bluuebunny/crossref_metadata_2025 huggingface dataset:
PRODUCT DEVELOPMENT OF FROZEN AND DEHYDRATED PHALSA (GREWIA ASIATICA)
Authors: Nawaz Saira
Published: September 2022

Phalsa (Grewia asiatica L.) belongs to family Malvaceae is a delicious fruit with wide range of therapeutic benefits. The current research work was planned to develop cream cheese using frozen and dehydrated (F & D) phalsa. The developed product quality and acceptability was subjected to sensory evaluation followed by various analysis to check the microbial activity of frozen & dehydrated phalsa-based product. The microbial count was 18cfu/mL in frozen phalsa-based product while 14cfu/mL in dehydrated phalsabased cream cheese. On comparison it is concluded based on results that dehydrated phalsa-based product was proved to be most effective as compared to frozen phalsa-based product.
TWO APPLICATIONS OF PB-ROPES AS AN EFFECTIVE MANAGEMENT TOOL FOR PECTINOPHORA GOSSYPIELLA (LEPIDOPTERA: GELECHIIDAE)
Authors: Qureshi Muhammad Awais
Published: September 2022

The experiment was conducted to observe the effectiveness and working duration of PB-Ropes in the cotton season 2018-19. The gossyplure baited traps were installed in the last week of June for monitoring of pink bollworm (PBW) while application of PB-Ropes was done @ 120 ropes / acre at pin head square stage on 30 acres of cotton during 1st week of July. The percent infestation of PBW in green bolls and number of moth catches were recorded from the plots treated with 2 applications of PB-Ropes alone and 1 application of PB-Ropes + insecticide application. The PBropes provide mating disruption for the period of 90 days. The percent infestation ingreen bolls was decreased effectively by two applications of PBropes as compared to one application of PB-Ropes and Control Plot.The number of moth catches were highly reduced in the plot treated with two applications of PB-ropes (6.07 ± 0.70) as compared to one application of PB-ropes (28.05 ± 3.16) and control plot (40.439 ± 3.62). The further application of pesticides was done to decrease the % infestation of pink bollworm in the plots treated with PB-Rope + Triazophos @ 600 ml /acre (9.6061 ± 0.9873), PB-Rope + Bifenthrin 10 % EC@ 250 ml / acre (11.848 ± 1.4921) and PB-Rope + Spintoram 12 % SC (14.273 ± 1.5838). The results of this study also provided best and long term approach to farmers for the effective management of pink bollwormby the two applications of PB-Ropes to cover full cotton season as compared to one application of PB-Ropes. The use of two applications of PB-Ropes proved effective and provides cost benefit to farmer as compared to the use of insecticide for the management of the Pink bollworm.
PERANCANGAN SISTEM INFORMASI ABSENSI KEHADIRAN ONLINE BERBASIS WEB DI BALAI DESA NAGRAK
Authors: Ginting Seliwati , Nur Afifah Risma
Published: September 2022

Penelitian ini bertujuan untuk merancang dan mengimplementasikan sistem informasi absensi kehadiran online berbasis web di Balai Desa Nagrak.Metode penelitian menggunakan metode kualitatif dengan pendekatan deskriptif. Teknik pengumpulan data yang digunakann dengan melakukan observasi, dokumentasi dan dilengkapi kajian pustaka yang memiliki relevansi dengan permasalahan. Dalam penelitian terdapat permasalahan absensi kehadiran menggunakan sistem yang berjalan manual sehingga kurang efektif dan efisien. maka dari itu diperlukan perancangan sistem informasi absensi kehadiran online berbasis web menggunakan bahasa pemodelan UML (Unifiend Modeling Laguage),diimplementasikan dengan bahasa pemograman framework laravel dan penyimpanan data menggunakan MySQL. Dengan adanya sistem ini sebagai pengolahan data absensi kehadiran online berbasis web dapat berjalan efektif dan efisien.
Budidaya Maggot Dalam Peningkatan Kewirausahaan Santri Yayasan Al-Kamilah
Authors: Ramdani Edon , Satiman Satiman , Suparmin  , Wiyanti Rahma , Maharani
Published: September 2022

Pertambahan Jumlah penduduk berimbas kepada meningkatnya kebutuhan pangan dan juga meningkatnya limbah/sampah. Kondisi ini harus dibarengi dengan peningkatan produksi pangan dan cara mengelola limbah agar tidak menjadi beban bagi lingkungan. Pemenuhan kebutuhan pangan salah satunya dapat dilakukan dengan meningkatkan sumber protein hewani. Meningkatnya kebutuhan protein hewani berimbas pula meningkatnya kebutuhan pakannya. Kebutuhan akan pakan unggas maupun ikan sampai saat ini masih didominasi pakan olahan industri seperti puur maupun pelet. Produk pakan tersebut dikuasai hanya beberapa perusahaan besar yang dapat dengan mudah memonopoli pasar. Ketergantungan terhadap pakan keluaran pabrik membebani peternak dari sisi ongkos produksi dan tidak jarang terjadi ongkos produksi lebih besar dari hasil penjualan unggas maupun perikanan. Perlu alternatif solusi pakan pengganti atau tambahan yang dapat mengurangi biaya produksi. Budidaya lalat tentara hitam (Maggot) menjadi salah satu solusi mengatasi permasalahan pakan sekaligus mengurangi limbah, karena makanan maggot berupa limbah sisa makanan, buah dan sayuran. Maggot mengandung protein yang tinggi dan dapat menjadi alternatif pakan pengganti selain puur maupun pelet dan harga jual maggot sangat kompetitif dibandingkan pakan hasil industi. Kemudian dari fenomena tersebut maka kami mengadakan kegiatan PKM bertujuan untuk meningkatkan kegiatan wirausaha melalui budidaya maggot dengan sasaran para santri yang berada di Yayasan Panti Asuhan Yatim Piatu Al Kamilah, Bojongsari, Depok. Metode kegiatan dilakukan berupa sosialisasi pentinganya wirausaha dengan pengembangan produk-produk yang bernilai ekonomis sehingga dapat meningkatkan pendapatan mereka. Hasil dari kegiatan ini diharapkan mampu menambah wawasan santri mengenai berbagai peluang usaha, salah satunya dengan budidaya maggot.
School Counselors Applying the ASCA 2016 Ethical Standards
Authors: Johnson Glenda , Carrico Josh
Published: September 2022

