Search results for: attacks and controls

Authors: Enrico Maria la Forgia

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Since the 80ies, in specific situations, France’s Muslims have enacted political actions to reply to attacks on their identity or assimilation attempts, using their religious affiliation as a resource for the organization and expression of collective claims. Indeed, despite Islam's internal sectarian and ethnic differences, religion may be politicized when minorities’ social and cultural rights are under attack. French Civil Society organizations, in this specific case with an Islamic background (ICSO - Islamic Civil Society Organizations), play an essential role in defending Muslims’ social and cultural rights. As a matter of fact, Civil Society organized on an ethnic or religious base is a way to strengthen minoritarian communities and their role as political actors, especially in multicultural contexts. Since the first 1983’s “Marche des Beurs” (slang word referring to French citizens with foreign origins), which involved many Muslims, the development of ICSO contributed to the strenghtening of Islam in France, here meant as a Social Movement aiming to constitute a French version of Islam, defending minorities’ cultural and religious rights, and change the perception of Islam itself in national society. However, since a visible and stigmatized minority, ICSO do not relate only to protests as a strategy to achieve their goals: on several occasions, pressure on authorities through personal networks and connections, or the introduction into public debates of bargaining through the exploitation of national or international crisis, might appear as more successfully - public discourses on minorities and Islam are generally considered favorable conditions to advance requests for cultural legitimation. The proposed abstract, based on a literary review and theoretical/methodological reflection on the state of knowledge on the topic, aims to open a new branch of studies and analysis of Civil Society and Social Movements in Europe, focusing on the French Islamic community as a political actor relating on ICSO to pressure society, local, and national authorities to improve Muslims' rights. The opted methodology relies on a qualitative approach based on ethnography and face-to-face interviews addressing heads and middle-high level activists from ICSO, in an attempt to individuate the strategies enacted by ICSO for mobilizing Muslims and build relations with, on one hand, local and national authorities; into the other, with actors belonging to the Civil Society/political sphere. The theoretical framework, instead, relies on the main Social Movements Theories (resources mobilization, political opportunity structure, and contentious/non-contentious movements), aiming to individuate eventual gaps in the analysis of Islamic Social Movements and Civil Society in minoritarian contexts.

Keywords: Islam, islamophobia, civil society, social movements, sociology, qualitative methodology, Islamic activism in social movement theory, political change, Islam as social movement, religious movements, protest and politics, France, Islamic civil society

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Authors: Marcel Schulze, Behrem Aslan, Silke Lux, Alexandra Philipsen

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Objective: Patients with Attention Deficit/Hyperactivity Disorder (ADHD) often report that they are being flooded by sensory impressions. Studies investigating sensory processing show hypersensitivity for sensory inputs across the senses in children and adults with ADHD. Especially the auditory modality is affected by deficient acoustical inhibition and modulation of signals. While studying unimodal signal-processing is relevant and well-suited in a controlled laboratory environment, everyday life situations occur multimodal. A complex interplay of the senses is necessary to form a unified percept. In order to achieve this, the unimodal sensory modalities are bound together in a process called multisensory integration (MI). In the current study we investigate MI in an adult ADHD sample using the McGurk-effect – a well-known illusion where incongruent speech like phonemes lead in case of successful integration to a new perceived phoneme via late top-down attentional allocation . In ADHD neuronal dysregulation at rest e.g., aberrant within or between network functional connectivity may also account for difficulties in integrating across the senses. Therefore, the current study includes resting-state functional connectivity to investigate a possible relation of deficient network connectivity and the ability of stimulus integration. Method: Twenty-five ADHD patients (6 females, age: 30.08 (SD:9,3) years) and twenty-four healthy controls (9 females; age: 26.88 (SD: 6.3) years) were recruited. MI was examined using the McGurk effect, where - in case of successful MI - incongruent speech-like phonemes between visual and auditory modality are leading to a perception of a new phoneme. Mann-Whitney-U test was applied to assess statistical differences between groups. Echo-planar imaging-resting-state functional MRI was acquired on a 3.0 Tesla Siemens Magnetom MR scanner. A seed-to-voxel analysis was realized using the CONN toolbox. Results: Susceptibility to McGurk was significantly lowered for ADHD patients (ADHDMdn:5.83%, ControlsMdn:44.2%, U= 160.5, p=0.022, r=-0.34). When ADHD patients integrated phonemes, reaction times were significantly longer (ADHDMdn:1260ms, ControlsMdn:582ms, U=41.0, p<.000, r= -0.56). In functional connectivity medio temporal gyrus (seed) was negatively associated with primary auditory cortex, inferior frontal gyrus, precentral gyrus, and fusiform gyrus. Conclusion: MI seems to be deficient for ADHD patients for stimuli that need top-down attentional allocation. This finding is supported by stronger functional connectivity from unimodal sensory areas to polymodal, MI convergence zones for complex stimuli in ADHD patients.

Keywords: attention-deficit hyperactivity disorder, audiovisual integration, McGurk-effect, resting-state functional connectivity

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Authors: Muhammad Waqas Baqai, Noman Shahzad, Rehman Alvi

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Communication among health care givers is the essence of quality patient care and any compromise results in errors and inefficiency leading to cumbersome outcomes. The use of smartphone among health professionals has increased tremendously. Almost every health professional carries it and majority of them uses a third party communication software called whatsApp for work related communications. It gives instant access to the person responsible for any particular query and therefore helps in efficient and timely decision making. It is also an easy way of sharing medical documents, multimedia and provides platform for consensual decision making through group discussions. However clinical communication through whatsApp has some demerits too including reduction in verbal communication, worsening professional relations, unprofessional behavior, risk of confidentiality breach and threats from cyber-attacks. On the other hand the traditional pager device being used in many health care systems is a unidirectional communication that lacks the ability to convey any information other than the number to which the receiver has to respond. Our study focused on these two widely used modalities of communication among doctors of the largest tertiary care center of Pakistan i.e. The Aga Khan University Hospital. Our aim was to note which modality is considered better and has fewer threats to medical data. Approval from ethical review committee of the institute was taken prior to conduction of this study. We submitted an online survey form to all the interns and residents working at our institute and collected their response in a month’s time. 162 submissions were recorded and analyzed using descriptive statistics. Only 20% of them were comfortable with using pagers exclusively, 52% with whatsApp and 28% with both. 65% think that whatsApp is time-saving and quicker than pager. 54% of them considered whatsApp to be causing nuisance from work related notifications in their off-work hours. 60% think that they are more likely to miss information through pager system because of the unidirectional nature. Almost all (96%) of residents and interns found whatsApp to be useful in terms of saving information for future reference. For urgent issues, majority (70%) preferred pager over whatsApp and also pager was considered more valid in terms of hospital policies and legal issues. Among major advantages of whatsApp as listed by them were; easy mass communication, sharing of clinical pictures, universal access and no need of carrying additional device. However the major drawback of using whatsApp for clinical communication that everyone shared was threat to patients’ confidentiality as clinicians usually share pictures of wounds, clinical documents etc. Lastly we asked them if they think there is a need of a separate application for instant communication dedicated to clinical communication only and 90% responded positively. Therefore, we concluded that both modalities have their merits and demerits but the greatest drawback with whatsApp is the risk of breach in patients’ confidentiality and off-work disturbance. Hence, we recommend a more secure, institute-run application for all intra hospital communications where they can share documents, pictures etc. easily under a controlled environment.

Keywords: WhatsApp, pager, clinical communication, confidentiality

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Authors: Thimira Pasas P, Nirmala Priyadarshani M, Ishani R

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Obesity is a global health issue. Early identification is essential to plan interventions and intervene than to reduce the worsening of obesity and its consequences on the health issues of the individual. Childhood obesity is multifactorial, with both modifiable and unmodifiable risk factors. A genetically susceptible individual (unmodifiable), when placed in an obesogenic environment (modifiable), is likely to become obese in onset and progression. The present study was conducted to identify the age of onset of childhood obesity and the influence of modifiable risk factors for childhood obesity among school children living in a suburban area of Sri Lanka. The study population was aged 11-12 years of Piliyandala Educational Zone. Data were collected from 11–12-year-old school children attending government schools in the Piliyandala Educational Zone. They were using a validated, pre-tested self-administered questionnaire. A stratified random sampling method was performed to select schools and to select a representative sample to include all 3 types of government schools of students due to the prevailing pandemic situation, information from the last school medical inspection on data from 2020used for this purpose. For each obese child identified, 2 non-obese children were selected as controls. A single representative from the area was selected by using a systematic random sampling method with a sampling interval of 3. Data was collected using a validated, pre-tested self-administered questionnaire and the Child Health Development Record of the child. An introduction, which included explanations and instructions for filing the questionnaire, was carried out as a group activity prior to distributing the questionnaire among the sample. The results of the present study aligned with the hypothesis that the age of onset of childhood obesity and prediction must be within the first two years of child life. A total of 130 children (66 males: 64 females) participated in the study. The age of onset of obesity was seen to be within the first two years of life. The risk of obesity at 11-12 years of age was Obesity risk was identified at 3-time s higher among females who underwent rapid weight gain within their infancy period. Consuming milk prior to breakfast emerged as a risk factor that increases the risk of obesity by three times. The current study found that the drink before breakfast tends to increase the obesity risk by 3-folds, especially among obese females. Proper monitoring must be carried out to identify the rapid weight gain, especially within the first 2 years of life. Consumption of mug milk before breakfast tends to increase the obesity risk by 3 times. Identification of the confounding factors, proper awareness of the mothers/guardians and effective proper interventions need to be carried out to reduce the obesity risk among school children in the future.

