Search results for: nutrition therapy guide

Authors: Rachel Byrne

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Background: Due to patient and student safety concerns, combined with clinical teachers being redeployed to clinical practice, COVID-19 has resulted in a reduction in face-to-face teaching sessions for medical students. Traditionally such sessions are particularly important for final year medical students, especially in preparing for their final practical exams. A reduced student presence on the wards has also resulted in fewer opportunities for junior doctors to provide teaching sessions. This has implications for junior doctors achieving their own curriculum outcomes for teaching, as well as potentially hindering the development of a future interest in medical education. Aims: The aims of the study are 1) To create a safe face-to-face teaching environment during COVID-19 which focussed on exam preparation for final year medical students, 2) To provide a platform for doctors to gain teaching experience, 3 ) to enable doctors to gain feedback or assessments on their teaching, 4) To create beginners guide to designing a new teaching program for future junior doctors. Methods: We created a program of timed clinical stations consisting of four sessions every five weeks during the student’s medicine attachment. Each session could be attended by 6 students and consisted of 6 stations ran by junior doctors, with each station following social distancing and personal protective equipment requirements. Junior doctors were asked to design their own stations. The sessions ran out-of-hours on weekday evenings and were optional for the students. Results: 95/95 students and 20/40 doctors involved in the programme completed feedback. 100% (n=95) of students strongly agreed/agreed that sessions were aimed at an appropriate level and provided constructive feedback. 100% (n=95) of students stated they felt more confident in their abilities and would recommend the session to peers. 90% (n=18) of the teachers strongly agreed/agreed that they felt more confident in their teaching abilities and that the sessions had improved their own medical knowledge. 85% (n=17) of doctors had a teaching assessment completed, and 83% (n=16) said the program had made them consider a career in medical education. The difficulties of creating such a program were highlighted throughout, and a beginner’s guide was created with the hopes of helping future doctors who are interested in teaching address the common obstacles.

Keywords: COVID-19, education, safety, medical

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Authors: Ziara Carmelli G. Tan, Irene Carmelle S. Tan

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Background: Trichotillomania (TTM) and Major Depressive Disorder (MDD) are two psychiatric conditions that frequently co-occur, presenting a significant challenge for treatment due to their complex interplay. TTM involves repetitive hair-pulling, leading to noticeable hair loss and distress, while MDD is characterized by persistent low mood and loss of interest or pleasure, leading to dysfunctionality. This case report examines the intricate relationship between TTM and MDD in a young adult female, emphasizing the need for a comprehensive, multifaceted therapeutic approach to address both disorders effectively. Case Presentation: The patient is a 21-year-old female college student and youth church leader who presented with chronic hair-pulling and depressive symptoms. Her premorbid personality was marked by low self-esteem and a strong need for external validation. Despite her academic and social responsibilities and achievements, she struggled with managing her emotional distress, which was exacerbated by her family dynamics and her role within her church community. Her hair-pulling and mood symptoms were particularly triggered by self-esteem threats and feelings of inadequacy. She was diagnosed with Trichotillomania, Scalp and Major Depressive Disorder. Intervention/Management: The patient’s treatment plan was comprehensive, incorporating both pharmacological and non-pharmacological interventions. Initial pharmacologic management was Fluoxetine 20mg/day up, titrated to 40mg/day with no improvement; hence, shifted to Escitalopram 20mg/day and started with N-acetylcysteine 600mg/day with noted significant improvement in symptoms. Psychotherapeutic strategies played a crucial role in her treatment. These included supportive-expressive psychodynamic psychotherapy, which helped her explore and understand underlying emotional conflicts. Cognitive-behavioral techniques were employed to modify her maladaptive thoughts and behaviors. Grief processing was integrated to help her cope with significant losses. Family therapy was done to address conflicts and collaborate with the treatment process. Psychoeducation was provided to enhance her understanding of her condition and to empower her in her treatment journey. A suicide safety plan was developed to ensure her safety during critical periods. An interprofessional approach, which involved coordination with the Dermatology service for co-management, was also a key component of her treatment. Outcome: Over the course of 15 therapy sessions, the patient demonstrated significant improvement in both her depressive symptoms and hair-pulling behavior. Her active engagement in therapy, combined with pharmacological support, facilitated better emotional regulation and a more cohesive sense of self. Her adherence to the treatment plan, along with the collaborative efforts of the interprofessional team, contributed to her positive outcomes. Discussion: This case underscores the significance of addressing both TTM and its comorbid conditions to achieve effective treatment outcomes. The intricate interplay between TTM and MDD in the patient’s case highlights the importance of a comprehensive treatment plan that includes both pharmacological and psychotherapeutic approaches. Supportive-expressive psychodynamic psychotherapy, Cognitive-behavioral techniques, and Family therapy were particularly beneficial in addressing the complex emotional and behavioral aspects of her condition. The involvement of an interprofessional team, including dermatology co-management, was crucial in providing holistic care. Future practice should consider the benefits of such a multidisciplinary approach to managing complex cases like this, ensuring that both the psychological and physiological aspects of the disorders are adequately addressed.

Keywords: cognitive-behavioral therapy, interprofessional approach, major depressive disorder, psychodynamic psychotherapy, trichotillomania

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Authors: Rafaella Nogaroli

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It is presented hypothetical cases in the context of AI algorithms to support clinical decisions, in order to discuss the importance of doctors to respect AI ethical principles. Regarding the principle of transparency and explanation, there is an impact on the new model of patient consent and on the understanding of qualified information. Besides, the human control of technology (AI as a tool) should guide the physician's activity; otherwise, he breaks the patient's legitimate expectation in a specific result, with the consequent transformation of the medical obligation nature.

Keywords: medical law, artificial intelligence, ethical principles, patient´s informed consent, medical obligations

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Authors: Priyanka Patil, Logan Manikam

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Background: The first 1000 days of life are a critical window and can result in adverse health consequences due to inadequate nutrition. South-Asian (SA) communities face significant health disparities, particularly in maternal and child health. Community-based interventions, often employing Participatory-Learning and Action (PLA) approaches, have effectively addressed health inequalities in lower-income nations. The aim of this study was to assess the feasibility of implementing a PLA intervention to improve infant feeding and care practices in SA communities living in London. Methods: Comprehensive analyses were conducted to assess the feasibility/fidelity of this pilot randomized controlled trial. Summary statistics were computed to compare key metrics, including participant consent rates, attendance, retention, intervention support, and perceived effectiveness, against predefined progression rules guiding toward a definitive trial. Secondary outcomes were analyzed, drawing insights from multiple sources, such as The Children’s-Eating-Behaviour Questionnaire (CEBQ), Parental-Feeding-Style Questionnaires (PFSQ), Food-diary, and the Equality-Impact-Assessment (EIA) tool. A video analysis of children's mealtime behavior trends was conducted. Feedback interviews were collected from study participants. Results: Process-outcome measures met predefined progression rules for a definitive trial, which deemed the intervention as feasible and acceptable. The secondary outcomes analysis revealed no significant changes in children's BMI z-scores. This could be attributed to the abbreviated follow-up period of 6 months, reduced from 12 months, due to COVID-19-related delays. CEBQ analysis showed increased food responsiveness, along with decreased emotional over/undereating. A similar trend was observed in PFSQ. The EIA tool found no potential discrimination areas, and video analysis revealed a decrease in force-feeding practices. Participant feedback revealed improved awareness and knowledge sharing. Conclusion: This study demonstrates that a co-adapted PLA intervention is feasible and well-received in optimizing infant-care practices among South-Asian community members in a high-income country. These findings highlight the potential of community-based interventions to enhance health outcomes, promoting health equity.

