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Real-world evidence can generate credible evidence to inform treatment decisions. Real-world evidence is in developmental stage and is fast evolving yet there are many unexplained attributes of real-world evidence. Real-world evidence informs benefit-risk decisions and is increasingly being used to support regulatory decision making. Potential benefits of real-world data include determination of extended outcomes including long-term outcomes, opportunities to partner with patients in innovative ways, and reduction in time and cost to generate dependable evidence. Limitations of real-world evidence include uncertainty in the quality of datasets and lack methodologic rigor in real-world studies. Use of real-world evidence for healthcare practices and policies is limited. Ensuring completeness, homogeneity, and linkage of datasets can enhance utility for epidemiological investigations and improvement in health outcomes. Research should be strengthened for real-world studies and technical standards should be reinforced. Collaborations of stakeholders is key to formulation and adoption of guidance for real-world evidence. Real-world data cannot be a substitute to randomized clinical studies but can possibly augment the generated evidence.

Corticosteroids are potent medications that have been extensively used to treat many inflammatory and autoimmune conditions. They have been used in a variety of life-threatening and disabling conditions and have saved or improved many lives. However, they cause numerous side effects on various body systems. Corticosteroids inhibit the immune system and increase susceptibility to infections. A regular dose of corticosteroids for 1-2 weeks can make the patient prone to infection.Therefore the study was conducted to assess the common infections related to steroidal treatment which are commonly associated with long-term use of these agents and provide practical recommendations for patient monitoring and the prevention and management of these infections. For this study, quantitative research approach was considered appropriate. A research design was Non-experimental exploratory design. This study was conducted in selected hospitals of city. The samples selected was Children on steroidal treatment admitted in hospitals who meet the inclusive and exclusive criteria. Sample size was 60 and non- probability purposive sampling was used. Self-structured infection assessment checklist format was found to be the most appropriate instrument to assess common infections related to steroidal treatment among children. Descriptive and inferential statistics used for data analysis Majority 38.3% of them had respiratory tract infection followed by 25% of them had skin infection, 15% of the children had gastrointestinal tract infection and 1.7% of them had Urinary tract infection. Duration of steroidal treatment and education of the parents were found to have significant association with gastrointestinal tract infection among children. Developmental stage of child and duration of steroidal treatment were found to have significant association with respiratory tract infection among children. None of the demographic variable was found to have significant association with urinary tract infection among children. Developmental stage of child and Education of the parents were found to have significant association with gastrointestinal tract infection among children.

Purpose The aim of this review is to give an overview of the current status of targeted optical fluorescence imaging in the field of oncology, cardiovascular, infectious and inflammatory diseases to further promote clinical translation. Methods A meta-narrative approach was taken to systematically describe the relevant literature. Consecutively, each field was assigned a developmental stage regarding the clinical implementation of optical fluorescence imaging. Results Optical fluorescence imaging is leaning towards clinical implementation in gastrointestinal and head and neck cancers, closely followed by pulmonary, neuro, breast and gynaecological oncology. In cardiovascular and infectious disease, optical imaging is in a less advanced/proof of concept stage. Conclusion Targeted optical fluorescence imaging is rapidly evolving and expanding into the clinic, especially in the field of oncology. However, the imaging modality still has to overcome some major challenges before it can be part of the standard of care in the clinic, such as the provision of pivotal trial data. Intensive multidisciplinary (pre-)clinical joined forces are essential to overcome the delivery of such compelling phase III registration trial data and subsequent regulatory approval and reimbursement hurdles to advance clinical implementation of targeted optical fluorescence imaging as part of standard practice.

Benson Relaxation is a technique for reducing pain, overcoming sleep disorders and dealing with anxiety. The developmental stage of the elderly is characterized by the loss of a lot of body cells and a decrease in the metabolism of body cells which causes a decrease in body function and changes in body composition as well as a decrease in strength and health. One of the complaints that are felt related to sleep is difficulty sleeping, often waking up during the night and feeling unrefreshed wh en awakened from sleep.

Founded in 1994, The Journal of Clinical Psychology in Medical Settings (JCPMS) has paralleled the development of psychology’s role in health care as well as contributing to its growth in science, services, and education in medical settings. JCPMS provides an essential, unique publishing outlet for health service psychology as represented by the recognized psychological specialties in those settings. At this point in its development, The Journal has turned its attention to generativity and contributing further to the field by helping prepare the next generation of journal manuscript reviewers and future psychological scientists. A brief developmental history of The Journal and its relationship to the evolution of health service psychology is offered followed by a description of a task-specific mentoring process for a new generation of manuscript reviewers. Building on work by other authors, a competency-based model is used to rearrange previously published guidance into categories of knowledge, skills, and attitudes required to become a competent manuscript reviewer. General competencies are described within each of those categories as well as specific behavioral anchors that a mentee must master in order to carry out a competent review.

Background: The incidence of depression in middle-aged adults is increasing and has been affected by physiological changes and various sociodemographic factors. The present study aimed to examine the longitudinal relationship between depression and changes in the family developmental stage based on child independence in South Korean middle-aged adults living with children.Methods: This study included 1,593 people in the age group of 45-64 years who participated in the first survey of the Korean longitudinal study of aging in 2006. Participants did not have depression, lived with unmarried children, and responded to Center for Epidemiologic Studies Depression 10 scale and child-related questions in the 7th survey (2018). The chi-squared test, t-test, and Mann-Whitney U test were used to compare differences in depression according to general characteristics and family developmental stage. The generalized estimating equation model was used to longitudinally examine the effect of changes in the family developmental stage on the incidence of depression from the 1st to the 7th survey.Results: Changes in the family developmental stage based on child independence have a significant effect on the incidence of depression in middle-aged adults (P=0.000). In addition, in the generalized estimating equation model, the longitudinal association between changes in the family developmental stage and the incidence of depression was confirmed.Conclusions: Therefore, confirming the independence of children as an important factor is essential in the management of depression in middle-aged adults.

Dental age estimation is considered to be an accurate method for identifying the age of an unknown person. This study aims to apply a deep-learning algorithm to assess mandibular third molar develo...

