Severe loss-of-function mutations in the adrenocorticotropin receptor (ACTHR, MC2R) can be found in patients diagnosed with salt-losing adrenal hypoplasia

Objective: Familial glucocorticoid deficiency type I (FGD1) is a rare form of primary adrenal insufficiency resulting from recessive mutations in the ACTH receptor (MC2R, MC2R). Individuals with this condition typically present in infancy or childhood with signs and symptoms of cortisol insufficiency, but disturbances in the renin-angiotensin system, aldosterone synthesis or sodium homeostasis are not a well-documented association of FGD1. As ACTH stimulation has been shown to stimulate aldosterone release in normal controls, and other causes of hyponatraemia can occur in children with cortisol deficiency, we investigated whether MC2R changes might be identified in children with primary adrenal failure who were being treated for mineralocorticoid insufficiency. Design: Mutational analysis of MC2R by direct sequencing. Patients: Children (n = 22) who had been diagnosed with salt-losing forms of adrenal hypoplasia (19 isolated cases, 3 familial), and who were negative for mutations in DAX1 (NR0B1) and SF1 (NR5A1). Results: MC2R mutations were found in three individuals or kindred (I: homozygous S74I; II: novel compound heterozygous R146H/560delT; III: novel homozygous 579-581delTGT). These changes represent severely disruptive loss-of-function mutations in this G-protein coupled receptor, including the first reported homozygous frameshift mutation. The apparent disturbances in sodium homeostasis were mild, manifest at times of stress (e.g. infection, salt-restriction, heat), and likely resolved with time. Conclusions: MC2R mutations should be considered in children who have primary adrenal failure with apparent mild disturbances in renin-sodium homeostasis. These children may have been misdiagnosed as having salt-losing adrenal hypoplasia. Making this diagnosis has important implications for treatment, counselling and long-term prognosi

Validation of the Waterpipe Tolerance Questionnaire Among Jordanian School-Going Adolescent Waterpipe Users

INTRODUCTION: Waterpipe use among adolescents has been increasing progressively. Yet no studies were reported to assess the validity and reliability of nicotine dependence scale. The current study aims to assess the validity and reliability of an Arabic version of the modified Waterpipe Tolerance Questionnaire WTQ among school-going adolescent waterpipe users. METHODS: In a cross-sectional study conducted in Jordan, information on waterpipe use among 333 school-going adolescents aged 11-18 years was obtained using the Arabic version of the WTQ. An exploratory factor analysis and correlation matrices were conducted to assess validity and reliability of the WTQ. RESULTS: The WTQ had a 0.73 alpha of internal consistency indicating moderate level of reliability. The scale showed multidimensionality with items loading on two factors, namely waterpipe consumption and morning smoking. CONCLUSION: This study report nicotine dependence level among school-going adolescents who identify themselves as waterpipe users using the WTQ

Website Phishing Detection Using Machine Learning Techniques

Phishing is a cybercrime that is constantly increasing in the recent years due to the increased use of the Internet and its applications. It is one of the most common types of social engineering that aims to disclose or steel users sensitive or personal information. In this paper, two main objectives are considered. The first is to identify the best classifier that can detect phishing among twenty-four different classifiers that represent six learning strategies. The second objective aims to identify the best feature selection method for websites phishing datasets. Using two datasets that are related to Phishing with different characteristics and considering eight evaluation metrics, the results revealed the superiority of RandomForest, FilteredClassifier, and J-48 classifiers in detecting phishing websites. Also, InfoGainAttributeEval method showed the best performance among the four considered feature selection methods

The validity and reliability of the exposure index as a metric for estimating the radiation dose to the patient