Keywords: child health, childhood obesity, community-based, infant nutrition

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Authors: Vanlounni Sibounheuang, Wanarat Anusornsangiam, Pattarin Kittiboonyakun, Chanthanom Manithip

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In worldwide, one of the most common use of oral anticoagulant is warfarin. Its margin between therapeutic inhibition of clot formation and bleeding complications is narrow. Mahosot Hospital, warfarin clinic had not been established yet. The descriptive study was conducted by investigating drug-related problems of outpatients using warfarin, the value of the international normalized ratio (INR) higher than normal ranges (25.40 % of the total 272 outpatients) were mostly identified at Lao-Luxembourg Heart Centre, Mahosot Hospital, Lao PDR. This result led to the present study conducting qualitative interviews in order to help establish a warfarin clinic at Mahosot Hospital for the better outcomes of patients using warfarin. The purpose of this study was to explore perspectives of healthcare professional providing services for outpatients using warfarin. The face to face, in-depth interviews were undertaken among nine healthcare professionals (doctor=3, nurse=3, pharmacist=3) working at out-patient clinic, Lao-Luxembourg Heart Centre, Mahosot Hospital, Lao PDR. The interview guides were developed, and they were validated by the experts in the fields of qualitative research. Each interview lasted approximately 20 minutes. Three major themes emerged; healthcare professional’s experiences of current practice problems with warfarin therapy, healthcare professionals’ views of medical problems related to patients using warfarin, and healthcare professionals’ perspectives on ways of service improvement. All healthcare professionals had the same views that it’s difficult to achieve INR goal for individual patients because of some important patient barriers especially lack of knowledge about to use warfarin properly and safety, patients not regularly follow-up due to problems with transportations and financial support. Doctors and nurses agreed to have a pharmacist running a routine warfarin clinic and provided counselling to individual patients on the following points: how to take drug properly and safety, drug-drug and food-drug interactions, common side effects and how to manage them, lifestyle modifications. From the interviews, some important components of the establishment of a warfarin clinic included financial support, increased human resources, improved the system of keeping patients’ medical records, short course training for pharmacists. This study indicated the acceptance of healthcare professionals on the important roles of pharmacists and the feasibility of setting up warfarin clinic by working together with the multidisciplinary health care team in order to help improve health outcomes of patients using warfarin at Mahosot Hospital, Lao PDR.

Keywords: perspectives, healthcare professional, warfarin therapy, Mahosot Hospital

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Authors: Mary Therese G. Caluna, Mark Justin B. Campanero, Erlin Maris T. Cantiller, Claudine Mae A. Cantillo, Nerissa L. Caño

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Objective: The study determined the effectiveness of cold tomato paste in relieving pain caused by exacerbation of arthritis in the elderly, specifically on clients 60 years old and above. The study focused on alternative, cost-effective and non-pharmacological techniques in relieving pain experienced by the older people with osteoarthritis and rheumatoid arthritis. Methods: Using purposive non-probability sampling, the researchers gathered a total number of 40 subjects that passed the inclusion criteria provided by the researchers. The subjects were divided into two groups, experimental group (20 subjects) and control groups (20 subjects). The Numeric Rating 11-point Scale (NRS-11) was utilized to assess the pain level of the subject prior the application of the treatment and after the application of the treatment. Key findings: There is a significant difference in the pain levels of the experimental group before and after the application of cold tomato paste. This indicates that that the application of cold tomato paste alleviates the pain experienced by elderly clients with exacerbation of arthritis. Conclusion: The effectiveness of cold tomato paste in relieving pain experienced by elderly clients who are in exacerbation of arthritis was proven to be evidence-based. The cold tomato paste application has significant impact in the field of nursing and therefore, can be used in both clinical trials and practices. The effectiveness of cold tomato application promotes innovation in the field of nursing, thus encouraging further researches regarding other uses of tomato and other herbal interventions to relieve the pain caused by osteoarthritis and rheumatoid arthritis.

Keywords: alternative therapy, arthritis, cold tomato paste, elderly clients, exacerbation

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Authors: Jinny Hong, Jeanne C. Watson

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Three types of autobiographical memory recall -specific, episodic, and generic- were examined in relation to the quality of descriptions and in-session levels of emotional arousal. Correlational analyses and general estimating equation were conducted to test the relationships between 1) quality of descriptions and type of memory, 2) type of memory and emotional arousal, and 3) quality of descriptions and emotional arousal. The data was transcripts drawn from an archival randomized-control study comparing cognitive-behavioral therapy and emotion-focused therapy in a 16-week treatment for depression. Autobiographical memory recall segments were identified and sorted into three categories: specific, episodic, and generic. Quality of descriptions of these segments was then operationalized and measured using the Referential Activity Scale, and each memory segment was rated on four dimensions: concreteness, specificity, clarity, and overall imagery. Clients’ level of emotional arousal for each recall was measured using the Client’s Expression Emotion Scale. Contrary to the predictions, generic memories are associated with higher emotional arousal ratings and descriptive language ratings compared to specific memories. However, a positive relationship emerged between the quality of descriptions and expressed emotional arousal, indicating that the quality of descriptions in which memories are described in sessions is more important than the type of memory recalled in predicting clients’ level of emotional arousal. The results from this study provide a clearer understanding of the role of memory recall types and use of language in activating emotional arousal in psychotherapy sessions in a depressed sample.