As the student population becomes more diverse in the United States (Human Rights Campaign, 2018; National Center for Education Statistics, 2018), school counselors (SCs) are also called upon to provide comprehensive school counseling programs to meet the needs of all students (ASCA, 2019). In addition to following the professionâ€™s national model, the American School Counseling Associationâ€™s Ethical Standards (2016) provide a set of guidelines including specific language aimed at providing culturally competent counseling services to students and stakeholders. With this in mind, the purpose of this manuscript is twofold. The first goal is to provide SCs with strategies for use when providing services to diverse students. Next, the authors will highlight sections of the ASCA Ethical Standards for School Counselors (ASCA, 2016) that specifically address diverse studentsâ€™ needs. Case scenarios will also be provided.
Best Practices in Multicultural Supervision in Counseling
Authors: Fernandes Caroline , Lane W.
Published: September 2022

The latest U.S. Census Bureau listed an increase in ethnic and racial diversity in the United States. Contributing to this are the growing statistics of refugees and immigrants whose intrapersonal experiences vary from the mainstream culture. Considering this growth, it is vital that counseling supervisors are aware of various cultures, ethnicity, social, and spiritual experiences of supervisees in training in order to provide ethical and competent supervision. This paper discusses supervisory issues, directions and trends, social justice issues, and the use of technology in multicultural supervision.
Counseling Adolescents Aging Out of Foster Care: A Neglected and Underserved Population
Authors: Tertocha-Ubelhor Taylor , Russ Bryan
Published: September 2022

The high prevalence of youth aging out of the foster care system and the numerous poor outcomes they experience during the transition to emerging adulthood has been well documented. Although addressing the complex needs and concerns of this distinct population can be difficult, mental health counselors maintain the philosophical tenants and training strengths necessary to successfully serve youth aging out of foster care. This article aims to provide counselors with the historical context, developmental framework, and specific challenges needed to better understand this population, as well as suggested counseling implications to address their unique needs by reviewing relevant literature.
Glossary of ICH terms and definitions
Authors:   CIOMS
Published: September 2022

This glossary combines the terms and definitions included in the guidelines of the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH). It was compiled by CIOMS from the publicly available guidelines found on the ICH website.
Constraining Tectonic Components During a Geomechanics-Aided Successful Hydrofracturing Campaign Targeting Deep Unconventional Reservoir
Authors: Kumar Rajeev Ranjan , Al-Busaidi Salim , Subbiah Surej Kumar
Published: September 2022

The horizontal stress profile plays a key role in managing the wellbore from drilling to well completion in unconventional reservoirs. A robust prediction of the stress profile and fracture initiation values in vertical wells is required to identify sweet zones and fracture height barriers to design a successful hydro-fracturing job. In this paper, we provide the details of a workflow adopted for building a pre-fracture geomechanical models using breakouts and advanced acoustic data to further history match post-fracture results. The analysis involves the effects of filter cake around permeable sandstone, variation in tensile strength, and quantification of horizontal stress contrast in the different clusters. Different reservoirs have been analyzed across multiple wells to map the variations in geological, petrophysical, and geomechanical parameters. Core test data was used to build dynamic-to-static rock elastic and mechanical properties, both of which reduced uncertainty in the model. The poroelastic horizontal strain met hod was used to estimate the horizontal stress profile. The aeolian deposits have a wide variation in horizontal stress, and fracture height is typically governed by the stiffness of the layers. The study shows that the geometry of hydraulic fractures in the area is strongly controlled by the in-situ stress state. The ratio of maximum horizontal stress-to-minimum horizontal stress varies between 1.18 and 1.28 based on the post-fracture analysis, which correlates well with the regional geological setting. Predrill models have been extremely useful for perforation design in different wells with a maximum deviation of 6% from the actual values for one set of reservoirs. Geomechanical analysis helped to optimize well drilling and hydro-fracture campaigns with cost savings.

