkar

Abstract:

The proposed research objective is to add to a framework for programmed recognition of sound. In this framework the real errand is to distinguish any information sound stream investigate it & anticipate the likelihood of diverse sounds show up in it. To create and industrially conveyed an adaptable sound web crawler a flexible sound search engine. The calculation is clamor and contortion safe, computationally productive, and hugely adaptable, equipped for rapidly recognizing a short portion of sound stream caught through a phone microphone in the presence of frontal area voices and other predominant commotion, and through voice codec pressure, out of a database of over accessible tracks. The algorithm utilizes a combinatorial hashed time-recurrence group of stars examination of the sound, yielding ordinary properties, for example, transparency, in which numerous tracks combined may each be distinguished.

Keywords: fingerprinting, pure tone, white noise, hash function

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3453 An Empirical Dynamic Fuel Cell Model Used for Power System Verification in Aerospace

Authors: Giuliano Raimondo, Jörg Wangemann, Peer Drechsel

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In systems development involving Fuel Cells generators, it is important to have from an early stage of the project a dynamic model for the electrical behavior of the stack to be shared between involved development parties. It allows independent and early design and tests of fuel cell related power electronic. This paper presents an empirical Fuel Cell system model derived from characterization tests on a real system. Moreover, it is illustrated how the obtained model is used to build and validate a real-time Fuel Cell system emulator which is used for aerospace electrical integration testing activities.

Keywords: fuel cell, modelling, real time emulation, testing

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3452 A Convolutional Deep Neural Network Approach for Skin Cancer Detection Using Skin Lesion Images

Authors: Firas Gerges, Frank Y. Shih

Abstract:

Malignant melanoma, known simply as melanoma, is a type of skin cancer that appears as a mole on the skin. It is critical to detect this cancer at an early stage because it can spread across the body and may lead to the patient's death. When detected early, melanoma is curable. In this paper, we propose a deep learning model (convolutional neural networks) in order to automatically classify skin lesion images as malignant or benign. Images underwent certain pre-processing steps to diminish the effect of the normal skin region on the model. The result of the proposed model showed a significant improvement over previous work, achieving an accuracy of 97%.

Keywords: deep learning, skin cancer, image processing, melanoma

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3451 Early Childhood Developmental Delay in 63 Low- and Middle-Income Countries: Prevalence and Inequalities Estimated from National Health Surveys

Authors: Jesus D. Cortes Gil, Fernanda Ewerling, Leonardo Ferreira, Aluisio J. D. Barros

Abstract:

Background: The sustainable development goals call for inclusive, equitable, and quality learning opportunities for all. This is especially important for children, to ensure they all develop to their full potential. We studied the prevalence and inequalities of suspected delay in child development in 63 low- and middle-income countries. Methods and Findings: We used the early child development module from national health surveys, which covers four developmental domains (physical, social-emotional, learning, literacy-numeracy) and provides a combined indicator (early child development index, ECDI) of whether children are on track. We calculated the age-adjusted prevalence of suspected delay at the country level and stratifying by wealth, urban/rural residence, sex of the child, and maternal education. We also calculated measures of absolute and relative inequality. We studied 330.613 children from 63 countries. The prevalence of suspected delay for the ECDI ranged from 3% in Barbados to 67% in Chad. For all countries together, 25% of the children were suspected of developmental delay. At regional level, the prevalence of delay ranged from 10% in Europe and Central Asia to 42% in West and Central Africa. The literacy-numeracy domain was by far the most challenging, with the highest proportions of delay. We observed very large inequalities, and most markedly for the literacy-numeracy domain. Conclusions: To date, our study presents the most comprehensive analysis of child development using an instrument especially developed for national health surveys. With a quarter of the children globally suspected of developmental delay, we face an immense challenge. The multifactorial aspect of early child development and the large gaps we found only add to the challenge of not leaving these children behind.

Keywords: child development, inequalities, global health, equity

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3450 The Impact of Speech Style on the Production of Spanish Vowels by Spanish-English Bilinguals and Spanish Monolinguals

Authors: Vivian Franco

Abstract:

