Tungsten nuclear rocket, phase II, part 1 Final report, Jan. 16 - Jun. 15, 1966

Critical experiments and nuclear analyses of tungsten water moderated nuclear rocket reacto

Content uniformity of quartered hydrocortisone tablets in comparison with mini-tablets for paediatric dosing

Objectives Children requiring cortisol replacement therapy are often prescribed hydrocortisone doses of 2.5 mg, but as this is commercially unavailable 10 mg tablets, with functional break lines, are split commonly in an attempt to deliver the correct dose. This study aimed to determine the dose variation obtained from quartered hydrocortisone tablets when different operators performed the splitting procedure and to ascertain whether better uniformity could be attained from mini-tablets as an alternative formulation. Methods Hydrocortisone 10 mg tablets were quartered by four different operators using a standard pill splitter. Hydrocortisone 2.5 mg mini-tablets (3 mm diameter) were formulated using a wet granulation method and manufactured using a high-speed rotary press simulator. The weight and content uniformity of the quartered tablets and mini-tablets were assessed according to pharmacopoeial standards. The physical strength and dissolution profiles of the mini-tablets were also determined. Results More than half of all quartered 10 mg tablets were outside of the ±10% of the stated US Pharmacopoeia hydrocortisone content (mean 2.34 mg, SD 0.36, coefficient of variation (CV) 15.18%) and more than 40% of the quartered tablets were outside the European Pharmacopoeia weight variation. Robust mini-tablets (tensile strengths of >4 MPa) were produced successfully. The mini-tablets passed the pharmacopoeial weight and content uniformity requirements (mean 2.54 mg, SD 0.04, CV 1.72%) and drug release criteria during in vitro dissolution testing. Conclusion This study confirmed that quartering 10 mg hydrocortisone tablets produces unacceptable dose variations and that it is feasible to produce 3 mm minitablets containing more accurate doses for paediatric patients

ADRIC: Adverse Drug Reactions In Children - a programme of research using mixed methods

Aims To comprehensively investigate the incidence, nature and risk factors of adverse drug reactions (ADRs) in a hospital-based population of children, with rigorous assessment of causality, severity and avoidability, and to assess the consequent impact on children and families. We aimed to improve the assessment of ADRs by development of new tools to assess causality and avoidability, and to minimise the impact on families by developing better strategies for communication. Review methods Two prospective observational studies, each over 1 year, were conducted to assess ADRs in children associated with admission to hospital, and those occurring in children who were in hospital for longer than 48 hours. We conducted a comprehensive systematic review of ADRs in children. We used the findings from these studies to develop and validate tools to assess causality and avoidability of ADRs, and conducted interviews with parents and children who had experienced ADRs, using these findings to develop a leaflet for parents to inform a communication strategy about ADRs. Results The estimated incidence of ADRs detected in children on admission to hospital was 2.9% [95% confidence