Search results for: developmental neurotoxicity

Authors: Sung Hyun Kim

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Introduction: Sleep disturbance is common in children with developmental disorders (D.D.). Sleep disturbance has a variety of negative effects, such as behavior problems, medical problems, and even developmental problems in children with D.D. However, to our best knowledge, there has been no proper treatment for sleep disorders in children with D.D. Therefore, we conduct this study to know the positive effects of intensive rehabilitation therapy in children with D.D. on the degree of sleep disturbance. Method: We prospectively recruited 22 patients with a diagnosis of D.D. during the period of January 2022 through May 2022. The inclusion criteria were as follows: 1) a patient who would participate in the intensive rehabilitation therapy of our institution; 2) the age participant under 18 years at the time of assessment; 3) a child who has consented to participate in the study by signing the consent form by the legal guardian. We investigated the clinical characteristics of participants by the medical record, including sex, age, underlying diagnosis of D.D., and Gross Motor Function Measures (GMFM). Before starting the intensive rehabilitation therapy, we conducted a Sleep disturbance scale for children (SDSC). It contains 26 questions about children’s sleep, and those questions are grouped into six subscales, such as Disorders of initiating and maintaining sleep (DIMS), Sleep Breathing Disorders(SBD), Disorders of arousal(DOA), Sleep-Wake Transition Disorders(SWTD), Disorders of excessive somnolence(DOES) and Sleep Hyperhydrosis(SHY). We used the t-score, which was calculated by comparing the scores of normal children. Twenty two patients received 8 weeks of intensive rehabilitation, including daily physical and occupational therapy. After that, we did follow up with SDSC. The comparison between SDSC before and after intensive rehabilitation was calculated using the paired t-test, and P< 0.05 was considered statistically significant. Results: Demographic data and clinical characteristics of 22 patients are enrolled. Patients were 4.03 ± 2.91 years old, and of the total 22 patients, 14 (64%) were male, and 8 (36%) were female. Twelve patients(45%) were diagnosed with Cerebral palsy(C.P.), and the mean value of participants’ GMFM was 47.82 ± 20.60. Each mean value of SDSC’s subscales was also calculated. DIMS was 62.36 ± 13.72, SBD was 54.18 ± 8.39, DOA was 49.59 ± 7.01, SWTD was 58.95 ± 9.20, DOES was 53.09 ± 15.15, SHY was 52.14 ± 8.82, and the total was 59.86 ± 13.18. These values suggest that children with D.D. have sleep disorders. After 8 weeks of intensive rehabilitation treatment, the score of DIMS showed improvement(p=0.016), but not the other subscale and total score of SDSC. Conclusion: This result showed that intensive rehabilitation could be helpful to patients of D.D. with sleep disorders. Especially intensive rehabilitation therapy itself can be a meaningful treatment in inducing and maintaining sleep.

Keywords: sleep disorder, developmental delay, intensive rehabilitation therapy, cerebral palsy

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Authors: Rebecca K. Blais, Lindsey Monteith, Hallie Tannahill

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Military sexual trauma (MST) includes sexual harassment or assault that occurred during military service. Studies conducted to date on the association of MST with mental health and suicide outcomes are generally circumscribed to either active duty or veteran samples, precluding a thorough analysis of developmental trajectories of distress following MST within the context of ongoing (vs. discharged from) military service. The Military Social Science Laboratory has collected data on mixed service samples of men and women service members, addressing this important literature gap. The purpose of this study was to examine the association of MST, suicide risk, PTSD, depression, alcohol use, and posttraumatic cognitions using two separate samples, which collectively allow for a comprehensive examination of the development of distress following MST. The first sample consisted of 1389 men and women service members and veterans with varying levels of MST severity, including no MST, harassment-only MST, and assault MST. The second sample consisted of 400 men and women service members, all reporting the highest severity of MST, assault MST. In both samples, roughly half reported being discharged from service. Participants completed self-report measures of MST exposure severity, suicide ideation, suicide risk, PTSD, depression, alcohol misuse, and posttraumatic cognitions, as well as perceptions of how the military responded to their MST. Relative to those still serving in the US military, veterans were more likely to endorse suicidal ideation, higher PTSD symptoms, and higher depression symptoms if they felt the military mishandled their experience of MST (referred to as perceived institutional betrayal). However, among those reporting the most severe MST, veterans reported lower alcohol misuse and more adaptive posttraumatic cognitions. These findings suggest that those separated from the military experience different posttraumatic aftermath following MST relative to those who are currently serving in the military. Such findings suggest critical differences in the developmental trajectory of distress, necessitating different interventions to successfully reduce distress and dysfunction. Additional analyses will explore the impact of gender on these associations and explore full mechanistic models of distress grouped by discharged status.

Keywords: military sexual trauma, PTSD, suicide, developmental trajectories, depression

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Authors: Susan Hall, Gary D. Grant, Catherine McDermott, Devinder Arora

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Introduction /Aim: The kynurenine pathway is thought to play an important role in the pathophysiology of numerous neurodegenerative diseases including depression, Alzheimer’s disease, and Parkinson’s disease. Numerous neuroactive compounds, including the neurotoxic 3-hydroxyanthranilic acid, 3-hydroxykynurenine and quinolinic acid and the neuroprotective kynurenic acid and picolinic acid, are produced through the metabolism of kynurenine and are thought to be the causative agents responsible for neurodegeneration. The toxicity of 3-hydroxykynurenine, 3-hydroxyanthranilic acid and quinolinic acid has been widely evaluated and demonstrated in primary cell cultures but to date only 3-hydroxykynurenine and 3-hydroxyanthranilic acid have been shown to cause toxicity in immortal tumour cells. The aim of this study was to evaluate the toxicity of kynurenine metabolites, both individually and in combination, on SH-SY5Y neuroblastoma cells after 24 and 72 h exposure in order to explore a cost-effective model to study their neurotoxic effects and potential protective agents. Methods: SH-SY5Y neuroblastoma cells were exposed to various concentrations of the neuroactive kynurenine metabolites, both individually and in combination, for 24 and 72 h, and viability was subsequently evaluated using the Resazurin (Alamar blue) proliferation assay. Furthermore, the effects of these compounds, alone and in combination, on specific death pathways including apoptosis, necrosis and free radical production was evaluated using various assays. Results: Consistent with literature, toxicity was shown with short-term 24-hour treatments at 1000 μM concentrations for both 3-hydroxykynurenine and 3-hydroxyanthranilic acid. Combinations of kynurenine metabolites showed modest toxicity towards SH-SY5Y neuroblastoma cells in a concentration-dependent manner. Specific cell death pathways, including apoptosis, necrosis and free radical production were shown to be increased after both 24 and 72 h exposure of SH-SY5Y neuroblastoma cells to 3-hydroxykynurenine and 3-hydroxyanthranilic acid and various combinations of neurotoxic kynurenine metabolites. Conclusion: It is well documented that neurotoxic kynurenine metabolites show toxicity towards primary human neurons in the nanomolar to low micromolar concentration range. Results show that the concentrations required to show significant cell death are in the range of 1000 µM for 3-hydroxykynurenine and 3-hydroxyanthranilic acid and toxicity of quinolinic acid towards SH-SY5Y was unable to be shown. This differs significantly from toxicities observed in primary human neurons. Combinations of the neurotoxic metabolites were shown to have modest toxicity towards these cells with increased toxicity and activation of cell death pathways observed after 72 h exposure. This study suggests that the 24 h model is unsuitable for use in neurotoxicity studies, however, the 72 h model better represents the observations of the studies using primary human neurons and may provide some benefit in providing a cost-effective model to assess possible protective agents against kynurenine metabolite toxicities.