There has been a great deal of research about vowel production of second language learners of Spanish, vowel variation across Spanish dialects, and more recently, research related to Spanish heritage speakers’ vowel production based on speech style. However, there is little investigation reported on Spanish heritage speakers’ vowel production in regard to task modality by incorporating own comparison groups of monolinguals and late bilinguals. Thus, the present study investigates the influence of speech style on Spanish heritage speakers’ vowel production by comparing Spanish-English early and late bilinguals and Spanish monolinguals. The study was guided by the following research question: How do early bilinguals (heritage speakers) differ/relate to advanced L2 speakers of Spanish (late bilinguals) and Spanish monolinguals in their vowel quality (acoustic distribution) and quantity (duration) based on speech style? The participants were a total of 11 speakers of Spanish: 7 early Spanish-English bilinguals with a similar linguistic background (simultaneous bilinguals of the second generation); 2 advanced L2 speakers of Spanish; and 2 Spanish monolinguals from Mexico. The study consisted of two tasks. The first one adopted a semi-spontaneous style by a solicited narration of life experiences and a description of a favorite movie with the purpose to collect spontaneous speech. The second task was a reading activity in which the participants read two paragraphs of a Mexican literary essay 'La nuez.' This task aimed to obtain a more controlled speech style. From this study, it can be concluded that early bilinguals and monolinguals show a smaller formant vowel space overall compared to the late bilinguals in both speech styles. In terms of formant values by stress, the early bilinguals and the late bilinguals resembled in the semi-spontaneous speech style as their unstressed vowel space overlapped with that of the unstressed vowels different from the monolinguals who displayed a slightly reduced unstressed vowel space. For the controlled data, the early bilinguals were similar to the monolinguals as their stressed and unstressed vowel spaces overlapped in comparison to the late bilinguals who showed a more clear reduction of unstressed vowel space. In regard to stress, the monolinguals revealed longer vowel duration overall. However, findings of duration by stress showed that the early bilinguals and the monolinguals remained stable with shorter values of unstressed vowels in the semi-spontaneous data and longer duration in the controlled data when compared to the late bilinguals who displayed opposite results. These findings suggest an implication for Spanish heritage speakers and L2 Spanish vowels research as it has been frequently argued that Spanish bilinguals differ from the Spanish monolinguals by their vowel reduction and centralized vowel space influenced by English. However, some Spanish varieties are characterized by vowel reduction especially in certain phonetic contexts so that some vowels present more weakening than others. Consequently, it would not be conclusive to affirm an English influence on the Spanish of these bilinguals.

Keywords: Spanish-English bilinguals, Spanish monolinguals, spontaneous and controlled speech, vowel production.

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3449 Science Process Skill and Interest Preschooler in Learning Early Science through Mobile Application

Authors: Seah Siok Peh, Hashimah Mohd Yunus, Nor Hashimah Hashim, Mariam Mohamad

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A country needs a workforce that encompasses knowledge, skilled labourers to generate innovation, productivity and being able to solve problems creatively via technology. Science education experts believe that the mastery of science skills help preschoolers to generate such knowledge on scientific concepts by providing constructive experiences. Science process skills are skills used by scientists to study or investigate a problem, issue, problem or phenomenon of science. In line with the skills used by scientists. The purpose of this study is to investigate the basic science process skill and interest in learning early science through mobile application. This study aimed to explore six spesific basic science process skills by the use of a mobile application as a learning support tool. The descriptive design also discusses on the extent of the use of mobile application in improving basic science process skill in young children. This study consists of six preschoolers and two preschool teachers from two different classes located in Perak, Malaysia. Techniques of data collection are inclusive of observations, interviews and document analysis. This study will be useful to provide information and give real phenomena to policy makers especially Ministry of education in Malaysia.

Keywords: science education, basic science process skill, interest, early science, mobile application

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3448 A Review on Disaster Risk Reduction and Sustainable Development in Nigeria

Authors: Kudu Dangana

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The occurrences of disaster often call for the support of both government and non-government organization. Consequently, disaster relief remains extremely important in disaster management. However, this approach alone does not proactively address the need to adduce the human and environment impacts of future disasters. Recent thinking in the area of disaster management is indicative of the need for a new paradigm that focuses on reducing the risk of disasters with the involvement and participation of communities. This paper reviews the need for communities to place more emphasis on a holistic approach to disaster risk reduction. This approach involves risk assessment, risk reduction, early warning and disaster preparedness in order to effectively address the reduction of social, economic, and environmental costs of disasters nationally and at the global level.