PURPOSE: In vitro developing embryos may apparently show no developmental progress during 24 h and resume their development up to the blastocyst stage. The present study was conducted to assess their ability to implant and to give rise to a live birth when replaced at day 5 (fresh or vitrified/warmed) as compared to continuously developing embryos. METHODS: Embryo development follow-up and grade were prospectively recorded in a photo database. The studied period was from April 2011 to July 2017. The studied embryos included transient arrested embryos (TAE) that showed the same developmental stage at two subsequent observations, i.e. between day 2 and day 3 (d2 and d3), between day 3 and day 4 (d3 and d4) and between day 4 and day 5 (d4 and d5). TAE were compared to continuously developing embryos (CDE). Elective day 5 embryo transfers were performed. RESULTS: Woman age was higher in TAE (34.3±3.9) than in CDE (32.9±4.8) (p

Objective: To determine the prevalence and distribution of premature eruption and agenesis of premolars in a sample of Turkish children. Study design: A sample of 1715 patients aged 5 to 11 years was selected. Panoramic radiographs were used to assess premature eruption and agenesis of premolars. Developmental stage of erupted premolars was assessed using Demirjian’s method and selecting prematurely erupted premolars on the basis of clinical eruption with a root length less than half of their final expected root lengths. Statistical analysis was performed using chi-square test (p

Background: Hyperbaric oxygen (HBO2) therapy is a safe and well-tolerated treatment modality. Seizures, one of the most severe central nervous system side effects of HBO2 therapy, can occur. Episodes of seizures during HBO2 therapy have not yet been reported in countries such as Korea, where hyperbaric medicine is still in the developmental stage. Methods: The registry data of all patients treated with HBO2 therapy in a tertiary academic hospital in Korea were prospectively collected, and patients who developed seizures during HBO2 therapy between October 2016 and December 2019 were evaluated. In addition, we reviewed previous studies on occurrence of seizures during HBO2 therapy. Results: During the study period, a total of 10,425 treatments were provided to 1,308 patients. The most frequently treated indication was carbon monoxide (CO) poisoning (n=547, 41.8%). During the HBO2 therapy sessions (total: 10,425), five seizure episodes occurred (patients with CO poisoning: n=4; patients with arterial gas embolism [AGE]: n=1). The frequency of seizures in patients with CO poisoning (0.148%) and AGE (3.448%) was significantly higher than that in patients with all indications (0.048%) (p=0.001). None of the patients had lasting effects due to the seizures. Conclusion: Our study revealed a similar frequency rate in terms of all indications and CO poisoning, and a slightly higher rate in AGE. Seizures were observed in patients with CO poisoning and AGE. Therefore, if clinicians plan to operate a hyperbaric center in a country like Korea, where there are several patients with acute CO poisoning, they should be prepared to handle seizures that may occur during HBO2 therapy

Schistosomiasis is a chronic and painful disease of poverty caused by the flatworm parasite Schistosoma. Drug discovery for antischistosomal compounds predominantly employs in vitro whole organism (phenotypic) screens against two developmental stages of Schistosoma mansoni, post-infective larvae (somules) and adults. We generated two rule books and associated scoring systems to normalize 3898 phenotypic data points to enable machine learning. The data were used to generate eight Bayesian machine learning models with the Assay Central software according to parasite's developmental stage and experimental time point (≤24, 48, 72, and >72 h). The models helped predict 56 active and nonactive compounds from commercial compound libraries for testing. When these were screened against S. mansoni in vitro, the prediction accuracy for active and inactives was 61% and 56% for somules and adults, respectively; also, hit rates were 48% and 34%, respectively, far exceeding the typical 1-2% hit rate for traditional high throughput screens.

Objectives: Dental caries remains among the most prevalent chronic conditions in childhood and remains highly prevalent among schoolchildren in Indonesia. Globally, atraumatic restorative treatment (ART) has been used to good effect in the management of carious lesions among high-risk cohorts, particularly in challenging environments. However, in settings, where labor, time, facilities, and materials are particularly limited, strategic triaging of teeth suitable for ART restorations may be valuable to better direct public health expenditure. Therefore, this study aims to (i) describe the prevalence of dental caries among Indonesian schoolchildren and (ii) evaluate the proportion of lesions indicated for ART. Materials and Methods: A cross-sectional cohort study of elementary schoolchildren from West Java, Indonesia, was examined and categorized according to Hellman’s dental development stages (Groups 1–4 corresponding to the early mixed dentition through to complete permanent dentition). Descriptive statistics and proportional analysis were conducted with the following variables being evaluated: Teeth with early caries (EC), late/advanced caries (LC), recurrent caries (RC), and total caries experience (TC = EC+ART+LC+RC). In evaluating the suitability for ART, additional variables of ART indicated carious lesions (ART) and lower molars with lesions indicated for ART (LM) were assessed. Results: A total of 437 children ranging from 8 to 14 years of age were examined. Out of 8882 teeth examined, 996 had active carious lesions and only 57 had received satisfactory restorative treatment. Children in Hellman’s Group 1 stage of development had the highest prevalence of EC (62%) and ART indicated caries (32%). Meanwhile, older children in Group 4 experienced the highest portion of advanced caries (15%). The proportion of lower molars indicated for ART was 87%, 76%, 70%, and 67% in Groups 1–4, respectively. Conclusion: Indonesian schoolchildren face a high burden of untreated dental caries from a young age. The younger the developmental stage, the higher the prevalence of early and ART-indicated lesions with the majority being found in lower permanent molars. Although ART and preventive strategies show the highest potential in the early mixed dentition, they alone cannot completely meet the dental needs of populations such as this where the severity and disease burden are extremely high.