1. INTRODUCTION

The hydraulic fracturing process in a low permeability unconventional reservoir involves the creation of new flow channels where the downhole fluid pressure exceeds the minimum principal stress value plus the tensile strength near the wellbore. Hydro-fracturing is intended to stimulate fractures within a target hydrocarbon zone with proper containment around the stress barrier. Inputs from three different domains, i.e., geomechanics, petrophysics, and geology, are crucial for successful hydrofracturing jobs.
Current concerns related to the research and exploitation of useful mineral deposits
Authors:   University of Petroşani, Fodor Dumitru
Published: September 2022

The profitable exploitation and beneficiation of the useful mineral deposits, under the economic circumstances existing worldwide require the attraction of most modern working methods and technologies in mining field. As a result, the present work presents the current preoccupations in the field of the deposit investigation and their exploitation and beneficiation. The focus is on the necessity to use more the geophysical working techniques for the deposit investigations and on the modernization and efficiency of the working methods and basic operations to be carried out within the mining industry: extraction of useful rocks and mineral from the massif, their loading, transport and stockpiling. There are also presented the current concerns and trends in the field of useful mineral processing. A suitable importance has been granted to the mechanization, automation and mining machine construction. The final part of work deals with the presentation of some conclusions regarding the possibility of modernizing the mining technologies.
FEM or SPH ?
Authors:   Military Technical Academy, Năstăsescu Vasile
Published: September 2022

This paper brings, in front of the reader, some aspects regarding the using of those numerical methods, perhaps most used, for analysis of the fluids and structures. Next to the FEM (Finite Element Method), new numerical methods appeared, among these, the methods named meshfree methods are nowadays most used. The SPH (Smoothed Particle Hydrodynamics) method belongs to this category of meshfree method, being the most used in different fields like astrophysical phenomena, fluid dynamics, structure dynamics and others. The paper put face to face some results obtained by FEM and SPH, so the reader can alone to appreciate which method is better in a given problem or other. For to facilitate analysis and to understand the results, the fundamentals of SPH method are presented. In contrast to FEM, the SPH method is less known and less used in Romania. This finding underlies the emergence of this article. The answer to the title question depends on every one and it is influenced by many factors. Finally, the author suggests an answer by a correction of the title question: FEM and SPH or FEM with SPH.
Advanced notions and differential principles of motion in analytical dynamics
Authors:   Technical University of Cluj-Napoca, Negrean Iuliu
Published: September 2022

Using the author's researches, this paper extends the study by new formulations regarding the acceleration energies of first, second, third and fourth order. The advanced notions will be implemented in the differential equations of higher order, corresponding to suddenly and transitory motions.
An integrated traffic and power grid simulator enabling the assessment of e-mobility impact on the grid: a tool for the implementation of the smart grid/city concept
Authors:   Department of Computer Science and Engineering, University of Bologna, Bologna, Italy, Bedogni Luca , Bononi L. ,   Department of Computer Science and Engineering, University of Bologna, Bologna, Italy, Borghetti Alberto
Published: September 2022

To successfully accomplish electro-mobility integration into city traffic, plans for the installation of adequate public charging infrastructures are of utmost importance. The assessment of the effects of the transients caused by the concurrent charging of a large number of electric vehicles to the operating conditions of the power network is part of such a planning development. The paper summarizes some of the work carried out in the authors’ laboratories to accomplish such an assessment. In particular it describes the co-simulation platform integrating a) a mobility simulator suitably adapted to reproduce e-mobility in a typical middle-size Italian city center with b) a dynamic simulator of the power distribution network and with c) a simulator of a UMTS communication network, which has been developed to this purpose. The platform is shown to be able to support the development and performance test of specific countermeasures against power components overload, voltage variations and unbalances.
A Policy Recommendation to Resolve E-Health Care Issues Through Non-Functional Requirements
Authors: Areeba Akbar  , Sana Sarwar  , Ahmad Muhammad Umair
Published: September 2022

Electronic Health is basically focused on computer-based techniques or applications for the interaction of patients and doctors through a single electronic environment. The E-Health care system’s development is facing major challenges such as time and cost, language barrier, cultural and norms differences, a difference of states, communication gap, coordination problems, lack of medical project guidance, lack of experienced software testers for health systems, user’s dissatisfaction, poor top project management and so on. These challenges have a major impact on a system’s quality in E-Health and decrease the acceptability among its users. In recent years, some strategies had been applied to reduce quality-related issues that exist in E-Health, however, there is still a need to develop effective and efficient methods, techniques and best practices that can lead to enhance the quality of health software development. The main objective of this study is to highlight existing issues of E-Health and to provide the policy recommendations to mitigate them. Therefore, a quantitative analysis has been performed on collected data to configure the issues of E-Health care system development that directly or indirectly affects the quality of system and services. A detailed study of literature is conducted to test the current proposed framework of E-Health system for security and privacy and to compete for these challenges. It also provides detailed statistical analysis on data by analyzing and applying the demographic profile, frequencies, descriptive studies, reliability test (achieving significance (0.796 > 0.70)), nonparametric test (rejected the null hypothesis with less than 0.5 significance) and one sample T-test (with 2-tailed significance difference 0.00) through SPSS. Hence, this work contributes to making strong policy recommendations to E-Health care system development issues. These policy recommendations explain how E-Health systems should be handled by selecting best process, and how to achieve maximum quality of system product for patients to satisfy them, improve the acceptance among its users, bring their trust back to gain more business and overall development in (medical related IT and software) industry.
Conducting User Research for Designing Better Software Products
Authors: Maham Irfan  , Omer Amin  , Aleena Marium
Published: September 2022