Keywords: disaster, early, management, warning, relief, risk vulnerability

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3447 Psoriasis Diagnostic Test Development: Exploratory Study

Authors: Salam N. Abdo, Orien L. Tulp, George P. Einstein

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The purpose of this exploratory study was to gather the insights into psoriasis etiology, treatment, and patient experience, for developing psoriasis and psoriatic arthritis diagnostic test. Data collection methods consisted of a comprehensive meta-analysis of relevant studies and psoriasis patient survey. Established meta-analysis guidelines were used for the selection and qualitative comparative analysis of psoriasis and psoriatic arthritis research studies. Only studies that clearly discussed psoriasis etiology, treatment, and patient experience were reviewed and analyzed, to establish a qualitative data base for the study. Using the insights gained from meta-analysis, an existing psoriasis patient survey was modified and administered to collect additional data as well as triangulate the results. The hypothesis is that specific types of psoriatic disease have specific etiology and pathophysiologic pattern. The following etiology categories were identified: bacterial, environmental/microbial, genetic, immune, infectious, trauma/stress, and viral. Additional results, obtained from meta-analysis and confirmed by patient survey, were the common age of onset (early to mid-20s) and type of psoriasis (plaque; mild; symmetrical; scalp, chest, and extremities, specifically elbows and knees). Almost 70% of patients reported no prescription drug use due to severe side effects and prohibitive cost. These results will guide the development of psoriasis and psoriatic arthritis diagnostic test. The significant number of medical publications classified psoriatic arthritis disease as inflammatory of an unknown etiology. Thus numerous meta-analyses struggle to report any meaningful conclusions since no definitive results have been reported to date. Therefore, return to the basics is an essential step to any future meaningful results. To date, medical literature supports the fact that psoriatic disease in its current classification could be misidentifying subcategories, which in turn hinders the success of studies conducted to date. Moreover, there has been an enormous commercial support to pursue various immune-modulation therapies, thus following a narrow hypothesis/mechanism of action that is yet to yield resolution of disease state. Recurrence and complications may be considered unacceptable in a significant number of these studies. The aim of the ongoing study is to focus on a narrow subgroup of patient population, as identified by this exploratory study via meta-analysis and patient survey, and conduct an exhaustive work up, aiming at mechanism of action and causality before proposing a cure or therapeutic modality. Remission in psoriasis has been achieved and documented in medical literature, such as immune-modulation, phototherapy, various over-the-counter agents, including salts and tar. However, there is no psoriasis and psoriatic arthritis diagnostic test to date, to guide the diagnosis and treatment of this debilitating and, thus far, incurable disease. Because psoriasis affects approximately 2% of population, the results of this study may affect the treatment and improve the quality of life of a significant number of psoriasis patients, potentially millions of patients in the United States alone and many more millions worldwide.

Keywords: biologics, early diagnosis, etiology, immune disease, immune modulation therapy, inflammation skin disorder, phototherapy, plaque psoriasis, psoriasis, psoriasis classification, psoriasis disease marker, psoriasis diagnostic test, psoriasis marker, psoriasis mechanism of action, psoriasis treatment, psoriatic arthritis, psoriatic disease, psoriatic disease marker, psoriatic patient experience, psoriatic patient quality of life, remission, salt therapy, targeted immune therapy

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3446 Effect of Combining Return Policy and Early Order Commitment on Supply Chain Performance

Authors: Hamed Homaei, Seyed Reza Hejazi, Iraj Mahdavi

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Return policy (RP) is a strategy for supply chain coordination, whereby the retailer returns the unsold products to the manufacturer or the manufacturer offers a credit on unsold products to the retailer at the end of selling season. Early order commitment (EOC) is another efficient mechanism for channel coordination wherein the retailer commits to purchasing from the manufacturer a fixed order quantity a few periods in advance of the regular delivery lead time. This paper studies the coordination issue of a two-level supply chain with one retailer and one manufacturer through combining two mentioned contracts. The main purpose of this paper is to present an analytical model to show that how the contract which is created by combining RP and EOC can improve supply chain performance. Numerical analyses show that the supply chain coordination through mentioned contract in compare with EOC mechanism, can improve supply chain performance under certain ranges of model parameters. Furthermore, some numerical analyses are done to determine the best buyback price in order to achieve maximum cost saving in the supply chain. Finally, a revenue sharing scheme is presented in order to achieve a win-win condition in the supply chain.

Keywords: supply chain coordination, early order commitment, return policy, revenue sharing

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3445 Prognostic Impact of Pre-transplant Ferritinemia: A Survival Analysis Among Allograft Patients