A survey was conducted in Dry Savannah and Atakora agroecological zones in northern Togo, between March and July 2018, to characterise indigenous guinea fowl management practices. A semi-structured questionnaire was administered to 82 farmers in 28 villages. The data were analysed using the chi-square test or Fisher's exact test, independent-sample t test and the multiple correspondence analysis with SPSS and XLSTAT. The results showed that guinea fowl production was mainly practised by men (91.5%) who did not have training in guinea fowl production (68.4%). In traditional poultry farming, the most popular management method was the semi-intensive system (86.2%). Guinea fowl, which was raised primarily for sale (100%), was the main bird species with 68.2 ± 92.5 birds per farmer. All respondents provided a dietary supplement to guinea fowl with a feeding management that varied according to the birds' developmental stage. Wing drooping (89.3%), diarrhoea (67.4%) and drowsiness (64.7%) were the main clinical symptoms of diseases observed. The majority of respondents (68.2%) used both conventional veterinary products and ethno-veterinary plant products as drugs in order to control guinea fowl diseases. Guinea fowl started laying at 8.4 ± 1.6 months and had 128.5 ± 51.2 eggs per year. The indigenous hen that hatched eggs naturally had 43.6 ± 17.1 hatching eggs per year with a hatchability of 85.0%. For 85.4% of the respondents, survivability was the main problem in guinea fowl production. Improving the survivability of the birds could improve their productivity, as they play an important socio-economic role for most rural households.

Enterovirus A71 (EV71) is one of the major causative agents of hand, foot and mouth disease (HFMD), and is sometimes associated with severe central nervous system syndromes. Vaccines against EV71 infection have been developed or are in development in several countries and few have been licensed in China. In response to requests from some of these countries, WHO convened a working group meeting in Shanghai China from 11 to 12 September 2019 to develop WHO Recommendations to assure the quality, safety and efficacy of EV71 vaccines. Meeting participants included members of the drafting group, experts from vaccine developers, manufacturers, regulators and academia. The epidemiology of EV71, as well as the development, regulation and standardization of EV71 vaccines were reviewed in the meeting. Information on R&D, manufacturing, quality control and standardization of EV71 vaccines was presented by vaccine developers, manufacturers and regulators. Based on their experience, the working group discussed the main principles that would determine WHO’s position on quality, safety and efficacy of EV71 vaccines. The working group agreed to develop WHO Recommendations to assure the quality, safety and efficacy of inactivated EV71 vaccines with a scope covering only whole virus inactivated vaccines. Other type of vaccines, such as EV71 virus-like particles (VLPs) will not be covered as they are still at the developmental stage. The outline of the document was agreed and will follow the usual style of WHO recommendations. It was also agreed to submit the draft Recommendations for review and adoption to the WHO ECBS in 2020 following discussion at a WHO informal consultation, which will include NRAs and vaccine manufacturers.

This report provides three-phase concept for treating skeletal Class III growing patients with severe space deficiency. Three cases are presented. All had received miniplate-anchored facemask treatment and followed till near completion of growth. Infrazygomatic miniplates were used for both facemask protraction and distalization of the dentition to relieve crowding. With the aid of bone-anchored facemask, maxillary protraction may be continued independent of the orthodontic tooth movement even in late postpubertal growth peak stage. With cephalometric superimpositions using the structural method, we have demonstrated how vertical dental change could affect the skeletal changes and overall clinical outcomes. The persistent mandibular growth during pubertal growth spurt plays a main role in decreasing the effects of maxillary protraction. To keep up with the mandibular growth, we recommend using skeletally anchored facemask long-term till the end of growth spurt. Applying maxillary protraction from infrazygomatic miniplates exposed at the molar area has the merits that it avoids unwanted palatal rotation and that the miniplates maybe used as orthodontic anchorage when indicated. We emphasize the importance of planning the treatment contemplating the skeletal developmental stage and the completion of dental arches. This prolonged orthopedic treatment may contribute to greater long-term effects and stability. Keywords: Class III, Maxillary protraction, Skeletal anchorage

Aim: It has been reported that repeated sevoflurane exposure induces cognitive impairment. On the other hand, there is evidence that rivastigmine can attenuate or antagonize the cognitive dysfunctions caused by anesthetic agents. The aims of this study were to determine the effect of repeated sevoflurane exposure on spatial learning and memory (SLM) in weanling rats and to assess whether rivastigmine provides protection against the neurotoxic effects of sevoflurane at this early developmental stage. Methods: Thirty-two weanling rats were randomly divided into four equal groups: sevoflurane (S: 2% sevoflurane for 2 hours), sevoflurane + rivastigmine (SR: 2% sevoflurane and 2 mg/kg rivastigmine), rivastigmine (R: 2 mg/kg), and control (C: 100% oxygen for 2 hours). Rats were treated four times over 10 days. Four days after the last treatment, the rats were subjected to a Morris water maze test protocol to examine SLM.Results: The escape latencies of all groups gradually decreased day by day during the training trials performed to evaluate spatial learning (ρ0.05).Conclusion: Sevoflurane negatively affects learning in weanling rat pups but has no detrimental effect on spatial memory. On the other hand, it can be claimed that sevoflurane offsets the memory-sparing effects of rivastigmine.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality worldwide, wherein treatment still remains a challenge. A promising experimental treatment for tumors that can potentially overcome some of the limitations faced by conventional therapies for HCC is nanoparticle – mediated hyperthermia (NMH). Currently at the developmental stage, NMH usually utilizes gold or iron oxide nanoparticles to convert radiofrequency or alternating magnetic field into heat that causes targeted cell death. In order to assess the effectiveness of NMH on a greater scale, and in the face of varying levels of effectiveness in published literature, this meta-analysis was conducted. A systematic literature search identified relevant studies in gold and iron oxide NMH for HCC cell lines published from 2008 – January 2019. Seven studies met the inclusion criteria, wherein three studies used gold NMH, and the remaining four used iron oxide NMH. Outcome of interest is cell viability after irradiation in the presence of the nanoparticles. A pooled risk ratio with 95% confidence interval (CI) was calculated using a random effects model. Iron oxide – based NMH was able to decrease HCC cell viability by 87% while 19% for gold-based NMH. Moderate to high heterogeneity is attributed to the different classes of nanoparticles, concentration, cell lines, and irradiation duration used in the pooled studies. The results provide encouraging insights for the continuous development of NMH for cancer treatment. Considering that iron oxide is more cost-effective than gold nanoparticles, focusing on the development of iron oxide nanoparticles for this nanomedical technology may accelerate the development and clinical application of NMH.