A user’s experience with a software product is crucial for the success of that product. For a long period of time, it was not considered to get an insight of what the users demanded from a product. User research is the best way to discover what the users need. With the increased use of mobile devices, the demand of software products has increased. Building an application is not as simple as hiring someone to code and deploy the application. A process has to be followed and user’s requirements must be understood before we start the design process. The research will help to take additional benefits from the results of user research. It would help to investigate and validate product ideas clearly. As more facts can help to reach a better conclusion, the results from multiple sources like interviews, surveys, user testing etc. Surveys has been conducted for different application i.e. E-commerce application and Facebook application. Proposed user experience (UX) model has been implemented on results and understands that how user experience (UX) research model helps to extract useful information. The recommended model is helpful in patching all the problems that come along during the user research process. The results produced by experiments can be processed through Atomic user experience (UX) model and a useful, shareable and easy to understand outcome can be drawn out of the research.
A Feature Fusion Based Hybrid Approach for Breast Cancer Classification
Authors: Fatima Iftikhar  , Hafiz Muhammad Mueez Amin  , Ghulam Abbas
Published: September 2022

A detected type of cancer is breast cancer commonly in women. According to some estimate one in nine women is diagnosed with breast cancer. It is unfortunate that due to a lack of proper facilities, the diagnosis of breast cancer in patients is being delayed, which is leading to an increase in the possible death rate. Many different statistical methods and Machine Learning algorithms are often employed in the study to make breast cancer detection more accurate. Machine learning (ML) has allowed doctors to achieve remarkable results, and healthcare is using ML-based models to detect breast cancer in women. This allows analyzing the healthcare data and uses the traditional computer-aided detection (CAD) to assess breast cancer. Machine learning has become an accepted clinical practice and allows doctors to evaluate the ML model to detect breasts at an early stage. A major aim is to diagnose patients with breast cancer by analyzing the data of patients and classifying them into two categories, having diagnosis results as Benign "B" or Malignant “M”. In this study different machine learning algorithms are used to classify cancer as either its malignant or benign. The Kaggle data set was used for applying these algorithms to get the best accuracy. MLP is more efficient and accurate algorithm to classify the breast tumor. And here also fitted the matthews_corrcoef for MLP is 0.89% and accuracy score for the random forest is 0.94%.
Pelakasanaan Program Pembiasaan Baik di Sekolah Sebagai Upaya Pembinaan Akhlak Siswa pada Masa Pandemi Covid-19
Authors: Hamidah Laila , Sari Mada Sumringah
Published: September 2022

Tujuan penulisan ini untuk membahas mengenai pelaksanaan program pembiasaan baik di sekolah sebagai upaya pembinaan akhlak siswa pada masa pandemi covid-19. Seperti kita ketahui bahwa Indonesia sedang mengalami krisis akhlak khususnya pada generasi muda calon pemimpin bangsa. Akhlak merupakan sistem nilai yang menentukan pola perilaku dan sikap atau tabiat seseorang. Sistem nilai yang dimaksud adalah ajaran Islam yang merujuk pada Al-Qur'an dan Sunnah sebagai sumber nilai serta ijtihad sebagai metode pemikiran Islam. Sikap dan perilakunya meliputi Allah SWT, sesama manusia (termasuk diri kita sendiri), dan hubungan dengan alam semesta. Akhlak seseorang adalah sifat yang tertanam dalam jiwa yang dapat dengan mudah menimbulkan berbagai tindakan tanpa perlu pemikiran atau perenungan. Ilmu atau materi yang membahas tentang nilai-nilai yang tertanam dalam jiwa dan perilaku manusia, dapat ditafsirkan dengan perilaku baik dan buruknya. Selain itu, akhlak juga berarti suatu kebiasaan yang selalu dilakukan dan menjadi kepribadian seseorang. Jika akhlaknya baik maka disebut akhlakul karimah, dan jika akhlaknya tidak baik maka disebut akhlakul madzmumah. Oleh karena itu, pembinaan akhlak harus diterapkan dalam kehidupan sehari-hari khususnya dalam lingkungan rumah, umunya di sekolah, maupun di lingkungan masyarakat. Metode penulisan ini adalah dengan metode Library Research. Penulis membahas tentang pembiasaan baik yang dilakukan di sekolah, pengertian akhlak, dan pembinaan akhlak melalui pembiasaan baik di sekolah.
Race and Other Disparate Demographic Variables Identified Among Emergency Department Boarders
Authors: Ruffo Robert , Shufflebarger Erin , Booth James , Walter Lauren
Published: September 2022

Introduction: Emergency department (ED) boarding, the process of holding patients in the ED due to a lack of inpatient beds after the decision is made to admit, has profound consequences. Increased ED boarding times are associated with adverse patient outcomes, including increased mortality. While previous studies have demonstrated racial disparities with regard to ED boarding, current literature lacks insight into discrepancies that may exist among other demographic groups as it pertains to ED boarding. We sought to review ED boarding times differentiated by demographic characteristics.

Methods: We conducted a retrospective review of all ED admissions from an academic ED in the Southeast from April–September 2019. The primary outcome assessed was boarding time, defined as time from decision to admit to ED departure. Patient demographic data including race, gender, and age were collected and analyzed. We performed descriptive statistics and chi-square analyses.