Keywords: childhood obesity, school children, age of onset, weight gain, feeding pattern, activity level

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Authors: Etibar Guliyev

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The breakdown of the Soviet Union in 1991 has led to a considerable rise in the religious self-consciousness of Muslim population of the Central Asia. Additionally, huge amount of money spent by various states further facilitated the spread of religious ideas. According to some sources, Saudi Arabia spent 87 billion dollars to propagate Wahhabism abroad during two decades, whereas the Communist Party of the Soviet Union spent just over 7 billion dollars to spread its ideology worldwide between 1921 and 1991. As the result, today once a remote area from international politics has turned into third major source of recruitment of fighters for global terrorist organizations. In order to illustrate to scope of the involvement of the Central Asian residents in international terrorist networks it is enough to mention the name of Colonel Gulmorod Khalimov, the former head of the Tajik special police forces who served as ISIS war minister between 2016 and 2017. The importance of the topic stems from the fact that the above-mentioned republics with a territory of 4 million square km and the population of around 80 million people borders Russia, Iran Afghanistan and China. Moreover, the fact that political and military activities motivated with religious feelings in those countries have implications not only for domestic but also for regional and global political relations and all of them has root in politics of religions adds value to the research. This research aims to provide an in-depth analyses of the marked features of the state policies to regulate religious activities and approach this question both from individual, domestic, regional and global levels of analyses. The research will enable us to better understand what implications have the state of religious freedom in post-Soviet Muslim republics for international relations and the rise of global jihadi terrorism. The paper tries to find a linkage between the mentioned terror attacks and underground rise of religious extremism in Central Asia. This research is based on multiple research methods, mainly on qualitative one. The process tracing method is also employed to review religious policies implemented from 1918-1991 and after the collapse of the Soviet Union in a chronological way. In terms of the quantitative method, it chiefly will be used in a bid to process various statistics disseminated in academic and official sources. The research mostly explored constructivist, securitization and social movement theories. Findings of the research suggests that the endemic problems peculiar to authoritarian regimes of Central Asia such as crackdown on the expression of religious believe and any kind of opposition, economic decline, instrumental use of religion and corruption and tribalism further accelerated the recruitment problem. Paper also concludes that the Central Asian states in some cases misused counter-terrorism campaign as a pretext to further restrict freedom of faith in their respective countries.

Keywords: identity, political Islam, religious extremism, security, terrorism

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Authors: Zsolt Kotroczó, Katalin Juhos, Áron Béni, Gábor Várbíró, Tamás Kocsis, István Fekete

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Soil organic matter plays an extremely important role in the functioning and regulation processes of ecosystems. It follows that the C content of organic matter in soil is one of the most important indicators of soil fertility. Part of the carbon stored in them is returned to the atmosphere during soil respiration. Climate change and inappropriate land use can accelerate these processes. Our work aimed to determine how soil CO2 emissions change over ten years as a result of organic matter manipulation treatments. With the help of this, we were able to examine not only the effects of the different organic matter intake but also the effects of the different microclimates that occur as a result of the treatments. We carried out our investigations in the area of the Síkfőkút DIRT (Detritus Input and Removal Treatment) Project. The research area is located in the southern, hilly landscape of the Bükk Mountains, northeast of Eger (Hungary). GPS coordinates of the project: 47°55′34′′ N and 20°26′ 29′′ E, altitude 320-340 m. The soil of the area is Luvisols. The 27-hectare protected forest area is now under the supervision of the Bükki National Park. The experimental plots in Síkfőkút were established in 2000. We established six litter manipulation treatments each with three 7×7 m replicate plots established under complete canopy cover. There were two types of detritus addition treatments (Double Wood and Double Litter). In three treatments, detritus inputs were removed: No Litter No Roots plots, No Inputs, and the Controls. After the establishment of the plots, during the drier periods, the NR and NI treatments showed the highest CO2 emissions. In the first few years, the effect of this process was evident, because due to the lack of living vegetation, the amount of evapotranspiration on the NR and NI plots was much lower, and transpiration practically ceased on these plots. In the wetter periods, the NL and NI treatments showed the lowest soil respiration values, which were significantly lower compared to the Co, DW, and DL treatments. Due to the lower organic matter content and the lack of surface litter cover, the water storage capacity of these soils was significantly limited, therefore we measured the lowest average moisture content among the treatments after ten years. Soil respiration is significantly influenced by temperature values. Furthermore, the supply of nutrients to the soil microorganisms is also a determining factor, which in this case is influenced by the litter production dictated by the treatments. In the case of dry soils with a moisture content of less than 20% in the initial period, litter removal treatments showed a strong correlation with soil moisture (r=0.74). In very dry soils, a smaller increase in moisture does not cause a significant increase in soil respiration, while it does in a slightly higher moisture range. In wet soils, the temperature is the main regulating factor, above a certain moisture limit, water displaces soil air from the soil pores, which inhibits aerobic decomposition processes, and so heterotrophic soil respiration also declines.

Keywords: soil biology, organic matter, nutrition, DIRT, soil respiration

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Authors: Michael A. Unbehauen, Gregory D. Sloan, Alberto J. Squatrito

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Missile proliferation and global stability are intrinsically linked. Missile threats continually appear at the forefront of global security issues. North Korea’s recently demonstrated nuclear and intercontinental ballistic missile (ICBM) capabilities, for the first time since the Cold War, renewed public interest in strategic missile defense capabilities. To protect from limited ICBM attacks from so-called rogue actors, the United States developed the Ground-based Midcourse Defense (GMD) system. This study examines if the GMD missile defense shield has contributed to a safer world or triggered a new arms race. Based upon increased missile-related developments and the lack of adherence to international missile treaties, it is generally perceived that the GMD system is a destabilizing factor for global security. By examining the current state of arms control treaties as well as existing missile arsenals and ongoing efforts in technologies to overcome U.S. missile defenses, this study seeks to analyze the contribution of GMD to global stability. A thorough investigation cannot ignore that, through the establishment of this limited capability, the U.S. violated longstanding, successful weapons treaties and caused concern among states that possess ICBMs. GMD capability contributes to the perception that ICBM arsenals could become ineffective, creating an imbalance in favor of the United States, leading to increased global instability and tension. While blame for the deterioration of global stability and non-adherence to arms control treaties is often placed on U.S. missile defense, the facts do not necessarily support this view. The notion of a renewed arms race due to GMD is supported neither by current missile arsenals nor by the inevitable development of new and enhanced missile technology, to include multiple independently targeted reentry vehicles (MIRVs), maneuverable reentry vehicles (MaRVs), and hypersonic glide vehicles (HGVs). The methodology in this study encapsulates a period of time, pre- and post-GMD introduction, while analyzing international treaty adherence, missile counts and types, and research in new missile technologies. The decline in international treaty adherence, coupled with a measurable increase in the number and types of missiles or research in new missile technologies during the period after the introduction of GMD, could be perceived as a clear indicator of GMD contributing to global instability. However, research into improved technology (MIRV, MaRV and HGV) prior to GMD, as well as a decline of various global missile inventories and testing of systems during this same period, would seem to invalidate this theory. U.S. adversaries have exploited the perception of the U.S. missile defense shield as a destabilizing factor as a pretext to strengthen and modernize their militaries and justify their policies. As a result, it can be concluded that global stability has not significantly decreased due to GMD; but rather, the natural progression of technological and missile development would inherently include innovative and dynamic approaches to target engagement, deterrence, and national defense.

Keywords: arms control, arms race, global security, GMD, ICBM, missile defense, proliferation

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Authors: Dipendra Kumar Yadav, Nabaraj Paudel, Anjana Yadav

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Background: Low Birth weight (LBW) is defined as the weight at birth less than 2500 grams, irrespective of the period of their gestation. LBW is an important indicator of general health status of population and is considered as the single most important predictors of infant mortality especially of deaths within the first month of life that is birth weight determines the chances of newborn survival. Objective of this study was to identify the maternal risk factors associated with low birth weight neonates. Materials and Methods: A hospital based case-control study was conducted in maternity ward of Manipal Teaching Hospital, Pokhara, Nepal from 23 September 2014 to 12 November 2014. During study period 59 cases were obtained and twice number of control group were selected with frequency matching of the mother`s age with ± 3 years and total controls were 118. Interview schedule was used for data collection along with record review. Data were entered in Epi-data program and analysis was done with help of SPSS software program. Results: From bivariate logistic regression analysis, eighteen variables were found significantly associated with LBW and these were place of residence, family monthly income, education, previous still birth, previous LBW, history of STD, history of vaginal bleeding, anemia, ANC visits, less than four ANC visits, de-worming status, counseling during pregnancy, CVD, physical workload, stress, extra meal during pregnancy, smoking and alcohol consumption status. However after adjusting confounding variables, only six variables were found significantly associated with LBW. Mothers who had family monthly income up to ten thousand rupees were 4.83 times more likely to deliver LBW with CI (1.5-40.645) and p value 0.014 compared to mothers whose family income NRs.20,001-60,000. Mothers who had previous still birth were 2.01 times more likely to deliver LBW with CI (0.69-5.87) and p value 0.02 compared to mothers who did not has previous still birth. Mothers who had previous LBW were 5.472 times more likely to deliver LBW with CI (1.2-24.93) and p value 0.028 compared to mothers who did not has previous LBW. Mothers who had anemia during pregnancy were 3.36 times more likely to deliver LBW with CI (0.77-14.57) and p value 0.014 compared to mothers who did not has anemia. Mothers who delivered female newborn were 2.96 times more likely to have LBW with 95% CI (1.27-7.28) and p value 0.01 compared to mothers who deliver male newborn. Mothers who did not get extra meal during pregnancy were 6.04 times more likely to deliver LBW with CI (1.11-32.7) and p value 0.037 compared to mothers who getting the extra meal during pregnancy. Mothers who consumed alcohol during pregnancy were 4.83 times more likely to deliver LBW with CI (1.57-14.83) and p value 0.006 compared to mothers who did not consumed alcohol during pregnancy. Conclusions: To reduce low birth weight baby through economic empowerment of family and individual women. Prevention and control of anemia during pregnancy is one of the another strategy to control the LBW baby and mothers should take full dose of iron supplements with screening of haemoglobin level. Extra nutritional food should be provided to women during pregnancy. Health promotion program will be focused on avoidance of alcohol and strengthen of health services that leads increasing use of maternity services.