Keywords: autobiographical memory recall, emotional arousal, psychotherapy for depression, quality of descriptions, referential activity

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Authors: Wissam Aljundi, Loay Daas, Yaser Abu Dail, Barbara Käsmann-Kellner, Berthold Seitz, Alaa Din Abdin

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Purpose: To investigate the effectiveness of nonsteroidal anti-inflammatory eye drops (NSAIDs) combined with oral acetazolamide for postoperative macular edema (PME) after uncomplicated phacoemulsification (PE) and to identify predictors of non-response. Methods: We analyzed data of uncomplicated PE and identified eyes with PME. First-line therapy included topical NSAIDs combined with oral acetazolamide. In case of non-response, triamcinolone was administered subtenonally. Outcome measures included best-corrected visual acuity (BCVA) and central macular thickness (CMT). Results: 94 eyes out of 9750 uncomplicated PE developed PME, of which 60 eyes were included. Follow-ups occurred 6.4±1.8, 12.5±3.7, and 18.6±6.0 weeks after diagnosis. BCVA and CMT improved significantly in all follow-ups. 40 eyes showed response to first-line therapy at first follow-up (G1). The remaining 20 eyes showed no response and required subtenon triamcinolone (G2), of which 11 eyes showed complete regression at the second follow-up and 4 eyes at the third follow-up. 5 eyes showed no response and required intravitreal injection. Multivariate linear regression model showed that diabetes mellitus (DM) and increased cumulative dissipated energy (CDE) are predictors of non-response. Conclusion: Topical NSAIDs with acetazolamide resulted in complete regression of PME in 67% of all cases. DM and increased CDE might be considered as predictors of nonresponse to this treatment.

Keywords: postoperative macular edema, intravitreal injection, cumulative energy, irvine gass syndrome, pseudophakie

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Authors: F. Moghtaderi, M. Burke, J. Troelsen

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There has been a significant decline in active travel as well as the massive increase use of car-dependent travel mode in many countries during past two decades. Evidential risks for people’s physical and mental health problems are followed by this increased use of motorized travel mode. These problems range from overweight and obesity to increasing air pollution. In response to these rising concerns, local councils and other interested organizations around the world have introduced a variety of initiatives regarding reduce the dominance of cars for the daily journeys. However, the nature of these kinds of interventions, which related to the human behavior, make lots of complexities. People’s travel behavior and changing this behavior, has two different aspects. People’s attitudes and perceptions toward the sustainable and healthy modes of travel, and motorized travel modes (especially private car use) is one these two aspects. The other one related to people’s behavior change processes. There are no comprehensive model in order to guide policy interventions to increase the level of succeed of such interventions. A comprehensive theoretical framework is required in accordance to facilitate and guide the processes of data collection and analysis to achieve the best possible guidelines for policy makers. Regarding this gaps in the travel behavior change research, this paper attempted to identify and suggest a multidimensional framework in order to facilitate planning interventions. A structured mixed-method is suggested regarding the expand the scope and improve the analytic power of the result according to the complexity of human behavior. In order to recognize people’s attitudes, a theory with the focus on people’s attitudes towards a particular travel behavior was needed. The literature around the theory of planned behavior (TPB) was the most useful, and had been proven to be a good predictor of behavior change. Another aspect of the research, related to the people’s decision-making process regarding explore guidelines for the further interventions. Therefore, a theory was needed to facilitate and direct the interventions’ design. The concept of the transtheoretical model of behavior change (TTM) was used regarding reach a set of useful guidelines for the further interventions with the aim to increase active travel and sustainable modes of travel. Consequently, a combination of these two theories (TTM and TPB) had presented as an appropriate concept to identify and design implemented travel behavior change interventions.

Keywords: behavior change theories, theoretical framework, travel behavior change interventions, urban research

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Authors: Gayani Ranawake

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Effective communication is widely regarded as an important aspect of any discipline. This particular study deals with written communication in science. Writing conventions and linguistic choices play a key role in conveying the message effectively to a target audience. Scientists are responsible for conveying their findings or research results not only to their discourse community but also to the general public. Recognizing appropriate linguistic choices is crucial since they vary depending on the target audience. The majority of scientists can communicate effectively with their discourse community, but public engagement seems more challenging to them. There is a lack of research into the language use of scientists, and in particular how it varies by discipline and audience (genre). A better understanding of the different linguistic conventions used in effective science writing by scientists for scientists and by scientists for the public will help to guide scientists who are familiar with their discourse community norms to write effectively for the public. This study investigates the differences and similarities of linguistic choices in biology articles written by scientists for their discourse community and biology magazine articles written by scientists and science communicators for the general public. This study is a part of a larger project investigating linguistic differences in different genres of science academic writing. The sample for this particular study is composed of 20 research articles from the journal Biological Reviews and 20 magazine articles from the magazine Australian Popular Science. Differences in the linguistic devices were analyzed using Hyland’s metadiscourse model for academic writing proposed in 2005. The frequency of the usage of interactive resources (transitions, frame markers, endophoric markers, evidentials and code glosses) and interactional resources (hedges, boosters, attitude markers, self-mentions and engagement markers) were compared and contrasted using the NVivo textual analysis tool. The results clearly show the differences in the frequency of usage of interactional and interactive resources in the two disciplines under investigation. The findings of this study provide a reference guide for scientists and science writers to understand the differences in the linguistic choices between the two genres. This will be particularly helpful for scientists who are proficient at writing for their discourse community, but not for the public.

Keywords: discourse analysis, linguistic choices, metadiscourse, science writing

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Authors: Huang Chiung Chiu

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This article is about the nursing experience of assisting an outpatient with premature menopause, osteoporosis and sarcopenia through a multi-discipline care model. The nursing period is from September 22nd, 2020, to December 7th, 2020, collecting data through interviews with the patient, observation, and physical assessment. It was found that the main health problems were insufficient nutrition, less physical need, insomnia, and potentially dangerous falls. As an outpatient nurse, the author observed that in recent years, the age group of women with premature menopause, osteoporosis and sarcopenia had shifted downward. Integrated multi-disciplinary interventions were provided upon the initial diagnosis of osteoporosis and sarcopenia. Under the outpatient care setting, the collaborative team works between the doctors, nutritionists, osteoporosis educators, rehabilitates, physical therapists and other specialized teams were applied to provide individualized, integrated multi-disciplinary care. Through empathy and the establishment of attentive care, companionship and trust, we discussed care plans and treatment guidelines with the case, providing accurate, complete disease information and feedback education to strengthen the patient’s knowledge and motivation for exercise. Nursing guidance regarding the dietary nutrition and adjustment of daily routine was provided to increase the self-care ability, improve the health problems of muscle weakness and insomnia, and prevent falls. For patients with postmenopausal osteoporosis and sarcopenia, it is recommended that the nurses coordinate the multi-discipline integrated care model, adjust patients’ lifestyle and diet, and establish a regular exercise plan so that the cases can be evaluated holistically to improve the quality of care and physical and mental comfort.

