Administrative Agencies Research Articles

Quality of Essential Medicines from Different Sources in Enugu and Anambra, Nigeria.

This study investigated the quality of 13 essential medicines in the states of Enugu and Anambra, Nigeria. A total of 260 samples were purchased from licensed pharmaceutical manufacturers and wholesalers and from vendors in pharmaceutical markets with unclear licensing status. Samples were analyzed for identity, content, and dissolution according to the United States Pharmacopeia (USP) 42 monographs. Forty-five samples of this study could be examined for authenticity with the Mobile Authentication Service scheme of the Nigerian National Agency for Food and Drug Administration and Control. Out of all samples, 25.4% did not comply with the USP 42 specifications. Strikingly, 21 out of 22 dexamethasone tablet samples (95%) were out of specification (OOS). Nine out of 19 glibenclamide samples (47%) failed dissolution testing, and 7 out of 17 cotrimoxazole samples (41%) failed assay testing. Medicines against noncommunicable diseases showed a slightly higher percentage of OOS samples than anti-infectives (21.2% versus 17.6%). The rates of OOS samples were similar in medicines stated to be produced in Nigeria, India, and China but were very different between individual manufacturers from each of these countries of origin. Therefore, prequalification of products, manufacturers, and suppliers are very important for quality assurance in medicine procurement. Unexpectedly, the total proportions of OOS samples were similar from licensed vendors (25.2%) and from markets (25.5%). Four samples (1.5%), all collected in markets, were clearly falsified and did not contain the declared active pharmaceutical ingredients. The proportion of falsified medicines was found to be lower than frequently reported in the media for Nigeria.

Real-world outcomes of combined lenvatinib and anti-PD-1 in advanced melanoma: the Lenvamel study, a multicenter retrospective study of the French Group of Skin Cancers (Groupe de Cancérologie Cutanée).

Currently, treatment options for patients with advanced melanoma who experience failed immunotherapy or targeted therapy are lacking. Recent studies suggest the antitumor activity of combined pembrolizumab and lenvatinib in patients with advanced melanoma progressing on immunotherapy. Herein, we report the clinical outcomes of combined lenvatinib and a programmed cell death protein-1 inhibitor (PD-1) in this population. This French multicenter real-world study was conducted between September 2020 and July 2023. The primary endpoint was the objective response rate (ORR) according to the Response Evaluation Criteria in Solid Tumours (version 1.1). Secondary variables were treatment-related adverse events (TRAEs), progression-free survival (PFS), overall survival (OS), and duration of response (DOR). Of the 67 patients included (median age, 69 years; median follow-up, 5.0 months), 85% had stage IV-M1c or M1d disease. The overall ORR was 28.4% (95% CI, 18%-41%), including 3 complete (4.5%) and 16 partial (23.9%) responses. Median DOR was 3.1 (interquartile range, 1.3-4.3) months. Median PFS and OS were 3.1 (95% CI, 2.5-3.7) and 9.8 (95% CI, 5.6-13.9) months, respectively. Grades 3-5 TRAEs occurred in 16 (24%) patients; common TRAEs were fatigue (43.3%), nausea/vomiting (26.8%), diarrhea (20.9%), and hypertension (20.9%). No treatment-related deaths occurred. Our real-world study demonstrates an interesting response rate and acceptable safety profile in a population with poor prognostic factors. Our data support this treatment option for refractory melanoma, as it is not approved by the Food and Drug Administration or European Medicines Agency, and highlight the need for new strategies.

Ambiguous Policies, Controversial Issues, and Strained Bureaucracies: Banning Critical Race Theory in Idaho

Absent coping strategies, ambiguity strains administrative agencies and democratic institutions on multiple fronts, particularly where controversy is amplified by different ways of thinking that are incompatible with each other. This is examined using a case study of the implementation of Idaho’s House Bill 377 (HB377), the first state-level ban on “critical race theory” in public education in the United States. The brief and ambiguously written bill leaves a lot to be “figured out” by educators. Using a modified grounded theory approach, interviews with 10 faculty reveal how making sense of HB377 caused significant distress for faculty and strained their relationships with administrators. Findings suggest that this bill may have damaged higher education institutions in Idaho, particularly by creating low faculty morale among those teaching in areas newly perceived to be controversial. Conclusions consider implications for administrative agencies when faced with ambiguous laws and conflicting messages from elected officials.