Authors: Mekni Sabrine, Nouira Mariem

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Background and aim: Allogeneic hematopoietic stem cell transplantation is a curative treatment for several hematological diseases; however, it has a non-negligible morbidity and mortality depending on several prognostic factors, including pre-transplant hyperferritinemia. The aim of our study was to estimate the impact of hyperferritinemia on survivals and on the occurrence of post-transplant complications. Methods: It was a longitudinal study conducted over 8 years and including all patients who had a first allograft. The impact of pretransplant hyperferritinemia (ferritinemia ≥1500) on survivals was studied using the Kaplan Meier method and the COX model for uni- and multivariate analysis. The Khi-deux test and binary logistic regression were used to study the association between pretransplant ferritinemia and post-transplant complications. Results: One hundred forty patients were included with an average age of 26.6 years and a sex ratio (M/F)=1.4. Hyperferritinemia was found in 33% of patients. It had no significant impact on either overall survival (p=0.9) or event -free survival (p=0.6). In multivariate analysis, only the type of disease was independently associated with overall survival (p=0.04) and event-free survival (p=0.002). For post-allograft complications: The occurrence of early documented infections was independently associated with pretransplant hyperferritinemia (p=0.02) and the presence of acute graft versus host disease( GVHD) (p<10-3). The occurrence of acute GVHD was associated with early documented infection (p=0.002) and Cytomegalovirus reactivation (p<10-3). The occurrence of chronic GVHD was associated with the presence of Cytomegalovirus reactivation (p=0.006) and graft source (p=0.009). Conclusion: Our study showed the significant impact of pre-transplant hyperferritinemia on the occurrence of early infections but not on survivals. Early and more accurate assessment iron overload by other tests such as liver magnetic resonance imaging with initiation of chelating treatment could prevent the occurrence of such complications after transplantation.

Keywords: allogeneic, transplants, ferritin, survival

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3444 An Investigation of Simultaneous Mixed Emotion Experiences for Self and Other in Early Childhood

Authors: Esther Burkitt, Dawn Watling

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Background: Four types of patterns of simultaneous mixed emotions have been identified in middle childhood, adolescence and adulthood. The present study applied an analogue emotion scale which permits measuring of intensity of opposite valence emotions over time rather than bipolar ratings and used an exhaustive coding scheme to investigate whether children in early childhood experience previously identified and additional types of mixed emotional experiences. Methods: To explore the presence of simultaneous mixed emotion experiences in early childhood, 112 children (59 girls) aged 5 years 1 month - 7 years 2 months (X=6 years 1 month; SD = 10 months) were recruited across the UK. They were allocated on the basis of alternation by gender on class lists to one of two conditions hearing vignettes describing mixed emotion events in an age and gender matched protagonist or themselves (other, n = 57 and self, n = 55). Findings: New types of flexuous, vertical and other experiences were identified alongside sequential, prevalent, highly parallel and inverse types of experiences identified in older populations. Conclusions: The analogue emotion scale uncovered a broader range of simultaneous mixed emotional experiences than previously identified. The value of exploring the utility of the findings in emotion assessments is discussed along with suggestions to explore impacts of educational and cultural influences on children’s mixed emotional experiences.

Keywords: childhood, emotion, graphing, self

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3443 Early Initiation of Breastfeeding among Postpartum Mothers at Two Rwandan Hospitals

Authors: Joella Mukashyaka, Rose Mukarubayiza, Emmanuel Habumugisha, Francois-Xavier Sunday, Kellen Muganwa, Valens Mbarushimana, Pamela Meharry

Abstract:

Background: Breastfeeding in the first hour post-birth can decrease neonatal morbidity and mortality. Disease prevention and health outcomes differ immensely between newborns who receive human milk and those who do not. Rwanda has high breastfeeding rates, though factors associated with early initiation of breastfeeding (EIBF) are unknown. Objective: To assess factors associated with EIBF among mothers in immediate postpartum units at two hospitals. Methods: A cross-sectional study design and a convenience sample of 187 mothers were used. An interviewer-administered questionnaire was used for data collection. A Chi-square test showed the relationship between EIBF and sociodemographic factors. Results: The findings showed less than one quarter (20.5%) breastfed within the first hour after birth. The majority was < 25 years (52.4%), had some primary education (27.7%) employed (66.7%), urban dweller (58.1%), attendance of one ANC visit or more (81.3%), vaginal birth (58.8%), and did not receive EIBF health education (92.0%). The majority (78.5%) was too tired to initiate breastfeeding, and many supplemented (41.9%) due to perceived insufficient breastmilk. Conclusion: Most mothers did not initiate breastfeeding within the first hour after birth. Sociodemographic factors were associated with EIBF. A program to promote, protect, and support EIBF is urgently needed the community.