International audience; Fish oocyte development monitoring is a mandatory operation when studying breeding in captivity as well as in the wild. In aquaculture, it is required to determine the best fertilization time. In the wild, it helps to detect spawning grounds, the distribution of fish species and the interaction between animals and their environment. In both settings, the conventional technique for developmental stage identification consists of handling the fish for oocyte sampling and sample observation using a binocular zoom head. Such an operation is difficult for the operator as well as for the fish. There is a need for repeated anesthesia and oocyte sampling, and it relies on operator expertise to identify the developmental stage. In this context, this publication proposes, for the first time, to study the potential of bioimpedance measurement as an alternative in fish breeding studies. We have set up an experiment combining the in vitro bioimpedance measurement of sampled oocytes with the conventional estimation technique for 69 sampled collected on farmed European sea bass. The statistical analysis has demonstrated that three of the four main developmental stages can be identified using bioimpedance measurement. The integrability of the bioimpedance technique with its implantable sensor makes this potential alternative approach very promising. Thanks to this sensor it could be possible, for the first time ever, to monitor in vivo the oocyte developmental stage in captivity as well as in the wild.

Many experimental procedures include steps where different developmental stages of zebrafish are subjected to painful or stressful procedures. Analgesia and anesthesia are in most cases used to suppress distress and/or pain sensation/perception. While anesthesia is often used mainly to immobilize animals for surgical and nonsurgical procedures, analgesia is a fairly new aspect added to zebrafish protocols to take into account the increasing awareness of pain sensation and animal welfare in fish. The decision concerning effective, safe, and humane methods of analgesia and anesthesia that are ethically justifiable as well as scientifically reproducible is still difficult and depends on the specific situation. There are different procedures with different levels of invasiveness and duration to which analgesia and anesthesia protocols must be adapted, as there is no “one size fits all.” Euthanasia or humane killing might be applied due to protocol requirements, but also to avoid more suffering, applying a final pain relief if ethical justification of a harmful state of the animal is not given. There are several euthanasia methods depending on the purpose and developmental stage of the animal. Chemical substances are involved in all the referred procedures, analgesia, anesthesia, and chemical euthanasia, thus one has to pay attention to legal considerations. In this chapter, we will discuss different protocols for analgesia, anesthesia, and euthanasia based on the different requirements of various protocols.

Omics data can be used to identify biological characteristics from genetic to phenotypic levels during the life span of a living being, while molecular interaction networks have a fundamental impact on life activities. Integrating omics data and molecular interaction networks will help researchers delve into comprehensive information hidden in the data. Here, we propose a new multimodal method — AutoGGN — to integrate multi-omics data with molecular interaction networks based on graph convolutional neural networks (GCNs). We evaluated AutoGGN using three classification tasks: single-cell embryonic developmental stage classification, pan-cancer type classification, and breast cancer subtyping. On all three tasks, AutoGGN showed better performance than other methods. This means AutoGGN has the potential to extract insights more effectively by means of integrating molecular interaction networks with multi-omics data. Additionally, in order to provide a better understanding of how our model makes predictions, we utilized the SHAP module and identified the key genes contributing to the classification, providing insight for the design of downstream biological experiments.

Heterogeneity in breast cancer leads to diverse morphological features and different clinical outcomes. There are inherent differences in breast cancer between the populations in Asia and in western countries. The use of immune-based treatment in breast cancer is currently in the developmental stage. The VGH-TAYLOR study is designed to understand the genetic profiling of different subtypes of breast cancer in Taiwan and define the molecular risk factors for breast cancer recurrence. The T-cell receptor repertoire and the potential effects of immunotherapy in breast cancer subjects is evaluated. The favorable biomarkers for early detection of tumor recurrence, diagnosis and prognosis may provide clues for the selection of individualized treatment regimens and improvement in breast cancer therapy.Lay abstract We describe the rationale and design for the VGH-TAYLOR study, which includes Taiwanese patients with breast cancer and with a wide spectrum of clinical scenarios covering different breast cancer subtypes and clinical settings, such as the neoadjuvant, adjuvant and metastatic settings. The gene expression profile and genetic mutations of breast cancer subjects with the primary and recurrent tumors are compared. We also explore whether immune-related gene expression and diversity have any impact on response to treatment and survival. This study aims to discover biomarkers of detection of cancer relapse, diagnosis and prognosis that may enable personalized medicine and improvement in breast cancer treatment.

Purpose: Adolescent patients with cancer experience unique stressors due to their developmental stage, with increased physical, emotional, and social distress. Palliative care (PC) serves an import...

Pregnancy is a tightly regulated immunological state. Mild environmental perturbations can affect the developing fetus significantly. Infections can elicit severe immunological cascades in the mother's body as well as the developing fetus. Maternal infections and resulting inflammatory responses can mediate epigenetic changes in the fetal genome, depending on the developmental stage. The craniofacial development begins at the early stages of embryogenesis. In this review, we will discuss the immunology of pregnancy and its responsive mechanisms on maternal infections. Further, we will also discuss the epigenetic effects of pathogens, their metabolites and resulting inflammatory responses on the fetus with a special focus on craniofacial development. Understanding the pathophysiological mechanisms of infections and dysregulated inflammatory responses during prenatal development could provide better insights into the origins of craniofacial birth defects.

Background Few longitudinal studies have examined associations of child weight trajectories, maternal demandingness and responsiveness during feeding, and child self-regulation. Objective We examined if child weight-for-length trajectories from 6 weeks to 2 years of age were associated with maternal demandingness and responsiveness at child age 3 years old, and if maternal feeding dimensions predicted child BMI trajectories from 4.5 to 7.5 years among Mexican American children from low-income families. Child self-regulation was evaluated as a potential mechanism linking maternal feeding with child BMI. Method Child (N = 322) weight and length/height were assessed at 10 timepoints from 6 weeks through 7.5 years. Mothers completed the Caregiver Feeding Style Questionnaire when the child was 3 years of age. Results A steeper slope of weight-for-length z scores from 6 weeks to 2 years (indicating more rapid weight gain) was associated with less maternal demands during feeding at 3 years. More maternal demandingness at child age 3 years predicted lower child BMI at 4.5 years, but not trajectories from 4.5 to 7 years. Child self-regulation was not associated with child BMI from 4.5 to 7.5 years. Conclusion The findings highlight how the relationship between mothers and children during feeding can be bidirectional and potentially influenced by the developmental stage.