Results: The study population included 17,606 patients with a mean age of 56.3. Nearly half (49.8%) of the patients were female. Additionally, 43.8% of patients were Black and 48.6% White. For all admissions, there was no difference in mean boarding time among Black and White patients (5.2 ± 8.8 vs 5.2 ± 8.2 hours, P = 0.11). Among Emergency Severity Index (ESI) level I admissions, Black patients boarded longer than White patients (4.1 ± 0.3 vs 2.7 ± 0.3 hours, P = 0.009). Black patients also boarded significantly longer than White patients for psychiatric admissions (22.7 ± 23.7 vs 18.5 ± 19.4 hours, P <0.05). For all admissions, males boarded longer than females (5.5 ± 8.5 vs 4.9 ± 8.2 hours, P <.0001). Patients older than 75 boarded for less time (3.8 ± 6.2 hours) compared to younger groups (15-24: 6.4 ± 10.8 hours; 25-44: 6.6 ± 10.8; 45-64: 5.0 ± 7.6; and 64-75: 4.7 ± 6.7; all P <.05).

Conclusion: This analysis demonstrated significant differences in ED boarding times between races among psychiatric and ESI I admissions, gender, and age. This data provides insight into differences in ED boarding times among demographic groups and provides a focal point for examining possible factors contributing to the observed differences.
Geriatric Falls: Patient Characteristics Associated with Emergency Department Revisits
Authors: Cox Dustin , Subramony Rachna , Supat Ben , Brennan Jesse , Hsia Renee , Castillo Edward
Published: September 2022

Introduction: Falls are the leading cause of traumatic injury among elderly adults in the United States, which represents a significant source of morbidity and leads to exorbitant healthcare costs. The purpose of this study was to characterize elderly fall patients and identify risk factors associated with seven-day emergency department (ED) revisits.

Methods: This was a multicenter, retrospective, longitudinal cohort study using non-public data from 321 licensed, nonfederal, general, and acute care hospitals in California obtained from the Department of Healthcare Access and Information from January 1–December 31, 2017. Included were patients 65 and older who had a fall-related ED visit identified by International Classification of Diseases codes W00x to W19x. Primary outcome was a return visit to the ED within a seven-day window following the index encounter. Demographics collected included age, gender, ethnicity/race, patient payer status, Charlson Comorbidity Index (CCI), psychiatric diagnoses, and alcohol/substance use disorder diagnoses. We performed multivariate logistic regression to identify characteristics associated with seven-day ED revisit.

Results: We identified a total of 2,758,295 ED visits during the study period with 347,233 (12.6%) visits corresponding to fall-related injuries. After applying exclusion criteria, 242,572 index ED visits were identified, representing 206,612 patients. Of these, 24,114 (11.7%) patients returned to an ED within seven days (revisit). Within this revisit population, 6,161 (22.6%) presented to a facility that was distinct from their index visit, and 4,970 (18.2%) were ultimately discharged with the same primary diagnosis as their index visit. Characteristics with the largest independent associations with a seven-day ED revisit were presence of a psychiatric diagnosis (odds ratio [OR] 1.75; 95% confidence interval [CI] 1.69 to 1.80), presence of an alcohol or substance use disorder (OR 1.70; 95% CI 1.64 to 1.78), and CCI ≥ 3 (OR 2.79; 95% CI 2.68 to 2.90).

Conclusion: In this study we identified 24,114 elderly fall patients who experienced a seven-day ED revisit. Patients with multiple comorbidities, a substance use disorder, or a psychiatric diagnosis exhibited increased odds of experiencing a return visit to the ED within seven days of a fall-related index visit. These findings will help target at-risk elderly fall patients who may benefit from preventative multidisciplinary intervention during index ED visits to reduce ED revisits.
Electronic Health Record-based COVID-19 Interprofessional Case Collaboration
Authors: Ringwald Bryce , Shawar Suhair , Curren Camilla , McCallister Jennifer , Bazan Jose , Mead Christopher , Kman Nicholas
Published: September 2022

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Systematic Review of Early Phase Pediatric Clinical Pharmacology Trials
Authors: Subramanian Deejesh , Cruz Cintia V. , Garcia-Bournissen Facundo
Published: September 2022

OBJECTIVE

Children have generally been excluded from early-stage clinical trials owing to safety concerns based in social expectations and not data. However, the repositioning of adult therapeutics for pediatric use and the increase in the development of therapies for pediatric only conditions require the participation of children in phase 1–2 trials. Therefore, the aim of this article is to systematically review the history and current state of early phase pediatric clinical pharmacology trials in order to understand safety concerns, trends, and challenges in pediatric trials.

METHODS

This review analyzed the nature of early phase pediatric clinical trials conducted for nononcology conditions through a systematic search that was performed for pediatric non-oncologic phase 1 or phase 1–2 drug and vaccine studies in MEDLINE.

RESULTS

The data show that the number of early phase pediatric clinical trials is still small relative to adults but has been on the rise in the past decade with relatively few serious adverse effects observed.

CONCLUSIONS

The widespread concerns about children's safety when they participate in early phase clinical trials seem disproportionate, based on our findings. The data confirm that these studies can be conducted safely, and that their results can contribute significantly to pediatric pharmacotherapy.
A Critical Assessment of Extemporaneous Formulations for Proton Pump Inhibitors: The Importance of Proper Vehicle Selection
Authors: Rahić Ognjenka , Hadžiabdić Jasmina , Tucak Amina , Sirbubalo Merima , Hindija Lamija , Elezović Alisa , Vranić Edina
Published: September 2022

OBJECTIVE

To examine the influence of vehicles on the stability of extemporaneous suspensions of proton pump inhibitors (PPIs), to single out the formulation most suitable for children, providing appropriate evidence and arguments.