Keywords: breastfeeding, early initiation, neonates, morbidity, mortality, sub-Saharan Africa

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3442 Identification of Potential Predictive Biomarkers for Early Diagnosis of Preeclampsia Growth Factors to microRNAs

Authors: Sadia Munir

Abstract:

Preeclampsia is the contributor to the worldwide maternal mortality of approximately 100,000 deaths a year. It complicates about 10% of all pregnancies and is the first cause of maternal admission to intensive care units. Predicting preeclampsia is a major challenge in obstetrics. More importantly, no major progress has been achieved in the treatment of preeclampsia. As placenta is the main cause of the disease, the only way to treat the disease is to extract placental and deliver the baby. In developed countries, the cost of an average case of preeclampsia is estimated at £9000. Interestingly, preeclampsia may have an impact on the health of mother or infant, beyond the pregnancy. We performed a systematic search of PubMed including the combination of terms such as preeclampsia, biomarkers, treatment, hypoxia, inflammation, oxidative stress, vascular endothelial growth factor A, activin A, inhibin A, placental growth factor, transforming growth factor β-1, Nodal, placenta, trophoblast cells, microRNAs. In this review, we have summarized current knowledge on the identification of potential biomarkers for the diagnosis of preeclampsia. Although these studies show promising data in early diagnosis of preeclampsia, the current value of these factors as biomarkers, for the precise prediction of preeclampsia, has its limitation. Therefore, future studies need to be done to support some of the very promising and interesting data to develop affordable and widely available tests for early detection and treatment of preeclampsia.

Keywords: activin, biomarkers, growth factors, miroRNA

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3441 Parental Education on Early Childhood Development Using Mobile App and Website in China

Authors: Margo O'Sullivan, Xuefeng Chen, Qi Zhao, J. Jiang, Ning Fu

Abstract:

Early childhood development, or ECD, is about the 'whole child' – the physical, social and emotional, cognitive thinking and language progression of each young individual. Overwhelming evidence is now available to support investment in Early Childhood Development internationally, attendance at ECD leads to: improved learning outcomes; improved completion and reduced less dropout rates; and most notably, Professor Heckman, Nobel Laureate’s, findings that for every dollar invested, there is an economic return of up to 17%. Notably, ECD has been included in the 2015-2030 Sustainable Development Goals. The Government of China (GOC) has embraced this research and in 2010, State Council, announced focus on ECD setting a target to provide access to ECD for 85% of 3-6 year olds by 2020; to date, the target has surpassed expectations and reached 70.4%. GoC is also increasingly focusing on the even more critical 0-3 age group, when the plasticity of the brain is at its peak and neurons form connections as fast as 1,000 per second. Key to ECD are parents and caregivers of young children, with parental education critical to fully exploiting the significant potential of the early years of children. In China, with such vast numbers, one in seven pre-school age children in the world live in China, the Ministry of Education (MoE) and the National Centre for Education Technology, explored how to best provide parental education and provide key child developmental related knowledge to parents and caregivers. In response, MoE and UNICEF created a resource for parenting information that began with a computer website in 2012, followed by piloting a kiosk service in 2013 for parents in remote areas without access to the internet, and then a mobile phone application in 2014. The resource includes 269 ECD messages and 200 micro-videos covering critical issues of early childhood development from birth to age 6 years: daily care, nutrition and feeding, disease prevention, immunization, development and education, and safety and protection. To date, there have been 397,599 unique views on the website, and data for the mobile app currently being analysed (Links: http://yuer.cbern.gov.cn/; App: https://appsto.re/cn/OiKPZ.i). This paper will explore the development of this resource, its use by parents and the public, efforts to assess the effectiveness in improving parenting and child development, and future plans to roll an updated version in 2016 to all parents.

Keywords: early childhood development, mobile apps for education, parental education, China

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3440 Discover a New Technique for Cancer Recognition by Analysis and Determination of Fractal Dimension Images in Matlab Software

Authors: Saeedeh Shahbazkhany

Abstract:

Cancer is a terrible disease that, if not diagnosed early, therapy can be difficult while it is easily medicable if it is diagnosed in early stages. So it is very important for cancer diagnosis that medical procedures are performed. In this paper we introduce a new method. In this method, we only need pictures of healthy cells and cancer cells. In fact, where we suspect cancer, we take a picture of cells or tissue in that area, and then take some pictures of the surrounding tissues. Then, fractal dimension of images are calculated and compared. Cancer can be easily detected by comparing the fractal dimension of images. In this method, we use Matlab software.