Tooth eruption is defined as the movement of a tooth from its site of development within the alveolar process to its functional position in the oral cavity. It is a complex process that can be influenced by a number of general factors like genetics, nutrition, preterm birth, socioeconomic factors, hormonal factors, various systemic diseases and some local factors. Timing of tooth eruption depends on the chronologic age. Marked deviation in eruption timing and developmental stage at which tooth erupts may confuse a clinician and affect the treatment planning so knowledge of such cases helps in delivering proper treatment. This article reports a case where eruption of rootless premolar is seen in a child of 7 year of age.

Research interests in machine learning (ML) and supply chain management (SCM) have yielded an enormous amount of publications during the last two decades. However, in the literature, there was no systematic examination on the research development in the discipline of ML application, in particular in SCM. Therefore, this study was carried out to present the latest research trends in the discipline by analyzing the publications between 1998/01/01 and 2018/12/31 in five major databases. The quantitative analysis of 123 shortlisted articles showed that ML applications in SCM were still in a developmental stage since there were not enough high-yielding authors to form a strong group force in the research of ML applications in SCM and their publications were still at a low level; even though 10 ML algorithms were found to be frequently used in SCM, the use of these algorithms were unevenly distributed across the SCM activities most frequently reported in the articles of the literature. The aim of this study is to provide a comprehensive view of ML applications in SCM, working as a reference for future research directions for SCM researchers and application insight for SCM practitioners.

The purpose of this research is determine the value of startup valuation from qualitative and quantitative factors on startup kostpedia.id. Kostpedia.id is a platform to help migrants in Indonesia to find and order residential dwellings. Kostpedia needs funds to support all of its operational and development activities, such as introducing Kostpedia.id to residents of rent and needs its own office. To get funding from investors requires startup valuation using the scorecard valuation method. Scorecard valuation method, which is a method for comparing similar companies at the same developmental stage with non-financial indicators.

Pediatric medical traumatic stress (PMTS) is common among injured/ill children and is associated with elevated distress, treatment non-adherence, and poor health outcomes. As survivorship of life-threatening pediatric injury and illness continues to increase alongside rapid medical advancements, rates of PMTS and negative sequelae are expected to grow; however, research on prevention and treatment of PMTS is limited. The current study sought to systematically review the literature using a developmental framework to highlight research gaps. Sixteen peer-reviewed studies were identified via a systematic literature search. Consistent with best practices for treatment of childhood trauma, caregiver involvement and CBT principles served as the foundation for most interventions. All studies reported improvements in PMTS; however, among the most methodologically rigorous, few found statistically superior reductions in PMTS between intervention and control groups. While many studies focused on a specific developmental stage and discussed developmental considerations, others took a "one-size-fits" approach. Interventions that demonstrated the most promising findings were online, self-guided, or time-limited. Future research would benefit from expanding diversity of participants, continuing to evaluate novel delivery methods, and integrating developmental considerations along with trauma-informed care (TIC) approaches, given their useful framework for understanding child traumatic stress responses and avenues for prevention and treatment.

Aflatoxins are carcinogenic secondary metabolites produced mainly by two species of Aspergillus fungi, (A. flavus and A. parasiticus). The toxin contaminates maize grains during the developmental stage as well as in storage. Grains with contamination levels above 20 ng/g are usually destroyed in the USA while the European Union and Japan allow 2–4 ng/g and nil respectively. Ghana lacks regulatory infrastructure for monitoring fungal contamination and detection of aflatoxin in grains prior to market. Therefore, this study assessed the extent of A. flavus contamination together with other mould on maize and total aflatoxin accumulation among stored maize grains across 34 towns and villages under three agro-ecologies in Ghana during the minor crop season of 2015–2016. A. flavus, was identified as the most predominant contaminant and recorded average percentage contamination of 56.7%, 30.6%, 53.5% and 45.6% on grains sampled across four communities (Fumesua, Wenchi, Ejura and Akomadan), respectively. Total aflatoxins recorded in the samples per community were in the range of below limit of detection (LOD) to 692 ng/g, 23 ng/g, 945 ng/g and 112 ng/g for Fumesua, Wenchi, Ejura and Akomadan, respectively. These dangerous upper limits demand urgent attention in the area of aflatoxin resistance breeding in maize to help address the aflatoxin menace in Ghana.

Adolescence is noted as a time of "storm and stress." In this developmental stage both rodents and humans exhibit an impairment in the extinction of learned fear; however, this impairment can be alleviated, at least in rodents, by increasing the amount of extinction training given or by administering the partial NMDA receptor agonist D-Cycloserine. In the present study we explored whether the benefits of these treatments would be reduced by chronic exogenous corticosterone (a commonly studied stress-related hormone). In 2 experiments, adolescent rats were given pairings of a white noise and shock (acquisition) and then given extinction training (white noise presented alone). In Experiment 1, adolescents exhibited impaired extinction retention even after 2 days of extinction training if they had been exposed to corticosterone in adolescence but not if the exposure occurred when they were juveniles. In Experiment 2, exposure to exogenous corticosterone in adolescence, but not during the juvenile period, reduced the efficacy of the pharmacological adjunct D-Cycloserine at enhancing extinction retention after 1 day of extinction training. Taken together, the results support the idea that adolescence is a time of particular susceptibility to elevated levels of the stress hormone corticosterone. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Objective To report evidence regarding pain assessment and management for children and adolescents receiving treatment for cancer. Data Sources Published research and clinical guidelines. Conclusion Children and adolescents experience multiple sources of pain across the cancer continuum. They require developmentally relevant approaches when assessing and managing pain. This review suggests that consideration of the developmental stage and age of the child are essential in both pain assessment and pain management. Implications for Nursing Practice Pediatric oncology nurses play a key role in developmentally appropriate pain assessment, identification of potential strategies to manage pain, and delivery of pharmacologic and nonpharmacologic therapies.