Keywords: kynurenine metabolites, neurotoxicity, quinolinic acid, SH-SY5Y neuroblastoma

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Authors: Hsiu-Ling Hsu, En-Minh (John) Lan

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Pronunciation has received more and more language researchers’ and teachers’ attention because it is important for effective or even successful communication. How to consistently and correctly orally produce verbal morphology, such as English regular past tense inflection, has been a big challenge and troublesome for FL learners. The research aims to explore EFL (English as a foreign language) learners’ developmental trajectory of the inflectional morphology, that is, what mediating processes and strategies EFL learners use, to attain native-like prosodic structure of inflectional morphemes (e.g., –ed and –s suffixes) by comparing the differences among EFL learners at different English levels. This research adopted a self-repair analysis and Prosodic Transfer Hypothesis with three developmental stages as a theoretical framework. To answer the research questions, we conducted two experiments, grammatical tense test written production (Experiment 1) and read-aloud oral production (Experiment 2), and recruited 30 participants who were divided into three groups, low-, middle-, and advanced EFL learners. Experiment 1 was conducted to ensure that participants had learned the knowledge of forming the English regular past tense rules and Experiment 2 was carried out to compare the data across FL English learner groups at different English levels. The EFL learners’ self-repair data showed at least four interesting findings. First, low achievers were more sensitive to the plural suffix -s than the past tense suffix -ed. Middle achievers exhibited a greater responsiveness to the past tense suffix, while high achievers demonstrated equal sensitivity to both suffixes. Additionally, two strategies used by EFL English learners to produce verbs and nouns with inflectional morphemes were to delete internal syllable and to divide a four-syllable verb (e.g., ‘graduated’) into two prosodic structures (e.g., ‘gradu’ and ‘ated’ or ‘gradua’ and ‘ted’). Third, true vowel epenthesis was found only in the low EFL achievers. Moreover fortition (native-like sound) was observed in the low and middle EFL achievers. These findings and self-repair data disclosed mediating processes between the developmental stages and provided insight on how Taiwan EFL learners attained the adjunction prosodic structures of inflectional Morphemes in English.

Keywords: inflectional morphology, prosodic structure, developmental trajectory, strategies and mediating processes, English as a foreign language

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Authors: P. P. Chandrasekera, P. B. Hewavithana, S. Rosairo, M. H. M. N. Herath, D. M. R. D. Mirihella

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Periventricular Leukomalacia (PVL) is a White Matter Injury (WMI) of preterm neonatal brain. Objectives of the study were to assess the neuro-developmental outcome at one year of age and to determine a good protocol of cranial ultrasonography to detect PVL. Two hundred and sixty four preterm neonates were included in the study. Series of cranial ultrasound scans were done by using a dedicated neonatal head probe 4-10 MHz of Logic e portable ultrasound scanner. Clinical history of seizures, abnormal head growth (hydrocephalus or microcephaly) and developmental milestones were assessed and neurological examinations were done until one year of age. Among live neonates, 57% who had cystic PVL (Grades2 and 3) manifested as cerebral palsy. In conclusion cystic PVL has permanent neurological disabilities like cerebral palsy. Good protocol of real time cranial ultrasonography to detect PVL is to perform scans at least once a week until one month and at term (40 weeks of gestation).

Keywords: cerebral palsy, cranial ultrasonography, Periventricular Leukomalacia, preterm neonates

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Authors: Lucy Adesomon Okukpon, Margaret Omolara Akerele

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Higher Education in Nigeria is sought after by women, they believe that the economic power and growth lies in the attainment and pursuit of higher Education. No nation in the world can boast of developmental growth when the women are not fully empowered educationally. The attainment of higher education spurs women to contribute meaningfully towards the growth and development of the Nigerian workforce. Recent innovations and trends reveal that over fifty per cent of Nigerian women have attained higher education within and outside the country. Women in Nigeria have expressed their growing concern of what becomes of the remaining 50 per cent who are unable to attain basic education. This concern has brought about the issue of funding which is a practical challenge towards the attainment of education for these vulnerable women. Another challenging factor is that most women often seek the permission of their husbands, brothers, fathers and uncles to enable them attain educational pursuit, especially when the institution is miles away from their place of abode. The solution to this problems from research findings reveal that the umbrella body which co-ordinates education for women in Nigeria (The National Council of Women Societies, NCWS) have taken it upon itself to provide educational learning centres in all the states of the Federation including Abuja the Nations capital city. This is to stem the ugly trend and enable women gain access to educational facilities provided for their growth and development. This positive stride has brought succour to women who hitherto have no hope of attaining any form of education. Moreover, awareness creation concerning higher education is translated into different Nigerian languages so that the women at the grassroots can benefit immensely and contribute towards the growth and development of the Nation. Their educational progress attest to the fact that Nigerian Women are happy for the educational opportunities provided and have vowed to attain greater heights particularly where higher education is concerned.

Keywords: developmental growth, educational attainment, higher education, women in higher education, Nigeria

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Authors: Aliza Lee, Mark Wilt, John Bonk, Scott Floyd, Bradley Hoffman, Karen Uchmanowicz

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Bipartite medial cuneiforms are relatively rare but may play a significant role in biomechanical and gait abnormalities. It is believed that a bipartite medial cuneiform may alter the available range of motion due to its larger morphological variant, thus limiting the metatarsal plantarflexion needed to achieve adequate hallux dorsiflexion for normal gait. Radiographic and clinical assessments were performed on 2 patients who reported foot pain along the first ray. Both patients had visible bipartite medial cuneiforms on MRI. Using gait plate and Metascan™ analysis, both were noted to have four measurements far beyond the expected range. Medial and lateral heel peak pressure, hallux peak pressure, and 1st metatarsal peak pressure were all noted to be increased. These measurements are believed to be increased due to the hindrance placed on the available ROM of the 1st ray by the increased size of the medial cuneiform. A larger patient population would be needed to fully understand this developmental anomaly.