Keywords: low birth weight, case-control, risk factors, hospital based study

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Authors: Fernanda Mary R. G. Da Silva, Adriana C. F. Mozzambani, Marcelo F. Mello

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Introduction: Sexual assault against children and adolescents is a public health problem with serious consequences on their quality of life, especially for those who develop post-traumatic stress disorder (PTSD). The broad literature in this research area points to greater losses in verbal learning, explicit memory, speed of information processing, attention and executive functioning in PTSD. Objective: To compare the neuropsychological functions of adolescents from 14 to 17 years of age, victims of sexual violence with PTSD with those of healthy controls. Methodology: Application of a neuropsychological battery composed of the following subtests: WASI vocabulary and matrix reasoning; Digit subtests (WISC-IV); verbal auditory learning test RAVLT; Spatial Span subtest of the WMS - III scale; abbreviated version of the Wisconsin test; concentrated attention test - D2; prospective memory subtest of the NEUPSILIN scale; five-digit test - FDT and the Stroop test (Trenerry version) in adolescents with a history of sexual violence in the previous six months, referred to the Prove (Violence Care and Research Program of the Federal University of São Paulo), for further treatment. Results: The results showed a deficit in the word coding process in the RAVLT test, with impairment in A3 (p = 0.004) and A4 (p = 0.016) measures, which compromises the verbal learning process (p = 0.010) and the verbal recognition memory (p = 0.012), seeming to present a worse performance in the acquisition of verbal information that depends on the support of the attentional system. A worse performance was found in list B (p = 0.047), a lower priming effect p = 0.026, that is, lower evocation index of the initial words presented and less perseveration (p = 0.002), repeated words. Therefore, there seems to be a failure in the creation of strategies that help the mnemonic process of retention of the verbal information necessary for learning. Sustained attention was found to be impaired, with greater loss of setting in the Wisconsin test (p = 0.023), a lower rate of correct responses in stage C of the Stroop test (p = 0.023) and, consequently, a higher index of erroneous responses in C of the Stroop test (p = 0.023), besides more type II errors in the D2 test (p = 0.008). A higher incidence of total errors was observed in the reading stage of the FDT test p = 0.002, which suggests fatigue in the execution of the task. Performance is compromised in executive functions in the cognitive flexibility ability, suggesting a higher index of total errors in the alternating step of the FDT test (p = 0.009), as well as a greater number of persevering errors in the Wisconsin test (p = 0.004). Conclusion: The data from this study suggest that sexual violence and PTSD cause significant impairment in the neuropsychological functions of adolescents, evidencing risk to quality of life in stages that are fundamental for the development of learning and cognition.

Keywords: adolescents, neuropsychological functions, PTSD, sexual violence

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Authors: Ana Paula Soares, Alexandrina Lages, Helena Oliveira, Francisco-Javier Gutiérrez-Domínguez, Marisa Lousada

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From an early age, exposure to a spoken language allows us to implicitly capture the structure underlying the succession of the speech sounds in that language and to segment it into meaningful units (words). Statistical learning (SL), i.e., the ability to pick up patterns in the sensory environment even without intention or consciousness of doing it, is thus assumed to play a central role in the acquisition of the rule-governed aspects of language and possibly to lie behind the language difficulties exhibited by children with development language disorder (DLD). The research conducted so far has, however, led to inconsistent results, which might stem from the behavioral tasks used to test SL. In a classic SL experiment, participants are first exposed to a continuous stream (e.g., syllables) in which, unbeknownst to the participants, stimuli are grouped into triplets that always appear together in the stream (e.g., ‘tokibu’, ‘tipolu’), with no pauses between each other (e.g., ‘tokibutipolugopilatokibu’) and without any information regarding the task or the stimuli. Following exposure, SL is assessed by asking participants to discriminate between triplets previously presented (‘tokibu’) from new sequences never presented together during exposure (‘kipopi’), i.e., to perform a two-alternative-forced-choice (2-AFC) task. Despite the widespread use of the 2-AFC to test SL, it has come under increasing criticism as it is an offline post-learning task that only assesses the result of the learning that had occurred during the previous exposure phase and that might be affected by other factors beyond the computation of regularities embedded in the input, typically the likelihood two syllables occurring together, a statistic known as transitional probability (TP). One solution to overcome these limitations is to assess SL as exposure to the stream unfolds using online techniques such as event-related potentials (ERP) that is highly sensitive to the time-course of the learning in the brain. Here we collected ERPs to examine the neurofunctional correlates of SL in preschool children with DLD, and chronological-age typical language development (TLD) controls who were exposed to an auditory stream in which eight three-syllable nonsense words, four of which presenting high-TPs and the other four low-TPs, to further analyze whether the ability of DLD and TLD children to extract-word-like units from the steam was modulated by words’ predictability. Moreover, to ascertain if the previous knowledge of the to-be-learned-regularities affected the neural responses to high- and low-TP words, children performed the auditory SL task, firstly, under implicit, and, subsequently, under explicit conditions. Although behavioral evidence of SL was not obtained in either group, the neural responses elicited during the exposure phases of the SL tasks differentiated children with DLD from children with TLD. Specifically, the results indicated that only children from the TDL group showed neural evidence of SL, particularly in the SL task performed under explicit conditions, firstly, for the low-TP, and, subsequently, for the high-TP ‘words’. Taken together, these findings support the view that children with DLD showed deficits in the extraction of the regularities embedded in the auditory input which might underlie the language difficulties.

Keywords: development language disorder, statistical learning, transitional probabilities, word segmentation

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Authors: Elisavet Kechagia

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Due to the interplay of different genetic and environmental risk factors and its heterogeneous nature, the concept of attention deficit hyperactivity disorder (ADHD) has shaped controversy and conflicts, which have been, in turn, reflected in the controversial arguments about its treatment. Taking into account recent well evidence-based researches suggesting that ADHD is a condition, in which biopsychosocial factors are all weaved together, the current paper explores the multiple risk-factors that are likely to influence ADHD, with a particular focus on adolescents with ADHD who might experience comorbid social, emotional and behavioural disorders (SEBD). In the first section of this paper, the primary objective was to investigate the conflicting ideas regarding the definition, diagnosis and treatment of ADHD at an international level as well as to critically examine and identify the limitations of the two most prevailing sets of diagnostic criteria that inform current diagnosis, the American Psychiatric Association’s (APA) diagnostic scheme, DSM-V, and the World Health Organisation’s (WHO) classification of diseases, ICD-10. Taking into consideration the findings of current longitudinal studies on ADHD association with high rates of comorbid conditions and social dysfunction, in the second section the author moves towards an investigation of the transitional points −physical, psychological and social ones− that students with ADHD might experience during early adolescence, as informed by neuroscience and developmental contextualism theory. The third section is an exploration of the different perspectives of ADHD as reflected in individuals’ with ADHD self-reports and the KENT project’s findings on school staff’s attitudes and practices. In the last section, given the high rates of SEBDs in adolescents with ADHD, it is examined how cognitive behavioural therapy (CBT), coupled with other interventions, could be effective in ameliorating anti-social behaviours and/or other emotional and behavioral difficulties of students with ADHD. The findings of a range of randomised control studies indicate that CBT might have positive outcomes in adolescents with multiple behavioural problems, hence it is suggested to be considered both in schools and other community settings. Finally, taking into account the heterogeneous nature of ADHD, the different biopsychosocial and environmental risk factors that take place during adolescence and the discourse and practices concerning ADHD and SEBD, it is suggested how it might be possible to make sense of and meaningful improvements to the education of adolescents with ADHD within a multi-modal and multi-disciplinary whole-school approach that addresses the multiple problems that not only students with ADHD but also their peers might experience. Further research that would be based on more large-scale controls and would investigate the effectiveness of various interventions, as well as the profiles of those students who have benefited from particular approaches and those who have not, will generate further evidence concerning the psychoeducation of adolescents with ADHD allowing for generalised conclusions to be drawn.

Keywords: adolescence, attention deficit hyperctivity disorder, cognitive behavioural theory, comorbid social emotional behavioural disorders, treatment

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Authors: Ali Kadir, O. Anwar Beg

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Thermal barrier coatings are among the most popular methods for providing corrosion protection in high temperature applications including aircraft engine systems, external spacecraft structures, rocket chambers etc. Many different materials are available for such coatings, of which ceramics generally perform the best. Motivated by these applications, the current investigation presents detailed finite element simulations of coating stress analysis for a 3- dimensional, 3-layered model of a test sample representing a typical gas turbine component scenario. Structural steel is selected for the main inner layer, Titanium (Ti) alloy for the middle layer and Silicon Carbide (SiC) for the outermost layer. The model dimensions are 20 mm (width), 10 mm (height) and three 1mm deep layers. ANSYS software is employed to conduct three types of analysis- static structural, thermal stress analysis and also computational fluid dynamic erosion/corrosion analysis (via ANSYS FLUENT). The specified geometry which corresponds to corrosion test samples exactly is discretized using a body-sizing meshing approach, comprising mainly of tetrahedron cells. Refinements were concentrated at the connection points between the layers to shift the focus towards the static effects dissipated between them. A detailed grid independence study is conducted to confirm the accuracy of the selected mesh densities. To recreate gas turbine scenarios; in the stress analysis simulations, static loading and thermal environment conditions of up to 1000 N and 1000 degrees Kelvin are imposed. The default solver was used to set the controls for the simulation with the fixed support being set as one side of the model while subjecting the opposite side to a tabular force of 500 and 1000 Newtons. Equivalent elastic strain, total deformation, equivalent stress and strain energy were computed for all cases. Each analysis was duplicated twice to remove one of the layers each time, to allow testing of the static and thermal effects with each of the coatings. ANSYS FLUENT simulation was conducted to study the effect of corrosion on the model under similar thermal conditions. The momentum and energy equations were solved and the viscous heating option was applied to represent improved thermal physics of heat transfer between the layers of the structures. A Discrete Phase Model (DPM) in ANSYS FLUENT was employed which allows for the injection of continuous uniform air particles onto the model, thereby enabling an option for calculating the corrosion factor caused by hot air injection (particles prescribed 5 m/s velocity and 1273.15 K). Extensive visualization of results is provided. The simulations reveal interesting features associated with coating response to realistic gas turbine loading conditions including significantly different stress concentrations with different coatings.