Adolescents are at a unique developmental stage that is well-primed for epidemiology instruction. Although a handful of pioneers have focused on expanding epidemiology instruction to teen audiences, there are still no systematic efforts in the United States to attain this goal. In this paper I posit that epidemiologists and other public health professionals are critical to this effort. Epidemiologists from public health agencies, academia and non-profit organizations can engage in partnerships with schools, such as by offering internships and pairing graduate students/mentees with teachers and adolescent learners. Through these efforts, we can leverage teens' natural interests in risk taking, health and wellness, and community change to learn population-level thinking. I posit that these measures can encourage widespread exposure to epidemiology principles, and also enhance the future of public health disciplines.

Optical diagnosis of diminutive colorectal polyps has been recently proposed as an alternative to histopathologic diagnosis. Recent developments in imaging techniques, new classification systems, and the use of artificial intelligence have allowed for increased viability of optical diagnosis. This review provides an up-to-date overview of optical diagnosis recommendations, classifications, outcomes, and recent developments. There are currently seven major classification systems and three major society recommendations for quality benchmarks for optical diagnosis of diminutive polyps. The NICE classification has been extensively studied and meets quality benchmarks for most imaging techniques but does not allow for the diagnosis of sessile serrated polyps (SSPs). The SIMPLE classification has met quality benchmarks for NBI and i-Scan and allows for the diagnosis of SSPs. Other classification systems need to be further studied to validate effectiveness. Computer-assisted diagnosis of colorectal polyps is a very promising recent development with first studies showing that society-recommended quality benchmarks for real-time colonoscopies on patients are being met. Limitations include a non-negligible percentage of failure to diagnose, low specificity, and low number of real-time diagnostic studies. More research needs to be performed to further understand the value of artificial intelligence for optical polyp diagnosis. Optical diagnosis of diminutive colorectal polyps is currently a viable strategy for experienced endoscopists using validated classifications and imaging-enhanced endoscopy. Artificial intelligence–based diagnosis could make optical diagnosis widely applicable but is currently in its early developmental stage.

Care for a child with spina bifida can be complex, requiring multiple specialists. Neurosurgical care centers around the initial closure or repair of the spinal defect, followed by management of hydrocephalus, symptoms of the Chiari 2 malformation, and tethered cord. This article reviews definitions and types of spina bifida, considerations surrounding the initial treatment, including fetal surgery, and the ongoing neurosurgical management of common comorbid conditions. The role of interdisciplinary care is stressed, as well as the importance of coordinated transition to adult care at an appropriate age and developmental stage.

Severe acute respiratory syndrome [SARS]-CoV-2, which is the causative agent of Coronavirus Disease 2019 [COVID-19] disease, has engulfed more than 2.4 million people and still counting. As this pandemic is at its peak and is responsible for more than 100 million infected people worldwide, there is an urgent need to develop an effective vaccine to stop the COVID-19 disease. More than 220 vaccine candidates are in the pre-development stage while 15 candidates are in the developmental stage, from which Pfizer/BioNTech, Moderna, and some other vaccines have received approval by some countries for emergency use only. Fever, tiredness, headache, joint pain, swelling at the injection site and some other common effects have been found by using these vaccines. Efficacy, rapid mass production, and long-term immunity as well as acceptance of vaccination by society are the main challenges in developing a safe vaccine against COVID-19 despite the fact that some vaccines have over 90% efficiency against COVID-19 and are useful in developing immunity as well.

Aim To describe the variation of eruption pattern of maxillary canines in the late mixed stage of dentition seen in PTG when eruption was later natural. Methods Material for this longitudinal and retrospective register-based study consisted of 1454 PTGs of children living in Eastern Finland (mean age 9.3 years, SD 0.6). Natural eruption of a canine consisted of 744 PTGs (336 girls and 408 boys) including 1488 maxillary canines. The variables examined were treatment/natural eruption, overlapping, inclination, dental age, developmental stage of the canine and lateral incisor. Results Only 2.0% of maxillary canines had clear overlapping and 56.2% no overlapping was detected at the age of 8.5–10.5 years. Large inclination angle (≥ 25°) was found for 5.5% of examined canines. Overlapping of canine with lateral incisor root decreased as the development of canine root exceeded 1/3. Larger inclinations occurred at earlier stages but decreased significantly as the root developed from 1/3 to 1/2. Mean inclination was significantly larger at children with normal dental age and/or incomplete lateral incisors when overlapping occurred. Regardless overlapping mean inclination was larger if dental age was delayed and/or lateral incisors incomplete. Conclusion Some overlapping and larger inclination in maxillary canine are features of normal eruption pattern at an earlier stage of canine development and while lateral incisor is incomplete in PTG (8.5–10.5 years). In addition to the overlapping and inclination, stages of canine and lateral incisor root as well as dental age should be observed radiologically when evaluating erupting maxillary canine in children of this age.

Despite the relative frequency of both bleeding and clotting disorders among patients treated in the neonatal intensive care unit, few clear guidelines exist for treatment of neonatal coagulopathies. The study and treatment of neonatal coagulopathies are complicated by the distinct hemostatic balance and clotting components present during this developmental stage as well as the relative scarcity of studies specific to this age group. This mini-review examines the current understanding of neonatal hemostatic balance and treatment of neonatal coagulopathies, with particular emphasis on emerging treatment methods and areas in need of further investigative efforts.