Keywords: multi-discipline care model, premature menopause, osteoporosis, sarcopenia, insomnia

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Authors: Silas Webb, Joseph Hartland

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Background: Long-term retention of patients on ART has become a major health challenge in Sub-Saharan Africa (SSA). In 2010 a systematic review of 39 papers found that 30% of patients were no longer taking their ARTs two years after starting treatment. In the same review, it was noted that there was a paucity of data as to why patients become lost to follow-up (LTFU) in SSA. This project was performed in Mulanje Mission Hospital in Malawi as part of Swindon Academy’s Global Health eSSC. The HIV prevalence for Malawi is 10.3%, one of the highest rates in the world, however prevalence soars to 18% in the Mulanje. Therefore it is essential that patients at risk of being LTFU are identified early and managed appropriately to help them continue to participate in the service. Methodology: All patients on adult antiretroviral formulations at MMH, who were classified as ‘defaulters’ (patients missing a scheduled follow up visit by more than two months) over the last 12 months were included in the study. Demographic varibales were collected from Mastercards for data analysis. A comparison group of patients currently not lost to follow up was created by using all of the patients who attended the HIV clinic between 18th-22nd July 2016 who had never defaulted from ART. Data was analysed using the chi squared (χ²) test, as data collected was categorical, with alpha levels set at 0.05. Results: Overall, 136 patients had defaulted from ART over the past 12 months at MMH. Of these, 43 patients had missing Mastercards, so 93 defaulter datasets were analysed. In the comparison group 93 datasets were also analysed and statistical analysis done using Chi-Squared testing. A higher proportion of men in the defaulting group was noted (χ²=0.034) and defaulters tended to be younger (χ²=0.052). 94.6% of patients who defaulted were taking Tenofovir, Lamivudine and Efavirenz, the standard first line ART therapy in Malawi. The mean length of time on ART was 39.0 months (RR: -22.4-100.4) in the defaulters group and 47.3 months (RR: -19.71-114.23) in the control group, with a mean difference of 8.3 less months in the defaulters group (χ ²=0.056). Discussion: The findings in this study echo the literature, however this review expands on that and shows the demographic for the patient at most risk of defaulting and being LTFU would be: a young male who has missed more than 4 doses of ART and is within his first year of treatment. For the hospital, this data is important at it identifies significant areas for public health focus. For instance, fear of disclosure and stigma may be disproportionately affecting younger men, so interventions can be aimed specifically at them to improve their health outcomes. The mean length of time on medication was 8.3 months less in the defaulters group, with a p-value of 0.056, emphasising the need for more intensive follow-up in the early stages of treatment, when patients are at the highest risk of defaulting.

Keywords: anti-retroviral therapy, ART, HIV, lost to follow up, Malawi

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Authors: Yasmin M. Attia, Hanan S. El-Abhar, Mahmoud M. Al Marzabani, Samia A. Shouman

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Background: Tamoxifen (TAM) is the most commonly used hormone therapy for the treatment of early and metastatic breast cancer. Although it significantly decreases the tumor recurrence rate and provides an overall benefit, as much as 20–30% of women still relapse during or after long-term therapy. 3-Bromopyruvate (3-BP) is a promising agent with impressive antitumor effects in several models of animal tumors and cell lines. Aim: This study was designed to investigate the combined effect of (TAM) and (3-BP) in breast cancer cells and to explore their molecular interaction via assessment of apoptotic, angiogenic, and metastatic markers. Methods: In vitro cytotoxicity study was carried out for both compounds to determine the combination regimen producing a synergistic effect and mechanistic pathways were studied using RT-PCR and western techniques. Moreover, the anti-oncolytic and anti-angiogenic potentials were assessed in mice bearing solid Ehrlich carcinoma (SEC). Results: The combined treatment significantly increased the expressions and protein levels of caspase 7, 9, and 3 and decreased of angiogenic markers VEGF, HIF-1α, and HK2 compared to cells treated with either drug individually. However, there were no significant changes in MMP-2 and MMP-9 protein levels. Interestingly, the in vivo results supported the in vitro findings; there was a decrease in the tumor volume and VEFG using immunohistochemistry in the combination-treated groups compared to either TAM or 3-BP treated one. Conclusion: 3-BP synergizes the cytotoxic effect of TAM by increasing apoptosis and decreasing angiogenesis which makes this combination a promising regimen to be applied clinically.

Keywords: tamoxifen, 3-bromopyruvate, breast cancer, cytotoxicity, angiogenesis

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Authors: David Lindström

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We evaluate the performance of a numerical method for global optimization of expensive functions. The method is using a response surface to guide the search for the global optimum. This metamodel could be based on radial basis functions, kriging, or a combination of different models. We discuss how to set the cycling parameters of the optimization method to get a balance between local and global search. We also discuss the eventual problem with Runge oscillations in the response surface.

Keywords: expensive function, infill sampling criterion, kriging, global optimization, response surface, Runge phenomenon

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Authors: Latif Apaassongo Ibrahim, Owusu-Addo Ebenezer, Isaac Bonuedo

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Structural barriers - including inadequate infrastructure, poor market linkages, and limited access to financial and extension services - have been the major constraints to improved welfare in the semi-arid regions of Ghana; food insecurity and malnutrition are persistent. The effects of infrastructural improvements as countermeasures are often misdirected by confounding effects of other economic, social, and environmental variables. This study applies Directed Acyclic Graphs (DAGs) to map the causal pathways between infrastructure development and household welfare, identifying key mediators and confounders for one such initiative in Ghana. Then, using Generalized Propensity Score (GPS) and Doubly Robust Estimation (IPWRA), this study evaluates the differential roles of government-supported infrastructure improvements in access and intensity of commercial relative to public infrastructure, on household food security and women’s nutritional diversity given three major value-chain improvements. The main findings suggest that these infrastructure improvements positively impact food security and nutrition, with women’s empowerment and nutritional education acting as key mediators. Market access emerged as a stronger causal mechanism relative to productivity gains in linking infrastructure to improved welfare. Membership in Farmer-Based Organizations (FBOs) and participation in agribusiness linkages further amplified these impacts. However, the effects of infrastructure improvements were less clear when combined with the adoption of climate resilience practices, suggesting potential trade-offs.