Keywords: bipartite medial cuneiforms, cuneiform, developmental anomaly, gait abnormality

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Authors: Suvorov Vasyl, Filipchuk Viktor

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Developmental Dysplasia of the Hip (DDH) is a frequent pathology in pediatric orthopedist’s practice. Neglected or residual cases of DDH in walking patients are usually treated using pelvic osteotomies. Plastic changes take place in hinge points due to acetabulum reorientation during surgery. Classically described hinge points and a traditional division of pelvic osteotomies on reshaping and reorientation are currently debated. The purpose of this article was to evaluate biomechanical changes during the most commonly used pelvic osteotomies (Salter, Dega, Pemberton) for DDH treatment in pediatric patients. Methods: virtual pelvic models of 2- and 6-years old patients were created, material properties were assigned, pelvic osteotomies were simulated and biomechanical changes were evaluated using finite element analysis (FEA). Results: it was revealed that the patient's age has an impact on pelvic bones and cartilages density (in younger patients the pelvic elements are more pliable - p<0.05). Stress distribution after each of the abovementioned pelvic osteotomy was assessed in 2- and 6-years old patients’ pelvic models; hinge points were evaluated. The new term "restriction point" was introduced, which means a place where restriction of acetabular deformity correction occurs. Pelvic ligaments attachment points were mainly these restriction points. Conclusions: it was found out that there are no purely reshaping and reorientation pelvic osteotomies as previously believed; the pelvic ring acts as a unit in carrying out the applied load. Biomechanical overload of triradiate cartilage during Salter osteotomy in 2-years old patient and in 2- and 6-years old patients during Pemberton osteotomy was revealed; overload of the posterior cortical layer in the greater sciatic notch in 2-years old patient during Dega osteotomy was revealed. Level of Evidence – Level IV, prognostic.

Keywords: developmental dysplasia of the hip, pelvic osteotomy, finite element analysis, hinge point, biomechanics

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Authors: Salma M. Wakil

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Advances in the field of genetics overwhelmed detecting large number of inherited disorders at the molecular level and directed to the development of innovative technologies. These innovations have led to gene sequencing, prenatal mutation detection, pre-implantation genetic diagnosis; population based carrier screening and genome wide analyses using microarrays. Microarrays are widely used in establishing clinical and diagnostic setup for genetic anomalies at a massive level, with the advent of cytoscan molecular karyotyping as a clinical utility card for detecting chromosomal aberrations with high coverage across the entire human genome. Unlike a regular karyotype that relies on the microscopic inspection of chromosomes, molecular karyotyping with cytoscan constructs virtual chromosomes based on the copy number analysis of DNA which improves its resolution by 100-fold. We have been investigating a large number of patients with Developmental Delay and Intellectual disability with this platform for establishing micro syndrome deletions and have detected number of novel CNV’s in the Arabian population with the clinical relevance.

Keywords: microarrays, molecular karyotyping, developmental delay, genetics

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Authors: Sunila John, B. Rajashekhar

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Initial letter fluency tasks are one of the simple behavioral measures to evaluate the complex nature of word retrieval ability. This task requires the participant to retrieve as many words as possible beginning with a particular letter in a fixed time frame. Though the task of verbal fluency is popular among adult clinical conditions, its role in children has been less emphasized. There exists a lack of in-depth understanding of processes underlying verbal fluency performance in typically developing children. The present study, therefore, aims to delineate the developmental trend on initial letter fluency task observed in typically developing Malayalam speaking children. The participants were aged between 5 to 10 years and categorized into three groups: Group I (class I and II, mean (SD) age years: 6.44(.78)), Group II (class III and IV, mean (SD) age years: 8.59 (.83)) and group III (class V and VI, mean (SD) age years: 10.28 (.80). On two tasks of initial letter fluency, the verbal fluency outcome measures were analyzed. The study findings revealed a distinct pattern of initial letter fluency development which may enhance its usefulness in clinical and research settings.

Keywords: children, development, initial letter fluency, word retrieval

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Authors: S. Ahmad, C. Yuan, Q. Zhang

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The assorted architectural plasticity of a plant is majorly specified by stooling, a phenomenon tackled by a combination of developmental, environmental and hormonal accelerators of lateral buds. Chrysanthemums (Chrysanthemum morifolium) are one of the most economically important ornamental plants worldwide on the account of having plentiful architectural patterns, diverse shapes and attractive colors. Side branching is the major determinant guaranteeing the consistent demand of cut chrysanthemum in flower industry. Presence of immense number of axillary branches devalues the economic importance of this imperative plant and is a major challenge for mum growers to hold a stake in the cut flower market. Restricting branches to a minimum level, or no branches at all, is the dire need of the day in order to introducing novelty in cut chrysanthemums. Temperature is a potent factor which affects largely the escalation, development of chrysanthemum, and also the genetic expression of various vegetative traits like branching. It affects differently the developmental characteristics and phenotypic expressions of inherent qualities, thereby playing a significant role in differentiating the developmental responses in different cultivars of chrysanthemum. A detailed study pertaining to the affect of temperature on branching in chrysanthemum is a clear lacking throughout the literature on mums. Therefore, searching with temperature as an effective means of reducing side branching to a desired level could be an influencing extension of struggles about how to nullify stooling. This requires plenty of research in order to reveal the extended penetration of temperature in manipulating the genetic control of various important traits like branching, which is a burning issue now a days in producing cut flowers in chrysanthemum. The present review will highlight the impact of temperature on branching control mechanism in chrysanthemum at morpho-physiological, hormonal and molecular levels.

Keywords: branching, chrysanthemum, genetic control, hormonal, morpho-physiological, temperature

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Authors: Deepa Gandhi, Pravin K. Naoghare, Amit Bafana, Krishnamurthi Kannan, Saravanadevi Sivanesana

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Oxidative stress is known to depreciate normal functioning of osteoblast cells. Present study reports oxidative/inflammatory signatures in fluoride exposed human osteosarcoma (HOS) cells and its possible association with the genes involved in bone developmental pathway. Microarray analysis was performed to understand the possible molecular mechanisms of stress-mediated bone lose in HOS cells. Cells were chronically exposed with sub-lethal concentration of fluoride. Global gene expression is profiling revealed 34 up regulated and 2598 down-regulated genes, which were associated with several biological processes including bone development, osteoblast differentiation, stress response, inflammatory response, apoptosis, regulation of cell proliferation. Microarray data were further validated through qRT-PCR and western blot analyses using key representative genes. Based on these findings, it can be proposed that chronic exposure of fluoride may impair bone development via oxidative and inflammatory stress. The present finding also provides important biological clues, which will be helpful for the development of therapeutic targets against diseases related bone.

