Search results for: multiple rare variants

Authors: Lai-Fen Yang

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In this increasingly visual world, how can we best decipher and understand the many ways that our everyday lives are organized around looking practices and the many images we encounter each day? Indeed, how we interact with and interpret visual images is a basic component of human life. Today, however, we are living in one of the most artificial visual and image-saturated cultures in human history, which makes understanding the complex construction and multiple social functions of visual imagery more important than ever before. Themes regarding our experience of a visually pervasive mediated culture, here, termed visual spectacle.

Keywords: visual culture, contemporary, images, literacy

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Authors: Bohsiu Wu

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Among serious crimes, child homicide is a rather rare event. However, the killing of children stirs up a special type of emotion in society that pales other criminal acts. This study examines the relevancy of three possible community-level explanations for child homicide: social deprivation, female empowerment, and social isolation. The social deprivation hypothesis posits that child homicide results from lack of resources in communities. The female empowerment hypothesis argues that a higher female status translates into a higher level of capability to prevent child homicide. Finally, the social isolation hypothesis regards child homicide as a result of lack of social connectivity. Child homicide data, aggregated by US postal ZIP codes in California from 1990 to 1999, were analyzed with a negative binomial regression. The results of the negative binomial analysis demonstrate that social deprivation is the most salient and consistent predictor among all other factors in explaining child homicide victimization at the ZIP-code level. Both social isolation and female labor force participation are weak predictors of child homicide victimization across communities. Further, results from the negative binomial regression show that it is the communities with a higher, not lower, degree of female labor force participation that are associated with a higher count of child homicide. It is possible that poor communities with a higher level of female employment have a lesser capacity to provide the necessary care and protection for the children. Policies aiming at reducing social deprivation and strengthening female empowerment possess the potential to reduce child homicide in the community.

Keywords: child homicide, deprivation, empowerment, isolation

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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: Ravindra P. Singh, Drupad Ram, Dinesh K. Gupta

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Rare earth ions doped metal oxides are a class of luminescent materials which have been proved to be excellent for applications in field emission displays and cathode ray tubes, plasma display panels. Under UV irradiation Eu+++ doped Y2O3 is a red phosphor and Tb+++ doped Y 2O3 is a green phosphor. It is possible that, due to their high quantum efficiency, they might serve as improved luminescent markers for identification of biomolecules, as already reported for CdSe and CdSe/ZnS nanocrystals. However, for any biological applications these particle powders must be suspended in water while retaining their phosphorescence. We hereby report synthesis and characterization of Eu+++ and Tb+++ doped yttrium oxide nanoparticles by sol-gel and hydrothermal processes. Eu+++ and Tb+++ doped Y2O3 nanoparticles have been synthesized by hydrothermal process using yttrium oxo isopropoxide [Y5O(OPri)13] (crystallized twice) and it’s acetyl acetone modified product [Y(O)(acac)] as precursors. Generally the sol-gel derived metal oxides are required to be annealed to the temperature ranging from 400°C-800°C in order to develop crystalline phases. However, this annealing also results in the development of aggregates which are undesirable for bio-conjugation experiments. In the hydrothermal process, we have achieved crystallinity of the nanoparticles at 300°C and the development of crystalline phases has been found to be proportional to the time of heating of the reactor. The average particle sizes as calculated from XRD were found to be 28 nm, 32 nm, and 34 nm by hydrothermal process. The particles were successfully suspended in chloroform in the presence of trioctyl phosphene oxide and TEM investigations showed the presence of single particles along with agglomerates.

Keywords: nanophosphors, Y2O3:Eu+3, Y2O3:Tb+3, sol-gel, hydrothermal method, TEM, XRD

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Authors: Reema K. AlEssa, Sahar Alshomer, Abdullah Alfaleh, Sultan ALkhenaizan, Mohammed Albalwi

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Ichthyosis is a disorder of abnormal keratinization, characterized by excessive scaling, and consists of more than twenty subtypes varied in severity, mode of inheritance, and the genes involved. There is insufficient data in the literature about the epidemiology and characteristics of ichthyosis locally. Our aim is to identify the histopathological features and genetic profile of ichthyosis. Method: It is an observational retrospective case series study conducted in March 2020, included all patients who were diagnosed with Ichthyosis and confirmed by histological and molecular findings over the last 20 years in King Abdulaziz Medical City (KAMC), Riyadh, Saudi Arabia. Molecular analysis was performed by testing genomic DNA and checking genetic variations using the AmpliSeq panel. All disease-causing variants were checked against HGMD, ClinVar, Genome Aggregation Database (gnomAD), and Exome Aggregation Consortium (ExAC) databases. Result: A total of 60 cases of Ichthyosis were identified with a mean age of 13 ± 9.2. There is an almost equal distribution between female patients 29 (48%) and males 31 (52%). The majority of them were Saudis, 94%. More than half of patients presented with general scaling 33 (55%), followed by dryness and coarse skin 19 (31.6%) and hyperlinearity 5 (8.33%). Family history and history of consanguinity were seen in 26 (43.3% ), 13 (22%), respectively. History of colloidal babies was found in 6 (10%) cases of ichthyosis. The most frequent genes were ALOX12B, ALOXE3, CERS3, CYP4F22, DOLK, FLG2, GJB2, PNPLA1, SLC27A4, SPINK5, STS, SUMF1, TGM1, TGM5, VPS33B. Most frequent variations were detected in CYP4F22 in 16 cases (26.6%) followed by ALOXE3 6 (10%) and STS 6 (10%) then TGM1 5 (8.3) and ALOX12B 5 (8.3). The analysis of molecular genetic identified 23 different genetic variations in the genes of ichthyosis, of which 13 were novel mutations. Homozygous mutations were detected in the majority of ichthyosis cases, 54 (90%), and only 1 case was heterozygous. Few cases, 4 (6.6%) had an unknown type of ichthyosis with a negative genetic result. Conclusion: 13 novel mutations were discovered. Also, about half of ichthyosis patients had a positive history of consanguinity.