Keywords: Matlab software, fractal dimension, cancer, surrounding tissues, cells or tissue, new method

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3439 The Perceptions of Parents Regarding the Appropriateness of the Early Childhood Financial Literacy Program for Children 3 to 6 Years of Age Presented at an Early Childhood Facility in South Africa: A Case Study

Authors: M. Naude, R. Joubert, A. du Plessis, S. Pelser, M. Trollip

Abstract:

Context: The study focuses on the perceptions of South African parents and teachers regarding a play-based financial literacy program for children aged 3 to 6 years at an early childhood facility. It emphasizes the importance of early interventions in financial education to reduce poverty and inequality. Research Aim: To explore how parental involvement in teaching money management concepts to young children can support financial literacy education both at school and at home. Methodology: A qualitative deductive case study was conducted at a South African early childhood facility involving 90 children, their teachers and their families. Thematic content analysis of online survey responses and focus group discussions with teachers were used to identify patterns and themes related to participants’ perceptions of the financial literacy program. Validity: The study's validity and reproducibility are ensured by the depth and honesty of the data, participant involvement, and the inquirer's objectivity. Reliability aligns with the interpretive paradigm of this study, while transparency in data gathering and analysis enhances its trustworthiness. Credibility is further supported by using two triangulation methods: focus group interviews with teachers and open-ended questionnaires from parents. Findings: Parents reported overall satisfaction with the program and highlighted the development of essential money management skills in their children. They emphasized the collaborative role of home and school environments in fostering financial literacy in early childhood. Teachers reported that communication and interaction with the parents increased and grew. Healthy and positive relationships were established between the teachers and the parents which contributed to the success of the classroom financial literacy program. Theoretical Importance: The study underscores the significance of play-based financial literacy education in early childhood and the critical role of parental involvement in reinforcing money management concepts. It contributes to laying a solid foundation for children's future financial well-being. Data Collection: Data was collected through an online survey administered to parents of children participating in the financial literacy program over a period of 10 weeks. Focus group discussions were utilized with the teachers of each class after the conclusion of the program. Analysis Procedures: Thematic content analysis was applied to the survey responses to identify patterns, themes, and insights related to the participants’ perceptions of the program's effectiveness in teaching money management concepts to young children. Question Addressed: How does parental involvement in teaching money management concepts to young children support financial literacy education in early childhood? Conclusion: The study highlights the positive impact of a play-based financial literacy program for children aged 3 to 6 years and underscores the importance of collaboration between home and school environments in fostering financial literacy skills.

Keywords: early childhood, financial literacy, money management, parent involvement, play-based learning, South Africa

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3438 Laparoscopic Resection Shows Comparable Outcomes to Open Thoracotomy for Thoracoabdominal Neuroblastomas: A Meta-Analysis and Systematic Review

Authors: Peter J. Fusco, Dave M. Mathew, Chris Mathew, Kenneth H. Levy, Kathryn S. Varghese, Stephanie Salazar-Restrepo, Serena M. Mathew, Sofia Khaja, Eamon Vega, Mia Polizzi, Alyssa Mullane, Adham Ahmed

Abstract:

Background: Laparoscopic (LS) removal of neuroblastomas in children has been reported to offer favorable outcomes compared to the conventional open thoracotomy (OT) procedure. Critical perioperative measures such as blood loss, operative time, length of stay, and time to postoperative chemotherapy have all supported laparoscopic use rather than its more invasive counterpart. Herein, a pairwise meta-analysis was performed comparing perioperative outcomes between LS and OT in thoracoabdominal neuroblastoma cases. Methods: A comprehensive literature search was performed on PubMed, Ovid EMBASE, and Scopus databases to identify studies comparing the outcomes of pediatric patients with thoracoabdominal neuroblastomas undergoing resection via OT or LS. After deduplication, 4,227 studies were identified and subjected to initial title screening with exclusion and inclusion criteria to ensure relevance. When studies contained overlapping cohorts, only the larger series were included. Primary outcomes include estimated blood loss (EBL), hospital length of stay (LOS), and mortality, while secondary outcomes were tumor recurrence, post-operative complications, and operation length. The “meta” and “metafor” packages were used in R, version 4.0.2, to pool risk ratios (RR) or standardized mean differences (SMD) in addition to their 95% confidence intervals in the random effects model via the Mantel-Haenszel method. Heterogeneity between studies was assessed using the I² test, while publication bias was assessed via funnel plot. Results: The pooled analysis included 209 patients from 5 studies (141 OT, 68 LS). Of the included studies, 2 originated from the United States, 1 from Toronto, 1 from China, and 1was from a Japanese center. Mean age between study cohorts ranged from 2.4 to 5.3 years old, with female patients occupying between 30.8% to 50% of the study populations. No statistically significant difference was found between the two groups for LOS (SMD -1.02; p=0.083), mortality (RR 0.30; p=0.251), recurrence(RR 0.31; p=0.162), post-operative complications (RR 0.73; p=0.732), or operation length (SMD -0.07; p=0.648). Of note, LS appeared to be protective in the analysis for EBL, although it did not reach statistical significance (SMD -0.4174; p= 0.051). Conclusion: Despite promising literature assessing LS removal of pediatric neuroblastomas, results showed it was non-superior to OT for any explored perioperative outcomes. Given the limited comparative data on the subject, it is evident that randomized trials are necessary to further the efficacy of the conclusions reached.