Insights on Nefecon®, a Targeted-Release Formulation of Budesonide and Its Selective Immunomodulatory Effects in Patients with IgA Nephropathy.

Immunoglobulin A nephropathy (IgAN) is a chronic, immune-mediated kidney disease characterized by the deposition of galactose-deficient immunoglobulin A1 (Gd-IgA1) in the kidneys. Excess Gd-IgA1 production in patients with IgAN is located within the mucosa-associated lymphoid tissue, particularly within the lamina propria in the distal ileum. Nefecon® is a targeted-release formulation of the corticosteroid budesonide, which became the first treatment approved by the US Food and Drug Administration (FDA; brand name, TARPEYO®) and European Medicines Agency (EMA; KINPEYGO®) for patients with primary IgAN at risk of rapid disease progression, after demonstrating clinically significant reduction of proteinuria in an interim analysis of the Phase III NefIgArd trial. After showing a significant reduction in estimated glomerular filtration rate decline in the full 2-year analysis of the trial, Nefecon was granted full approval by the FDA to reduce the loss of kidney function. Nefecon was specifically designed to deliver budesonide to the distal ileum, selectively targeting excess Gd-IgA1 production in the gut-associated lymphoid tissue. In this review, we describe the properties of Nefecon and the evidence to date that confirms its localized treatment effect. We also present unpublished evidence from Phase I trials investigating the pharmacokinetics and cortisol suppression effects of Nefecon in healthy participants. These studies demonstrated that Nefecon has a distinct pharmacokinetic profile from other budesonide products, allowing for targeted, localized action in the distal ileum. When considered alongside existing clinical trial data showing the effect of Nefecon on gut-associated biomarkers, available evidence indicates that Nefecon has a selective immunomodulatory mechanism of action and a direct disease-modifying effect in patients with IgAN, while having low systemic exposure and adverse effects.

Feasibility of Short-Term Use of Ivabradine in Critical Ill Patients Who Have Atrial Fibrillation and Tachycardia.

Ivabradine is approved for heart rate reduction in patients with stable symptomatic heart failure (HF). The United States Food and Drug Administration and Taiwan Central Health Insurance Agency approved the use of ivabradine for patients with chronic stable HF with sinus rhythm, but it has not yet been approved for patients with acute decompensated HF or with atrial fibrillation (AF). To investigate whether short-term ivabradine use is feasible in critically ill patients with AF and rapid ventricular response (RVR). This study retrospectively analyzed 23 patients admitted to an intensive care unit with acute HF and AF-RVR who received ivabradine. All patients initially received a slow IV of amiodarone. Other medications for HF were prescribed according to current HF guidelines. The time taken for ivabradine to reduce HR to 80 beats per minute, referred to as "Time to 80," was measured in each patient. Overall, 69.6 % (16/23) of the patients had New York Heart Association functional class IV HF. In addition, 60.9% (14/23) of the patients required endotracheal intubation and ventilatory support, with more than half receiving vasopressor treatment to manage hypotension. Five patients died during the study period. The surviving patients had a significantly shorter "Time to 80" compared to those who did not survive (p = 0.037). Adding ivabradine to standard treatment might be feasible for critically ill patients with AF and tachycardia. The finding that surviving patients had a shorter "Time to 80" duration than those who did not survive may have clinical implications. However, further investigations are needed to assess its clinical utility.