Keywords: thermal coating, corrosion, ANSYS FEA, CFD

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Authors: Efstratios Karavasilis, Foteini Christidi, Georgios Velonakis, Agapi Plousi, Kalliopi Platoni, Nikolaos Kelekis, Ioannis Evdokimidis, Efstathios Efstathopoulos

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Introduction: Advanced structural and functional neuroimaging techniques contribute to the study of anatomical and functional brain connectivity and its role in the pathophysiology and symptoms’ heterogeneity in several neurodegenerative disorders, including multiple sclerosis (MS). Aim: In the present study, we applied multiparametric neuroimaging techniques to investigate the structural and functional cortico-cerebellar changes in MS patients. Material: We included 51 MS patients (28 with clinically isolated syndrome [CIS], 31 with relapsing-remitting MS [RRMS]) and 51 age- and gender-matched healthy controls (HC) who underwent MRI in a 3.0T MRI scanner. Methodology: The acquisition protocol included high-resolution 3D T1 weighted, diffusion-weighted imaging and echo planar imaging sequences for the analysis of volumetric, tractography and functional resting state data, respectively. We performed between-group comparisons (CIS, RRMS, HC) using CAT12 and CONN16 MATLAB toolboxes for the analysis of volumetric (cerebellar gray matter density) and functional (cortico-cerebellar resting-state functional connectivity) data, respectively. Brainance suite was used for the analysis of tractography data (cortico-cerebellar white matter integrity; fractional anisotropy [FA]; axial and radial diffusivity [AD; RD]) to reconstruct the cerebellum tracts. Results: Patients with CIS did not show significant gray matter (GM) density differences compared with HC. However, they showed decreased FA and increased diffusivity measures in cortico-cerebellar tracts, and increased cortico-cerebellar functional connectivity. Patients with RRMS showed decreased GM density in cerebellar regions, decreased FA and increased diffusivity measures in cortico-cerebellar WM tracts, as well as a pattern of increased and mostly decreased functional cortico-cerebellar connectivity compared to HC. The comparison between CIS and RRMS patients revealed significant GM density difference, reduced FA and increased diffusivity measures in WM cortico-cerebellar tracts and increased/decreased functional connectivity. The identification of decreased WM integrity and increased functional cortico-cerebellar connectivity without GM changes in CIS and the pattern of decreased GM density decreased WM integrity and mostly decreased functional connectivity in RRMS patients emphasizes the role of compensatory mechanisms in early disease stages and the disintegration of structural and functional networks with disease progression. Conclusions: In conclusion, our study highlights the added value of multimodal neuroimaging techniques for the in vivo investigation of cortico-cerebellar brain changes in neurodegenerative disorders. An extension and future opportunity to leverage multimodal neuroimaging data inevitably remain the integration of such data in the recently-applied mathematical approaches of machine learning algorithms to more accurately classify and predict patients’ disease course.

Keywords: advanced neuroimaging techniques, cerebellum, MRI, multiple sclerosis

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Authors: Husham Bayazed

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Purpose of Presentation: Obesity and overweight are among the biggest health challenges of the 21st century, according to the WHO. Obviously, obese individuals suffer different courses of disease – from infections and allergies to cancer- and even respond differently to some treatment options. Of note, obesity often seems to predispose and triggers several secondary diseases such as diabetes, arteriosclerosis, or heart attacks. Since decades it seems that immunological signals gear inflammatory processes among obese individuals with the aforementioned conditions. This review aims to shed light how obesity sparks or rewire the immune system and predisposes to such unpleasant health outcomes. Moreover, lessons from the Covid-19 pandemic ascertain that people living with pre-existing conditions such as obesity can develop severe acute respiratory syndrome (SARS), which needs to be elucidated how obesity and its adjuvant inflammatory process distortion contribute to enhancing severe COVID-19 consequences. Recent Findings: In recent clinical studies, obesity was linked to alter and sparks the immune system in different ways. Adipose tissue (AT) is considered as a secondary immune organ, which is a reservoir of tissue-resident of different immune cells with mediator release, making it a secondary immune organ. Adipocytes per se secrete several pro-inflammatory cytokines (IL-6, IL-4, MCP-1, and TNF-α ) involved in activation of macrophages resulting in chronic low-grade inflammation. The correlation between obesity and T cells dysregulation is pivotal in rewiring the immune system. Of note, autophagy occurrence in adipose tissues further rewire the immune system due to flush and outburst of leptin and adiponectin, which are cytokines and influencing pro-inflammatory immune functions. These immune alterations among obese individuals are collectively incriminated in triggering several metabolic disorders and playing role in increasing cancers incidence and susceptibility to different infections. During COVID-19 pandemic, it was verified that patients with pre-existing obesity being at greater risk of suffering severe and fatal clinical outcomes. Beside obese people suffer from increased airway resistance and reduced lung volume, ACE2 expression in adipose tissue seems to be high and even higher than that in lungs, which spike infection incidence. In essence, obesity with pre-existence of pro-inflammatory cytokines such as LI-6 is a risk factor for cytokine storm and coagulopathy among COVID-19 patients. Summary: It is well documented that obesity is associated with chronic systemic low-grade inflammation, which sparks and alter different pillars of the immune system and triggers different metabolic disorders, and increases susceptibility of infections and cancer incidence. The pre-existing chronic inflammation in obese patients with the augmented inflammatory response against the viral infection seems to increase the susceptibility of these patients to developing severe COVID-19. Although the new weight loss drugs and bariatric surgery are considered as breakthrough news for obesity treatment, but preventing is easier than treating it once it has taken hold. However, obesity and immune system link new insights dispute the role of immunotherapy and regulating immune cells treating diet-induced obesity.

Keywords: immunity, metabolic disorders, cancer, COVID-19

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Authors: Neeraj Vij, Amber Brennan, Jenni Winters, Hadi Salehi, Hamy Temkit, Emily Andrisevic, Mohan V. Belthur

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Idiopathic clubfoot is a common lower extremity deformity with an incidence of 1:500. The Ponseti Method is well known as the gold standard of treatment. However, there is limited functional data demonstrating correction of the clubfoot after treatment with the Ponseti method. The purpose of this study was to study the clinical and functional outcomes after the Ponseti method with the Clubfoot Disease-Specific Instrument (CDS) and pedobarography. This IRB-approved prospective study included patients aged 3-18 who were treated for idiopathic clubfoot with the Ponseti method between January 2008 and December 2018. Age-matched controls were identified through siblings of clubfoot patients and other community members. Treatment details were collected through a chart review of the included patients. Laboratory assessment included a physical exam, gait analysis, and pedobarography. The Pediatric Outcomes Data Collection Instrument and the Clubfoot Disease-Specific Instrument were also obtained on clubfoot patients (CF). The Wilcoxson rank-sum test was used to study differences between the CF patients and the typically developing (TD) patients. Statistical significance was set at p < 0.05. There were a total of 37 enrolled patients in our study. 21 were priorly treated for CF and 16 were TD. 94% of the CF patients had bilateral involvement. The age at the start of treatment was 29 days, the average total number of casts was seven to eight, and the average total number of casts after Achilles tenotomy was one. The reoccurrence rate was 25%, tenotomy was required in 94% of patients, and ≥1 tenotomy was required in 25% of patients. There were no significant differences between step length, step width, stride length, force-time integral, maximum peak pressure, foot progression angles, stance phase time, single-limb support time, double limb support time, and gait cycle time between children treated with the Ponseti method and typically developing children. The average post-treatment Pirani and Dimeglio scores were 5.50±0.58 and 15.29±1.58, respectively. The average post-treatment PODCI subscores were: Upper Extremity: 90.28, Transfers: 94.6, Sports: 86.81, Pain: 86.20, Happiness: 89.52, Global: 88.6. The average post-treatment Clubfoot Disease-Specific Instrument scores subscores were: Satisfaction: 73.93, Function: 80.32, Overall: 78.41. The Ponseti Method has a very high success rate and remains to be the gold standard in the treatment of idiopathic clubfoot. Timely management leads to good outcomes and a low need for repeated Achilles tenotomy. Children treated with the Ponseti method demonstrate good functional outcomes as measured through pedobarography. Pedobarography may have clinical utility in studying congenital foot deformities. Objective measures for hours of brace wear could represent an improvement in clubfoot care.