Keywords: ichthyosis, genetic profile, molecular characterization, congenital ichthyosis

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Authors: Viktor R. Stoynov, Zlatka V. Valkova-Jarvis

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The intelligent management and optimisation of radio resource technologies will lead to a considerable improvement in the overall performance in Next Generation Networks (NGNs). Carrier Aggregation (CA) technology, also known as Spectrum Aggregation, enables more efficient use of the available spectrum by combining multiple Component Carriers (CCs) in a virtual wideband channel. LTE-A (Long Term Evolution–Advanced) CA technology can combine multiple adjacent or separate CCs in the same band or in different bands. In this way, increased data rates and dynamic load balancing can be achieved, resulting in a more reliable and efficient operation of mobile networks and the enabling of high bandwidth mobile services. In this paper, several distinct CA deployment strategies for the utilisation of spectrum bands are compared in indoor-outdoor scenarios, simulated via the recently-developed Realistic Indoor Environment Generator (RIEG). We analyse the performance of the User Equipment (UE) by integrating the average throughput, the level of fairness of radio resource allocation, and other parameters, into one summative assessment termed a Comparative Factor (CF). In addition, comparison of non-CA and CA indoor mobile networks is carried out under different load conditions: varying numbers and positions of UEs. The experimental results demonstrate that the CA technology can improve network performance, especially in the case of indoor scenarios. Additionally, we show that an increase of carrier frequency does not necessarily lead to improved CF values, due to high wall-penetration losses. The performance of users under bad-channel conditions, often located in the periphery of the cells, can be improved by intelligent CA location. Furthermore, a combination of such a deployment and effective radio resource allocation management with respect to user-fairness plays a crucial role in improving the performance of LTE-A networks.

Keywords: comparative factor, carrier aggregation, indoor mobile network, resource allocation

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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: Anshika Kankane, Dongshik Kang

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Marine debris has a significant influence on coastal environments, damaging biodiversity, and causing loss and damage to marine and ocean sector. A functional cost-effective and automatic approach has been used to look up at this problem. Computer vision combined with a deep learning-based model is being proposed to identify and categorize marine debris of seven kinds on different beach locations of Japan. This research compares state-of-the-art deep learning models with a suggested model architecture that is utilized as a feature extractor for debris categorization. The model is being proposed to detect seven categories of litter using a manually constructed debris dataset, with the help of Mask R-CNN for instance segmentation and a shape matching network called HOGShape, which can then be cleaned on time by clean-up organizations using warning notifications of the system. The manually constructed dataset for this system is created by annotating the images taken by fixed KaKaXi camera using CVAT annotation tool with seven kinds of category labels. A pre-trained HOG feature extractor on LIBSVM is being used along with multiple templates matching on HOG maps of images and HOG maps of templates to improve the predicted masked images obtained via Mask R-CNN training. This system intends to timely alert the cleanup organizations with the warning notifications using live recorded beach debris data. The suggested network results in the improvement of misclassified debris masks of debris objects with different illuminations, shapes, viewpoints and litter with occlusions which have vague visibility.

Keywords: computer vision, debris, deep learning, fixed live camera images, histogram of gradients feature extractor, instance segmentation, manually annotated dataset, multiple template matching

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Authors: Apoorva Bamal, Agnieszka Indiana Olbert

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Floods are known to be one of the most devastating hydro-climatic events, impacting a wide range of stakeholders in terms of environmental, social and economic losses. With difference in inundation durations and level of impact, flood hazards are of different degrees and strength. Amongst various set of domains being impacted by floods, environmental degradation in terms of water quality deterioration is one of the majorly effected but less highlighted domains across the world. The degraded water quality is caused by numerous natural and anthropogenic factors that are both point and non-point sources of pollution. Therefore, it is essential to understand the nature and source of the water pollution due to flooding. The major impact of floods is not only on the physico-chemical water quality parameters, but also on the biological elements leading to a vivid influence on the aquatic ecosystem. This deteriorated water quality is impacting many water categories viz. agriculture, drinking water, aquatic habitat, and miscellaneous services requiring an appropriate water quality to survive. This study identifies, reviews, evaluates and assesses multiple researches done across the world to determine the impact of floods on water quality. With a detailed statistical analysis of top relevant researches, this study is a synopsis of the methods used in assessment of impact of floods on water quality in different geographies, and identifying the gaps for further abridgement. As per majority of the studies, different flood magnitudes have varied impact on the water quality parameters leading to either increased or decreased values as compared to the recommended values for various categories. There is also an evident shift of the biological elements in the impacted waters leading to a change in its phenology and inhabitants of the specified water body. This physical, chemical and biological water quality degradation by floods is dependent upon its duration, extent, magnitude and flow direction. Therefore, this research provides an overview into the multiple impacts of floods on water quality, along with a roadmap of way forward to an efficient and uniform linkage of floods and impacted water quality dynamics.

Keywords: floods, statistical analysis, water pollution, water quality

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Authors: Guillaume Lemahieu, Matthias Sentis, Giovanni Brambilla, Gérard Meunier

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Static Multiple Light Scattering (SMLS) has been shown to be a straightforward technique for the characterization of colloidal dispersions without dilution, as multiply scattered light in backscattered and transmitted mode is directly related to the concentration and size of scatterers present in the sample. In this view, the use of SMLS for stability measurement of various dispersion types has already been widely described in the literature. Indeed, starting from a homogeneous dispersion, the variation of backscattered or transmitted light can be attributed to destabilization phenomena, such as migration (sedimentation, creaming) or particle size variation (flocculation, aggregation). In a view to investigating more on the dispersibility of colloidal suspensions, an experimental set-up for “at the line” SMLS experiment has been developed to understand the impact of the formulation parameters on particle size and dispersibility. The SMLS experiment is performed with a high acquisition rate (up to 10 measurements per second), without dilution, and under direct agitation. Using such experimental device, SMLS detection can be combined with the Hansen approach to optimize the dispersing and stabilizing properties of TiO₂ particles. It appears that the dispersibility and the stability spheres generated are clearly separated, arguing that lower stability is not necessarily a consequence of poor dispersibility. Beyond this clarification, this combined SMLS-Hansen approach is a major step toward the optimization of dispersibility and stability of colloidal formulations by finding solvents having the best compromise between dispersing and stabilizing properties. Such study can be intended to find better dispersion media, greener and cheaper solvents to optimize particles suspensions, reduce the content of costly stabilizing additives or satisfy product regulatory requirements evolution in various industrial fields using suspensions (paints & inks, coatings, cosmetics, energy).