Keywords: bone, HOS cells, microarray, stress

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Authors: Rebecca Richards Steed, James Van Derslice, Ken Smith, Richard Medina, Amanda Bakian

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Elucidating gene-environment interactions for heritable disease outcomes is an emerging area of disease research, with genetic studies informing hypotheses for environment and gene interactions underlying some of the most confounding diseases of our time, like autism spectrum disorder (ASD). Geography has thus far played a key role in identifying environmental factors contributing to disease, but its use can be broadened to include genetic and environmental factors that have a synergistic effect on disease. Through the use of family pedigrees and disease outcomes with life-course residential histories, space-time clustering of generations at critical developmental windows can provide further understanding of (1) environmental factors that contribute to disease patterns in families, (2) susceptible critical windows of development most impacted by environment, (3) and that are most likely to lead to an ASD diagnosis. This paper introduces a retrospective case-control study that utilizes pedigree data, health data, and residential life-course location points to find space-time clustering of ancestors with a grandchild/child with a clinical diagnosis of ASD. Finding space-time clusters of ancestors at critical developmental windows serves as a proxy for shared environmental exposures. The authors refer to geographic life-course exposures as geographic legacies. Identifying space-time clusters of ancestors creates a bridge for researching exposures of past generations that may impact modern-day progeny health. Results from the space-time cluster analysis show multiple clusters for the maternal and paternal pedigrees. The paternal grandparent pedigree resulted in the most space-time clustering for birth and childhood developmental windows. No statistically significant clustering was found for adolescent years. These results will be further studied to identify the specific share of space-time environmental exposures. In conclusion, this study has found significant space-time clusters of parents, and grandparents for both maternal and paternal lineage. These results will be used to identify what environmental exposures have been shared with family members at critical developmental windows of time, and additional analysis will be applied.

Keywords: family pedigree, environmental exposure, geographic legacy, medical geography, transgenerational inheritance

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Authors: Simran Sharda

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There is increasing evidence that leads psychologists today to believe that the attachment formed between a mother and child plays a much more profound role in later-life outcomes than previously expected. Particularly, the fact that a link may exist between maternal attachment and the development in addition to the severity of social anxiety in middle childhood seems to be gaining ground. This research will examine and address a myriad of major issues related to the impact of mother-child attachment: behaviors of children with different levels of secure attachment, various aspects of anxiety in relation to attachment security as well as other styles of mother-child attachments, especially avoidant attachment and over-attachment. This analysis serves to compile previous literature on the subject and touch light upon a logical extension of the research. Moreover, researchers have identified links between attachment and the externalization of problem behaviors: these behaviors may later manifest as social anxiety as well as increased severity and likelihood of PTSD diagnosis (an anxiety disorder). Furthermore, secure attachment has been linked to increased health benefits, cognitive skills, emotive socialization, and developmental psychopathology.

Keywords: child development, anxiety, cognition, developmental psychopathology, mother-child relationships, maternal, cognitive development

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Authors: Cristiano Giordani, Marco Diociaiuti, Cecilia Bombelli, Laura Zanetti-Polzi, Marcello Belfiore, Raoul Fioravanti, Gianfranco Macchia

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We investigated induced functional effects by evaluating Ca2+-influx in liposomes and cell viability in HT22-DIFF neurons. Only solutions rich in unstructured Prefibrillar-Oligomers (PFOs) were able, in the presence of Monosialoganglioside-GM1 (GM1), to induce Ca2+-influx and were also neurotoxic, suggesting a correlation between the two phenomena. Thus, in the presence of GM1, we investigated the protein conformation and liposome modification due to the interaction. Circular Dichroism showed that GM1 fostered the formation of β-structures and Energy Filtered-Transmission Electron Microscopy that PFOs formed “amyloid-channels” as reported for Aβ. We speculate that electrostatic forces occurring between the positive PFOs and negative GM1 drive the initial binding, while the hydrophobic profile of the flexible PFO is responsible for the subsequent pore formation. Conversely, the rigid β-structured mature/fibers (MFs) and proto-fibers (PFs) were unable to induce membrane damage and Ca2+- influx.

Keywords: amyloid proteins, neurotoxicity, lipid-rafts, GM1

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Authors: Hannah R. Devens, Phillip L. Davidson, Dione Deaker, Kathryn E. Smith, Gregory A. Wray, Maria Byrne

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Marine invertebrate species with calcifying larvae are especially vulnerable to ocean acidification (OA) caused by rising atmospheric CO₂ levels. Acidic conditions can delay development, suppress metabolism, and decrease the availability of carbonate ions in the ocean environment for skeletogenesis. These stresses often result in increased larval mortality, which may lead to significant ecological consequences including alterations to the larval settlement, population distribution, and genetic connectivity. Importantly, many of these physiological and developmental effects are caused by genetic and molecular level changes. Although many studies have examined the effect of near-future oceanic pH levels on gene expression in marine invertebrates, little is known about the impact of OA on gene expression in a developmental context. Here, we performed mRNA-sequencing to investigate the impact of environmental acidity on gene expression across three developmental stages in the sea urchin Heliocidaris erythrogramma. We collected RNA from gastrula, early larva, and 1-day post-metamorphic juvenile sea urchins cultured at present-day and predicted future oceanic pH levels (pH 8.1 and 7.7, respectively). We assembled an annotated reference transcriptome encompassing development from egg to ten days post-metamorphosis by combining these data with datasets from two previous developmental transcriptomic studies of H. erythrogramma. Differential gene expression and time course analyses between pH conditions revealed significant alterations to developmental transcription that are potentially associated with pH stress. Consistent with previous investigations, genes involved in biomineralization and ion transport were significantly upregulated under acidic conditions. Differences in gene expression between the two pH conditions became more pronounced post-metamorphosis, suggesting a development-dependent effect of OA on gene expression. Furthermore, many differences in gene expression later in development appeared to be a result of broad downregulation at pH 7.7: of 539 genes differentially expressed at the juvenile stage, 519 of these were lower in the acidic condition. Time course comparisons between pH 8.1 and 7.7 samples also demonstrated over 500 genes were more lowly expressed in pH 7.7 samples throughout development. Of the genes exhibiting stage-dependent expression level changes, over 15% of these diverged from the expected temporal pattern of expression in the acidic condition. Through these analyses, we identify novel candidate genes involved in development, metabolism, and transcriptional regulation that are possibly affected by pH stress. Our results demonstrate that pH stress significantly alters gene expression dynamics throughout development. A large number of genes differentially expressed between pH conditions in juveniles relative to earlier stages may be attributed to the effects of acidity on transcriptional regulation, as a greater proportion of mRNA at this later stage has been nascent transcribed rather than maternally loaded. Also, the overall downregulation of many genes in the acidic condition suggests that OA-induced developmental delay manifests as suppressed mRNA expression, possibly from lower transcription rates or increased mRNA degradation in the acidic environment. Further studies will be necessary to determine in greater detail the extent of OA effects on early developing marine invertebrates.