To assess and compare the developmental stages and angulations of third molars between the class II and class I sides in class II subdivision malocclusions.This retrospective study was performed using panoramic x‑rays of 38 individuals (mean age: 15.5 years; 24 females, 14 males) with class II subdivision malocclusions, which were further divided into type 1 and 2 subgroups according to midline deviation, and a control group of 42 individuals (mean age: 17.0 years; 30 females, 12 males) with normal occlusion. Third molars were categorized using the developmental stages defined by the Demirjian method. Angles between the third molars and horizontal reference lines and also to the second molars were measured.No difference was found in developmental stages or angulations between the left and right third molars in the control group. In the class II subdivision malocclusion cases, no difference in third molar developmental stages was observed, but the angle between the long axes of the mandibular third and second molars was significantly greater on the class II side. In the type 2 subgroup, developmental stage of the maxillary third molar was more advanced on the class II side. In both subgroups, the angles of the maxillary third molars' long axis to the interorbital plane differed significantly between the two sides.Class II subdivision malocclusion may cause differences in third molar development and angulations between the two sides. Orthodontic treatment should be planned considering the third molars in this malocclusion.ZIELSETZUNG: Beurteilung und Vergleich der Entwicklungsstadien und Angulationen der dritten Molaren zwischen der Klasse-II- und Klasse-I-Seite bei Subdivisionsfehlstellungen der Klasse II.Diese retrospektive Studie wurde anhand der Panoramaröntgenbilder von 38 Personen (Durchschnittsalter: 15,5 Jahre; 24 Frauen, 14 Männer) mit Klasse-II-Subdivisionsfehlstellungen durchgeführt, die je nach Mittellinienabweichung in Untergruppen vom Typ 1 und 2 eingeteilt wurden, sowie einer Kontrollgruppe von 42 Personen (Durchschnittsalter: 17,0 Jahre; 30 Frauen, 12 Männer) mit normaler Okklusion. Die dritten Molaren wurden anhand der Entwicklungsstadien nach der Demirjian-Methode kategorisiert. Die Winkel zwischen den dritten Molaren und den horizontalen Referenzlinien sowie zu den zweiten Molaren wurden gemessen.In der Kontrollgruppe wurde kein Unterschied hinsichtlich der Entwicklungsstadien oder Achsstellung zwischen den linken und rechten dritten Molaren festgestellt. In der Untergruppe der Klasse-II-Fehlstellungen wurde kein Unterschied hinsichtlich der Entwicklungsstadien der dritten Molaren festgestellt, aber der Winkel zwischen den Längsachsen der dritten und zweiten Molaren des Unterkiefers war auf der Seite der Klasse II signifikant größer. In der Untergruppe Typ 2 war das Entwicklungsstadium des dritten Molaren im Oberkiefer auf der Klasse-II-Seite weiter fortgeschritten. In beiden Untergruppen unterschieden sich die Winkel der Längsachse der oberen dritten Molaren zur Interorbitalebene signifikant zwischen den beiden Seiten.Eine Klasse-II-Subdivisionsfehlstellung kann Unterschiede in der Entwicklung und der Achsstellung der dritten Molaren zwischen den beiden Seiten verursachen. Die kieferorthopädische Behandlung sollte bei dieser Malokklusion unter Berücksichtigung der dritten Molaren geplant werden.

Simple Summary The expansion of the aquaculture industry depends mainly on aquafeed availability at reasonable prices. The common ingredients of aquafeed (e.g., fish and soybean meals) are not sustainable due to a lack of resources and increasing prices. Seeking alternative non-traditional ingredients is among the choices of nutritionists to produce high-quality feed at a feasible cost. Yellow mealworms (Tenebrio molitor) (TM) have been introduced to the feed industry as protein sources of a circular economy. Many studies have investigated the possibility of including T. molitor meals as a substitute for fish and soybean meals in aquafeed. Thus, this review exclusively presents an assemblage of the literature on the possibility of including T. molitor in aquafeed as a suggestion for the sustainability of the aquaculture industry. Abstract The success of the aquafeed industry mainly depends on the availability of raw ingredients with high nutritional value, such as fishmeal (FM). However, the increased demand for FM elevates its prices and leads to high feed costs. Thus, there is an urgent need to find suitable alternatives for FM in fish diets to achieve sustainability in aquaculture. Currently, attention is being paid to the possibility of using insect meals as FM substitutes in aquafeed because of their relatively high nutritional quality. TM is one of those insects that can be regarded as a unique candidate because of its relatively high nutritional value. TM are rich sources of essential amino acids (methionine), lipids, and fatty acids, which vary based on the developmental stage of the worms. Although TM have an abundant amount of chitin as a fiber source and other anti-nutritional factors, numerous studies have investigated the efficacy of partial or complete substitution of FM by T. molitor in fish diets. In this context, we reviewed the current research findings on the achievable inclusion levels of T. molitor versus FM substitution in the diets of several finfish and shellfish species. We discussed the potential use of T. molitor as an FM substitute in fish diets and evaluated its effects on growth, biometric indices, and body composition. Besides, the hematological parameters, immunological responses, antioxidative efficacy, intestinal health status, and sensory criteria of fish fed T. molitor-based diets were also assessed.

Using interpretative phenomenological analysis and Robert Kegan’s constructive-developmental theory, this study investigated how developmental stage shaped the subjective experiences of 13 adolescents ( Mage= 15.92 years, 54% females) in a developmental coaching and outdoor adventure education program. Participants were drawn from socioeconomically disadvantaged schools in Sydney, Australia, and represented Asian, Middle Eastern, and European ethnicities. A single, semi-structured interview was conducted with participants postprogram, following protocols approved by an institutional ethics committee. Interview data were used to investigate participants’ meaning-making structures as evidence of constructive-developmental stage both at the time of interview and program participation. We found that, despite being similar ages at program commencement, participants displayed a range of constructive-developmental stages. The data demonstrate how participants at different stages of meaning-making experienced the same activities differently, including what they experienced as challenging and supportive. Furthermore, our findings suggest that there is a valuable role for developmental coaching in scaffolding program challenges to stimulate constructive-developmental growth. Constructive-developmental theory provides a novel framework for understanding the different ways in which adolescents make meaning of developmental programs. We hope the findings from this study will help those who design and implement these programs to appreciate constructive-developmental differences in their participants to better target interventions aimed at facilitating developmental growth.