Keywords: dispersibility, stability, Hansen parameters, particles, solvents

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Authors: Min Jee Lee, Young Sun Park, Shin Ahn, Chang Hwan Sohn, Dong Woo Seo, Jae Ho Lee, Yoon Seon Lee, Kyung Soo Lim, Won Young Kim

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Background: Acute myocardial infarction (AMI) concomitant with acute aortic syndrome (AAS) is rare but prompt recognition of concomitant AAS is crucial, especially in patients with ST-segment elevation myocardial infarction (STEMI) because misdiagnosis with early thrombolytic or anticoagulant treatment may result in catastrophic consequences. Objectives: This study investigated the clinical features of patients of STEMI concomitant with AAS that may lead to the diagnostic clue. Method: Between 1 January 2010 and 31 December 2014, 22 patients who were the initial diagnosis of acute coronary syndrome (AMI and unstable angina) and AAS (aortic dissection, intramural hematoma and ruptured thoracic aneurysm) in our emergency department were reviewed. Among these, we excluded 10 patients who were transferred from other hospital and 4 patients with non-STEMI, leaving a total of 8 patients of STEMI concomitant with AAS for analysis. Result: The mean age of study patients was 57.5±16.31 years and five patients were Standford type A and three patients were type B aortic dissection. Six patients had ST-segment elevation in anterior leads and two patients had in inferior leads. Most of the patients had acute onset, severe chest pain but no patients had dissecting nature chest pain. Serum troponin I was elevated in three patients but all patients had D-dimer elevation. Aortic regurgitation or regional wall motion abnormality was founded in four patients. However, widened mediastinum was seen in all study patients. Conclusion: When patients with STEMI have elevated D-dimer and widened mediastinum, concomitant AAS may have to be suspected.

Keywords: aortic dissection, myocardial infarction, ST-segment, d-dimer

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Authors: Sotirios Longinos, Anna Loskutova, Assel Tolegenova, Assem Imanzhussip, Lei Wang

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Hot, dry rock (HDR) has substantial potential as a thermal energy source. It has been exploited by hydraulic fracturing to extract heat and generate electricity, which is a well-developed technique known for creating the enhanced geothermal systems (EGS). These days, LN2 is being tested as an environmental friendly fracturing fluid to generate densely interconnected crevices to augment heat exchange efficiency and production. This study examines experimentally the efficacy of LN2 cryogenic fracturing for granite samples in Kazakhstan with immersion method. A comparison of two different experimental models is carried out. The first mode is rock heating along with liquid nitrogen treatment (heating with freezing time), and the second mode is multiple times of heating along with liquid nitrogen treatment (heating with LN2 freezing-thawing cycles). The experimental results indicated that with multiple heating and LN2-treatment cycles, the permeability of granite first ameliorates with increasing number of cycles and later reaches a plateau after a certain number of cycles. On the other hand, density, P-wave velocity, uniaxial compressive strength, elastic modulus, and tensile strength indicate a downward trend with increasing heating and treatment cycles. The thermal treatment cycles do not seem to have an obvious effect on the Poisson’s ratio. The changing rate of granite rock properties decreases as the number of cycles increases. The deterioration of granite primarily happens within the early few cycles. The heating temperature during the cycles shows an important influence on the deterioration of granite. More specifically, mechanical deterioration and permeability amelioration become more remarkable as the heating temperature increases.LN2 fracturing generates many positives compared to conventional fracturing methods such as little water consumption, requirement of zero chemical additives, lessening of reservoir damage, and so forth. Based on the experimental observations, LN2 can work as a promising waterless fracturing fluid to stimulate hot, dry rock reservoirs.

Keywords: granite, hydraulic fracturing, liquid nitrogen, Kazakhstan

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Authors: Zixuan Liu, Xin Zhang, Kexin He

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In the context of widespread prevalence of multiple diseases, medication safety has become a highly concerned issue affecting patient safety. Medication reconciliation plays a vital role in preventing potential medication risks. However, in medical practice, medication reconciliation faces various challenges, and there is a wide variety of medication reconciliation tools, making the selection of appropriate tools somewhat difficult. The article introduces and analyzes the currently available medication reconciliation tools, providing a reference for healthcare professionals to choose and apply the appropriate medication reconciliation tools.

Keywords: patient safety, medication reconciliation, tools, review

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Authors: Shivani Dolas, A. Richa Mishra

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The existence of Courtyards in India can be traced back to ‘Indus valley civilization’ and various layers of history bearing implications like socio-cultural, traditional, religious, climatic, etc., moreover serving as a breathing space in case of historical core areas. Over time, with the overlay of various historic layers within the historic urban cores and the present high density populace, the cores are getting congested day by day. In this case, courtyards may emerge out as an efficient medium to provide quality of life through livable spaces. Presently, with the growing population of the historic town of Gwalior, town in Madhya Pradesh holds remarkable essence of courtyards with its multiple concepts over time. Its scale and function varies from an imposing grand appearance in palatial form, up to functional practices as residential. Its privilege can also be drawn in urban forms, in sharing single space by multiple dwellings and in temples which can be sketched specifically in the region. Moreover, the effectiveness of courtyards has proven balance and control of micro-climate in such composite climate region. The research paper aims to underline the concept of courtyards in case of a mixed use neighborhood, Naya bazar, in Lashkar area of Gwalior, which developed during 19th century, highlighting the need of its preservation. The paper also elaborates its various implications on user-space relationship as in the present context, and growing congestion in the area, user and space relationship is seen lost. The noticeable change in the behavioral context in buildings and users can be noticed with the downfall of courtyards, isolating users with land. Also, a concern has been expressed on negligence of courtyard planning in future development, suggesting recommendations on preserving the courtyard typology as heritage.