METHODS

A review was performed of data identified from Medline, Embase, Science Direct, as well as public digital archive PubMed, including reference texts, related to the field of stability testing of extemporaneous PPI suspensions.

RESULTS

Fourteen selected formulations of extemporaneous suspensions are presented and discussed. Depending on the vehicle and its composition, which was analyzed and explained in detail, the suspensions had various beyond-use dates (BUDs).

CONCLUSIONS

Selected vehicles and the process of preparation had great influence on the stability of extemporaneous PPI suspensions. The suspension with the longest BUD has been singled out, which is especially suitable for use in newborns. Because an explanation is provided for the influence of individual vehicle components on the stability of the mentioned suspensions, this can aid not only in the selection of an adequate formulation, but also in the development of new ones, which will be suited to individual patients.
Pediatric Practitioner Knowledge of Arsenic in Baby Food
Authors: Palmer Maria J. G. , Parbuoni Kristine A. , Morgan Jill A.
Published: September 2022

OBJECTIVE

Rice, one of the first solid foods introduced to infants, is 10 times more absorbent of inorganic arsenic than any other grain. An evaluation has not been performed about practitioner knowledge of arsenic content in infant foods. The purpose of this survey was to determine pediatric practitioners' knowledge of current US Food and Drug Administration (FDA) recommendations to limit exposure to arsenic-containing foods in infants.

METHODS

This was a convenience sample of pediatric practitioners conducted as an online survey. The survey contained 19 questions related to knowledge of arsenic-containing foods, FDA recommendations, practitioner recommendations on feeding infants, and demographic information. Participants were recruited using organization list servs. Participants were reminded to complete the survey 2 months after the initial email. An infographic on arsenic was provided at the end of the survey.

RESULTS

One hundred thirty-seven individuals completed the survey. The majority of respondents were physicians or pharmacists and have been in practice less than 6 years. Nine percent of respondents (11/123) stated the FDA arsenic limit of 100 ppb. Sixteen percent (20/123) identified white rice as having a lower inorganic arsenic content than brown rice and 27% (36/132) identified that there is no difference in inorganic arsenic content between organic infant rice cereal and conventional infant rice cereal.

CONCLUSIONS

The vast majority of participants were not aware of the FDA's proposed limit on arsenic consumption or the concern of heavy metals in baby foods. More education is needed to increase knowledge regarding arsenic in baby foods.
Extended Infusion β-Lactams for the Treatment of Gram-Negative Bacteremia in Children
Authors: Zembles Tracy N. , Kuhn Evelyn M. , Thompson Nathan E. , Mitchell Michelle L.
Published: September 2022

OBJECTIVE

The pharmacokinetics of β-lactam antibiotics favor administration via an extended infusion. Although literature to support extended infusion β-lactams exists for adults, few data are available in pediatrics, especially among patients with bacteremia. The purpose of this study was to compare clinical outcomes between extended and standard infusions in children with Gram-negative bacteremia.

METHODS

This retrospective chart analysis included hospitalized patients ages 0 to 18 years who received at least 72 hours of cefepime, meropenem, or piperacillin-tazobactam between January 1, 2013 and July 30, 2021. Clinical outcomes included duration of antibiotic therapy, hospital length of stay, readmission within 30 days, all-cause mortality, time to blood culture clearance, and time to normalization of inflammatory markers.

RESULTS

A total of 124 patients (51 extended infusion, 73 standard infusion) met criteria for evaluation. Duration of antibiotic therapy was shorter in the extended infusion group (6.6 days versus 10.2 days; p = 0.01). There were no differences in hospital length of stay, readmission rates, all-cause mortality, time to normalization of inflammatory markers, or time to blood culture clearance.

CONCLUSIONS

Use of extended infusion β-lactam antibiotics in children with Gram-negative bacteremia was associated with shorter durations of therapy and should be the preferred method of administration when feasible.
On the association of interpersonal trust with right-wing extremist and authoritarian attitudes
Authors: Heller Ayline , Wicke Felix S. , Kasinger Christoph , Beutel Manfred E. , Decker Oliver , Schuler Julia , Brähler Elmar
Published: September 2022

Right-wing extremism and authoritarianism have been identified as major, if not the major threats to democracy in recent years. The rise of right-wing extremist and populist parties in many democratic countries throughout the world has renewed the interest in identifying the roots and determinants of these anti-democratic attitudes. Even though factors on many levels of analysis (macro-, meso- and micro-level) have been taken into consideration as possible sources of the development of these kinds of positions, the relationship of interpersonal trust with both right-wing extremism and authoritarianism has yet to be systematically examined. The aim of the current study was to shed light on the connection between these constructs by analyzing data from a German representative study conducted in 2018 (N = 2,416). Multiple linear regression found interpersonal trust to reliably predict all facets of right-wing extremism and authoritarianism included in the study, even when controlling for standard socioeconomic factors (e.g. age, gender, education, income). The lack of interpersonal trust may thus be seen as a major contributing factor to right-wing extremist and authoritarian attitudes. As such, it should be included in future studies about this topic and the nature of the revealed connection should be further examined.
Fibroblast-derived Hgf controls recruitment and expansion of muscle during morphogenesis of the mammalian diaphragm
Authors: Sefton Elizabeth M , Gallardo Mirialys , Tobin Claire E , Collins Brittany C , Colasanto Mary P , Merrell Allyson J , Kardon Gabrielle
Published: September 2022