Keywords: development, gene expression, ocean acidification, RNA-sequencing, sea urchins

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Authors: Anna Bak-Klimek, Emily Spencer, Siew Lee, Karen Campbell, Wendy McInally

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Background & Significance: Over half of Teenagers and Young Adults (TYAs) say that they experience psychological distress after cancer diagnosis and TYAs with cancer are at higher risk of developing distress compared to other age groups. Despite this there are no age-appropriate interventions to help TYAs manage distress and there is a lack of conceptual understanding of what causes distress in this population group. This makes it difficult to design a targeted, developmentally appropriate intervention. This review aims to identify the key determinants of distress in TYAs affected by cancer and to propose an integrative model of cancer-related distress for TYAs. Method: A literature search was performed in Cochrane Database of Systematic Reviews, MEDLINE, PsycINFO, CINAHL, EMBASE and PsycArticles in May-June, 2022. Quantitative literature was systematically reviewed on the relationship between psychological distress experienced by TYAs affected by cancer and a wide range of factors i.e. individual (demographic, psychological, developmental, and clinical factors) and contextual (social/environmental) factors. Evidence was synthesized and correlates were categorized using the Biopsychosocial Model. The full protocol is available from PROSPERO (CRD42022322069) Results: Thirty eligible quantitative studies met criteria for the review. A total of twenty-six studies were cross-sectional, three were longitudinal and one study was a case control study. The evidence on the relationship between the socio-demographic, illness and treatment-related factors and psychological distress is inconsistent and unclear. There is however consistent evidence on the link between psychological factors and psychological distress. For instance, the use of cognitive and defence coping, negative meta-cognitive beliefs, less optimism, a lack of sense of meaning and lower resilience levels were significantly associated with higher psychological distress. Furthermore, developmental factors such as poor self-image, identity issues and perceived conflict were strongly associated with higher distress levels. Conclusions: The current review suggests that psychological and developmental factors such as ineffective coping strategies, poor self-image and identity issues may play a key role in the development of psychological distress in TYAs affected by cancer. The review proposes a Positive Developmental Psychology Model of Distress for Teenagers and Young Adults affected by cancer. The review highlights that implementation of psychological interventions that foster optimism, improve resilience and address self-image may result in reduced distress in TYA’s with cancer.

Keywords: cancer, determinant, psychological distress, teenager and young adult, theoretical model

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Authors: Hassan Abbas, Rehmat Ali, Muhammad Akbar

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This study has been conducted in Sassi-Haramosh conservancy District Gilgit, Gilgit-Baltistan of Pakistan, under the Conservation Leadership Programme of Fauna and Flora International. The main objectives of the study were to assess the socio-economic impact of community-based conservation in Sassi-Haramosh conservancy and identify effects of trophy hunting on the conservation of wildlife in the area. The first trophy hunting program of Astor Markhor was held in year February 21, 2015, and the second on February 21, 2016. The community received a share of 49200 USD and 52400 USD from the first and second hunting, and the total earning was 101600 USD which are Rs. 10,871,200 in Pak Rs. The amounts from the trophy hunting are being managed by the Wildlife Conservation and Social Development Organization (WCSDO) Sassi. The village-based organization WCSDO is spending 50% of the trophy hunting amount in the protection of wildlife, its habitat and other natural resources, 30% in developmental sectors of the village and 20% of the amount in the office expenses. Several developmental projects, like construction of 300 KVA hydropower stations, purchase of 8 acres of land for agriculture, potable water supply project, construction of treks, and other social welfare activities have been carried in the village utilizing the trophy hunting grant. These developmental activities have uplifted the socio-economic conditions of the conservancy. Furthermore, trophy hunting program has positive impacts on the wildlife in the area, as the population of Markhor and Ibex has been increased, results in increasing number of other carnivores in the area. The WCSDO has banned any illegal activities in the habitat of wildlife and grazing of livestock in the core habitats. The program raised the level of awareness in communities and reduced poaching, illegal hunting, cutting of shrubs and extraction of Artemisia species from the pastures.

Keywords: Markhor, trophy hunting, Sassi-Haramosh, Gilgit

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Authors: Divyanshi Singh

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Women’s right to have choices, sense of self-worth and their right to have access to opportunities have been a subject of serious concern. The health of women and their children in Indian society is adversely affected by the woman’s inferior status within households. The level of human development in society is a reflection of the better status of a woman, which has a clear impact on the usage of contraceptive methods and maternal health. The study is an attempt to assess the performance of Indian states on the parameters of levels of development and to see how the developmental trajectory is influencing the choice for contraception and maternal health. The objective of the paper is to study the relationship between usage of contraception, maternal health and levels of human development in Indian states. Data from NFHS-4th round, AHS (2012-13) and census 2011 is used. Three indicators of human development (effective literacy, infant mortality and gross district domestic product) have been taken. Maternal health for the study has been measured in MMR, IMR and pregnancy resulted in abortions, stillbirths and miscarriage. The multiple regression analysis has been done to analyze the relationship between them. The Developmental factor is found to be greatly influencing the choice of family planning and thus they both show strong relation with maternal health.