Keywords: laparoscopy, neuroblastoma, thoracoabdominal, thoracotomy

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3437 The Magnification of Early Detect Nutrition Case through Local Potential Utilization in Urban Region, Indonesia

Authors: Oktia Woro Kasmini Handayani, Sri Ratna Rahayu, Efa Nugroho, Bertakalswa Hermawati

Abstract:

The double burden of nutrition problem must be faced by Indonesia as developing country. The implemented program did not improve the nutritional status, therefore need to consider to utilize local potential. The objective of this research was to find out the effectivity of magnification model of early detect through local potential utilization in urban region, Semarang, Central Java, Indonesia. The research used an experimental design with the quantitative-qualitative approach. The population was all toddlers under five within the research region, sample determination by purposive sampling, as many as 216 toddlers. Quantitative data analysis used effectively criteria by Sugiono. Qualitative data was analyzed using NVivo. The optimization of local potential in the effort of nutrition status improvement shows number of nutrition case found was increased 225% (very effective), number of cases treated was increased 175% (very effective), number of cases counselled was increased 200% (effective), and number of cases that have improvement increase 75% (effective). The local potential need to be utilized in the effort of nutrition program improvement one of it is through the community empowerment, particularly health care and health high education institution as partner.

Keywords: early detection, nutrition status, local potential, health cadre

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3436 The Community Stakeholders’ Perspectives on Sexual Health Education for Young Adolescents in Western New York, USA: A Qualitative Descriptive Study

Authors: Sadandaula Rose Muheriwa Matemba, Alexander Glazier, Natalie M. LeBlanc

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In the United States, up to 10% of girls and 22 % of boys 10-14 years have had sex, 5% of them had their first sex before 11 years, and the age of first sexual encounter is reported to be 8 years. Over 4,000 adolescent girls, 10-14 years, become pregnant every year, and 2.6% of the abortions in 2019 were among adolescents below 15 years. Despite these negative outcomes, little research has been conducted to understand the sexual health education offered to young adolescents ages 10-14. Early sexual health education is one of the most effective strategies to help lower the rate of early pregnancies, HIV infections, and other sexually transmitted. Such knowledge is necessary to inform best practices for supporting the healthy sexual development of young adolescents and prevent adverse outcomes. This qualitative descriptive study was conducted to explore the community stakeholders’ experiences in sexual health education for young adolescents ages 10-14 and ascertain the young adolescents’ sexual health support needs. Maximum variation purposive sampling was used to recruit a total sample of 13 community stakeholders, including health education teachers, members of youth-based organizations, and Adolescent Clinic providers in Rochester, New York State, in the United States of America from April to June 2022. Data were collected through semi-structured individual in-depth interviews and were analyzed using MAXQDA following a conventional content analysis approach. Triangulation, team analysis, and respondent validation to enhance rigor were also employed to enhance study rigor. The participants were predominantly female (92.3%) and comprised of Caucasians (53.8%), Black/African Americans (38.5%), and Indian-American (7.7%), with ages ranging from 23-59. Four themes emerged: the perceived need for early sexual health education, preferred timing to initiate sexual health conversations, perceived age-appropriate content for young adolescents, and initiating sexual health conversations with young adolescents. The participants described encouraging and concerning experiences. Most participants were concerned that young adolescents are living in a sexually driven environment and are not given the sexual health education they need, even though they are open to learning sexual health materials. There was consensus on the need to initiate sexual health conversations early at 4 years or younger, standardize sexual health education in schools and make age-appropriate sexual health education progressive. These results show that early sexual health education is essential if young adolescents are to delay sexual debut, prevent early pregnancies, and if the goal of ending the HIV epidemic is to be achieved. However, research is needed on a larger scale to understand how best to implement sexual health education among young adolescents and to inform interventions for implementing contextually-relevant sexuality education for this population. These findings call for increased multidisciplinary efforts in promoting early sexual health education for young adolescents.