Keywords: functional outcomes, pediatric deformity, patient-reported outcomes, talipes equinovarus

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Authors: P. H. G. J. Pushpakumara, A. M. P. Adikari, S. U. B. Tennakoon, Ranil Abeysinghe, Andrew Dawson

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Introduction: Deliberate Self-harm (DSH) is a global public health problem. Since 1950, suicide rates in Sri Lanka are among the highest national rates in the world. It has become an increasingly common response to emotional distress in young adults. However, it remains unclear the reason for this occurrence. Objectives: The descriptive component of this study was conducted to identify of epidemiological pattern of DSH and suicide in Kurunegala District (KD). Assessment of association between DSH socio-cultural, economical and psychological factors were the objectives of the case control component. Methods: Prospective data collection of DSH and suicide was conducted at all (46) hospitals and all (28) police stations in the KD for thirty six months, from 1st January 2011, as the descriptive component. Case control component was conducted at T.H. Kurunegala (THK) for eighteen months duration, from 1st July 2011. Cases (n=439) were randomly selected from a block of 7 consecutively admitted consenting DSP patients using a computer program. Age, sex and residential divisional secretariat division one to one matched, individuals were randomly selected as controls from patients presented to Out Patient Department. Structured Clinical Interview for DSM-IV-TR Axis I and II Disorders was used to diagnose psychiatric disorders. Validated tools were used to measure other constructs. Results: Suicide incidences in KD were, 21.6, 20.7 and 24.3 per 100,000 population in 2011- 2013 (Male:female ratio 5.7, 4.4 and 6.4). 60% of suicides were due to poisoning. DSP incidences were 205.4, 248.3 and 202.5 per 100,000 population in 2011- 2013. Highest age standardized male DSP incidence reported in 20-24 years (769.6/100,000) and female in 15-19 years (1304.0/100,000). Bing married (age >25 years), monthly family income less than Rs.30,000, not achieving G.C.E (O/L) qualifications, a school drop-out, not in a permanent position in occupation, being a manual and an own account worker, were significantly associated with DSP. Perceiving the quality of relationship as bad or very bad with parents, spouse/ girlfriend/ boyfriend and sibling as associated with 8, 40 and 10.5 times higher risk respectively. Feeling and experiences of neglect, other emotional abuses, feeling of insecurity with the family, in child hood, and having a contact history carried an excess risk for DSP. Cases were less likely to seek help. Further, they had significantly lower scores for life skills and life skills application ability. 25.6% DSH patients had DSM TR axis-I and/or TR axis-II disorder. The presence of psychiatric disorder carried 7.7 (95% CI 4.3 – 13.8) times higher risk for DSP. Conclusion: In general, pattern of DSH and suicide is, unique, different from developed, upper and middle income and lower and middle income countries. It is a learned way of expressing emotions in difficult situations of vulnerable people.

Keywords: deliberate self-harm, help-seeking, life-skills, mental- health, psychological, social, suicide

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Authors: Dada Durojaye Joshua

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The study examined the combined effect of internal control system and whistle blowing policy while it pursues the following specific objectives, which are to: examine the relationship between monitoring activities and fraud’s detection and prevention; investigate the effect of control activities on fraud’s detection and prevention in Nigerian Deposit Money Banks (DMBs). The population of the study comprises the 89,275 members of staff in the 20 DMBs in Nigeria as at June 2019. Purposive and convenient sampling techniques were used in the selection of the 80 members of staff at the supervisory level of the Internal Audit Departments of the head offices of the sampled banks, that is, selecting 4 respondents (Audit Executive/Head, Internal Control; Manager, Operation Risk Management; Head, Financial Crime Control; the Chief Compliance Officer) from each of the 20 DMBs in Nigeria. A standard questionnaire was adapted from 2017/2018 Internal Control Questionnaire and Assessment, Bureau of Financial Monitoring and Accountability Florida Department of Economic Opportunity. It was modified to serve the purpose for which it was meant to serve. It was self-administered to gather data from the 80 respondents at the respective headquarters of the sampled banks at their respective locations across Nigeria. Two likert-scales was used in achieving the stated objectives. A logit regression was used in analysing the stated hypotheses. It was found that effect of monitoring activities using the construct of conduct of ongoing or separate evaluation (COSE), evaluation and communication of deficiencies (ECD) revealed that monitoring activities is significant and positively related to fraud’s detection and prevention in Nigerian DMBS. So also, it was found that control activities using selection and development of control activities (SDCA), selection and development of general controls over technology to prevent financial fraud (SDGCTF), development of control activities that gives room for transparency through procedures that put policies into actions (DCATPPA) contributed to influence fraud detection and prevention in the Nigerian DMBs. In addition, it was found that transparency, accountability, reliability, independence and value relevance have significant effect on fraud detection and prevention ibn Nigerian DMBs. The study concluded that the board of directors demonstrated independence from management and exercises oversight of the development and performance of internal control. Part of the conclusion was that there was accountability on the part of the owners and preparers of the financial reports and that the system gives room for the members of staff to account for their responsibilities. Among the recommendations was that the management of Nigerian DMBs should create and establish a standard Internal Control System strong enough to deter fraud in order to encourage continuity of operations by ensuring liquidity, solvency and going concern of the banks. It was also recommended that the banks create a structure that encourages whistleblowing to complement the internal control system.

Keywords: internal control, whistleblowing, deposit money banks, fraud prevention, fraud detection

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Authors: Dada Durojaye Joshua

Abstract:

The study examined the combined effect of internal control system and whistle blowing policy while it pursues the following specific objectives, which are to: examine the relationship between monitoring activities and fraud’s detection and prevention; investigate the effect of control activities on fraud’s detection and prevention in Nigerian Deposit Money Banks (DMBs). The population of the study comprises the 89,275 members of staff in the 20 DMBs in Nigeria as at June 2019. Purposive and convenient sampling techniques were used in the selection of the 80 members of staff at the supervisory level of the Internal Audit Departments of the head offices of the sampled banks, that is, selecting 4 respondents (Audit Executive/Head, Internal Control; Manager, Operation Risk Management; Head, Financial Crime Control; the Chief Compliance Officer) from each of the 20 DMBs in Nigeria. A standard questionnaire was adapted from 2017/2018 Internal Control Questionnaire and Assessment, Bureau of Financial Monitoring and Accountability Florida Department of Economic Opportunity. It was modified to serve the purpose for which it was meant to serve. It was self-administered to gather data from the 80 respondents at the respective headquarters of the sampled banks at their respective locations across Nigeria. Two likert-scales was used in achieving the stated objectives. A logit regression was used in analysing the stated hypotheses. It was found that effect of monitoring activities using the construct of conduct of ongoing or separate evaluation (COSE), evaluation and communication of deficiencies (ECD) revealed that monitoring activities is significant and positively related to fraud’s detection and prevention in Nigerian DMBS. So also, it was found that control activities using selection and development of control activities (SDCA), selection and development of general controls over technology to prevent financial fraud (SDGCTF), development of control activities that gives room for transparency through procedures that put policies into actions (DCATPPA) contributed to influence fraud detection and prevention in the Nigerian DMBs. In addition, it was found that transparency, accountability, reliability, independence and value relevance have significant effect on fraud detection and prevention ibn Nigerian DMBs. The study concluded that the board of directors demonstrated independence from management and exercises oversight of the development and performance of internal control. Part of the conclusion was that there was accountability on the part of the owners and preparers of the financial reports and that the system gives room for the members of staff to account for their responsibilities. Among the recommendations was that the management of Nigerian DMBs should create and establish a standard Internal Control System strong enough to deter fraud in order to encourage continuity of operations by ensuring liquidity, solvency and going concern of the banks. It was also recommended that the banks create a structure that encourages whistleblowing to complement the internal control system.

Keywords: internal control, whistleblowing, deposit money banks, fraud prevention, fraud detection

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Authors: Gift Udoh, Diane S. Rohlman, Benjamin Sindt

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BACKGROUND: There is concern regarding the widespread use of pesticides and impacts on public health. Farmers in Nigeria frequently apply pesticides, including organophosphate pesticides which are known neurotoxicants. They receive little guidance on how much to apply or information about safe handling practices. Pesticide poisoning is one of the major hazards that farmers face in Nigeria. Farmers continue to use highly neurotoxic pesticides for agricultural activities. Because farmers receive little or no information on safe handling and how much to apply, they continue to develop severe and mild illnesses caused by high exposures to pesticides. The project aimed to reduce pesticide exposure among rural farmers in Nigeria by identifying hazards associated with pesticide use and developing and pilot testing training to reduce exposures to pesticides utilizing the hierarchy of controls system. METHODS: Information on pesticide knowledge, behaviors, barriers to safety, and prevention methods was collected from farmers in Nigeria through workplace observations, questionnaires, and interviews. Pre and post-surveys were used to measure farmer’s knowledge before and after the delivery of pesticide safety training. Training topics included the benefits and risks of using pesticides, routes of exposure and health effects, pesticide label activity, use and selection of PPE, ways to prevent exposure and information on local resources. The training was evaluated among farmers and changes in knowledge, attitudes and behaviors were collected prior to and following the training. RESULTS: The training was administered to 60 farmers, a mean age of 35, with a range of farming experience (<1 year to > 50 years). There was an overall increase in knowledge after the training. In addition, farmers perceived a greater immediate risk from exposure to pesticides and their perception of their personal risk increased. For example, farmers believed that pesticide risk is greater to children than to adults, recognized that just because a pesticide is put on the market doesn’t mean it is safe, and they were more confident that they could get advice about handling pesticides. Also, there was greater awareness about behaviors that can increase their exposure (mixing pesticides with bare hands, eating food in the field, not washing hands before eating after applying pesticides, walking in fields recently sprayed, splashing pesticides on their clothes, pesticide storage). CONCLUSION: These results build on existing evidence from a 2022 article highlighting the need for pesticide safety training in Nigeria which suggested that pesticide safety educational programs should focus on community-based, grassroots-style, and involve a family-oriented approach. Educating farmers on agricultural safety while letting them share their experiences with their peers is an effective way of creating awareness on the dangers associated with handling pesticides. Also, for rural communities, especially in Nigeria, pesticide safety pieces of training may not be able to reach some locations, so intentional scouting of rural farming communities and delivering pesticide safety training will improve knowledge of pesticide hazards. There is a need for pesticide information centers to be situated in rural farming communities or agro supply stores, which gives rural farmers information.