Keywords: courtyards, Gwalior, historic settlement, heritage

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Authors: Sanjiv Kumar Soni, Chetna Janveja

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The approach of utilizing zero cost kitchen waste residues for growing suitable strains of fungi for the induction of a cocktail of hydrolytic enzymes and ethanol generation has been validated in the present study with the objective of developing an indigenous biorefinery for low cost bioethanol production with the generation of zero waste. Solid state fermentation has been carried out to evaluate the potential of various steam pretreated kitchen waste residues as substrates for the co-production of multiple carbohydrases including cellulases, hemicellulases, pectinase and amylases by a locally isolated strain of Aspergillus niger C-5. Of all the residues, potato peels induced the maximum yields of all the enzyme components corresponding to 64.0±1.92 IU of CMCase, 17.0±0.54 IU of FPase , 42.8±1.28 IU of β-glucosidase, 990.0±28.90 IU of xylanase, 53.2±2.12 IU of mannanase, 126.0±3.72 IU of pectinase, 31500.0±375.78 IU of α-amylase and 488.8±9.82 IU of glucoamylase/g dry substrate respectively. Saccharification of various kitchen refuse residues using inhouse produced crude enzyme cocktail resulted in the release of 610±10.56, 570±8.89, 435±6.54, 475±4.56, 445±4.27, 385±4.49, 370±6.89, 490±10.45 mg of total reducing sugars/g of dried potato peels, orange peels, pineapple peels, mausami peels, onion peels, banana stalks, pea pods and composite mixture respectively revealing carbohydrate conversion efficiencies in the range of 97.0-99.4%. After fermentation of released hexoses by Saccharomyces cerevisae, ethanol yields ranging from 80-262 mL/ kg of dry residues were obtained. The study has successfully evaluated the valorization of kitchen garbage, a highly biodegradable component in Municipal Solid Waste by using it as a substrate for the in-house co-production of multiple carbohydrases and employing the steam treated residues as a feed stock for bioethanol production. Such valorization of kitchen garbage may reduce the level of Municipal Solid Waste going into land-fills thus lowering the emissions of greenhouse gases. Moreover, the solid residue left after the bioconversion may be used as a biofertilizer for improving the fertility of the soils.

Keywords: kitchen waste, bioethanol, solid waste, bioconversion, waste management

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Authors: Kalkidan Worku, Eniyew Tegegne, Menichil Amsalu, Samuel Derbie Habtegiorgis

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Introduction: Because of the seasonal nature of the work, day laborers are exposed to risky sexual practices. Since the majority of them are living far away from their birthplace and family, they engage in unplanned and multiple sexual practices. These unplanned and unprotected sexual experiences are a risk for different types of sexual-related health crises. This study aimed to assess the pooled prevalence of risky sexual practices and its determinants among day laborers in Ethiopia. Methods: Online databases, including PubMed, Google Scholar, Science Direct, African Journal of Online, Academia Edu, Semantic Scholar, and university repository sites, were searched from database inception until March 2023. PRISMA 2020 guideline was used to conduct the review. Among 851 extracted studies, ten articles were retained for the final quantitative analysis. To identify the source of heterogeneity, a sub-group analysis and I² test were performed. Publication bias was assessed by using a funnel plot and the Egger and Beg test. The pooled prevalence of risky sexual practices was calculated. Besides, the association between determinant factors and risky sexual practice was determined using a pooled odds ratio (OR) with a 95% confidence interval. Result: The pooled prevalence of risky sexual practices among day laborers was 46.00% (95% CI: 32.96, 59.03). Being single (OR: 2.49; 95% CI: 1.29 to 4.83), substance use (OR: 1.79; 95% CI: 1.40 to 2.29), alcohol intake (OR: 4.19; 95% CI: 2.19 to 8.04), watching pornographic (OR: 5.49; 95% CI: 2.99 to 10.09), discussion about SRH (OR: 4.21; 95% CI: 1.34 to 13.21), visiting night clubs (OR: 2.86 95% CI: 1.79 to 4.57) and risk perception (OR: 0.37 95% CI: 0.20 to 0.70) were the possible factors for risky sexual practice of day laborers in Ethiopia. Conclusions: A large proportion of day laborers engaged in risky sexual practices. Interventions targeting creating awareness of sexual and reproductive health for day laborers should be implemented. Continuous peer education on sexual health should be given to day laborers. Sexual and reproductive health services should be accessible in their workplaces to maximize condom utilization and to facilitate sexual health education for all day laborers.

Keywords: day laborers, sexual health, risky sexual practice, unsafe sex, multiple sexual partners

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Authors: Masbubul Ishtiaque Ahmed

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Food chain contamination by heavy metals has become a critical issue in recent years because of their potential accumulation in bio systems through contaminated water, soil and irrigation water. Industrial discharge, fertilizers, contaminated irrigation water, fossil fuels, sewage sludge and municipality wastes are the major sources of heavy metal contamination in soils and subsequent uptake by crops. The main objectives of this project were to determine the levels of minerals, trace elements and heavy metals in major foods and beverages consumed by the poor and non-poor households of Dhaka city and assess the dietary risk exposure to heavy metal and trace metal contamination and potential health implications as well as recommendations for action. Heavy metals are naturally occurring elements that have a high atomic weight and a density of at least 5 times greater than that of water. Their multiple industrial, domestic, agricultural, medical and technological applications have led to their wide distribution in the environment; raising concerns over their potential effects on human health and the environment. Their toxicity depends on several factors including the dose, route of exposure, and chemical species, as well as the age, gender, genetics, and nutritional status of exposed individuals. Because of their high degree of toxicity, arsenic, cadmium, chromium, lead, and mercury rank among the priority metals that are of public health significance. These metallic elements are considered systemic toxicants that are known to induce multiple organ damage, even at lower levels of exposure. This review provides an analysis of their environmental occurrence, production and use, potential for human exposure, and molecular mechanisms of toxicity, and carcinogenicity.