Keywords: food security, nutrition, infrastructure, market access, women's empowerment, farmer-based organizations, climate resilience, Ghana

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Authors: S. A. N. Rashani, S. Pigera, P. N. J. Fernando, S. Jayawickema, M. A. Niriella, A. P. De Silva

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Dietary supplement (DS) consumption is drastically trending among the young athlete generation in developing countries. Many athletes try to fulfill their nutrition requirements using dietary supplements without knowing their effects on health and performance. This study aimed to assess the DS usage patterns of university athletes in Sri Lanka. A self-administered questionnaire was employed to collect data from state university students representing a university team, and a sample of 200 respondents was selected based on a stratified random sampling technique. Incomplete questionnaires were omitted from the analysis. The data were analyzed using IBM SPSS statistics for Windows version 25. The level of significance was set at p<0.05 in the data analysis. The prevalence of DS was 48.2% (n= 94), with no significant association between gender and DS intake. Protein (15.9%), vitamin (14.9%), sports drinks (12.8%), and creatine (8.2%) were the most consumed DS by students. Weightlifting (85.0%), football (62.5%), rugby (57.7%), and wrestling (40.9%) players showed higher DS usage among other sports. Coaches were reported as the most frequent person who was advised to use DS (43.0%). Students who won interuniversity games showed significantly low DS intake (p = 0.002) compared to others. Interestingly, DS use was significantly affected by the season of use (p = 0.000), pointing out that during competition and training seasons (62.4%) was the most frequent use. The pharmacy (27.0%) was the commonest place to buy DS. Students who used nutrient-dense meal plans during the training and competition period still showed a 61.0% tendency to consume DS. Most claimed reason to use DS was to increase energy and strength (29.0%). A majority reported that they used DS for less than one month (35.5%), while the second-highest duration was over three years (17.2%). Considering body mass index (BMI), healthy weight students showed 71.0% DS prevalence. DS prevalence was moderate among Sri Lankan university students, highlighting that the highest DS use was during competition and training seasons. Moreover, it emphasizes the need for nutrition and anti-doping counseling in the Sri Lankan university system.

Keywords: athlete, dietary, supplements, university

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Authors: Gordon Weight, Hermione Tsoi, Patrick Cutinha, Sanjay Rajpal

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Aim: Greenlight-laser prostatectomy (GLLP) is becoming a popular treatment option for bladder outlet obstruction and lower urinary tract symptoms (LUTS). In this retrospective study, we aim to explore the patient selection, perioperative morbidity, and functional outcomes of GLLP. Methods: Patients who underwent GLLP at a UK tertiary centre between June 2018 and November 2021 were included in this study. Retrospective data covering patient demographics, perioperative parameters and postoperative outcomes were collected using the electronic records systems. Results: 305 patients were included in this study with a mean age of 73 (range 30-90) years. The most common indication (62.6%) for the procedure was patient’s wish to be free from long-term catheters (LTC) or intermittent catheterisation (ISC), followed by failed medical therapy for LUTS (36.4%). 84.6% of patients had an ASA ≥2, and 32.1% took anticoagulant or antiplatelet therapy. Inpatient stays were minimal, with the majority (68.2%) of patients were performed as day case, and only 10.5% of patients requiring more than a single night admission. The 3-month readmission rate was 10.8%, with the most common causes being haematuria and urinary-tract infection. The successful TWOC rate at follow up was 91.2%. Amongst the 19 patients who failed TWOC, 14 had LTC prior to the procedure and 4 had been performing ISC. Conclusions: Our study shows that GLLP is a safe and effective day case treatment and can be suitable for elderly and comorbid patients. Patients requiring LTC or ISC pre-operatively should be counselled carefully about the risk of not being catheter-free post procedure.

Keywords: urology, endourology, prostate, bladder outlet obstruction, laser

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Authors: Khadeeja Munawar, Shamsul Haque

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The claim that traumatic events influence the recalled memories and mental health has received mixed empirical support. This study examines the memories of a sample drawn from Pakistan, a country that has witnessed many life-changing socio-political events, wars, and natural disasters in 72 years of its history. A sample of 210 senior citizens (Mage = 64.35, SD = 6.33) was recruited from Pakistan. The aim was to investigate if participants retrieved more memories related to past traumatic events using a word-cueing technique. Each participant reported ten memories to ten neutral cue words. The results revealed that past traumatic events were not adversely affecting the memories and mental health of participants. When memories were plotted with respect to the ages at which the events happened, a pronounced bump at 11-20 years of age was seen. Memories within as well as outside of the bump were mostly positive. The multilevel logistic regression modelling showed that the memories recalled were personally important and played a role in enhancing resilience. The findings revealed that despite facing an array of ethnic, religious, political, economic, and social conflicts, the participants were resilient, recalled predominantly positive memories, and had intact mental health. The findings have clinical implications in Cognitive Behavioral Therapy (CBT). The patients can be made aware of their negative emotions, troublesome/traumatic memories, and the distorted thinking patterns and their memories can be restructured. The findings can also be used to teach Memory Specificity Training (MEST) by psycho-educating the patients around changes in memory functioning and enhancing the recall of memories, which are more specific, vivid, and filled with sensory details.

Keywords: cognitive behavioral therapy, memories, mental health, resilience, trauma

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Authors: Vadim A. Kuznetsov, Anna M. Soldatova, Tatyana N. Enina, Elena A. Gorbatenko, Dmitrii V. Krinochkin

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The aim of the study was to evaluate potential parameters related with super-response to CRT. Methods: 60 CRT patients (mean age 54.3 ± 9.8 years; 80% men) with congestive heart failure (CHF) II-IV NYHA functional class, left ventricular ejection fraction < 35% were enrolled. At baseline, 1 month, 3 months and each 6 months after implantation clinical, electrocardiographic and echocardiographic parameters, NT-proBNP level were evaluated. According to the best decrease of left ventricular end-systolic volume (LVESV) (mean follow-up period 33.7 ± 15.1 months) patients were classified as super-responders (SR) (n=28; reduction in LVESV ≥ 30%) and non-SR (n=32; reduction in LVESV < 30%). Results: At baseline groups differed in age (58.1 ± 5.8 years in SR vs 50.8 ± 11.4 years in non-SR; p=0.003), gender (female gender 32.1% vs 9.4% respectively; p=0.028), width of QRS complex (157.6 ± 40.6 ms in SR vs 137.6 ± 33.9 ms in non-SR; p=0.044). Percentage of LBBB was equal between groups (75% in SR vs 59.4% in non-SR; p=0.274). All parameters of mechanical dyssynchrony were higher in SR, but only difference in left ventricular pre-ejection period (LVPEP) was statistically significant (153.0 ± 35.9 ms vs. 129.3 ± 28.7 ms p=0.032). NT-proBNP level was lower in SR (1581 ± 1369 pg/ml vs 3024 ± 2431 pg/ml; p=0.006). The survival rates were 100% in SR and 90.6% in non-SR (log-rank test P=0.002). Multiple logistic regression analysis showed that LVPEP (HR 1.024; 95% CI 1.004–1.044; P = 0.017), baseline NT-proBNP level (HR 0.628; 95% CI 0.414–0.953; P=0.029) and age at baseline (HR 1.094; 95% CI 1.009-1.168; P=0.30) were independent predictors for CRT super-response. ROC curve analysis demonstrated sensitivity 71.9% and specificity 82.1% (AUC=0.827; p < 0.001) of this model in prediction of super-response to CRT. Conclusion: Super-response to CRT is associated with better survival in long-term period. Presence of LBBB was not associated with super-response. LVPEP, NT-proBNP level, and age at baseline can be used as independent predictors of CRT super-response.