Keywords: pesticide exposure, pesticide safety, nigeria, rural farming, pesticide education

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Authors: Alexandra Sargent, Sarah Ferris, Ioannis Theofanous

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The Abbott RealTime High Risk HPV test (RealTime HPV) is one of five assays clinically validated and approved by the English NHS Cervical Screening Programme (CSP) for HPV triage of low grade dyskaryosis and test-of-cure of treated Cervical Intraepithelial Neoplasia. The assay is a highly automated multiplex real-time PCR test for detecting 14 high risk (hr) HPV types, with simultaneous differentiation of HPV 16 and HPV 18 versus non-HPV 16/18 hrHPV. An endogenous internal control ensures sample cellularity, controls extraction efficiency and PCR inhibition. The original cervical specimen collected in SurePath (SP) liquid-based cytology (LBC) medium (BD Diagnostics) and the SP post-gradient cell pellets (SPG) after cytological processing are both CE marked for testing with the RealTime HPV test. During the 2011 NHSCSP validation of new tests only the original aliquot of SP LBC medium was investigated. Residual sample volume left after cytology slide preparation is low and may not always have sufficient volume for repeat HPV testing or for testing of other biomarkers that may be implemented in testing algorithms in the future. The SPG samples, however, have sufficient volumes to carry out additional testing and necessary laboratory validation procedures. This study investigates the correlation of RealTime HPV results of cervical specimens collected in SP LBC medium from women with low grade cytological abnormalities observed with matched pairs of original SP LBC medium and SP post-gradient cell pellets (SPG) after cytology processing. Matched pairs of SP and SPG samples from 750 women with borderline (N = 392) and mild (N = 351) cytology were available for this study. Both specimen types were processed and parallel tested for the presence of hrHPV with RealTime HPV according to the manufacturer´s instructions. HrHPV detection rates and concordance between test results from matched SP and SPGCP pairs were calculated. A total of 743 matched pairs with valid test results on both sample types were available for analysis. An overall-agreement of hrHPV test results of 97.5% (k: 0.95) was found with matched SP/SPG pairs and slightly lower concordance (96.9%; k: 0.94) was observed on 392 pairs from women with borderline cytology compared to 351 pairs from women with mild cytology (98.0%; k: 0.95). Partial typing results were highly concordant in matched SP/SPG pairs for HPV 16 (99.1%), HPV 18 (99.7%) and non-HPV16/18 hrHPV (97.0%), respectively. 19 matched pairs were found with discrepant results: 9 from women with borderline cytology and 4 from women with mild cytology were negative on SPG and positive on SP; 3 from women with borderline cytology and 3 from women with mild cytology were negative on SP and positive on SPG. Excellent correlation of hrHPV DNA test results was found between matched pairs of SP original fluid and post-gradient cell pellets from women with low grade cytological abnormalities tested with the Abbott RealTime High-Risk HPV assay, demonstrating robust performance of the test with both specimen types and reassuring the utility of the assay for cytology triage with both specimen types.

Keywords: Abbott realtime test, HPV, SurePath liquid based cytology, surepath post-gradient cell pellet

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Authors: Amir Shouri, Fereshteh Tabe

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Master planning and urban infrastructure’s thoughtful and sequential design strategies will play the major role in reducing the damages of natural disasters, war and or social/population related conflicts for cities. Defensive strategies have been revised during the history of mankind after having damages from natural depressions, war experiences and terrorist attacks on cities. Lessons learnt from Earthquakes, from 2 world war casualties in 20th century and terrorist activities of all times. Particularly, after Hurricane Sandy of New York in 2012 and September 11th attack on New York’s World Trade Centre (WTC) in 21st century, there have been series of serious collaborations between law making authorities, urban planners and architects and defence related organizations to firstly, getting prepared and/or prevent such activities and secondly, reduce the human loss and economic damages to minimum. This study will work on developing a model of planning for New York City, where its citizens will get minimum impacts in threat-full time with minimum economic damages to the city after the stress is passed. The main discussion in this proposal will focus on pre-hazard, hazard-time and post-hazard transformative policies and strategies that will reduce the “Life casualties” and will ease “Economic Recovery” in post-hazard conditions. This proposal is going to scrutinize that one of the key solutions in this path might be focusing on all overlaying possibilities on architectural platforms of three fundamental infrastructures, the transportation, the power related sources and defensive abilities on a dynamic-transformative framework that will provide maximum safety, high level of flexibility and fastest action-reaction opportunities in stressful periods of time. “Planning Fore Stress” is going to be done in an analytical, qualitative and quantitative work frame, where it will study cases from all over the world. Technology, Organic Design, Materiality, Urban forms, city politics and sustainability will be discussed in deferent cases in international scale. From the modern strategies of Copenhagen for living friendly with nature to traditional approaches of Indonesian old urban planning patterns, the “Iron Dome” of Israel to “Tunnels” in Gaza, from “Ultra-high-performance quartz-infused concrete” of Iran to peaceful and nature-friendly strategies of Switzerland, from “Urban Geopolitics” in cities, war and terrorism to “Design of Sustainable Cities” in the world, will all be studied with references and detailed look to analysis of each case in order to propose the most resourceful, practical and realistic solutions to questions on “New City Divisions”, “New City Planning and social activities” and “New Strategic Architecture for Safe Cities”. This study is a developed version of a proposal that was announced as winner at MoMA in 2013 in call for ideas for Rockaway after Sandy Hurricane took place.

Keywords: urban scale, city safety, natural disaster, war and terrorism, city divisions, architecture for safe cities

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Authors: Elena Filova, Ondrej Kaplan, Marie Markova, Helena Dragounova, Roman Matejka, Eduard Brynda, Lucie Bacakova

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Decellularized vessels have been evaluated as small-diameter vascular prostheses. Reseeding autologous cells onto decellularized tissue prior implantation should prolong prostheses function and make them living tissues. Suitable cell types for reseeding are both endothelial cells and bone marrow-derived stem cells, with a capacity for differentiation into smooth muscle cells upon mechanical loading. Endothelial cells assure antithrombogenicity of the vessels and MSCs produce growth factors and, after their differentiation into smooth muscle cells, they are contractile and produce extracellular matrix proteins as well. Fibrin is a natural scaffold, which allows direct cell adhesion based on integrin receptors. It can be prepared autologous. Fibrin can be modified with bound growth factors, such as basic fibroblast growth factor (FGF-2) and vascular endothelial growth factor (VEGF). These modifications in turn make the scaffold more attractive for cells ingrowth into the biological scaffold. The aim of the study was to prepare thin surface-attached fibrin assemblies with bound FGF-2 and VEGF, and to evaluate growth and differentiation of bone marrow-derived mesenchymal stem cells on the fibrin (Fb) assemblies. Following thin surface-attached fibrin assemblies were prepared: Fb, Fb+VEGF, Fb+FGF2, Fb+heparin, Fb+heparin+VEGF, Fb+heparin+FGF2, Fb+heparin+FGF2+VEGF. Cell culture poly-styrene and glass coverslips were used as controls. Human MSCs (passage 3) were seeded at the density of 8800 cells/1.5 mL alpha-MEM medium with 2.5% FS and 200 U/mL aprotinin per well of a 24-well cell culture. The cells have been cultured on the samples for 6 days. Cell densities on day 1, 3, and 6 were analyzed after staining with LIVE/DEAD cytotoxicity/viability assay kit. The differentiation of MSCs is being analyzed using qPCR. On day 1, the highest density of MSCs was observed on Fb+VEGF and Fb+FGF2. On days 3 and 6, there were similar densities on all samples. On day 1, cell morphology was polygonal and spread on all sample. On day 3 and 6, MSCs growing on Fb assemblies with FGF2 became apparently elongated. The evaluation of expression of genes for von Willebrand factor and CD31 (endothelial cells), for alpha-actin (smooth muscle cells), and for alkaline phosphatase (osteoblasts) is in progress. We prepared fibrin assemblies with bound VEGF and FGF-2 that supported attachment and growth of mesenchymal stem cells. The layers are promising for improving the ingrowth of MSCs into the biological scaffold. Supported by the Technology Agency of the Czech Republic TA04011345, and Ministry of Health NT11270-4/2010, and BIOCEV – Biotechnology and Biomedicine Centre of the Academy of Sciences and Charles University” project (CZ.1.05/1.1.00/02.0109), funded by the European Regional Development Fund for their financial supports.

Keywords: fibrin assemblies, FGF-2, mesenchymal stem cells, VEGF

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Authors: Oleg Reva, Ilya Korotetskiy, Marina Lankina, Murat Kulmanov, Aleksandr Ilin

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Molecular docking approaches are widely used for design of new antibiotics and modeling of antibacterial activities of numerous ligands which bind specifically to active centers of indispensable enzymes and/or key signaling proteins of pathogens. Widespread drug resistance among pathogenic microorganisms calls for development of new antibiotics specifically targeting important metabolic and information pathways. A generally recognized problem is that almost all molecular targets have been identified already and it is getting more and more difficult to design innovative antibacterial compounds to combat the drug resistance. A promising way to overcome the drug resistance problem is an induction of reversion of drug resistance by supplementary medicines to improve the efficacy of the conventional antibiotics. In contrast to well established computer-based drug design, modeling of drug resistance reversion still is in its infancy. In this work, we proposed an approach to identification of compensatory genetic variants reducing the fitness cost associated with the acquisition of drug resistance by pathogenic bacteria. The approach was based on an analysis of the population genetic of Mycobacterium tuberculosis and on results of experimental modeling of the drug resistance reversion induced by a new anti-tuberculosis drug FS-1. The latter drug is an iodine-containing nanomolecular complex that passed clinical trials and was admitted as a new medicine against MDR-TB in Kazakhstan. Isolates of M. tuberculosis obtained on different stages of the clinical trials and also from laboratory animals infected with MDR-TB strain were characterized by antibiotic resistance, and their genomes were sequenced by the paired-end Illumina HiSeq 2000 technology. A steady increase in sensitivity to conventional anti-tuberculosis antibiotics in series of isolated treated with FS-1 was registered despite the fact that the canonical drug resistance mutations identified in the genomes of these isolates remained intact. It was hypothesized that the drug resistance phenotype in M. tuberculosis requires an adjustment of activities of many genes to compensate the fitness cost of the drug resistance mutations. FS-1 cased an aggravation of the fitness cost and removal of the drug-resistant variants of M. tuberculosis from the population. This process caused a significant increase in genetic heterogeneity of the Mtb population that was not observed in the positive and negative controls (infected laboratory animals left untreated and treated solely with the antibiotics). A large-scale search for linkage disequilibrium associations between the drug resistance mutations and genetic variants in other genomic loci allowed identification of target proteins, which could be influenced by supplementary drugs to increase the fitness cost of the drug resistance and deprive the drug-resistant bacterial variants of their competitiveness in the population. The approach will be used to improve the efficacy of FS-1 and also for computer-based design of new drugs to combat drug-resistant infections.