interval (CI) 2.5% to 3.3%]. Of the reactions, 22.1% (95% CI 17% to 28%) were either definitely or possibly avoidable. Prescriptions originating in the community accounted for 44 out of 249 (17.7%) of ADRs, the remainder originating from hospital. A total of 120 out of 249 (48.2%) reactions resulted from treatment for malignancies. Off-label and/or unlicensed (OLUL) medicines were more likely to be implicated in an ADR than authorised medicines [relative risk (RR) 1.67, 95% CI 1.38 to 2.02; p  48 hours, the overall incidence of definite and probable ADRs based on all admissions was 15.9% (95% CI 15.0 to 16.8). Opiate analgesic drugs and drugs used in general anaesthesia (GA) accounted for > 50% of all drugs implicated in ADRs. The odds ratio of an OLUL drug being implicated in an ADR compared with an authorised drug was 2.25 (95% CI 1.95 to 2.59; p < 0.001). Risk factors identified were exposure to a GA, age, oncology treatment and number of medicines. The systematic review estimated that the incidence rates for ADRs causing hospital admission ranged from 0.4% to 10.3% of all children [pooled estimate of 2.9% (95% CI 2.6% to 3.1%)] and from 0.6% to 16.8% of all children exposed to a drug during hospital stay. New tools to assess causality and avoidability of ADRs have been developed and validated. Many parents described being dissatisfied with clinician communication about ADRs, whereas parents of children with cancer emphasised confidence in clinician management of ADRs and the way clinicians communicated about medicines. The accounts of children and young people largely reflected parents’ accounts. Clinicians described using all of the features of communication that parents wanted to see, but made active decisions about when and what to communicate to families about suspected ADRs, which meant that communication may not always match families’ needs and expectations. We developed a leaflet to assist clinicians in communicating ADRs to parents. Conclusion The Adverse Drug Reactions In Children (ADRIC) programme has provided the most comprehensive assessment, to date, of the size and nature of ADRs in children presenting to, and cared for in, hospital, and the outputs that have resulted will improve the management and understanding of ADRs in children and adults within the NHS. Recommendations for future research: assess the values that parents and children place on the use of different medicines and the risks that they will find acceptable within these contexts; focusing on high-risk drugs identified in ADRIC, determine the optimum drug dose for children through the development of a gold standard practice for the extrapolation of adult drug doses, alongside targeted pharmacokinetic/pharmacodynamic studies; assess the research and clinical applications of the Liverpool Causality Assessment Tool and the Liverpool Avoidability Assessment Tool; evaluate, in more detail, morbidities associated with anaesthesia and surgery in children, including follow-up in the community and in the home setting and an assessment of the most appropriate treatment regimens to prevent pain, vomiting and other postoperative complications; further evaluate strategies for communication with families, children and young people about ADRs; and quantify ADRs in other settings, for example critical care and neonatology