The diaphragm is a domed muscle between the thorax and abdomen essential for breathing in mammals. Diaphragm development requires the coordinated development of muscle, connective tissue, and nerve, which are derived from different embryonic sources. Defects in diaphragm development cause the common and often lethal birth defect, congenital diaphragmatic hernias (CDH). HGF/MET signaling is required for diaphragm muscularization, but the source of HGF and the specific functions of this pathway in muscle progenitors and effects on phrenic nerve have not been explicitly tested. Using conditional mutagenesis in mice and pharmacological inhibition of MET, we demonstrate that the pleuroperitoneal folds (PPFs), transient embryonic structures that give rise to the connective tissue in the diaphragm, are the source of HGF critical for diaphragm muscularization. PPF-derived HGF is directly required for recruitment of MET+ muscle progenitors to the diaphragm and indirectly (via its effect on muscle development) required for phrenic nerve primary branching. In addition, HGF is continuously required for maintenance and motility of the pool of progenitors to enable full muscularization. Localization of HGF at the diaphragm’s leading edges directs dorsal and ventral expansion of muscle and regulates its overall size and shape. Surprisingly, large muscleless regions in HGF and Met mutants do not lead to hernias. While these regions are likely more susceptible to CDH, muscle loss is not sufficient to cause CDH.
Fat2 polarizes the WAVE complex in trans to align cell protrusions for collective migration
Authors: Williams Audrey Miller , Donoughe Seth , Munro Edwin , Horne-Badovinac Sally
Published: September 2022

For a group of cells to migrate together, each cell must couple the polarity of its migratory machinery with that of the other cells in the cohort. Although collective cell migrations are common in animal development, little is known about how protrusions are coherently polarized among groups of migrating epithelial cells. We address this problem in the collective migration of the follicular epithelial cells in Drosophila melanogaster. In this epithelium, the cadherin Fat2 localizes to the trailing edge of each cell and promotes the formation of F-actin-rich protrusions at the leading edge of the cell behind. We show that Fat2 performs this function by acting in trans to concentrate the activity of the WASP family verprolin homolog regulatory complex (WAVE complex) at one long-lived region along each cell’s leading edge. Without Fat2, the WAVE complex distribution expands around the cell perimeter and fluctuates over time, and protrusive activity is reduced and unpolarized. We further show that Fat2’s influence is very local, with sub-micron-scale puncta of Fat2 enriching the WAVE complex in corresponding puncta just across the leading-trailing cell-cell interface. These findings demonstrate that a trans interaction between Fat2 and the WAVE complex creates stable regions of protrusive activity in each cell and aligns the cells’ protrusions across the epithelium for directionally persistent collective migration.
Hepatic AMPK signaling dynamic activation in response to REDOX balance are sentinel biomarkers of exercise and antioxidant intervention to improve blood glucose control
Authors: Wu Meiling , Zhao Anda , Yan Xingchen , Gao Hongyang , Zhang Chunwang , Liu Xiaomin , Luo Qiwen , Xie Feizhou , Liu Shanlin , Shi Dongyun
Published: September 2022

Antioxidant intervention is considered to inhibit reactive oxygen species (ROS) and alleviate hyperglycemia. Paradoxically, moderate exercise can produce ROS to improve diabetes. The exact redox mechanism of these two different approaches remains largely unclear. Here, by comparing exercise and antioxidant intervention on type 2 diabetic rats, we found moderate exercise upregulated compensatory antioxidant capability and reached a higher level of redox balance in the liver. In contrast, antioxidant intervention achieved a low-level redox balance by inhibiting oxidative stress. Both of these two interventions could promote glucose catabolism and inhibit gluconeogenesis through activation of hepatic AMP-activated protein kinase (AMPK) signaling; therefore, ameliorating diabetes. During exercise, different levels of ROS generated by exercise have differential regulations on the activity and expression of hepatic AMPK. Moderate exercise-derived ROS promoted hepatic AMPK glutathionylation activation. However, excessive exercise increased oxidative damage and inhibited the activity and expression of AMPK. Overall, our results illustrate that both exercise and antioxidant intervention improve blood glucose control in diabetes by promoting redox balance, despite different levels of redox state(s). These results indicate that the AMPK signaling activation, combined with oxidative damage markers, could act as sentinel biomarkers, reflecting the threshold of redox balance that is linked to effective glucose control in diabetes. These findings provide theoretical evidence for the precise management of diabetes by antioxidants and exercise.
Differential requirements for mitochondrial electron transport chain components in the adult murine liver
Authors: Lesner Nicholas P , Wang Xun , Chen Zhenkang , Frank Anderson , Menezes Cameron J , House Sara , Shelton Spencer D , Lemoff Andrew , McFadden David G , Wansapura Janaka , DeBerardinis Ralph J , Mishra Prashant
Published: September 2022