Keywords: community stakeholders’ perspectives, sexual development, sexual health education, young adolescents

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3435 The Effects of the Interaction between Prenatal Stress and Diet on Maternal Insulin Resistance and Inflammatory Profile

Authors: Karen L. Lindsay, Sonja Entringer, Claudia Buss, Pathik D. Wadhwa

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Maternal nutrition and stress are independently recognized as among the most important factors that influence prenatal biology, with implications for fetal development and poor pregnancy outcomes. While there is substantial evidence from non-pregnancy human and animal studies that a complex, bi-directional relationship exists between nutrition and stress, to the author’s best knowledge, their interaction in the context of pregnancy has been significantly understudied. The aim of this study is to assess the interaction between maternal psychological stress and diet quality across pregnancy and its effects on biomarkers of prenatal insulin resistance and inflammation. This is a prospective longitudinal study of N=235 women carrying a healthy, singleton pregnancy, recruited from prenatal clinics of the University of California, Irvine Medical Center. Participants completed a 4-day ambulatory assessment in early, middle and late pregnancy, which included multiple daily electronic diary entries using Ecological Momentary Assessment (EMA) technology on a dedicated study smartphone. The EMA diaries gathered moment-level data on maternal perceived stress, negative mood, positive mood and quality of social interactions. The numerical scores for these variables were averaged across each study time-point and converted to Z-scores. A single composite variable for 'STRESS' was computed as follows: (Negative mood+Perceived stress)–(Positive mood+Social interaction quality). Dietary intakes were assessed by three 24-hour dietary recalls conducted within two weeks of each 4-day assessment. Daily nutrient and food group intakes were averaged across each study time-point. The Alternative Healthy Eating Index adapted for pregnancy (AHEI-P) was computed for early, middle and late pregnancy as a validated summary measure of diet quality. At the end of each 4-day ambulatory assessment, women provided a fasting blood sample, which was assayed for levels of glucose, insulin, Interleukin (IL)-6 and Tumor Necrosis Factor (TNF)-α. Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) was computed. Pearson’s correlation was used to explore the relationship between maternal STRESS and AHEI-P within and between each study time-point. Linear regression was employed to test the association of the stress-diet interaction (STRESS*AHEI-P) with the biological markers HOMA-IR, IL-6 and TNF-α at each study time-point, adjusting for key covariates (pre-pregnancy body mass index, maternal education level, race/ethnicity). Maternal STRESS and AHEI-P were significantly inversely correlated in early (r=-0.164, p=0.018) and mid-pregnancy (-0.160, p=0.019), and AHEI-P from earlier gestational time-points correlated with later STRESS (early AHEI-P x mid STRESS: r=-0.168, p=0.017; mid AHEI-P x late STRESS: r=-0.142, p=0.041). In regression models, the interaction term was not associated with HOMA-IR or IL-6 at any gestational time-point. The stress-diet interaction term was significantly associated with TNF-α according to the following patterns: early AHEI-P*early STRESS vs early TNF-α (p=0.005); early AHEI-P*early STRESS vs mid TNF-α (p=0.002); early AHEI-P*mid STRESS vs mid TNF-α (p=0.005); mid AHEI-P*mid STRESS vs mid TNF-α (p=0.070); mid AHEI-P*late STRESS vs late TNF-α (p=0.011). Poor diet quality is significantly related to higher psychosocial stress levels in pregnant women across gestation, which may promote inflammation via TNF-α. Future prenatal studies should consider the combined effects of maternal stress and diet when evaluating either one of these factors on pregnancy or infant outcomes.

Keywords: diet quality, inflammation, insulin resistance, nutrition, pregnancy, stress, tumor necrosis factor-alpha

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3434 De Novo Design of a Minimal Catalytic Di-Nickel Peptide Capable of Sustained Hydrogen Evolution

Authors: Saroj Poudel, Joshua Mancini, Douglas Pike, Jennifer Timm, Alexei Tyryshkin, Vikas Nanda, Paul Falkowski

Abstract:

On the early Earth, protein-metal complexes likely harvested energy from a reduced environment. These complexes would have been precursors to the metabolic enzymes of ancient organisms. Hydrogenase is an essential enzyme in most anaerobic organisms for the reduction and oxidation of hydrogen in the environment and is likely one of the earliest evolved enzymes. To attempt to reinvent a precursor to modern hydrogenase, we computationally designed a short thirteen amino acid peptide that binds the often-required catalytic transition metal Nickel in hydrogenase. This simple complex can achieve hundreds of hydrogen evolution cycles using light energy in a broad range of temperature and pH. Biophysical and structural investigations strongly indicate the peptide forms a di-nickel active site analogous to Acetyl-CoA synthase, an ancient protein central to carbon reduction in the Wood-Ljungdahl pathway and capable of hydrogen evolution. This work demonstrates that prior to the complex evolution of multidomain enzymes, early peptide-metal complexes could have catalyzed energy transfer from the environment on the early Earth and enabled the evolution of modern metabolism

Keywords: hydrogenase, prebiotic enzyme, metalloenzyme, computational design

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