Akt and SGK protein kinases are required for efficient feeding by macropinocytosis

Macropinocytosis is an actin-driven process of large-scale and non-specific fluid uptake used for feeding by some cancer cells and the macropinocytosis model organism Dictyostelium discoideum. In Dictyostelium, macropinocytic cups are organized by ‘macropinocytic patches’ in the plasma membrane. These contain activated Ras, Rac and phospholipid PIP3, and direct actin polymerization to their periphery. We show that a Dictyostelium Akt (PkbA) and an SGK (PkbR1) protein kinase act downstream of PIP3 and, together, are nearly essential for fluid uptake. This pathway enables the formation of larger macropinocytic patches and macropinosomes, thereby dramatically increasing fluid uptake. Through phosphoproteomics, we identify a RhoGAP, GacG, as a PkbA and PkbR1 target, and show that it is required for efficient macropinocytosis and expansion of macropinocytic patches. The function of Akt and SGK in cell feeding through control of macropinosome size has implications for cancer cell biology.<br/

Tungsten nuclear rocket, phase I, part 1 Final report

Tungsten water moderated nuclear rocket reactor experiments and analyse

Expectation-Confirmation Model and IPA Continuance Behavior

With the emergence of Intelligent Personal Assistants (IPAs) such as Amazon Alexa, Google Home, and Apple Siri, etc., IPA arises as one of the fastest-growing artificial intelligence applications in recent years. Since the success of information technology (IT) depends on the continuance of its usage (Bhattacherjee, 2001), studies on IPA continuance behavior should also attract academic attention. IPA continuance refers to long-term or sustainable use of intelligent personal assistants, which make use of Natural Language User Interfaces (NLUI) to provide users with information about the weather, maps, schedules, calls, events, etc. (Kennington & Shukla, 2017). Prior studies in the IPA usability domain mainly focus on improving user interactions, understanding how people use IPAs, and explaining their uses (de Barcelos Silva et al., 2020). Previous literature related to IT continuance behavior captures satisfaction, attitude or habitual responses, and emotional attachment (Mamun et al., 2020), ignoring the usability of specific IT applications like IPAs, especially the interaction quality between humans and IPAs. Exploring IPA Continuance based on the expectation-confirmation theory (ECT) is the goal of this study. Oliver (1980)’s expectation-confirmation theory (ECT) is broadly used in consumer behavior studies to examine consumer satisfaction and post-purchase behaviors. Derived from ECT, Bhattacherjee (2001)’s expectation-confirmation model (ECM) investigates user continuance intention for a system, which is widely accepted by IS scholars Whether the API can accurately recognize natural human language and respond quickly may determine the user\u27s satisfaction with the API product. Therefore, we introduced the concept of API Interaction Quality, based on the ECM, to extend the original model, exploring the key factors affecting the continued use of IPA. The proposed model was empirically tested within the context of most popular IPAs, such as Amazon Alexa, Google Home and Apple Siri. we will collect empirical data from college students who are users of IPA, a class of conversational, where ages limit from 18 to 30. This research will contribute to both theory and practice in the IT area. It will enrich the theory of ECT and extend expectation-confirmation model in IS research. Tech giants who have developed their own IPAs like Apple, Microsoft, and Amazon may benefit from our research findings in the perspective of how to improve interaction quality between their IPA products and potential users

How does the Trust Affect Continuation Intention Toward IPAs?

The continued use of Intelligent Personal Assistants (IPAs) has received increasing attention in Information Technology (IT) and information systems (IS) research, assisting users in managing the dynamically expanding applications, devices, and services in their daily lives (Hu.et.al, 2021). IPAs are a class of autonomous agents designed as human-assisted aids that perform routine tasks according to the needs or preferences of users (Han & Yang, 2018). Likewise, IPA allows hands-free human-computer interaction, and this technology unlocks the potential of computing to work in new areas that have not yet been explored. Communication occurs between the human and computer using voice devices, such as Amazon Alexa, Microsoft Cortana, Google Assistant, Or Apple Siri. IPAs allow people to search for various topics, schedule meetings, or make calls from their car or home, eliminating the need to hold any mobile devices. The question remains about some of the factors that enhance the continued use of IPAs. This study aims to understand users\u27 continued use intentions towards IPAs regarding trust satisfaction and its relationship to user satisfaction. According to Davis (1989), the expectation-confirmation model (ECM) assumes that affirmation of perceived usefulness leads to satisfaction, leading to persistent intention. Embracing the practical value of technology, the model presupposes perceived usefulness, widely accepted as a strong predictor of information system usage. Furthermore, it uses satisfaction, which is considered an essential factor in enhancing users\u27 willingness to continue using the system. Satisfactory behavioral experiences are crucial for sustained intentions because they increase the tendency to repeat the same course of action. This study aims to develop a model to investigate IPA\u27s continuation intention where trust predicts satisfaction. Further to test the model, empirical data will be collected from employees with some experience using IPAs. In surveys on how user satisfaction and unique insights, we believe experienced employees will provide some valuable references. The theoretical implications of this study will help managers identify potential discontinuers with the goal of corrective action. Managers can consider technology\u27s cognitive and emotional aspects when adopting new technology. The study provides new IT post-adoption behavioral research guidelines that consider trust and satisfaction