Analysis of ‘Publicity’ and ‘Information’ in Public Language of Administrative Agencies : Focusing on the Press Release of Gyeongsangbuk-do Office of Education and Korea Housing Finance Corporation

Since the Press Release of the Administrative Agency is it is necessary to deliver accurate information regarding Public Nature. If the Public Language of the Press Release undermines the publicity, some readers may perceive the Press Release itself negatively. In addition, if the information of the Press Release is not accurately communicated, the public may have difficulty understanding the content of the article. In particular, topics such as education and housing directly affect the lives of the people, so this is especially true. Therefore, in this study, press releases from the the Gyeongsangbuk-do Office and Korea Housing Finance Corporation of Education were analyzed focusing on Public Nature and Informativity. First, Public Nature was examined based on overbearing or authoritative expressions and discriminatory expressions, In the case of discriminatory expressions, direct, indirect, and personal information were examined. Next, Informativity was reviewed focusing on the format, quantity, and arrangement of information. As a result, there were few cases in which overbearing or discriminatory expressions were directly revealed in press releases from the Gyeongsangbuk-do Office of Education and the Korea Housing Finance Corporation. However, indirect discriminatory expressions or unnecessary personal information exposure were found. In terms of Informativity, errors were found in the format of information common to both institutions, and there were differences in the amount and arrangement of information in the two institutions. It is hoped that the results of this study, which reviewed Press Releases focusing on Public Nature and Informativity, will be helpful in writing better and easier to understand Press Releases.

Update on the Use of Thrombopoietin-Receptor Agonists in Pediatrics.

This review summarizes the rationale and current data on the use of thrombopoietin receptor agonists (TPO-RAs) for treating severe thrombocytopenia in infants, children, and adolescents. It focuses on substances that have been approved by the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) for pediatric patients. Romiplostim and eltrombopag are already established as second-line treatment for persistent or chronic immune thrombocytopenia (ITP). As in adults, TPO-RAs are currently also evaluated in severe aplastic anemia (SAA), chemotherapy-induced thrombocytopenia (CIT), myelodysplastic syndromes (MDS), and poor engraftment after hematopoietic stem cell transplantation in pediatric and adolescent patients. Moreover, studies on the implication of TPO-RA in treating rare inherited thrombocytopenias, such as Wiskott-Aldrich syndrome (WAS), congenital amegakaryocytic thrombocytopenia (CAMT), or MYH9-associated thrombocytopenia, deserve future attention. Current developments include testing of avatrombopag and lusutrombopag that are approved for the treatment of thrombocytopenia associated with chronic liver disease (CLD) in adult patients. In pediatric and adolescent medicine, we expect in the near future a broader use of TPO-RAs as first-line treatment in primary ITP, thereby considering immunomodulatory effects that increase the rate of sustained remission off-treatment, and a selective use in rare inherited thrombocytopenias based on current clinical trials.

Advancing safety in short-term utility work zones: Assessing the role of work zone intrusion alert technologies (WZIATs)

Work zone safety is significantly impacted by vehicle intrusions, which are challenging incidents to control. Although the Federal Highway Administration and US state transportation agencies have implemented safety procedures to enhance worker and motorist safety, the rate of intrusions in work zones remains high, necessitating the development of additional solutions. Work zone intrusion alert technologies (WZIATs) have shown promise in highway work zones; however, their application in short-term utility settings remains insufficiently studied. This research aims to characterize the features of intrusion alert systems that can enhance the safety of workers in utility work zones. To achieve this aim, the study adopted a mixed-method design approach, relying on literature review, archival data analysis, experimental assessments, and a case study. The study reveals that motorist/driver behavior is a primary safety risk factor in utility work zone intrusions. Insights from deploying two technologies, AWARE and Alpha SafeNet, in experimental and live utility work zones indicate that an effective WZIAT must be able to alert both drivers and workers, be deployable in less than three minutes, integrate audio, visual, and haptic alarms, have an adjustable warning light, incorporate a pneumatic tube triggering mechanism, and be waterproof. This study contributes to both knowledge and practice by characterizing the safety risks associated with utility work zones and identifying key performance and operational features for deploying WZIATs in short-term work zones.

QbD-Based Development and Evaluation of Pazopanib Hydrochloride Extrudates Prepared by Hot-Melt Extrusion Technique: In Vitro and In Vivo Evaluation.