Keywords: cardiac resynchronisation therapy, superresponse, congestive heart failure, left bundle branch block

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Authors: Alina M. Udall, Judith de Groot, Simon de Jong, Avi Shankar

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There are many ways in which environmentally significant behavior can be explained. Dominant psychological theories, namely, the theory of planned behavior, the norm-activation theory, its extension, the value-belief-norm theory, and the theory of habit do not explain large parts of environmentally significant behaviors. A new and rapidly growing approach is to focus on how consumer’s identities predict environmentally significant behavior. Identity may be relevant because consumers have many identities that are assumed to guide their behavior. Therefore, we assume that many identities will guide environmentally significant behavior. Many identities can be relevant for environmentally significant behavior. In reviewing the literature, over 200 identities have been studied making it difficult to establish the key identities for explaining environmentally significant behavior. Therefore, this paper first aims to establish the key identities previously used for explaining environmentally significant behavior. Second, the aim is to test which key identities explain environmentally significant behavior. To address the aims, an online survey study (n = 578) is conducted. First, the exploratory factor analysis reveals 15 identity factors. The identity factors are namely, environmentally concerned identity, anti-environmental self-identity, environmental place identity, connectedness with nature identity, green space visitor identity, active ethical identity, carbon off-setter identity, thoughtful self-identity, close community identity, anti-carbon off-setter identity, environmental group member identity, national identity, identification with developed countries, cyclist identity, and thoughtful organisation identity. Furthermore, to help researchers understand and operationalize the identities, the article provides theoretical definitions for each of the identities, in line with identity theory, social identity theory, and place identity theory. Second, the hierarchical regression shows only 10 factors significantly uniquely explain the variance in environmentally significant behavior. In order of predictive power the identities are namely, environmentally concerned identity, anti-environmental self-identity, thoughtful self-identity, environmental group member identity, anti-carbon off-setter identity, carbon off-setter identity, connectedness with nature identity, national identity, and green space visitor identity. The identities explain over 60% of the variance in environmentally significant behavior, a large effect size. Based on this finding, the article reveals a new, theoretical framework showing the key identities explaining environmentally significant behavior, to help improve and align the field.

Keywords: environmentally significant behavior, factor analysis, place identity, social identity

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Authors: Larissa Burruano, Sergey Grabovyj, Irina Nguen

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The study aimed to assess the level of adherence to anti retroviral therapy (ART) and to examine the relationship between adherence and risk behavior factor (drug use) among patients infected with HIV. The patients with newly diagnosed or established HIV infection under follow-up at the Sumskij Regional Centre for AIDS Prevention in Ukraine were eligible for this study. Medical records were used to measure the patient’s adherence to medication. Measurements were obtained at month 6 and at month 12 to calculate the number of medication omission during the past 30 days: (on a 2-point scale – once until three in a month – were considered adherent, three and more in a month – were considered non-adherent). Of the 50 study participants, 27 (54.0%) were men and 23 (46.0%) women. The mean age is 35.2 years (SD= 5.1). A majority of the patients (82.0%) is in the age group of 25-30 years. The main level of adherence was 74.0% and 66.0% at 6 and 12 months, respectively. The main routes of HIV transmission were drug injection among men 12 (44.4%) and sexual contact among women 11 (47.8%). Univariate analyses indicated that patients who had lower level of education were more likely to have been non-adherent at month 6- (X2 =5.1, n=50, p < .05) and at month 12 (X2 = 4.34, n=50, p < .05). Multivariate tests showed that only age (OR= 1.163 [95% CI 0.98–1.370]) was significant independent predictor of treatment adherence, while gender, education, employment status were not predictive for the risk of developing non-compliance. There was not a significant interaction between non-adherence and intravenous drug use. Consistent with these findings, younger people were more likely to have missed a dose of their medication because they had a greater sense of invulnerability than older patients. The study indicates that the socio demographic characteristic should be taken into an account in the future research regarding adherence in the case of HIV infection. If the patient anti retroviral adherence can be improved by qualitatively better medical care in all regions of the Ukraine, behavioral changes in the population can to be expected in the long term.

Keywords: HIV, antiretroviral therapy, adherence, Ukraine, Eastern Europe

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Authors: Dawei Cai

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In this paper, we present an autonomous guidance service by combining the position information from NFC and the orientation information from a 6 axis acceleration and terrestrial magnetism sensor. We developed an algorithm to calculate the device orientation based on the data from acceleration and terrestrial magnetism sensor. If visitors want to know some explanation about an exhibit in front of him, what he has to do is just lift up his mobile device. The identification program will automatically identify the status based on the information from NFC and MEMS, and start playing explanation content for him. This service may be convenient for old people or disables or children.

Keywords: NFC, ubiquitous computing, guide sysem, MEMS

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Authors: Khadija Rafi, Neha Jamil, Laiba Khalid, Meerub Nawaz, Mahwish Farooq

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Speech articulation is a complex process to produce intelligible sounds with the help of precise movements of various structures within the vocal tract. All these structures in the vocal tract are named as articulators, which comprise lips, teeth, tongue, and palate. These articulators work together to produce a range of distinct phonemes, which happen to be the basis of language. It starts with the airstream from the lungs passing through the trachea and into oral and nasal cavities. When the air passes through the mouth, the tongue and the muscles around it form such coordination it creates certain sounds. It can be seen when the tongue is placed in different positions- sometimes near the alveolar ridge, soft palate, roof of the mouth or the back of the teeth which end up creating unique qualities of each phoneme. We can articulate vowels with open vocal tracts, but the height and position of the tongue is different every time depending upon each vowel, while consonants can be pronounced when we create obstructions in the airflow. For instance, the alphabet ‘b’ is a plosive and can be produced only by briefly closing the lips. Articulation disorders can not only affect communication but can also be a hurdle in speech production. To improve articulation skills for such individuals, doctors often recommend speech therapy, which involves various kinds of exercises like jaw exercises and tongue twisters. However, this disorder is more common in children who are going through developmental articulation issues right after birth, but in adults, it can be caused by injury, neurological conditions, or other speech-related disorders. In short, speech articulation is an essential aspect of productive communication, which also includes coordination of the specific articulators to produce different intelligible sounds, which are a vital part of spoken language.

Keywords: linguistics, speech articulation, speech therapy, language learning

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Authors: Maya Jaber

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Climate change is one of the biggest challenges that require immediate attention and mitigation for the continued prosperity of human existence. The transformation will need to occur that is top-down and bottom-up on holistic scales. A new way of thinking will need to be adopted that is innovative, human-centric, and global. Designers and researchers are vital leaders in this movement that can help guide other practitioners in the strategy development, critical thinking process, and alignment of transformative solutions. Holistic critical thinking strategies will be essential to change behaviors and cultures for future generations' survival. This paper will discuss these topics associated with Dr. Jaber's research.