Keywords: complete genome sequencing, computational modeling, drug resistance reversion, Mycobacterium tuberculosis

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Authors: Roberta Mugellesi Dow

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As the climate crisis becomes unignorable, it is imperative that new services are developed addressing not only the needs of customers but also taking into account its impact on the environment. The Telecommunication and Integrated Application (TIA) Directorate of ESA is supporting the green transition with particular attention to the sustainable mobility.“Accelerating the shift to sustainable and smart mobility” is at the core of the European Green Deal strategy, which seeks a 90% reduction in related emissions by 2050 . Transforming the way that people and goods move is essential to increasing mobility while decreasing environmental impact, and transport must be considered holistically to produce a shared vision of green intermodal mobility. The use of space technologies, integrated with terrestrial technologies, is an enabler of smarter traffic management and increased transport efficiency for automated and connected multimodal mobility. Satellite connectivity, including future 5G networks, and digital technologies such as Digital Twin, AI, Machine Learning, and cloud-based applications are key enablers of sustainable mobility.SatCom is essential to ensure that connectivity is ubiquitously available, even in remote and rural areas, or in case of a failure, by the convergence of terrestrial and SatCom connectivity networks, This is especially crucial when there are risks of network failures or cyber-attacks targeting terrestrial communication. SatCom ensures communication network robustness and resilience. The combination of terrestrial and satellite communication networks is making possible intelligent and ubiquitous V2X systems and PNT services with significantly enhanced reliability and security, hyper-fast wireless access, as well as much seamless communication coverage. SatNav is essential in providing accurate tracking and tracing capabilities for automated vehicles and in guiding them to target locations. SatNav can also enable location-based services like car sharing applications, parking assistance, and fare payment. In addition to GNSS receivers, wireless connections, radar, lidar, and other installed sensors can enable automated vehicles to monitor surroundings, to ‘talk to each other’ and with infrastructure in real-time, and to respond to changes instantaneously. SatEO can be used to provide the maps required by the traffic management, as well as evaluate the conditions on the ground, assess changes and provide key data for monitoring and forecasting air pollution and other important parameters. Earth Observation derived data are used to provide meteorological information such as wind speed and direction, humidity, and others that must be considered into models contributing to traffic management services. The paper will provide examples of services and applications that have been developed aiming to identify innovative solutions and new business models that are allowed by new digital technologies engaging space and non space ecosystem together to deliver value and providing innovative, greener solutions in the mobility sector. Examples include Connected Autonomous Vehicles, electric vehicles, green logistics, and others. For the technologies relevant are the hybrid satcom and 5G providing ubiquitous coverage, IoT integration with non space technologies, as well as navigation, PNT technology, and other space data.

Keywords: sustainability, connectivity, mobility, satellites

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Authors: Maryam Nazari

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COVID-19 is a respiratory disease triggered by the novel coronavirus, SARS-CoV-2, that has reached pandemic status today. Acute inflammation and immune cells infiltration into lung injuries result in multi-organ failure. The presence of other non-communicable diseases (NCDs) with systemic inflammation derived from COVID-19 may exacerbate the patient's situation and increase the risk for adverse effects and mortality. This pandemic is a novel situation and the scientific community at this time is looking for vaccines or drugs to treat the pathology. One of the biggest challenges is focused on reducing inflammation without compromising the correct immune response of the patient. In this regard, addressing the nutritional factors should not be overlooked not only as a matter of avoiding the presence of NCDs with severe infections but also as an adjunctive way to modulate the inflammatory status of the patients. Despite the pivotal role of nutrition in modifying immune response, due to the novelty of the COVID-19 disease, information about the effects of specific dietary agents is limited in this area. From the macronutrients point of view, protein deficiency (quantity or quality) has negative effects on the number of functional immunoglobulins and gut-associated lymphoid tissue (GALT). High biological value proteins or some amino acids like arginine and glutamine are well known for their ability to augment the immune system. Among lipids, fish oil has the ability to inactivate enveloped viruses, suppress pro-inflammatory prostaglandin production and block platelet-activating factors and their receptors. In addition, protectin D1, which is an Omega-3 PUFAs derivation, is a novel antiviral drug. So it seems that these fatty acids can reduce the severity and/or improve recovery of patients with COVID-19. Carbohydrates with lower glycemic index and fibers are associated with lower levels of inflammatory cytokines (CRP, TNF-α, and IL-6). Short-Chain Fatty acids not only exert a direct anti-inflammatory effect but also provide appropriate gut microbial, which is important in gastrointestinal issues related to COVID-19. From the micronutrients point of view, Vitamins A, C, D, E, iron, magnesium, zinc, selenium and copper play a vital role in the maintenance of immune function. Inadequate status in these nutrients may result in decreased resistance against COVID-19 infection. There are specific bioactive compounds in the diet that interact with the ACE2 receptor, which is the gateway for SARS and SARS-CoV-2, and thus controls the viral infection. Regarding this, the potential benefits of probiotics, resveratrol (a polyphenol found in grape), oleoylethanolamide (derived from oleic acid), and natural peroxisome proliferator-activated receptor γ agonists in foodstuffs (like curcumin, pomegranate, hot pepper) are suggested. Yet, it should be pointed out that most of these results have been reported in animal models and further human studies are needed to be verified.

Keywords: Covid-19, inflammation, nutrition, dietary agents

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Authors: Mathula Thangarajh

Abstract:

Duchenne muscular dystrophy (DMD) is a severe form of X-linked muscular dystrophy caused by mutations in the dystrophin gene resulting in progressive skeletal muscle weakness. Boys with DMD also have significant cognitive disabilities. The intelligence quotient of boys with DMD, compared to peers, is approximately one standard deviation below average. Detailed neuropsychological testing has demonstrated that boys with DMD have a global developmental impairment, with verbal memory and visuospatial skills most significantly affected. Furthermore, the total brain volume and gray matter volume are lower in children with DMD compared to age-matched controls. These results are suggestive of a significant structural and functional compromise to the developing brain as a result of absent dystrophin protein expression. There is also some genetic evidence to suggest that mutations in the 3’ end of the DMD gene are associated with more severe neurocognitive problems. Our working hypothesis is that (i) boys with DMD do not make gains in neurodevelopmental skills compared to typically developing children and (ii) women carriers of DMD mutations may have subclinical cognitive deficits. We also hypothesize that there may be an intergenerational vulnerability of cognition, with boys of DMD-carrier mothers being more affected cognitively than boys of non-DMD-carrier mothers. The objectives of this study are: 1. Assess the neurodevelopment in boys with DMD at 4-time points and perform baseline neuroradiological assessment, 2. Assess cognition in biological mothers of DMD participants at baseline, 3. Assess possible correlation between DMD mutation and cognitive measures. This study also explores functional brain abnormalities in people with DMD by exploring how regional and global connectivity of the brain underlies executive function deficits in DMD. Such research can contribute to a better holistic understanding of the cognition alterations due to DMD and could potentially allow clinicians to create better-tailored treatment plans for the DMD population. There are four study visits for each participant (baseline, 2-4 weeks, 1 year, 18 months). At each visit, the participant completes the NIH Toolbox Cognition Battery, a validated psychometric measure that is recommended by NIH Common Data Elements for use in DMD. Visits 1, 3, and 4 also involve the administration of the BRIEF-2, ABAS-3, PROMIS/NeuroQoL, PedsQL Neuromuscular module 3.0, Draw a Clock Test, and an optional fMRI scan with the N-back matching task. We expect to enroll 52 children with DMD, 52 mothers of children with DMD, and 30 healthy control boys. This study began in 2020 during the height of the COVID-19 pandemic. Due to this, there were subsequent delays in recruitment because of travel restrictions. However, we have persevered and continued to recruit new participants for the study. We partnered with the Muscular Dystrophy Association (MDA) and helped advertise the study to interested families. Since then, we have had families from across the country contact us about their interest in the study. We plan to continue to enroll a diverse population of DMD participants to contribute toward a better understanding of Duchenne Muscular Dystrophy.