Pazopanib hydrochloride (PZB) is a protein kinase inhibitor approved by the United States Food and Drug Administration and European agencies for the treatment of renal cell carcinoma and other renal malignancies. However, it exhibits poor aqueous solubility and inconsistent oral drug absorption. In this regard, the current research work entails the development and evaluation of the extrudates of pazopanib hydrochloride by the hot-melt extrusion (HME) technique for solubility enhancement and augmenting oral bioavailability. Solid dispersion of the drug was prepared using polymers such as Kollidon VA64, hydroxypropylmethylcellulose (HPMC), Eudragit EPO, and Affinisol 15LV in a 1:2 ratio by the HME process through a lab-scale 18 mm extruder. Systematic optimization of the formulation variables was carried out with the help of custom screening design (JMP Software by SAS, Version 14.0) to study the impact of polymer type and plasticizer level on the quality of extrudate processability by measuring the torque value, appearance, and disintegration time as the responses. The polymer blends containing Kollidon VA64 and Affinisol 15LV resulted in respective clear transparent extrudates, while Eudragit EPO and HPMC extrudates were found to be opaque white and brownish, respectively. Furthermore, evaluation of the impact of process parameters such as screw rpm and barrel temperature was measured using a definitive screening design on the extrude appearance, torque, disintegration time, and dissolution profile. Based on the statistical outcomes, it can be concluded that barrel temperature has a significant impact on torque, disintegration time, and dissolution at 30 min, while screw speed has an insignificant impact on the response variables. Affinisol extrudates showed less moisture uptake and faster dissolution in comparison to Kollidon VA64 extrudates. Affinisol extrudates were evaluated for polymorphic stability up to a 3-month accelerated condition and found no recrystallization. PZB-Extrudates using the Affinisol polymer (Test formulation A) revealed significantly higher bioavailability (AUC) in comparison to the free Pazopanib drug and marketed formulation.

Factors Influencing Engineering Assets Management Decisions in Food Manufacturing Companies in Nigeria

This paper assessed the factors influencing Engineering Assets Management decisions in small and medium-scale food manufacturing companies in Southwestern Nigeria. Data were collected from 30 selected food manufacturing companies registered with National Agency for Food and Drug Administration and Control in the study area. The data were analyzed using descriptive and inferential statistics. The results reveal that food manufacturing companies practice some elements of Engineering Assets Management. There were no explicit guidelines and policy statements that guide their decisions and actions. However, a) how maintenance was to be carried out; and b) the amount and intensity of service that maintenance was expected to provide in order to satisfy the need of production, were the major factors that guided ways of making Engineering Asset Management decisions.

Automatic text classification of drug-induced liver injury using document-term matrix and XGBoost.

Regulatory agencies generate a vast amount of textual data in the review process. For example, drug labeling serves as a valuable resource for regulatory agencies, such as U.S. Food and Drug Administration (FDA) and Europe Medical Agency (EMA), to communicate drug safety and effectiveness information to healthcare professionals and patients. Drug labeling also serves as a resource for pharmacovigilance and drug safety research. Automated text classification would significantly improve the analysis of drug labeling documents and conserve reviewer resources. We utilized artificial intelligence in this study to classify drug-induced liver injury (DILI)-related content from drug labeling documents based on FDA's DILIrank dataset. We employed text mining and XGBoost models and utilized the Preferred Terms of Medical queries for adverse event standards to simplify the elimination of common words and phrases while retaining medical standard terms for FDA and EMA drug label datasets. Then, we constructed a document term matrix using weights computed by Term Frequency-Inverse Document Frequency (TF-IDF) for each included word/term/token. The automatic text classification model exhibited robust performance in predicting DILI, achieving cross-validation AUC scores exceeding 0.90 for both drug labels from FDA and EMA and literature abstracts from the Critical Assessment of Massive Data Analysis (CAMDA). Moreover, the text mining and XGBoost functions demonstrated in this study can be applied to other text processing and classification tasks.