Keywords: human development, contraceptive usage, maternal health, effective literacy

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Authors: Varun Joshi, M. S. Rawat

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The Indian Himalayan Region (IHR) is inherently fragile and susceptible to landslide hazard due to its extremely weak geology, highly rugged topography and heavy monsoonal rainfall. One of the most common hazards in the IHR is landslide, and this event is particularly frequent in Himalayan states of India i.e. Jammu & Kashmir, Himachal Pradesh, Uttarakhand, Sikkim, Manipur and Arunachal Pradesh. Landslides are mostly triggered by extreme rainfall events but the incidence increases during monsoon months (June to September). Natural slopes which are otherwise stable but they get destabilized due to anthropogenic activities like construction of various developmental activities and deforestation. These activities are required to fulfill the developmental needs and upliftment of societal status in the region. Landslides also trigger during major earthquakes and reported most observable and damaging phenomena. Studies indicate that the landslide phenomenon has increased many folds due to developmental activities in Himalayan region. Gradually increasing and devastating consequences of landslides turned into one of the most important hydro-geological hazards in Himalayan states especially in Uttarakhand and Sikkim states of India. The recent most catastrophic rainfall in June 2013 in Uttarakhand lead to colossal loss of life and property. The societal damage due to this incident is still to be recovered even after three years. Sikkim earthquake of September 2011 is witnessed for triggering of large number of coseismic landslides. The rescue and relief team faced huge problem in helping the trapped villagers in remote locations of the state due to road side blockade by landslides. The recent past incidences of landslides in Uttarakhand, as well as Sikkim states, created a new domain of research in terms of understanding the phenomena of landslide and management of disaster in such situation. Every year at many locations landslides trigger which force dwellers to either evacuate their dwelling or lose their life and property. The communication and transportation networks are also severely affected by landslides at several locations. Many times the drinking water supply disturbed and shortage of daily need household items reported during monsoon months. To minimize the severity of landslide in IHR requires in-depth research and developmental planning. For most of the areas in the present study, landslide hazard zonation is done on 1:50,000 scale. The land use planning maps on extensive basis are not available. Therefore, there is a need of large-scale landslide hazard zonation and land use planning maps. If the scientist conduct research on desired aspects and their outcome of research is utilized by the government in developmental planning then the incidents of landslide could be minimized, subsequent impact on society, life and property would be reduced. Along with the scientific research, there is another need of awareness generation in the region for stake holders and local dwellers to combat with the landslide hazard, if triggered in their location.

Keywords: coseismic, Indian Himalayan Region, landslide hazard zonation, Sikkim, societal, Uttarakhand

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Authors: Miranda E. Karban

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A distinctive pattern of occipital squama convexity, known as the occipital bun or chignon, has traditionally been considered a derived Neandertal trait. However, some early modern and extant Homo sapiens share similar occipital bone morphology, showing pronounced internal and external occipital squama curvature and paralambdoidal flattening. It has been posited that these morphological patterns are homologous in the two groups, but this claim remains disputed. Many developmental hypotheses have been proposed, including assertions that the chignon represents a developmental response to a long and narrow cranial vault, a narrow or flexed basicranium, or a prognathic face. These claims, however, remain to be metrically quantified in a large subadult sample, and little is known about the feature’s developmental, functional, or evolutionary significance. This study assesses patterns of chignon development and covariation in a comparative sample of extant human growth study cephalograms. Cephalograms from a total of 549 European-derived North American subjects (286 male, 263 female) were scored on a 5-stage ranking system of chignon prominence. Occipital squama shape was found to exist along a continuum, with 34 subjects (6.19%) possessing defined chignons, and 54 subjects (9.84%) possessing very little occipital squama convexity. From this larger sample, those subjects represented by a complete radiographic series were selected for metric analysis. Measurements were collected from lateral and posteroanterior (PA) cephalograms of 26 subjects (16 male, 10 female), each represented at 3 longitudinal age groups. Age group 1 (range: 3.0-6.0 years) includes subjects during a period of rapid brain growth. Age group 2 (range: 8.0-9.5 years) includes subjects during a stage in which brain growth has largely ceased, but cranial and facial development continues. Age group 3 (range: 15.9-20.4 years) includes subjects at their adult stage. A total of 16 landmarks and 153 sliding semi-landmarks were digitized at each age point, and geometric morphometric analyses, including relative warps analysis and two-block partial least squares analysis, were conducted to study covariation patterns between midsagittal occipital bone shape and other aspects of craniofacial morphology. A convex occipital squama was found to covary significantly with a low, elongated neurocranial vault, and this pattern was found to exist from the youngest age group. Other tested patterns of covariation, including cranial and basicranial breadth, basicranial angle, midcoronal cranial vault shape, and facial prognathism, were not found to be significant at any age group. These results suggest that the chignon, at least in this sample, should not be considered an independent feature, but rather the result of developmental interactions relating to neurocranial elongation. While more work must be done to quantify chignon morphology in fossil subadults, this study finds no evidence to disprove the developmental homology of the feature in modern humans and Neandertals.

Keywords: chignon, craniofacial covariation, human cranial development, longitudinal growth study, occipital bun

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Authors: Prama Mukhopadhyay, Rishika Mukhopadhyay

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The twentieth century has seen the world getting divided into three distinct blocks, created by the proponents of the mainstream developmental discourse. India, which has now gained the label of being a ‘developing nation’, stands in between these three groups, as it constantly tries to ‘catch up’ and emulate the developmental standards of the ‘west’. In this endeavour, we find our country trying really hard to blindly replicate the health care infrastructures of the ‘first worlds’, without realizing the needs of evaluating the ground reality. In such a situation, the sudden outbreak of child death in the district of Malda, WB, poses an obvious questions towards the kind of development that our country has been engaging in, ever since its Post Colonial inception. Through this paper we thus try to understand the harsh veracity of the health care facility that exists in rural Bengal, and thereby challenge the conventional notion of ‘health-care’ as is normally discussed in the mainstream developmental discourse. Grounding our research work on detailed ethnography and through the help of questionnaire, interviews and focus group discussions with the local government officials(BDOs), health workers (ICDS, ASHA workers, ANHM and BMOHs) and members of families with experiences of child deaths, we have tried to find out the real and humane factors behind the sudden rise of reported infant deaths in the district, issues which are normally neglected and left out while discussing and evaluating IMR in the mainstream studies on health care and planning in our nation. Therefore the main aim of this paper is to try and look at child death from a ‘wider perspective’, where it is seen from an eye not bounded by the common registers of caste, class and religion. This paper, would thus be an eye opener in some sense, bringing in stories from the rural belt of the country; where the people are regularly torn between the binaries of the developing and shining modernity of ‘India’ which now gets ready to run the last lap and gain the status of becoming a ‘developed nation’ by 2020, and the staggering, dark traditional ‘ Bharat, which lags behind.