Keywords: neurology, Duchenne muscular dystrophy, muscular dystrophy, cognition, neurodevelopment, x-linked disorder, DMD, DMD gene

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Authors: Laura O’Halloran, Zhipeng Cao, Clare M. Kelly, Hugh Garavan, Robert Whelan

Abstract:

Reaction time (RT) variability on cognitive tasks provides the index of the efficiency of executive control processes (e.g. attention and inhibitory control) and is considered to be a hallmark of clinical disorders, such as attention-deficit disorder (ADHD). Increased RT variability is associated with structural and functional brain differences in children and adults with various clinical disorders, as well as poorer task performance accuracy. Furthermore, the strength of functional connectivity across various brain networks, such as the negative relationship between the task-negative default mode network and task-positive attentional networks, has been found to reflect differences in RT variability. Although RT variability may provide an index of attentional efficiency, as well as being a useful indicator of neurological impairment, the brain substrates associated with RT variability remain relatively poorly defined, particularly in a healthy sample. Method: Firstly, we used the intra-individual coefficient of variation (ICV) as an index of RT variability from “Go” responses on the Stop Signal Task. We then examined the functional and structural neural correlates of ICV in a large sample of 14-year old healthy adolescents (n=1719). Of these, a subset had elevated symptoms of ADHD (n=80) and was compared to a matched non-symptomatic control group (n=80). The relationship between brain activity during successful and unsuccessful inhibitions and gray matter volume were compared with the ICV. A mediation analysis was conducted to examine if specific brain regions mediated the relationship between ADHD symptoms and ICV. Lastly, we looked at functional connectivity across various brain networks and quantified both positive and negative correlations during “Go” responses on the Stop Signal Task. Results: The brain data revealed that higher ICV was associated with increased structural and functional brain activation in the precentral gyrus in the whole sample and in adolescents with ADHD symptoms. Lower ICV was associated with lower activation in the anterior cingulate cortex (ACC) and medial frontal gyrus in the whole sample and in the control group. Furthermore, our results indicated that activation in the precentral gyrus (Broadman Area 4) mediated the relationship between ADHD symptoms and behavioural ICV. Conclusion: This is the first study first to investigate the functional and structural correlates of ICV collectively in a large adolescent sample. Our findings demonstrate a concurrent increase in brain structure and function within task-active prefrontal networks as a function of increased RT variability. Furthermore, structural and functional brain activation patterns in the ACC, and medial frontal gyrus plays a role-optimizing top-down control in order to maintain task performance. Our results also evidenced clear differences in brain morphometry between adolescents with symptoms of ADHD but without clinical diagnosis and typically developing controls. Our findings shed light on specific functional and structural brain regions that are implicated in ICV and yield insights into effective cognitive control in healthy individuals and in clinical groups.

Keywords: ADHD, fMRI, reaction-time variability, default mode, functional connectivity

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Authors: Chinasa U. Imo, Queen Chikwendu, Jonathan Ajuma, Mario Banuelos

Abstract:

Background: Sociocultural norms primarily influence the health-seeking behavior of populations in rural communities. In the Nkporo community, Abia State, Nigeria, their sociocultural perception of diseases runs counter to biomedical definitions, wherein they rely heavily on traditional medicine and practices. In a state where birth asphyxia and sepsis account for the significant causes of death for neonates, malaria leads to the causes of other mortalities, followed by common preventable diseases such as diarrhea, pneumonia, acute respiratory tract infection, malnutrition, and HIV/AIDS. Most local mothers attribute their health conditions and that of their children to witchcraft attacks, the hand of God, and ancestral underlining. This influences how they see antenatal and postnatal care, choice of place of accessing care and birth delivery, response to children's illnesses, immunization, and nutrition. Method: To implement a community health improvement program, we adopted an asset-based community development model to address health's normative and social determinants. The first step was to use a qualitative approach to conduct a community health needs baseline assessment, involving focus group discussions with twenty-five (25) youths aged 18-25, semi-structured interviews with ten (10) officers-in-charge of primary health centers, eight (8) ward health committee members, and nine (9) community leaders. Secondly, we designed an intervention program. Going forward, we will proceed with implementing and evaluating this program. Result: The priority needs identified by the communities were malaria, lack of clean drinking water, and the need for behavioral change information. The study also highlighted the significant influence of youths on their peers, family, and community as caregivers and information interpreters. Based on the findings, the NGO SieDi-Hub collaborated with the Abia State Ministry of Health, the State Primary Healthcare Agency, and Empower Next Generations to design a one-year "Community Health Youth Champions Pilot Program." Twenty (20) youths in the community were trained and equipped to champion a participatory approach to bridging the gap between access and delivery of primary healthcare, to adjust sociocultural norms to improve health equity for people in Nkporo community – with limited education, lack of access to health information, and quality healthcare facilities using an innovative community-led improvement approach. Conclusion: Youths play a vital role in achieving health equity, being a vulnerable population with significant influence. To ensure effective primary healthcare, strategies must include cultural humility. The asset-based community development model offers valuable tools, and this article will share ongoing lessons from the intervention's behavioral change strategies with young people.

Keywords: asset-based community development, community health, primary health systems strengthening, youth empowerment

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Authors: Aleksandra Rajewska-Rager, Maria Skibinska, Monika Dmitrzak-Weglarz, Natalia Lepczynska, Pawel Kapelski, Joanna Pawlak, Joanna Hauser

Abstract:

Introduction: Inflammation and cytokines have emerged as a promising target in mood disorders research; however there are still very limited numbers of study regarding inflammatory alterations among adolescents and young adults with mood disorders. The Macrophage Migration Inhibitory Factor (MIF) and Stem Cell Factor (SCF) are the pleiotropic cytokines which may play an important role in mood disorders pathophysiology. The aim of this study was to investigate levels of these factors in serum of adolescent and young adults with mood disorders compared to healthy controls. Subjects: We involved 79 patients aged 12-24 years in 2-year follow-up study with a primary diagnosis of mood disorders: bipolar disorder (BP) and unipolar disorder with BP spectrum. Study group includes 23 males (mean age 19.08, SD 3.3) and 56 females (18.39, SD 3.28). Control group consisted 35 persons: 7 males (20.43, SD 4.23) and 28 females (21.25, SD 2.11). Clinical diagnoses according to DSM-IV-TR criteria were assessed using Kiddie-Schedule for Affective Disorders and Schizophrenia-Present and Lifetime Version (K-SADS-PL) and Structured Clinical Interview for the Diagnostic and Statistical Manual (SCID) in young adults respectively. Clinical assessment includes evaluation of clinical factors and symptoms severity (rated using the Hamilton Depression Rating Scale and Young Mania Rating Scale). Clinical and biological evaluations were made at control visits respectively at baseline (week 0), euthymia (at month 3 or 6) and after 12 and 24 months. Methods: Serum protein concentration was determined by Enzyme-Linked Immunosorbent Assays (ELISA) method. Human MIF and SCF DuoSet ELISA kits were used. In the analyses non-parametric tests were used: Mann-Whitney U test, Kruskal-Wallis ANOVA, Friedman’s ANOVA, Wilcoxon signed rank test, Spearman correlation. We defined statistical significance as p < 0.05. Results: Comparing MIF and SCF levels between acute episode of depression/hypo/mania at baseline and euthymia (at month 3 or 6) we did not find any statistical differences. At baseline patients with age above 18 years old had decreased MIF level compared to patients younger than 18 years. MIF level at baseline positively correlated with age (p=0.004). Positive correlations of SCF level at month 3 and 6 with depression or mania occurrence at month 24 (p=0.03 and p=0.04, respectively) was detected. Strong correlations between MIF and SCF levels at baseline (p=0.0005) and month 3 (p=0.03) were observed. Discussion: Our results did not show any differences in MIF and SCF levels between acute episode of depression/hypo/mania and euthymia in young patients. Further studies on larger groups are recommended. Grant was founded by National Science Center in Poland no 2011/03/D/NZ5/06146.

Keywords: cytokines, MIF, mood disorders, SCF

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Authors: Isaac Martin, Abigail Lark, Sandra Morales, Eric W. Alton, Jane C. Davies

Abstract:

Objectives: The cystic fibrosis (CF) lung is a unique microbiological niche, wherein harmful bacteria persist for many years despite antibiotic therapy. Pseudomonas aeruginosa (Pa), the major culprit leading to lung decline and increased mortality, thrives in the lungs of patients with CF due to several factors that have been linked with poor antibiotic performance. Our group is investigating alternative therapies including bacteriophage cocktails with which we have previously demonstrated efficacy against planktonic organisms. In this study, we explored the effects of a 4-phage cocktail on Pa grown in two different conditions, intended to mirror the CF lung: a) alongside standard antibiotic treatment in pre-formed biofilms (structures formed by Pa-secreted exopolysaccharides which provide both physical and cell division barriers to antimicrobials and host defenses and b) in an acidic environment postulated to be present in the CF airway due both to the primary defect in bicarbonate secretion and secondary effects of inflammation. Methods: 16 Pa strains from CF patients at the Royal Brompton Hospital were selected based on sensitivity to a) ceftazidime/ tobramycin and b) the phage cocktail in a conventional plaque assay. To assess efficacy of phage in biofilms, 96 well plates with Pa (5x10⁷ CFU/ ml) were incubated in static conditions, allowing adherent bacterial colonies to form for 24 hr. Ceftazidime and tobramycin (both at 2 × MIC) were added, +/- bacteriophage (4x10⁸ PFU/mL) for a further 24 hr. Cell viability and biomass were estimated using fluorescent resazurin and crystal violet assays, respectively. To evaluate the effect of pH, strains were grown planktonically in shaking 96 well plates at pH 6.0, 6.6, 7.0 and 7.5 with tobramycin or phage, at varying concentrations. Cell viability was quantified by fluorescent resazurin assay. Results: For the biofilm assay, treatment groups were compared with untreated controls and expressed as percent reduction in cell viability and biomass. Addition of the 4-phage cocktail resulted in a 1.3-fold reduction in cell viability and 1.7-fold reduction in biomass (p < 0.001) when compared to standard antibiotic treatment alone. Notably, there was a 50 ± 15% reduction in cell viability and 60 ± 12% reduction in biomass (95% CI) for the 4 biofilms demonstrating the most resistance to antibiotic treatment. 83% of strains tested (n=6) showed decreased bacterial killing by tobramycin at acidic pHs (p < 0.01). However, 25% of strains (n=12) showed improved phage killing at acidic pHs (p < 0.05), with none showing the pattern of reduced efficacy at acidic pH demonstrated by tobramycin. Conclusion: The 4-phage anti-Pa cocktail tested against Pa performs well in pre-formed biofilms and in acidic environments; two conditions intended to mimic the CF lung. To our knowledge, these are the first data looking at the effects of subtle pH changes on phage-mediated bacterial killing in the context of Pa infection. These findings contribute to a growing body of evidence supporting the use of nebulised lytic bacteriophage as a treatment in the context of lung infection.

Keywords: biofilm, cystic fibrosis, pH, Pseudomonas aeruginosa, lytic bacteriophage

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