CoDuBoTeSS: A Pilot Study to Eradicate Counterfeit Drugs via a Blockchain Tracer Support System on the Nigerian Frontier

The pharma-sector has maintained improved productivity and profitability via a concerted effort to address critical issues such as an unorganized regulatory system, lack of safety data, no standards in manufacture process, non-adaptation to pharma-chain, and no-harmony of inventory supports. Study proposes blockchain trace-support to ensure drugs quality, consumer safety, and its trading as asset. It uses a radio-frequency identification sensor to register manufacture and administration process, and provide a databank to trace drug records. Results notes: (a) presents a roadmap for adoption by the National Agency for Food and Drug Administration and Control (NAFDAC) to ensure a traceable pharmaceutical blockchain, (b) show ensemble is scalable for up-to 7500users to yield a performance of 1138-transactions per seconds with response time of 88secs for page retrieval and 128secs for queries respectively, and (c) yields slightly longer time for increased number of users via its world-state as stored in the permissionless blockchain hyper-fabric ledger. Thus, the framework can directly query and retrieve data without it traversing the whole ledger. This, in turn, improves the efficiency and effectiveness of the traceability system. Keywords: Blockchain, Counterfeit drugs, Healthcare, Nigeria, CORDA, hyper-ledger fabric, HIPPA Journal Reference Format: Ifioko, A.M., Yoro, R.E., Okpor, M.D., Brizimor, S.E, Obasuyi, D., Emordi, F.U., Odiakaose, C.C., Ojugo, A.A., Atuduhor, R.R, Abere, R.A., Ejeh, P.O., Ako, R.E. & Geteloma, V.O. (2024): CoDuBoTeSS: A Pilot Study to Eradicate Counterfeit Drugs via a Blockchain Tracer Support System on the Nigerian Frontier. Journal of Behavioural Informatics, Digital Humanities and Development Rese Vol. 10 No. 2. Pp 53-74 https://www.isteams.net/behavioralinformaticsjournal dx.doi.org/10.22624/AIMS/BHI/V10N2P6

CoDuBoTeSS: A Pilot Study to Eradicate Counterfeit Drugs via a Blockchain Tracer Support System on the Nigerian Frontier

The pharma-sector has maintained improved productivity and profitability via a concerted effort to address critical issues such as an unorganized regulatory system, lack of safety data, no standards in manufacture process, non-adaptation to pharma-chain, and no-harmony of inventory supports. Study proposes blockchain trace-support to ensure drugs quality, consumer safety, and its trading as asset. It uses a radio-frequency identification sensor to register manufacture and administration process, and provide a databank to trace drug records. Results notes: (a) presents a roadmap for adoption by the National Agency for Food and Drug Administration and Control (NAFDAC) to ensure a traceable pharmaceutical blockchain, (b) show ensemble is scalable for up-to 7500users to yield a performance of 1138-transactions per seconds with response time of 88secs for page retrieval and 128secs for queries respectively, and (c) yields slightly longer time for increased number of users via its world-state as stored in the permissionless blockchain hyper-fabric ledger. Thus, the framework can directly query and retrieve data without it traversing the whole ledger. This, in turn, improves the efficiency and effectiveness of the traceability system. Keywords: Blockchain, Counterfeit drugs, Healthcare, Nigeria, CORDA, hyper-ledger fabric, HIPPA Journal Reference Format: Ifioko, A.M., Yoro, R.E., Okpor, M.D., Brizimor, S.E, Obasuyi, D., Emordi, F.U., Odiakaose, C.C., Ojugo, A.A., Atuduhor, R.R, Abere, R.A., Ejeh, P.O., Ako, R.E. & Geteloma, V.O. (2024): CoDuBoTeSS: A Pilot Study to Eradicate Counterfeit Drugs via a Blockchain Tracer Support System on the Nigerian Frontier. Journal of Behavioural Informatics, Digital Humanities and Development Rese Vol. 10 No. 2. Pp 53-74 https://www.isteams.net/behavioralinformaticsjournal dx.doi.org/10.22624/AIMS/BIJ/V10N1P6