The Role of Trust and Privacy Concern in IPA Continuance Intention

Abstract Intelligent personal assistants (IPAs) are self-contained software agents that may aid users with a variety of daily tasks. IPA\u27s devices include smartphones, smart speakers, smart glasses, desktop computers, and unique devices (de Barcelos Silva et al., 2020 ), which communicate with users to give an anthropomorphic interface for services (Saad et al., 2017). The best predictors of a person’s conduct are behavioral intentions (Davis, 1989). A user may elect to use a piece of technology for a single purpose and not for others. Businesses benefit from continuous technology use since it costs five times as much to acquire a new user as it does to maintain an existing user (Reichheld & Schefter, 2000). Additionally, Gao et al. (2015) note that obtaining new consumers and boosting consumption is merely the first phase; organizations have to retain regular customers and make purchasing more convenient for them. As a result, the question of continued use is gaining traction in an ever-more-competitive landscape. The confirmation-satisfaction research model (CSR), based on the expectation-confirmation model (ECM) and the expectation confirmation theory (ECT), is a widely utilized theory in the literature on consumer behavior (Yan et al., 2021). The CSR elucidates cognitive and emotional fulfillment. Additionally, we examine privacy concerns and trust as mediators. The purpose of this study is to investigate the relationship between privacy concerns, trust, satisfaction, perceived usefulness, benefits, and intention to continue using IPAs. Internal relationships between each construct are analyzed using partial least squares structural equation modeling. Data was collected via an online survey distributed to students at a big public institution. 382 valid responses were included in the final dataset. We found that (1)the direct effect of perceived benefit and emotional pleasure on intention to continue is considerable and favorable; (2)Confirmation had a positive and significant influence on the perceived benefit when used directly. On the other hand, confirmation had a considerable beneficial influence on cognitive satisfaction. A confirmation has a big effect on emotional satisfaction and privacy concerns. (3)The findings reveal that perceived benefit has a favorable and significant effect on trust, cognitive satisfaction, emotional satisfaction, and intention to continue to use IPAs. (4)However, no relationship between privacy concerns and emotional satisfaction was discovered. By evaluating psychological aspects (satisfaction, privacy concerns, and trust), technological ones (perceived usefulness), and a performance factor (perceived benefits), this study will add to a more thorough understanding of post-adoption behaviors. Managers may have a holistic view of various stakeholder groups and make informed decisions about how to promote new technologies to customers

Properties of the Interstitial in the Diamond-Type Lattice

Linear combination of atomic orbital—molecular orbital cluster calculations using extended Hückel theory suggest that the interstitial carbon atom in diamond prefers an interstitialcy configuration. The predicted minimum-energy configuration changes with charge state, providing a possible example of the Bourgoin mechanism for athermal migration of the interstitial in the presence of ionizing radiation

Otitis media: recent advances in otitis media vaccine development and model systems

Otitis media is an inflammatory disorder of the middle ear caused by airways-associated bacterial or viral infections. It is one of the most common childhood infections as globally more than 80% of children are diagnosed with acute otitis media by 3 years of age and it is a common reason for doctor’s visits, antibiotics prescriptions, and surgery among children. Otitis media is a multifactorial disease with various genetic, immunologic, infectious, and environmental factors predisposing children to develop ear infections. Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis are the most common culprits responsible for acute otitis media. Despite the massive global disease burden, the pathogenesis of otitis media is still unclear and requires extensive future research. Antibiotics are the preferred treatment to cure middle ear infections, however, the antimicrobial resistance rate of common middle ear pathogens has increased considerably over the years. At present, pneumococcal and influenza vaccines are administered as a preventive measure against otitis media, nevertheless, these vaccines are only beneficial in preventing carriage and/or disease caused by vaccine serotypes. Otitis media caused by non-vaccine serotype pneumococci, non-typeable H. influenza, and M. catarrhalis remain an important healthcare burden. The development of multi-species vaccines is an arduous process but is required to reduce the global burden of this disease. Many novel vaccines against S. pneumoniae, non-typeable H. influenza, and M. catarrhalis are in preclinical trials. It is anticipated that these vaccines will lower the disease burden and provide better protection against otitis media. To study disease pathology the rat, mouse, and chinchilla are commonly used to induce experimental acute otitis media to test new therapeutics, including antibiotics and vaccines. Each of these models has its advantages and disadvantages, yet there is still a need to develop an improved animal model providing a better correlated mechanistic understanding of human middle ear infections, thereby underpinning the development of more effective otitis media therapeutics. This review provides an updated summary of current vaccines against otitis media, various animal models of otitis media, their limitations, and some future insights in this field providing a springboard in the development of new animal models and novel vaccines for otitis media