Keywords: food chain, determine the levels of minerals, trace elements, heavy metals, production and use, human exposure, toxicity, carcinogenicity

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Authors: Mathias Schlenk, Susanne Seibt, Sabine Rosenfeldt, Josef Breu, Stephan Foerster

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Thin liquid jets on micrometer scale play an important role in processing such as in fiber fabrication, inkjet printing, but also for sample delivery in modern synchrotron X-ray devices. In all these cases the liquid jets contain solvents and dissolved materials such as polymers, nanoparticles, fibers pigments or proteins. As liquid flow in liquid jets differs significantly from flow in capillaries and microchannels, particle localization and orientation will also be different. This is of critical importance for applications, which depend on well-defined homogeneous particle and fiber distribution and orientation in liquid jets. Investigations of particle orientation in liquid microjets of diluted solutions have been rare, despite their importance. With the arise of micro-focused X-ray beams it has become possible to scan across samples with micrometer resolution to locally analyse structure and orientation of the samples. In the present work, we used this method to scan across liquid microjets to determine the local distribution and orientation of anisotropic particles. The compromise wormlike block copolymer micelles as an example of long flexible fibrous structures, hectorite materials as a model of extended nanosheet structures, and gold nanorods as an illustration of short stiff cylinders to comprise all relevant anisotropic geometries. We find that due to the different velocity profile in the liquid jet, which resembles plug flow, the orientation of the particles which was generated in the capillary is lost or changed into non-oriented or bi-axially orientations depending on the geometrical shape of the particle.

Keywords: anisotropic particles, liquid microjets, reorientation, SAXS

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Authors: D. Avnieli

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Immunity of judges from liability represents a departure from the principle that all are equal under the law, and that victims may be granted compensation from their offenders. The purpose of the study is to determine if judicial immunity coincides with the need to ensure the existence of highly independent and incorruptible judiciary. Judges are immune from civil and criminal liability for their judicial acts. Judicial immunity is justified by the need to maintain complete independence and discretion of the judiciary. Scholars and judges believe that absolute immunity is needed to shield judges from pressures, threats, or outside interference. It is commonly accepted, that judges should be free to perform their judicial role in accordance with their assessment of the fact and their understanding of the law, without any restrictions, influences, inducements or interferences. In most countries, immunity applies when judges act in excess of jurisdiction. In some countries, it applies even when they act maliciously or corruptly. The only exception to absolute immunity applicable in all judicial systems is when judges act without jurisdiction over the subject matter. The Israeli Supreme Court recently decided to embrace absolute immunity and strike off a lawsuit of a refugee, who was unlawfully incarcerated. The Court ruled that the plaintiff cannot sue the State or the judge for damages. The questions of malice, dignity, and public scrutiny were not discussed. This paper, based on comparative analysis of many cases, aims to determine if immunity affects the dignity and behavior of judges. It demonstrates that most judges maintain their dignity and ethical code of behavior, but sometimes do not hesitate to act consciously in excess of jurisdiction, and in rare cases even corruptly. Therefore, in order to maintain independent and incorruptible judiciary, immunity should not be applied where judges act consciously in excess of jurisdiction or with malicious incentives.

Keywords: incorruptible judiciary, immunity, independent, judicial, judges, jurisdiction

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Authors: Davoud Mokhtari

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One of the factors behind the increasing development of geotourism is the identification and introduction of new facets of amazing geosphere phenomena. The Misho-Dagh Mountains in northwestern Iran are one of the rich geodiversity areas. The presence of some rare and interesting phenomena in this mountain has increased the potential of this region for geotourism development. Active pressure ridges, arcuate valleys, sag Ponds, granite complexes, glacial rock springs, and displaced habitats due to tectonic activity are among the most significant phenomena in the study area. The research is based on the literature review of geotourism and personal research experiences on geomorphosites of the northwest of Iran. Monitoring the changes of geomorphosites and evaluation of corresponding changes in the geomorphosite̕s location and their capabilities using satellite images and fieldwork is done. In this study, six geomorphosite were introduced, each with special characteristics and with one of the geotourism topics. Selection of this location of northwestern Iran is due to the focus of author of this paper is on this part of the country, and there is no doubt that such places, even with higher values of geotourism, there are in various parts of Iran and the world that could be interested in this field of emerging science. From in situ observations taken in the field and estimating a level of impact, employing assessment techniques, and then finally extrapolating the resultant factors across all case studies, we have been able to generate a geotourism map for future planning purposes. Accordingly, it should be noted that we are not just part of the landscape of the geomorphosites. The geomorphosites are also part of our landscape. It is hoped that the findings of this paper can open a new world of geotourism that, if is not associated with geomorphological processes, will be very short.

Keywords: geotourism, sources of geotourism, geotouristic areas, mishow_dagh, northwest of Iran

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Authors: Rosaria Tizzani, Tomas Morosinotto, Fabrizio Bezzo, Eleonora Sforza