Mitochondrial electron transport chain (ETC) dysfunction due to mutations in the nuclear or mitochondrial genome is a common cause of metabolic disease in humans and displays striking tissue specificity depending on the affected gene. The mechanisms underlying tissue-specific phenotypes are not understood. Complex I (cI) is classically considered the entry point for electrons into the ETC, and in vitro experiments indicate that cI is required for basal respiration and maintenance of the NAD+/NADH ratio, an indicator of cellular redox status. This finding has largely not been tested in vivo. Here, we report that mitochondrial complex I is dispensable for homeostasis of the adult mouse liver; animals with hepatocyte-specific loss of cI function display no overt phenotypes or signs of liver damage, and maintain liver function, redox and oxygen status. Further analysis of cI-deficient livers did not reveal significant proteomic or metabolic changes, indicating little to no compensation is required in the setting of complex I loss. In contrast, complex IV (cIV) dysfunction in adult hepatocytes results in decreased liver function, impaired oxygen handling, steatosis, and liver damage, accompanied by significant metabolomic and proteomic perturbations. Our results support a model whereby complex I loss is tolerated in the mouse liver because hepatocytes use alternative electron donors to fuel the mitochondrial ETC.
Validation of a Metabolic Network forSaccharomyces cerevisiaeUsing Mixed Substrate Studies
Authors: Vanrolleghem Peter A. , de Jong‐Gubbels Patricia , van Gulik Walter M. , Pronk Jack T. , van Dijken Johannes P. , Heijnen Sef
Published: July 2002

Setting up a metabolic network model for respiratory growth ofSaccharomyces cerevisiaerequires the estimation of only two (energetic) stoichiometric parameters: (1) the operationalPOratio and (2) a growth‐related maintenance factork. It is shown, both theoretically and practically, how chemostat cultivations with different mixtures of two substrates allow unique values to be given to these unknowns of the proposed metabolic model. For the yeast and model considered, an effectivePOratio of 1.09 mol of ATP/mol of O (95% confidence interval 1.07−1.11) and akfactor of 0.415 mol of ATP/C‐mol of biomass (0.385−0.445) were obtained from biomass substrate yield data on glucose/ethanol mixtures. Symbolic manipulation software proved very valuable in this study as it supported the proof of theoretical identifiability and significantly reduced the necessary computations for parameter estimation. In the transition from 100% glucose to 100% ethanol in the feed, four metabolic regimes occur. Switching between these regimes is determined by cessation of an irreversible reaction and initiation of an alternative reaction. Metabolic network predictions of these metabolic switches compared well with activity measurements of key enzymes. As a second validation of the network, the biomass yield ofS. cerevisiaeon acetate was also compared to the network prediction. An excellent agreement was found for a network in which acetate transport was modeled with a proton symport, while passive diffusion of acetate gave significantly higher yield predictions.
Peptide Stability in Solids and Solutions
Authors: Bell Leonard N.
Published: July 2002

A discussion of the factors influencing peptide stability illustrates the challenges of formulation and shelf‐life prediction which face biotechnologists. The activation energies of peptide degradation vary with pH and moisture content. Peptide degradation rates are influenced by both buffer type and concentration. Lyophilization results in an increase in buffer concentration which also enhances peptide degradation in low‐moisture solids. Small peptides have degradation rates that depend upon water activity rather than upon mobility limitations associated with the state of the system. The pH−rate profiles for peptide degradation in solution and solids are quite different. Dehydration and partial rehydration change the pH of reduced‐moisture solids, which change both the rates and mechanisms of degradation. The properties of the peptide and the system as well as potential interactions between the two need to be identified to maximize peptide stability. In addition, solution data cannot be used to predict the shelf life of reduced‐moisture solids.
The score for allergic rhinitis (SFAR): a simple and valid assessment method in population studies
Authors: Annesi‐Maesano I. , Didier A. , Klossek M. , Chanal I. , Moreau D. , Bousquet J.
Published: July 2002

Background: No validated assessment of allergic rhinitis (AR) is presently available that can be used in population studies in the absence of medical diagnosis and of objective measurements of allergy. To compensate for this lack, a quantitative Score For Allergic Rhinitis (SFAR) ranging between 0 and 16 has been developed by experts.

Methods: The SFAR, encompassing eight features of AR, was validated in three different ways: 1) among 269 outpatients taking the specialist's diagnosis of AR and skin prick tests (SPT) positivity as a gold standard (diagnosis validation); 2) using psychometric methods (internal validation); and 3) in a random population‐based sample of 3001 individuals by telephone interview (population acceptability).

Results: A SFAR value ≥ 7 allowed satisfactory discrimination between the outpatients with AR from those without (sensitivity = 74% [95% confidence interval CI: 0.69,0.79], specificity = 83% [0.79, 0.87], positive predictive value = 84% [0.80, 0.88], negative predictive value = 74% [0.69, 0.79] and Youden's index = 0.57, respectively). Internal consistency of the score was also high (among others, Cronbach's alpha coefficient = 0.79). On average, it took only 3 min for the individuals interviewed on the phone to complete the questionnaire, the questions of which were well understood. Among these subjects, the prevalence of AR was 21% [95% CI: 19.5%, 22.5%], which is comparable to other determinations in France.

Conclusions: The newly a priori proposed Score For Allergic Rhinitis (SFAR) is easy to use and can be useful to estimate prevalence and to study causation of AR in population settings.