Keywords: environmental social governance (ESG), integral design thinking (IDT), organizational transformation, sustainability management

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Authors: B. Makoudi, R. Ghanimi, A. Bargaz, M. Mouradi, M. Farissi, A. Kabbaj, J. J. Drevon, C. Ghoulam

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Legume species are able to establish a nitrogen fixing symbiosis with soil rhizobia that allows them, when it operates normally, to ensure their necessary nitrogen nutrition. This biological process needs high phosphorus (P) supply and consequently it is limited under low phosphorus availability. To overcome this constraint, legume-rhizobia symbiosis develops many mechanisms to increase P availability in the rhizosphere and also the efficiency of P fertilizers. The objectives of our research works are to understand the physiological and biochemical mechanisms implemented by legume-rhizobia symbiosis to increase its P use efficiency (PUE) in order to select legume genotypes-rhizobia strains combination more performing for BNF under P deficiency. Our studies were carried out on two grain legume species, common bean (Phaseolus vulgaris) and faba bean (Vicia faba) tested in farmers’ fields and in experimental station fewer than two soil phosphorus levels. Under field conditions, the P deficiency caused a significant decrease of Plant and nodule biomasses in all of the tested varieties with a difference between them. This P limitation increased the contents of available P in the rhizospheric soils that was positively correlated with the increase of phosphatases activities in the nodules and the rhizospheric soil. Some legume genotypes showed a significant increase of their P use efficiency under P deficiency. The P solubilization test showed that some rhizobia strains isolated from Haouz region presented an important capacity to grow on solid and liquid media with tricalcium phosphate as the only P source and their P solubilizing activity was confirmed by the assay of the released P in the liquid medium. Also, this P solubilizing activity was correlated with medium acidification and the excretion of acid phosphatases and phytases in the medium. Thus, we concluded that medium acidification and excretion of phosphatases in the rhizosphere are the prominent reactions for legume-rhizobia symbiosis to improve its P nutrition.

Keywords: legume, phosphorus deficiency, rhizobia, rhizospheric soil

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Authors: Sree Bash Chandra Debnath, Didier Tonneau, Carole Fauquet, Agnes Tallet, Julien Darreon

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Purpose: Inorganic scintillating dosimetry is the most recent promising technique to solve several dosimetric issues and provide quality assurance in radiation therapy. Despite several advantages, the major issue of using scintillating detectors is the Cerenkov effect, typically induced in the visible emission range. In this context, the purpose of this research work is to evaluate the performance of a novel infrared inorganic scintillator detector (IR-ISD) in the radiation therapy treatment to ensure Cerenkov free signal and the best matches between the delivered and prescribed doses during treatment. Methods: A simple and small-scale infrared inorganic scintillating detector of 100 µm diameter with a sensitive scintillating volume of 2x10-6 mm3 was developed. A prototype of the dose verification system has been introduced based on PTIR1470/F (provided by Phosphor Technology®) material used in the proposed novel IR-ISD. The detector was tested on an Elekta LINAC system tuned at 6 MV/15MV and a brachytherapy source (Ir-192) used in the patient treatment protocol. The associated dose rate was measured in count rate (photons/s) using a highly sensitive photon counter (sensitivity ~20ph/s). Overall measurements were performed in IBATM water tank phantoms by following international Technical Reports series recommendations (TRS 381) for radiotherapy and TG43U1 recommendations for brachytherapy. The performance of the detector was tested through several dosimetric parameters such as PDD, beam profiling, Cerenkov measurement, dose linearity, dose rate linearity repeatability, and scintillator stability. Finally, a comparative study is also shown using a reference microdiamond dosimeter, Monte-Carlo (MC) simulation, and data from recent literature. Results: This study is highlighting the complete removal of the Cerenkov effect especially for small field radiation beam characterization. The detector provides an entire linear response with the dose in the 4cGy to 800 cGy range, independently of the field size selected from 5 x 5 cm² down to 0.5 x 0.5 cm². A perfect repeatability (0.2 % variation from average) with day-to-day reproducibility (0.3% variation) was observed. Measurements demonstrated that ISD has superlinear behavior with dose rate (R2=1) varying from 50 cGy/s to 1000 cGy/s. PDD profiles obtained in water present identical behavior with a build-up maximum depth dose at 15 mm for different small fields irradiation. A low dimension of 0.5 x 0.5 cm² field profiles have been characterized, and the field cross profile presents a Gaussian-like shape. The standard deviation (1σ) of the scintillating signal remains within 0.02% while having a very low convolution effect, thanks to lower sensitive volume. Finally, during brachytherapy, a comparison with MC simulations shows that considering energy dependency, measurement agrees within 0.8% till 0.2 cm source to detector distance. Conclusion: The proposed scintillating detector in this study shows no- Cerenkov radiation and efficient performance for several radiation therapy measurement parameters. Therefore, it is anticipated that the IR-ISD system can be promoted to validate with direct clinical investigations, such as appropriate dose verification and quality control in the Treatment Planning System (TPS).

Keywords: IR-Scintillating detector, dose measurement, micro-scintillators, Cerenkov effect

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Authors: Andreea Halunga, Chris D. Orme, Takashi Yamagata

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This paper proposes a heteroskedasticity-robust Breusch-Pagan test of the null hypothesis of zero cross-section (or contemporaneous) correlation in linear panel-data models, without necessarily assuming independence of the cross-sections. The procedure allows for either fixed, strictly exogenous and/or lagged dependent regressor variables, as well as quite general forms of both non-normality and heteroskedasticity in the error distribution. The asymptotic validity of the test procedure is predicated on the number of time series observations, T, being large relative to the number of cross-section units, N, in that: (i) either N is fixed as T→∞; or, (ii) N²/T→0, as both T and N diverge, jointly, to infinity. Given this, it is not expected that asymptotic theory would provide an adequate guide to finite sample performance when T/N is "small". Because of this, we also propose and establish asymptotic validity of, a number of wild bootstrap schemes designed to provide improved inference when T/N is small. Across a variety of experimental designs, a Monte Carlo study suggests that the predictions from asymptotic theory do, in fact, provide a good guide to the finite sample behaviour of the test when T is large relative to N. However, when T and N are of similar orders of magnitude, discrepancies between the nominal and empirical significance levels occur as predicted by the first-order asymptotic analysis. On the other hand, for all the experimental designs, the proposed wild bootstrap approximations do improve agreement between nominal and empirical significance levels, when T/N is small, with a recursive-design wild bootstrap scheme performing best, in general, and providing quite close agreement between the nominal and empirical significance levels of the test even when T and N are of similar size. Moreover, in comparison with the wild bootstrap "version" of the original Breusch-Pagan test our experiments indicate that the corresponding version of the heteroskedasticity-robust Breusch-Pagan test appears reliable. As an illustration, the proposed tests are applied to a dynamic growth model for a panel of 20 OECD countries.