Keywords: child mortality, development discourse, health care, tradition and modernity

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Authors: Waraporn Boonchieng, Ekkarat Boonchieng, Sivaporn Aungwattana, Decha Tamdee, Wongamporn Pinyavong

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Drug addiction represents one of the most important public health issues in both developed and developing countries. The purpose of this study was to develop a drug abuse health information in a community in Northern Thailand using developmental research design. The developmental researchers performed four phases to develop drug abuse health information, including 1) synthesizing knowledge related to drug abuse prevention and identifying the components of drug abuse health information; 2) developing the system in mobile application and website; 3) implementing drug abuse health information in the rural community; and 4) evaluating the feasibility of drug abuse health information. Data collection involved both qualitative and quantitative procedures. The qualitative data and quantitative data were analyzed using content analysis and descriptive statistics, respectively. The findings of this study showed that drug abuse health information consisted of five sections, including drug-related prevention knowledge for teens, drug-related knowledge for adults and professionals, the database for drug dependence treatment centers, self-administered questionnaires, and supportive counseling sections. First, in drug-related prevention knowledge for teens, the developmental researchers designed four infographics and animation to provide drug-related prevention knowledge, including types of illegal drugs, causes of drug abuse, consequences of drug abuse, drug abuse diagnosis and treatment, and drug abuse prevention. Second, in drug-related knowledge for adults and professionals, the developmental researchers developed many documents in a form of PDF file to provide drug-related knowledge, including types of illegal drugs, causes of drug abuse, drug abuse prevention, and relapse prevention guideline. Third, database for drug dependence treatment centers included the place, direction map, operation time, and the way for contacting all drug dependence treatment centers in Thailand. Fourth, self-administered questionnaires comprised preventive drugs behavior questionnaire, drug abuse knowledge questionnaire, the stages of change readiness and treatment eagerness to drug use scale, substance use behaviors questionnaire, tobacco use behaviors questionnaire, stress screening, and depression screening. Finally, for supportive counseling, the developmental researchers designed chatting box through which each user could write and send their concerns to counselors individually. Results from evaluation process showed that 651 participants used drug abuse health information via mobile application and website. Among all users, 48.8% were males and 51.2% were females. More than half (55.3%) were 15-20 years old and most of them (88.0%) were Buddhists. Most users reported ever getting knowledge related to drugs (86.1%), and drinking alcohol (94.2%) while some of them (6.9%) reported ever using tobacco. For satisfaction with using the drug abuse health information, more than half of users reflected that the contents of drug abuse health information were interesting (59%), up-to date (61%), and highly useful to their self-study (59%) at high level. In addition, half of them were satisfied with the design in terms of infographics (54%) and animation (51%). Thus, this drug abuse health information can be adopted to explore drug abuse situation and serves as a tool to prevent drug abuse and addiction among Thai community people.

Keywords: drug addiction, health informatics, big data, development research

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Authors: Pierre Brocas, Konstantinos Rizos

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This study was conducted to test the effects of introducing a consistent pace and volume of reading whole narratives on adolescents' reading comprehension with a diagnosis of autism spectrum disorder (ASD). The study was inspired by previous studies conducted on poorer adolescent readers in English schools. The setting was a Free Special Education Needs school in England. Nine male and one female student, between 11-13 years old, across two classrooms participated in the study. All students had a diagnosis of ASD, and all were classified as advanced learners. The classroom teachers introduced reading a whole challenging novel in 12 weeks with consistency as the independent variable. The study used a before-and-after design of testing the participants’ reading comprehension using standardised tests. The participants made a remarkable 1.8 years’ mean progress on the standardised tests of reading comprehension, with three participants making 4+ years progress. The researchers hypothesise that reading novels aloud and at a fast pace in each lesson, that are challenging but appropriate to the participants’ learning level, may have a beneficial effect on the reading comprehension of adolescents with learning difficulties, giving them a more engaged uninterrupted reading experience over a sustained period. However, more studies need to be conducted to test the independent variable across a bigger and more diverse population with a stronger design.

Keywords: autism, reading comprehension, developmental disabilities, narratives

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Authors: Bunki Enid Pitsoane

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This study was influenced by the radical change in the tutorial system of UNISA, immigrating from face to face to E-tutoring. The study was undertaken to investigate the perceptions, experiences, and views of E-tutors in relation to active learning. The study is aimed at capturing the views and experiences of E-tutors as they are deemed to implement active learning within their E-tutoring. The problem was traced from Developmental and behaviorist’s theorists perspective and factors related to perception, experience, and views of E-tutors on active learning. The research is aligned with the views of constructivism which put more emphasis on situated learning, chaos, and digital factors. The basis of the theory is that learning is developmental, situational and context-sensitive and also digital. The theorists further purports that the tutor’s conception of teaching and learning influence their tutoring style. In order to support or reject the findings of the literature study, qualitative research in the form of interviews and document analysis were conducted. The sample of the study constituted of 10 E-tutors who are involved in tutoring modules from the College of Education. The identified E-tutors were randomly selected based on their availability. The data concerning E-tutors perception and experience was analysed and interpreted. The results of the empirical study indicated that some tutors are struggling to implement active learning because they are digital immigrants or they lack in digital knowledge which affect productivity in their teaching.

Keywords: E-Tutoring, active learning, perceptions, views

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Authors: Taher Abofol, Yaakov Kareev, Judith Avrahami, Peter M. Todd

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Are children sensitive to their relative strength in competitions against others? Performance on tasks that require cooperation or coordination (e.g. the Ultimatum Game) indicates that early precursors of adult-like notions of fairness and reciprocity, as well as altruistic behavior, are evident at an early age. However, not much is known regarding developmental changes in interactive decision-making, especially in competitive interactions. Thus, it is important to study the developmental aspects of strategic behavior in these situations. The present research focused on cognitive-developmental changes in a competitive interaction. Specifically, it aimed at revealing how children engage in strategic interactions that involve the allocation of limited resources over a number of fields of competition, by manipulating relative strength. Relative strength refers to situations in which player strength changes midway through the game: the stronger player becomes the weaker one, while the weaker player becomes the stronger one. An experiment was conducted to find out if the behavior of children of different age groups differs in the following three aspects: 1. Perception of relative strength. 2. Ability to learn while gaining experience. 3. Ability to adapt to change in relative strength. The task was composed of a resource allocation game. After the players allocated their resources (privately and simultaneously), a competition field was randomly chosen for each player. The player who allocated more resources to the field chosen was declared the winner of that round. The resources available to the two competitors were unequal (or equal, for control). The theoretical solution for this game is that the weaker player should give up on a certain number of fields, depending on the stronger opponent’s relative strength, in order to be able to compete with the opponent on equal footing in the remaining fields. Participants were of three age groups, first-graders (N = 36, mean age = 6), fourth-graders (N = 36, mean age = 10), and eleventh-graders (N = 72, mean age = 16). The games took place between players of the same age and lasted for 16 rounds. There were two experimental conditions – a control condition, in which players were of equal strength, and an experimental condition, in which players differed in strength. In the experimental condition, players' strength was changed midway through the session. Results indicated that players in all age groups were sensitive to their relative strength, and played in line with the theoretical solution: the weaker players gave up on more fields than the stronger ones. This understanding, as well as the consequent difference in allocation between weak and strong players, was more pronounced among older participants. Experience led only to minimal behavioral change. Finally, the children from the two older groups, particularly the eleventh graders adapted quickly to the midway switch in relative strength. In contrast, the first-graders hardly changed their behavior with the change in their relative strength, indicating a limited ability to adapt. These findings highlight young children’s ability to consider their relative strength in strategic interactions and its boundaries.