지방자치와 자치경찰 실태 검토

At the present time, when the autonomous police system is being implemented, it is necessary to review the meaning of the autonomous police system and whether it is in line with the purpose of the local autonomy system through its actual situation. The purpose of the autonomous police system is to establish regional security through a police system that matches the local circumstances. The autonomous police system must be institutionalized to meet the needs of regional security and suit the characteristics of each region. However, it is questionable whether the autonomous police system currently in effect is structured and operated to suit the characteristics of the region. The constitutional purpose of local autonomy is to implement self-governance to improve the welfare of residents. When approaching local autonomy from the perspective of promoting the welfare of residents, it is necessary to reexamine the extent to which the autonomous police system is contributing to improving the welfare of residents. The autonomous police system must be organized and operated to reflect the opinions of residents. However, the current police law has limitations in that it does not provide an opportunity for the autonomous police committee, which is an autonomous police agency, to reflect the opinions of residents. According to the current law, the Autonomous Police Committee directs and supervises the city/provincial police chiefs regarding autonomous police affairs. However, it cannot be said that these autonomous police committees have a status that allows them to actually perform their functions in command and supervision of city/provincial police chiefs. The Autonomous Police Committee is granted the status of a consensus-based administrative agency for autonomous police affairs, but exercises command and supervision rights through deliberation and voting rights only on simple administrative affairs, not direct autonomous police affairs. Therefore, in this study, we analyzed the current state of the law and presented improvement measures to meet the purpose of local autonomy, which is to promote the welfare of residents in order to achieve institutional guarantee of local autonomy. However, the limitations of this study are that the analysis of the actual situation was conducted through a literature review, and it was limited to the actual state of the legislation and the actual state of the system.

Genetic alteration of SJ293TS cells and modification of serum-free media enhances lentiviral vector production

Successful cell and gene therapy clinical trials have resulted in the United States Food and Drug Administration and European Medicines Agency approving their use for treatment of patients with certain types of cancers and monogenetic diseases. These novel therapies, which rely heavily on lentiviral vectors to deliver therapeutic transgenes to patient cells, have driven additional investigations, increasing demand for both pre-clinical and current Good Manufacturing Practices-grade viral vectors. To better support novel studies by improving current production methods, we report the development of a genetically modified HEK293T-based cell line that is null for expression of both Protein Kinase R and Beta-2 microglobulin and grows in suspension using serum-free media, SJ293TS-DPB. Absence of Protein Kinase R increased anti-sense lentiviral vector titers by more than 7-fold, while absence of Beta-2 microglobulin, a key component of Major Histocompatibility Complex class I molecules, has been reported to reduce the immunogenicity of lentiviral particles. Furthermore, we describe an improved methodology for culturing SJ293TS-DPB which facilitates expansion, reduces handling, and increases titers by 2-fold compared to previous methods. SJ293TS-DPB stably produced lentiviral vectors for over four months and generated lentiviral vectors that efficiently transduce healthy human donor T cells and CD34+ hematopoietic stem cells.

Facts and myths about use of esketamine for treatment-resistant depression: a narrative clinical review.

Treatment-resistant depression (TRD) occurs when at least two different antidepressants, taken at the right dosage, for adequate period of time and with continuity, fail to give positive clinical effects. Esketamine, the S-enantiomer of ketamine, was recently approved for TRD treatment from U.S. Food and Drug Administration and European Medicine Agency. Despite proved clinical efficacy, many misconceptions by clinicians and patients accompany this medication. We aimed to review the most common "false myths" regarding TRD and esketemine, counterarguing with evidence-based facts. The keywords "esketamine", "treatment resistance depression", "depression", "myth", "mythology", "pharmacological treatment", and "misunderstanding" were entered in the main databases and combined through Boolean operators. Misconceptions regarding the TRD prevalence, clinical features and predictors have been found. With respect of esketamine, criteria to start treatment, dissociative symptoms, potential addiction and aspects of administration and monitoring, were found to be affected by false beliefs by clinicians and patients. TRD represents a challenging condition, requiring precise diagnosis in order to achieve patient's full recovery. Esketamine has been proved as an effective medication to treat TRD, although it requires precautions. Evidence can inform clinical practice, in order to offer this innovative treatment to all patients with TRD.