Background: Adolescence is a developmental stage when there is a high risk of engaging in non-suicidal self-injury (NSSI). There is recent interest in the study of thwarted belongingness and perceived burdensome as variables associated with the frequency of NSSI in adolescents. Meaning in life (MIL) might be negatively associated with thwarted belongingness and perceived burdensomeness. To date, no studies have analyzed the buffering role of MIL in the association between thwarted belongingness and perceived burdensomeness and the frequency of lifetime NSSI in Spanish adolescents. Aims: (a) To test whether thwarted belongingness and perceived burdensomeness are associated with frequency of lifetime NSSI; (b) to test whether MIL moderates the association between thwarted belongingness and frequency of lifetime NSSI; and (c) to test whether MIL moderates the association between perceived burdensomeness and frequency of lifetime NSSI. Method: The sample consisted of N = 1531 participants (n = 736, 48.1%, were men, and n = 795, 51.9%, were women) between 12 and 18 years old from Spain. The participants filled out the Inventory of Statements about Self-Injury, Purpose-In-Life Test-Adolescent Version, and Interpersonal Needs Questionnaire. Moderation analyses were performed. Results: No statistically significant differences were found in the frequency of lifetime NSSI in the adolescents based on gender. Thwarted belongingness and perceived burdensomeness were positively associated with the frequency of lifetime NSSI in Spanish adolescents. MIL was a moderating variable between thwarted belongingness and the frequency of lifetime NSSI, and between perceived burdensomeness and the frequency of lifetime NSSI. Conclusions: Thwarted belongingness and perceived burdensomeness might be positively associated with the frequency of lifetime NSSI, and MIL might be negatively associated with the frequency of lifetime NSSI. Thus, adding these variables to current descriptive theories of NSSI in adolescents would allow us to improve assessment and treatment protocols for adolescents with NSSI. Keywords: Spanish adolescents; meaning in life; non-suicidal self-injuries; perceived burdensomeness; thwarted belongingness.

Software engineering emphasises to adopt a well-defined and structured approach to develop any software. Nonetheless, serious challenges exist in the software development process and these challenges are faced in developing software in today's scenario. This is majorly to satisfy the need for developing good quality product which has the capability to meet the “volatile user requirements” in organizations. As new products are developed to tend to the current technological needs, new challenges arise inevitably. So, until a new challenge is encountered, solutions to these unknown and newly arising challenges cannot be devised. Hence, a better software development strategy would be to realise all the previously encountered, more frequent or obvious challenges, and to design an efficient solution to these known challenges beforehand so that no more extra resources and time need to be diverted during the software development cycle in order to overcome the challenges. Therefore, recognizing and addressing the challenges in software development at each and every developmental stage is extremely necessary in order for organizations to succeed. In this study, the authors have attempted to structurally and systematically reviewing the literature to arrive at the software development challenges and provided ways of addressing those challenges. The study also provided for possible solutions and recommendations and scope for future research in this area.

Fetal alcohol spectrum disorder (FASD) remains one of the commonest causes of intellectual disability; however, the awareness amongst clinicians who see children with a possible FASD diagnosis remains limited. Children with FASD can present with physical as well as neurodevelopmental disorders. Professionals seeing children should be aware of the various ways in which the children can present at each developmental stage. Early detection of children with FASD and accompanying early intervention has been shown to result in a more favourable outcome for the children. There remains significant underrecognition and underdiagnosis of FASD in children seen by various clinicians including Paediatricians. Surveys have shown that many paediatricians are aware of FASD; however a significant number feel less confident in assessing children with suspected FASD [1].

Author(s): Jordan, Jaime; Bavolek, Rebecca A.; Dyne, Pamela L.; Richard, Chase E.; Villa, Stephen; Wheaton, Natasha | Abstract: Introduction: Professional development is an important component of graduate medical education, but it is unclear how to best deliver this instruction. Book clubs have been used outside of medicine as a professional development tool. We sought to create and evaluate a virtual professional development book club for emergency medicine interns.Methods: We designed and implemented a virtual professional development book club during intern orientation. Afterward, participants completed an evaluative survey consisting of Likert and free-response items. Descriptive statistics were reported. We analyzed free-response data using a thematic approach.Results: Of 15 interns who participated in the book club, 12 (80%) completed the evaluative survey. Most (10/12; 83.3%) agreed or strongly agreed that the book club showed them the importance of professional development as a component of residency training and helped them reflect on their own professional (11/12; 91.7%) and personal development (11/12; 91.7%). Participants felt the book club contributed to bonding with their peers (9/12; 75%) and engagement with the residency program (9/12; 75%). Our qualitative analysis revealed five major themes regarding how the book club contributed to professional and personal development: alignment with developmental stage; deliberate practice; self-reflection; strategies to address challenges; and communication skills.Conclusion: A virtual book club was feasible to implement. Participants identified multiple ways the book club positively contributed to their professional development. These results may inform the development of other book clubs in graduate medical education.

Wnt/β-catenin signaling has been broadly implicated in human cancers and experimental cancer models of animals. Aberrant activation of Wnt/β-catenin signaling is tightly linked with the increment of prevalence, advancement of malignant progression, development of poor prognostics, and even ascendence of the cancer-associated mortality. Early experimental investigations have proposed the theoretical potential that efficient repression of this signaling might provide promising therapeutic choices in managing various types of cancers. Up to date, many therapies targeting Wnt/β-catenin signaling in cancers have been developed, which is assumed to endow clinicians with new opportunities of developing more satisfactory and precise remedies for cancer patients with aberrant Wnt/β-catenin signaling. However, current facts indicate that the clinical translations of Wnt/β-catenin signaling-dependent targeted therapies have faced un-neglectable crises and challenges. Therefore, in this study, we systematically reviewed the most updated knowledge of Wnt/β-catenin signaling in cancers and relatively targeted therapies to generate a clearer and more accurate awareness of both the developmental stage and underlying limitations of Wnt/β-catenin-targeted therapies in cancers. Insights of this study will help readers better understand the roles of Wnt/β-catenin signaling in cancers and provide insights to acknowledge the current opportunities and challenges of targeting this signaling in cancers.

Examination of the placenta is an important tool for understanding adverse pregnancy outcomes. Best practice suggests that placental tissues from all pregnancies ending either spontaneously or for medical indications before 37 weeks be submitted for pathologic evaluation. Indications for submission after 37 weeks range from liberal to conservative and are the focus of two recent policy statements [1, 2]. These guidelines ensure a detailed and accurate recording of pathologically confirmed pregnancies by gestational age, developmental stage, and pathophysiologic category which can be very useful for subsequent clinical management and genetic counseling. It also ensures that, based on the pathologic findings, appropriate follow-up testing of the mother, fetus, or placenta can be initiated.