Keywords: children, competition, decision making, developmental changes, strategic behavior

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Authors: Rogerio Vieira Dos Reis

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Countries like Brazil that despite fighting hard against corruption are not improving their corruption perception, especially due to systemic political corruption, should review their corruption prevention strategies. This thesis brings a case study based on an alternative way of preventing corruption: addressing the corruption drivers in public policies that lead to poor economic performance. After discussing the Brazilian industrial policies adopted recently, especially the measures towards the automotive sector, two corruption issues in this sector are analyzed: facilitating payment for fiscal benefits and buying the extension of fiscal benefits. In-depth interviews conducted with a policymaker and an executive of the automobile sector provide insights for identifying three main corruption drivers: excessive and unnecessary bureaucracy, a complex tax system and the existence of a closed market without setting performance requirements to be achieved by the benefited firms. Both the identification of the drivers of successful industrial policies and the proposal of anti-corruption strategies to ensure developmental outcomes are based on the economic perspective of industrial policy advocated by developmental authors and on the successful South Korean economic development experience. Structural anti-corruption measures include tax reform, the regulation of lobbying and legislation to allow corporate political contribution. Besides improving policymakers’ technical capabilities, measures at the ministry level include redesigning the automotive regimes as long-term policies focused on national investment with simple and clear rules and making fiscal benefits conditional upon performance targets focused on suppliers. This case study is of broader interest because it recommends the importance of adapting performance audits conducted by anti-corruption agencies, to focus not only on the delivery of public services, but also on the identification of potentially highly damaging corruption drivers in public policies that grant fiscal benefits to achieve developmental outcomes.

Keywords: Brazilian automotive sector, corruption, economic development, industrial policy, Inovar-Auto

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Authors: Manjunatha Bangeppagari, Lee Sang Joon

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Recently, graphene-related nanomaterials are receiving fast-increasing attention with augmented applications in various fields. Especially, graphene-related materials have been widely applied to the biomedical field in the past years. In the present study, we evaluated the adverse effects of pristine graphene (pG) in zebrafish (Danio rerio) embryos in various aspects, such as mortality rate, heart rate, hatching rate, cardiotoxicity, cardiovascular defect, cardiac looping, apoptosis, and globin expression. For various trace concentrations of pG (1, 5, 10, 15, 20, 25, 30, 35, 40, 45, and 50 μg/L), early life-stage parameters were observed at 24, 48, 72, and 96 hpf. As a result, pG induces significant developmental defects including yolk sac edema, pericardial edema, embryonic mortality, delayed hatching, heartbeat, several morphological defects, pericardial toxicity, and bradycardia. Moreover, the exposure to pG was found to be a potential risk factor to the cardiovascular system of zebrafish embryos. However, further study on their properties which vary according to production methods and surface functionalization is essentially required. In addition, the possible risks of pG flakes to aquatic animals, and public health should be evaluated before releasing them to the surrounding environment.

Keywords: apoptosis, cardiovascular toxicity, globin expression, pristine graphene, zebrafish embryos

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Authors: Athena Pedro, Laura Bradfield, Mike Dare, Zandile Bantwana, Ashley Nayman

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The purpose of the research was to explore mother’s unique experience and knowledge of mothering in the first 1000 day of their child’s life, from birth to age 2. The study used a qualitative research methodology with an exploratory research design. A sample of 12 mothers was used, comprising different racial backgrounds from low income areas in the Western Cape. The data was collected by means of semi-structured, in-depth interviews, which were transcribed verbatim, analysed using Braun’s and Clark’s (2006) six phases of thematic analysis. Some of the findings revealed that the mothers who participated in the study were consistently unable to feed their children and themselves due to profound and extreme situations of poverty, stress, and lack of infrastructural support. These mothers residing in low-income communities are not adequately supported both financially and socially and are often unable to meet the needs of their infants within the first 1000 days. Given the consequential nature of this period, it is imperative that mothers are able to access such support. Single mothers especially are in need of social and financial support. Appropriate interventions are required to assist mothers generally but more specifically, mothers who have children within the first 1000 days of life. By implementing appropriate interventions to address these needs, it will assist mothers to ensure optimal developmental growth of their children. This will positively impact the developmental trajectory of children in South Africa.

Keywords: caring, economic hardship, first one thousand days, mothers

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Authors: Jana Tchekalarova, Stela Georgieva, Petia Peneva, Petar Todorov

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In the present study, a series of bioconjugates of N-modified hemorphine analogs containing second pharmacophore cinnamic acids (CA) or caffeic acid (KA) were synthesized by a traditional solid-phase Fmoc chemistry method for peptide synthesis. Electrochemical and fluorometric analysis and in vivo anticonvulsant activity in mice were conducted on the compounds. The three CA (H4-CA, H5-CA, and H7-CA) and three KA (H4-KA, H5-KA, and H7-KA)-conjugated hemorphine derivatives showed dose-dependent anticonvulsant activity in the maximal electroshock test (MES) in mice. The KA-conjugated H5-KA derivate was the only compound that suppressed clonic seizures at the lowest dose of 0.5 µg/mouse in the scPTZ test. The activity against the psychomotor seizures in the 6-Hz test was detected only for the H4-CA (0.5 µg) and H4-KA (0.5 µg and 1 µg), respectively. The peptide derivates did not exhibit neurotoxicity in the rotarod test. Our findings suggest that conjugated CA and KA hemorphine peptides can be used as a background for developing hemorphin-related analogs with anticonvulsant activity. Acknowledgments: This study is funded by the European Union-NextGenerationEU, through the National Recovery and Resilience Plan of the Republic of Bulgaria, project № BG-RRP-2.004-0002, "BiOrgaMCT".

Keywords: hemorphins, SPSS, caffeic/cinnamic acid, anticonvulsant activity, electrochemistry, fluorimetry

Procedia PDF Downloads 125