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Red microalga Porphyridium marinum CCAP 13807/10 has the potential to produce a broad range of commercially valuable chemicals such as PhycoErytrin (PE) and sulphated ExoPolySaccharides (EPS). Multiple abiotic factors influence the growth of Porphyridium sp., e.g. the wavelength of the light source and different cultivation strategies (one or two steps, batch, semi-, and continuous regime). The microalga of interest is cultivated in a two-step system. First, the culture grows photoautotrophically in a controlled bioreactor with pH-dependent CO2 injection, temperature monitoring, light intensity, and LED wavelength remote control in a semicontinuous mode. In the second step, the harvested biomass is subjected to mixotrophic conditions to enhance further growth. Preliminary tests have been performed to define the suitable media, salinity, pH, and organic carbon substrate to obtain the highest biomass productivity. Dynamic light and operational conditions (e.g. HRT) are evaluated to achieve high biomass production, high PE accumulation in the biomass, and high EPS release in the medium. Porphyridium marinum is able to chromatically adapt the photosynthetic apparatus to efficiently exploit the full light spectra composition. The effect of specific narrow LED wavelengths (white W, red R, green G, blue B) and a combination of LEDs (WR, WB, WG, BR, BG, RG) are identified to understand the phenomenon of chromatic adaptation under photoautotrophic conditions. The effect of light intensity, residence time, and light quality are investigated to define optimal operational strategies for full scale commercial applications. Production of biomass, phycobiliproteins, PE, EPS, EPS sulfate content, EPS composition, Chlorophyll-a, and pigment content are monitored to determine the effect of LED wavelength on the cultivation Porphyridium marinum in order to optimize the production of these multiple, highly valuable bioproducts of commercial interest.

Keywords: red microalgae, LED, exopolysaccharide, phycoerythrin

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Authors: Chamtouri I., Kechida M.

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Background: Evaluation has a prominent role in medical education and graduation. This evaluation has usually done in face-to-face, by written or oral questions. Simulation is increasingly taking a part as a method of evaluation. Due to the Covid-19 pandemic, which disrupted face-to-face evaluation, simulation using serious games (SG) is emerging in the field of training and assessment of medical students. The aim of our study is to compare the results of the evaluation of medical students by virtual simulation by online serious games versus clinical case-multiple choice questions (MCQ) and to assess the degree of satisfaction from these two evaluation methods. Methods: Medical students from the same study level were voluntarily participated in this study. Groupe 1 had an evaluation by SG dealing with “diagnosis and management of ST-segment elevationmyocardialinfarction (STEMI)alreadyprepared on the website www.Mediactiv.com. Groupe 2 were evaluated by clinical case-MCQ having thes same topic as SG. Results of the two groups were compared. Satisfaction questionnaire was filled by the two groups. Satisfaction degree was compared between the two groups. Results. In this study, 64 medical students (G1:31 and G2: 33) were enrolled. Obtaining complete notes in the "questioning" and "clinical examination" parts is significantly more important in-group 1 compared to group 2. No significant difference detected between the two groups in terms of “ECG interpretation” and “diagnosis of STEMI” parts. A greater number of students of group 1 obtained the full note compared to group 2 in “the initial treatment part” (54.8% vs. 39.4%; p = 0.04). Thirty learners (96.8%) in-group 1 obtained a total score ≥ 50% versus 69.7% in-group 2 (p = 0.004). The full score of 100% was obtained in three learners in-group1, while no student scored 100% in-group2 (p = 0.027). Medical evaluation using SG was reported as more innovative, fun, and realistic compared to evaluation by clinical case-MCQ. No significant difference detected between the two methods in terms of stress. Conclusion: Simulation by SG can be considered as an innovative and effective method in evaluating medical students with a higher degree of satisfaction.

Keywords: evaluation, serious games, medical students, satisfaction

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Authors: Moh’d Anwer Al-Shboul

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The year 2011 was a challenging year for Jordanian economy, which felt a variety of effects from the Arab Spring which took place in neighboring countries. Since February, 5th 2012, the Arab Gas Supply Pipeline, which carries natural gas from Egypt through the Sinai Peninsula and to Jordan and Israel, has been attacked more than 39 times. Jordan imported about 80 percent of its necessity of natural gas (about 250 million cubic feet of natural gas per day) from Egypt to generate particularly electricity, with the reminder of being produced locally. Jordan has utilized multiple alternatives to address the interruption of available natural gas supply from Egypt. The Jordanian distributed power plants now rely on the use of heavy fuel oil and diesel for electricity generation, in this case, it costs Jordan about four times than natural gas. The substitution of Egyptian natural gas supplies by fuel oil and diesel, coupled with the 32 percent rise in global fuel prices, has increased Jordan’s energy import bill by over 50 percent in 2011, reaching more than 16 percent of the 2011 GDP. The increase in the cost of electricity generation pushed the Jordanian economy to borrow from multiple internal and external resource channels, thus increasing the public debt. The Jordanian government’s short-term solution to the reduced natural gas supply from Egypt was alternatively purchasing the necessary quantities from some Gulf countries such as Qatar and/or Saudi Arabia, which can be imported with two possible methods. The first method is to rent a ship equipped with a liquefied natural gas (LNG) terminal, which is currently operating. The second method requires equipping the Aqaba port with an LNG terminal, which also currently is operating. In the long-term, a viable solution to depending on importing expensive and often unreliable natural gas supplies from surrounding countries is to depend more heavily on renewable supply energy, including solar, wind, and water energy.

Keywords: energy supply resources, Arab spring, liquefied natural gas, pipeline, Jordan

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Authors: Node Smith

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Developmental psychology has long focused on modeling consciousness, often neglecting practical application and clinical utility. This paper aims to bridge this gap by exploring the practical application of physical and sensory tracking and awareness in fostering essential skills for conscious development. Higher conscious development requires practical skills such as self-agency, the ability to hold multiple perspectives, and genuine altruism. These are not personality characteristics but areas of skillfulness that address many cultural deficiencies impacting our world. They are intertwined with individual as well as collective conscious development. Physical, sensory tracking and awareness are crucial for developing these skills and offer the added benefit of cultivating healthy communication, emotional regulation, and introspection. Unlike skills such as throwing a baseball, which can be developed through practice or innate ability, the ability to introspect, track physical sensations, and observe oneself objectively is essential for advancing consciousness. Lacking these skills leads to cultural and individual anxiety, helplessness, and a lack of agency, manifesting as blame-shifting and irresponsibility. The inability to hold multiple perspectives stifles altruism, as genuine consideration for a global community requires accepting other perspectives without conditions. Physical and sensory tracking enhances self-awareness by grounding individuals in their bodily experiences. This grounding is critical for emotional regulation, allowing individuals to identify and process emotions in real-time, preventing overwhelm and fostering balance. Techniques like mindfulness meditation and body scan exercises attune individuals to their physical sensations, providing insights into their emotional states. Sensory awareness also facilitates healthy communication by fostering empathy and active listening. When individuals are in tune with their physical sensations, they become more present in interactions, picking up on subtle cues and responding thoughtfully. This presence reduces misunderstandings and conflicts, promoting more effective communication. The ability to introspect and observe oneself objectively is key to emotional introspection. This skill allows individuals to reflect on their thoughts, feelings, and behaviors, identify patterns, recognize areas for growth, and make conscious choices aligned with their values and goals. In conclusion, physical and sensory tracking and awareness are vital for developing the skills necessary for higher consciousness development. By fostering self-agency, emotional regulation, and the ability to hold multiple perspectives, these practices contribute to healthier communication, deeper emotional introspection, and a more altruistic and connected global community. Integrating these practices into developmental psychology and therapeutic interventions holds significant promise for both individual and societal transformation.