Introduction With the introduction of digital radiography, the feedback between image quality and over-exposure has been partly lost which in some cases has led to a steady increase in dose. Over the years the introduction of exposure index (EI) has been used to resolve this phenomenon referred to as ‘dose creep’. Even though EI is often vendor specific it is always a related of the radiation exposure to the detector. Due to the nature of this relationship EI can also be used as a patient dose indicator, however this is not widely investigated in literature. Methods A total of 420 dose-area-product (DAP) and EI measurements were taken whilst varying kVp, mAs and body habitus on two different anthropomorphic phantoms (pelvis and chest). Using linear regression, the correlation between EI and DAP were examined. Additionally, two separate region of interest (ROI) placements/per phantom where examined in order to research any effect on EI. Results When dividing the data into subsets, a strong correlation between EI and DAP was shown with all R-squared values > 0.987. Comparison between the ROI placements showed a significant difference between EIs for both placements. Conclusion This research shows a clear relationship between EI and radiation dose which is dependent on a wide variety of factors such as ROI placement, body habitus. In addition, pathology and manufacturer specific EI’s are likely to be of influence as well. Implications for practice The combination of DAP and EI might be used as a patient dose indicator. However, the influencing factors as mentioned in the conclusion should be considered and examined before implementation

Effects of body part thickness on low‐contrast detail detection and radiation dose during adult chest radiography

Introduction Differences in patient size often provide challenges for radiographers, particularly when choosing the optimum acquisition parameters to obtain radiographs with acceptable image quality (IQ) for diagnosis. This study aimed to assess the effect of body part thickness on IQ in terms of low‐contrast detail (LCD) detection and radiation dose when undertaking adult chest radiography (CXR). Methods This investigation made use of a contrast detail (CD) phantom. Polymethyl methacrylate (PMMA) was utilised to approximate varied body part thicknesses (9, 11, 15 and 17 cm) simulating underweight, standard, overweight and obese patients, respectively. Different tube potentials were tested against a fixed 180 cm source to image distance (SID) and automatic exposure control (AEC). IQ was analysed using bespoke software thus providing an image quality figure inverse (IQFinv) value which represents LCD detectability. Dose area product (DAP) was utilised to represent the radiation dose. Results IQFinv values decreased statistically (P = 0.0001) with increasing phantom size across all tube potentials studied. The highest IQFinv values were obtained at 80 kVp for all phantom thicknesses (2.29, 2.02, 1.8 and 1.65, respectively). Radiation dose increased statistically (P = 0.0001) again with increasing phantom thicknesses. Conclusion Our findings demonstrate that lower tube potentials provide the highest IQFinv scores for various body part thicknesses. This is not consistent with professional practice because radiographers frequently raise the tube potential with increased part thickness. Higher tube potentials did result in radiation dose reductions. Establishing a balance between dose and IQ, which must be acceptable for diagnosis, can prevent the patient from receiving unnecessary additional radiation dose

Characteristics of post hoc subgroup analyses of oncology clinical trials: A systematic review

BACKGROUND: Subgroup analyses in clinical trials assess intervention effects on specific patient subgroups, ensuring generalizability. However, they are usually only able to generate hypotheses rather than definitive conclusions. This study examined the prevalence and characteristics of post hoc subgroup analysis in oncology. METHODS: We systematically reviewed published subgroup analyses from 2000 to 2022. We included articles presenting secondary, post hoc, or subgroup analyses of interventional clinical trials in oncology, cancer survivorship, or cancer screening, published separately from the original clinical trial publication. We collected cancer type, year of publication, where and how subgroup analyses were reported, and funding. RESULTS: Out of 16 487 screened publications, 1612 studies were included, primarily subgroup analyses of treatment trials for solid tumors (82%). Medical writers contributed to 31% of articles, and 58% of articles reported conflicts of interest. Subgroup analyses increased significantly over time, with 695 published between 2019 and 2022, compared to 384 from 2000 to 2014. Gastrointestinal tumors (25%) and lymphoid lineage tumors (39%) were the most frequently studied solid and hematological malignancies, respectively. Industry funding and reporting of conflicts of interest increased over time. Subgroup analyses often neglected to indicate their secondary nature in the title. Most authors were from high-income countries, most commonly North America (45%). CONCLUSIONS: This study demonstrates the rapidly growing use of post hoc subgroup analysis of oncology clinical trials, revealing that the majority are supported by pharmaceutical companies, and they frequently fail to indicate their secondary nature in the title. Given the known methodological limitations of subgroup analyses, caution is recommended among authors, readers, and reviewers when conducting and interpreting these studies