Alien invasive pathogens and pests in the changing environment: Focus on North Europe

On 12–13 September 2023, a panel of forest pathologists and entomologists gathered in Visby, Gotland Island, Baltic Sea, Sweden. The participants, a total of 20, represented all five Nordic Countries, three Baltic States, and Ukraine, and also joined by the local stakeholders representing the Swedish Forestry Agency and Gotland Administration. The purpose was to conduct a scientific workshop focusing on invasive tree pests and diseases emerging in each respective country, as well as to participate in an excursion to damaged woodland sites of Gotland. The Nordic Forest Research (SNS) financially supported the event (https://nordicforestresearch.org/n2023-01/). Keywords: Corinectria / Neonectria cankers; Hymenoscyphus fraxineus; Emerald Ash Borer; Diplodia sapinea; Acute Oak Decline; Polygraphus proximus; emerging birch pests; Bronze Birch Borer; Thekopsora areolata; seedborn conifer fungi

Identifying Deficiencies in Children's Residential Care in Finland: Inspectors' Views on Working With Information

ABSTRACTAbusive and illegal practices in residential care are a recognised issue in child welfare internationally; thus, the question of how these institutions are supervised is important. However, children's residential care is complex by nature, making its supervision a challenging task. This article examines residential care supervision by looking at the ‘knowledge work’ that two central legality supervisors in Finland—the Parliamentary Ombudsman and Regional State Administrative Agencies—conduct when inspecting children's residential homes. Here, ‘knowledge work’ refers to the process of working with information to identify deficiencies in care. Eleven interviews and 16 inspection reports are analysed with a focus on the nature of the information that these supervisors gather when inspecting residential units and how they evaluate the significance and reliability of the information. The results show that to complete their institutional task, the inspectors gather information from various sources, including documents and interviews with children. The significance of the information is then assessed by comparing it with legislation and the supervisory mandate, and its reliability is verified by considering the diverse information sources as a whole collection of information. The results suggest that how well ‘knowledge work’ is conducted highly affects the impact of supervision.

Effects of two commonly used antidepressants amitriptyline and fluoxetine on the pharmacokinetics of abrocitinib in rats

Abrocitinib is approved to treat moderate-to-severe atopic dermatitis and eliminated mainly through cytochrome P450 (CYP450) enzyme. Two commonly used antidepressants, amitriptyline and fluoxetine, could inhibit the activities of CYP2C19 and CYP3A4. In this study, we developed a new and quick ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method for quantitatively analyzing the plasma concentration of abrocitinib, and further investigated the effects of amitriptyline or fluoxetine on the pharmacokinetics of abrocitinib in rats. The selectivity, linearity, recovery, accuracy, precision, matrix effect and stability of UPLC-MS/MS assay were satisfied according to the United States Food and Drug Administration (FDA) and European Medicines Agency (EMA) guidelines. Our result showed that when co-administered with amitriptyline and fluoxetine, the CLz/F of abrocitinib was reduced by 44.4 % and 33.3 %, respectively, while the AUC(0–t) of abrocitinib was increased by 77.7 % and 49.4 %, respectively. It indicated that amitriptyline and fluoxetine could significantly increase the plasma concentration of abrocitinib in rats. Thus, dose adjustment of abrocitinib may be required when it is combined with amitriptyline or fluoxetine in ongoing clinical practice.

Multi-agency counter-terrorism in Britain and Norway: Intelligence agencies and the administration of welfare

This article explores the emergence of new counter-terrorism programmes in the Britain and Norway through which intelligence and security agencies administer welfare. Support and resources are covertly allocated to persons identified as potential threats, through multi-agency structures led by intelligence and security agencies. Unlike Countering Violent Extremism programmes, this multi-agency management is not led by the local municipality; nor are its participants asked to consent to participation. These new programmes are covert. To conceptualize the significance of intelligence agencies entering the space of welfare administration, Mitchell Dean’s work ‘Liberal Government and Authoritarianism’ is used to underline the traditional separation of agencies within liberal governmentality. Governing through freedom entails the ostensible separation of policing, education and care agencies – reflecting the categorization of the population into groups requiring varying levels of coercion to self-govern. To avoid governing too much, each category of population is allocated a specific agency. Traditionally, intelligence and security agencies have been positioned at the highest tier of repression. By entering the space of welfare administration (and thus social policy), intelligence and security agencies have disturbed the sectoral separation integral to liberal governmentality, leaving care and repression in an ever more ambiguous relationship.