Keywords: conscious development, emotional introspection, emotional regulation, self-agency, stages of development

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Authors: Hao-Yuan Tseng, Chuan-Yang Chang, Ying-Hui Chen, Sheng-Che Chen, Chih-Han Chang

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Orthodontic tooth treatment has demonstrated a high success rate in clinical studies. It has been agreed upon that orthodontic tooth movement is based on the ability of surrounding bone and periodontal ligament (PDL) to react to a mechanical stimulus with remodeling processes. However, the mechanism of the tooth movement is still unclear. Recent studies focus on the simple principle compression-tension theory while rare studies directly measure tooth movement. Therefore, tracking tooth movement information during orthodontic treatment is very important in clinical practice. The aim of this study is to investigate the mechanism responses of the tooth movement during the orthodontic treatments. A stereovision system applied to track the tooth movement of the patient with the stamp brackets. The system was established by two cameras with their relative position calibrate. And the orthodontic force measured by 3D printing model with the six-axis load cell to determine the initial force application. The result shows that the stereovision system accuracy revealed the measurement presents a maximum error less than 2%. For the study on patient tracking, the incisor moved about 0.9 mm during 60 days tracking, and half of movement occurred in the first few hours. After removing the orthodontic force in 100 hours, the distance between before and after position incisor tooth decrease 0.5 mm consisted with the release of the phenomenon. Using the stereovision system can accurately locate the three-dimensional position of the teeth and superposition of 3D coordinate system for all the data to integrate the complex tooth movement.

Keywords: orthodontic treatment, tooth movement, stereovision system, long-term tracking

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Authors: Sadam Elayah, Yang Li, Bing Shi

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Background: The impact of relaxing incisions on maxillofacial growth during palatoplasty remains a topic of debate, and further research is needed to understand its effects fully. Thus, the current study is the first long-term study that aimed to assess the maxillofacial growth of patients with isolated cleft palate following the Sommerlad-Furlow modified (S.F) technique and to estimate the impact of relaxing incisions on maxillofacial growth following S.F technique in patients with isolated cleft palate. Methods: A total of 85 participants, 55 patients with non-syndromic isolated soft and hard cleft palate underwent primary palatoplasty with our technique (30 patients received the Sommerlad-Furlow modified technique without relaxing incision (S.F+RI group), and 25 received Sommerlad-Furlow modified technique without relaxing (S.F-RI group) with no significant difference found between them regarding the cleft type, cleft width, and age at repair. While the other 30 were normal participants with skeletal class I pattern (C group). The control group was matched with the study group in number, age, and sex. All the study variables were measured using stable landmarks, including 12 linear and 10 angular variants. Results: The mean ages at collection of cephalograms were 6.03±0.80 in the S.F+RI group, 5.96±0.76 in the S.F-RI group, and 5.91±0.87 in the C group. Regarding cranial base, the results showed no statistically significant differences between the three groups in S-N and S-N-Ba. The S.F+R.I group had a significantly shorter S-Ba than the S.F-R.I & C groups (P= 0.01). However, there was no statistically significant difference between the S.F-R.I & C groups (P=0.80). Regarding the skeletal maxilla, there was no significant difference between the S.F+R.I and S.F-R.I groups in all linear measurements (N-ANS, S- PM & SN-PP ) except Co-A, the S.F+R.I group had significantly shorter Co-A than the S.F-R.I & C groups (P= <0.01). While the angular measurement, S.F+R.I group had significantly less SNA angle than the S.F-R.I & C groups (P= <0.01). Regarding mandibular bone, there were no statistically significant differences in all linear and angular mandibular measurements between the S.F+R.I and S.F-R.I groups. Regarding intermaxillary relation, the S.F+R.I group had significant differences in Co-Gn - Co-A and ANB compared to the S.F-R.I & C groups (P= <0.01). There was no statistically significant difference in PP-MP among the three groups. Conclusion: As a preliminary report, the Sommerlad-Furlow modified technique without relaxing incisions was found to have good maxillary positioning in the face and a satisfactory intermaxillary relationship compared to the Sommerlad-Furlow modified technique with relaxing incisions.