Defining criteria for disease activity states in systemic juvenile idiopathic arthritis based on the systemic Juvenile Arthritis Disease Activity Score

Objective To develop and validate cutoff values in the systemic Juvenile Arthritis Disease Activity Score 10 (sJADAS10) that distinguish the states of inactive disease (ID), minimal disease activity (MiDA), moderate disease activity (MoDA), and high disease activity (HDA) in children with systemic juvenile idiopathic arthritis (sJIA), based on subjective disease state assessment by the treating pediatric rheumatologist. Methods The cutoffs definition cohort was composed of 400 patients enrolled at 30 pediatric rheumatology centers in 11 countries. Using the subjective physician rating as an external criterion, 6 methods were applied to identify the cutoffs: mapping, calculation of percentiles of cumulative score distribution, Youden index, 90% specificity, maximum agreement, and ROC curve analysis. Sixty percent of the patients were assigned to the definition cohort and 40% to the validation cohort. Cutoff validation was conducted by assessing discriminative ability. Results The sJADAS10 cutoffs that separated ID from MiDA, MiDA from MoDA, and MoDA from HDA were ≤ 2.9, ≤ 10, and > 20.6. The cutoffs discriminated strongly among different levels of pain, between patients with or without morning stiffness, and between patients whose parents judged their disease status as remission or persistent activity/flare or were satisfied or not satisfied with current illness outcome. Conclusion The sJADAS cutoffs revealed good metrologic properties in both definition and validation cohorts, and are therefore suitable for use in clinical trials and routine practice

The steel–concrete interface

Although the steel–concrete interface (SCI) is widely recognized to influence the durability of reinforced concrete, a systematic overview and detailed documentation of the various aspects of the SCI are lacking. In this paper, we compiled a comprehensive list of possible local characteristics at the SCI and reviewed available information regarding their properties as well as their occurrence in engineering structures and in the laboratory. Given the complexity of the SCI, we suggested a systematic approach to describe it in terms of local characteristics and their physical and chemical properties. It was found that the SCI exhibits significant spatial inhomogeneity along and around as well as perpendicular to the reinforcing steel. The SCI can differ strongly between different engineering structures and also between different members within a structure; particular differences are expected between structures built before and after the 1970/1980s. A single SCI representing all on-site conditions does not exist. Additionally, SCIs in common laboratory-made specimens exhibit significant differences compared to engineering structures. Thus, results from laboratory studies and from practical experience should be applied to engineering structures with caution. Finally, recommendations for further research are made

Transitioning from recruit to officer : An investigation of how stress appraisal, and coping influence engagement

This study investigated stress, coping, and work engagement among Portuguese police officers while undergoing academy training and then 1 year later, when on duty. It was hypothesized that stress appraisal and coping preferences predicted engagement. Additionally, in order to test a full cross‐lagged prediction model, it was hypothesized that stress, coping, and engagement in recruits predicted these variables later when working as police officers. Structural equation modeling was used to test the research hypotheses. Results suggest that coping and stress appraisals do not seem to be strong predictors of work engagement among recruits and police officers on duty. With the exception of self‐blame, that seems to be a strong predictor of work engagement among police officers on duty. These results highlight the need to investigate other potential variables such as working conditions that may better explain work engagement. Considering the positive influence of engagement on health, wellbeing, and performance of police recruits and officers future applied and theoretical implications are discussed.Fundação para a Ciência e a Tecnologia - FCT; FEDERinfo:eu-repo/semantics/acceptedVersio