Keywords: cross-section correlation, time-series heteroskedasticity, dynamic panel data, heteroskedasticity robust Breusch-Pagan test

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Authors: Sibgha Noreen, Muhammad Salim Akhter, Seema Mahmood

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Salt stress is an abiotic stress that causes a heavy toll on growth and development and also reduces the productivity of arable and horticultural crops. Globally, a quarter of total arable land has fallen prey to this menace, and more is being encroached because of the usage of brackish water for irrigation purposes. Though barley is categorized as salt-tolerant crop, but cultivars show a wide genetic variability in response to it. In addressing salt stress, silicon nutrition would be a facile tool for enhancing salt tolerant to sustain crop production. A greenhouse study was conducted to evaluate the response of barley (Hordeum vulgare L.) cultivars to silicon nutrition under salt stress. The treatments included [(a) four barley cultivars (Jou-87, B-14002, B-14011, B-10008); (b) two salt levels (0, 200 mM, NaCl); and (c) two silicon levels (0, 200ppm, K2SiO3. nH2O), arranged in a factorial experiment in a completely randomized design with 16 treatments and repeated 4 times. Plants were harvested at 15 days after exposure to different experimental salinity and silicon foliar conditions. Results revealed that various physiological and biochemical attributes differed significantly (p<0.05) in response to different treatments and their interactive effects. Cultivar “B-10008” excelled in biological yield, chlorophyll constituents, antioxidant enzymes, and grain yield compared to other cultivars. The biological yield of shoot and root organs was reduced by 27.3 and 26.5 percent under salt stress, while it was increased by 14.5 and 18.5 percent by exogenous application of silicon over untreated check, respectively. The imposition of salt stress at 200 mM caused a reduction in total chlorophyll content, chl ‘a’ , ‘b’ and ratio a/b by 10.6,16.8,17.1 and 7.1, while spray of 200 ppm silicon improved the quantum of the constituents by 10.4,12.1,10.2,10.3 over untreated check, respectively. The quantum of free amino acids and protein content was enhanced in response to salt stress and the spray of silicon nutrients. The amounts of superoxide dismutase, catalases, peroxidases, hydrogen peroxide, and malondialdehyde contents rose to 18.1, 25.7, 28.1, 29.5, and 17.6 percent over non-saline conditions under salt stress. However, the values of these antioxidants were reduced in proportion to salt stress by 200 ppm silicon applied as rooting medium on barley crops. The salt stress caused a reduction in the number of tillers, number of grains per spike, and 100-grain weight to the amount of 29.4, 8.6, and 15.8 percent; however, these parameters were improved by 7.1, 10.3, and 9.6 percent by foliar spray of silicon over untreated crop, respectively. It is concluded that the barley cultivar “B-10008” showed greater tolerance and adaptability to saline conditions. The yield of barley crops could be potentiated by a foliar spray of 200 ppm silicon at the vegetative growth stage under salt stress.

Keywords: salt stress, silicon nutrition, chlorophyll constituents, antioxidant enzymes, barley crop

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Authors: Tomomi Uchiyama, Tomoko Okayama, Yukio Ide

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This study is concerned with the development of a micro-hydraulic turbine for power generation installed in sewer pipes. The runner has a circular hollow around the central (rotating) axis so that solid materials included in water can be easily flow through the runner without blocking the turbine. The laboratory experiments are also conducted. The hollow is very effective to make polyester fibers pass through the turbine. The guide vane is useful to heighten the turbine performance. But it is easily blocked by the fibers, making the turbine lose the function.

Keywords: micro-hydraulic turbine, power generation, sewage, sewer pipe

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Authors: Maryam Mohammad Hadi, Heather Nesbitt, Hamzah Masood, Hashim Ahmed, Mark Emberton, John Callan, Alexander MacRobert, Anthony McHale, Nikolitsa Nomikou

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Sonodynamic therapy (SDT) utilises ultrasound in combination with sensitizers, such as porphyrins, for the production of cytotoxic reactive oxygen species (ROS) and the confined ablation of tumours. Ultrasound can be applied locally, and the acoustic waves, at frequencies between 0.5-2 MHz, are transmitted efficiently through tissue. SDT does not require highly toxic agents, and the cytotoxic effect only occurs upon ultrasound exposure at the site of the lesion. Therefore, this approach is not associated with adverse side effects. Further highlighting the benefits of SDT, no cancer cell population has shown resistance to therapy-triggered ROS production or their cytotoxic effects. This is particularly important, given the as yet unresolved issues of radiation and chemo-resistance, to the authors’ best knowledge. Another potential future benefit of this approach – considering its non-thermal mechanism of action – is its possible role as an adjuvant to immunotherapy. Substantial pre-clinical studies have demonstrated the efficacy and targeting capability of this therapeutic approach. However, SDT has yet to be fully characterised and appropriately exploited for the treatment of cancer. In this study, a formulation based on multistimulus-responsive sensitizer-containing nanoparticles that can accumulate in advanced prostate tumours and increase the therapeutic efficacy of SDT has been developed. The formulation is based on a polyglutamate-tyrosine (PGATyr) co-polymer carrying hematoporphyrin. The efficacy of SDT in this study was demonstrated using prostate cancer as the translational exemplar. The formulation was designed to respond to the microenvironment of advanced prostate tumours, such as the overexpression of the proteolytic enzymes, cathepsin-B and prostate-specific membrane antigen (PSMA), that can degrade the nanoparticles, reduce their size, improving both diffusions throughout the tumour mass and cellular uptake. The therapeutic modality was initially tested in vitro using LNCaP and PC3 cells as target cell lines. The SDT efficacy was also examined in vivo, using male SCID mice bearing LNCaP subcutaneous tumours. We have demonstrated that the PGATyr co-polymer is digested by cathepsin B and that digestion of the formulation by cathepsin-B, at tumour-mimicking conditions (acidic pH), leads to decreased nanoparticle size and subsequent increased cellular uptake. Sonodynamic treatment, at both normoxic and hypoxic conditions, demonstrated ultrasound-induced cytotoxic effects only for the nanoparticle-treated prostate cancer cells, while the toxicity of the formulation in the absence of ultrasound was minimal. Our in vivo studies in immunodeficient mice, using the hematoporphyrin-containing PGATyr nanoparticles for SDT, showed a 50% decrease in LNCaP tumour volumes within 24h, following IV administration of a single dose. No adverse effects were recorded, and body weight was stable. The results described in this study clearly demonstrate the promise of SDT to revolutionize cancer treatment. It emphasizes the potential of this therapeutic modality as a fist line treatment or in combination treatment for the elimination or downstaging of difficult to treat cancers, such as prostate, pancreatic, and advanced colorectal cancer.

Keywords: sonodynamic therapy, nanoparticles, tumour ablation, ultrasound

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