Keywords: relaxing incisions, cleft palate, palatoplasty, maxillofacial growth

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Authors: Maiko Kiyohara, Toshiki Ito

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In this study, we used a psychotherapy process for patient with dissociative disorder and the graphic Rorschach (Digital version) (GRD). A dissociative disorder is a type of dissociation characterized by multiple alternating personalities (also called alternate identity or another identity). "dissociation" is a state in which consciousness, memory, thinking, emotion, perception, behavior, body image, and so on are divided and experienced. Dissociation symptoms, such as lack of memory, are seen, and the repetition of blanks in daily events causes serious problems in life. Although the pathological mechanism of dissociation has not yet been fully elucidated, it is said that it is caused by childhood abuse or shocking trauma. In case of Japan, no reliable data has been reported on the number of patients and prevalence of dissociative disorders, no drug is compatible with dissociation symptoms, and no clear treatment has been established. GRD is a method that the author revised in 2017 to a Graphic Rorschach, which is a special technique for subjects to draw language responses when enforce Rorschach. GRD reduces the burden on both the subject and the examiner, reduces the complexity of organizing data, improves the simplicity of organizing data, and improves the accuracy of interpretation by introducing a tablet computer during the drawing reaction. We are conducting research for the purpose. The patient in this case is a woman in her 50s, and has multiple personalities since childhood. At present, there are about 10 personalities whose main personality is just grasped. The patients is raising her junior high school sons as single parent, but personal changes often occur at home, which makes the home environment inferior and economically oppressive, and has severely hindered daily life. In psychotherapy, while a personality different from the main personality has appeared, I have also conducted psychotherapy with her son. In this case, the psychotherapy process and the GRD were performed to understand the personality characteristics, and the possibility of therapeutic significance to personality integration is reported.

Keywords: GRD, dissociative disorder, a case study of psychotherapy process, dissociation

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Authors: Maria Angela Bedini, Fabio Bronzini

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Most of the Italian territory is at seismic risk. Many earthquakes have hit Italy, and devastating effects have been generated. The specific objective of the research is to distinguish the negative approaches that have generated unacceptable social situations of marginalization, abandonment, and economic regression, from positive methodological approaches. On the basis of the different situations examined, the study proposes strategies and guidelines to obtain the best possible results, in Italy or abroad, in the event of new earthquakes. At national and international level, many theoretical studies address the aspects of prevention, while the comparisons, carried out in this study, between the techniques and the operative procedures applied and the results obtained are rare. The adopted methodology compares the different pre-earthquake urban-planning approaches, for the emergency (temporary urban planning), and for the post-earthquake (socio-economic-territorial processes) in Italy. Attention is placed on the current consolidated planning and programming acquisitions, pre and post-earthquake. The main results of the study concern the prospects in Italy of protection from seismic risks in the next decades. An integrated settlement system for a new economic and social model, aimed at the rebirth of territories in crisis, is proposed. Finally, the conclusions describe the disciplinary positions, procedures and the fundamental points generally shared by the scientific community for each approach, in order to identify the strategic choices and the disciplinary and management paths that will be followed in the coming decades.

Keywords: post-earthquake, seismic emergency, seismic prevention, urban planning interventions in Italy

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Authors: M. A. Ojo, E. O. Ogbole, A. O. Ojo

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This study analysed improved household solid waste management system in Minna metropolis, Niger state. Multi-staged sampling technique was used to administer 155 questionnaires to respondents, where Minna was divided into two income groups A and B based on the quality of the respondent’s houses. Primary data was collected with the aid of structured questionnaires and analysed using descriptive statistics to obtain results for the socioeconomic characteristics of respondents, types of waste generated and methods of disposing solid waste, the level of awareness and reliability of waste disposal methods as well as the willingness of households to pay for solid waste management in the area. The results revealed that majority of the household heads in the study area were male, 94.20% of the household heads fell between the ages of 21 and 50 and also that 96.80% of them had one form of formal education or the other. The results also revealed that 47.10% and 43.20% of the households generated food wastes and polymers respectively as a major constituent of waste disposed. The results of this study went further to reveal that 81.90% of the household heads were aware of the use of collection cans as a method of waste disposal while only 32.90% of them considered the method highly reliable. Multiple regression was used to determine the factors affecting the willingness of households to pay for waste disposal in the study area. The results showed that 76.10% of the respondents were willing to pay for solid waste management which indicates that households in Minna are concerned and willing to cater for their immediate environment. The multiple regression results revealed that age, income, environmental awareness and household expenditure have a positive and statistically significant relationship with the willingness of households to pay for waste disposal in the area while household size has a negative and statistically significant relationship with households’ willingness to pay. Based on these findings, it was recommended that more waste management services be made readily available to residents of Minna, waste collection service should be privatised to increase their effectiveness through increased competition and also that community participatory approach be used to create more environmental awareness amongst residents.

Keywords: household, solid waste, management, WTP

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Authors: Yutong Wan, John N. Wood

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Introduction: SCN9A encoded Nav1.7 is an ideal therapeutic target with minimal side effects for the pharmaceutical industry because SCN9A variants can cause both human gains of function pain-related mutations and loss of function pain-free mutations. This study reviews the clinical effectiveness of existing Nav1.7 inhibitors, which theoretically should be powerful analgesics. Methods: A systematic review is conducted on the effectiveness of current Nav1.7 blockers undergoing clinical trials. Studies were mainly extracted from PubMed, U.S. National Library of Medicine Clinical Trials, World Health Organization International Clinical Trials Registry, ISRCTN registry platform, and Integrated Research Approval System by NHS. Only studies with full text available and those conducted using double-blinded, placebo controlled, and randomised designs and reporting at least one analgesic measurement were included. Results: Overall, 61 trials were screened, and eight studies covering PF 05089771 (Pfizer), TV 45070 (Teva & Xenon), and BIIB074 (Biogen) met the inclusion criteria. Most studies were excluded because results were not published. All three compounds demonstrated insignificant analgesic effects, and the comparison between PF 05089771 and pregabalin/ibuprofen showed that PF 05089771 was a much weaker analgesic. All three drug candidates only have mild side effects, indicating the potentials for further investigation of Nav1.7 antagonists. Discussion: The failure of current Nav1.7 small molecule inhibitors might attribute to ignorance of the key role of endogenous systems in Nav1.7 null mutants, the lack of selectivity and blocking potency, and central impermeability. The synergistic combination of analgesic drugs, a recent UCL patent, combining a small dose of Nav1.7 blockers and opioids or enkephalinase inhibitors dramatically enhanced the analgesic effects. Conclusion: The current clinical testing Nav1.7 blockers are generally disappointing. However, the newer generation of Nav1.7 targeting analgesics has overcome the major constraints of its predecessors.

Keywords: chronic pain, Nav1.7 blockers, SCN9A, systematic review

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