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Environmental monitoring (EM) is the cornerstone for the assurance of sterility during aseptic manufacturing. In this study, the EM quality aspects in the radiopharmaceutical cleanrooms of the University Medical Center Groningen (UMCG), The Netherlands, were evaluated. Hereto, data obtained from EM over the period 2010–2022 were analyzed. The data were sorted according to the Good Manufacturing Practice (GMP) classification of the respective premises with their corresponding limits, and frequencies of excursions were determined per location. The frequency of conducted measurements gradually increased between the start and end of the assessed period. There was a trend of increased action limit excursions observed between 2010–2022. We found that EM in grade A areas appeared to be significantly less compliant with GMP specifications than the combined data from all sampled premises at the facility (p < 0.00001; two-sided Fisher’s exact test). A trend was found for reduced action limit excursions for passive air sampling and particle counting, suggesting improved GMP compliance over time for this specific type of EM. The contamination recovery rate (CRR) found for cleanroom conditions, around 10%, was considered sufficient. From this comprehensive data analysis, we learn that, in order to be fully compliant with the requirements set in the recent revision of EU (European Union)-GMP Annex 1 ‘Manufacture of sterile medicinal products’ (in force as of 25 August 2023), strategies to further improve product protection are justified. For example, improved cleaning and disinfection procedures, more efficient working methods as well as optimization of the conditions under which aseptic manufacturing is performed are to be considered.

Shani Reich,1 Maria Lopez,2,&ast; Jacqueline Leff,3,&ast; Jordan Herman1 1Clinical Research Center of Florida, Pompano Beach, FL, USA; 2New England Eye Center/Tufts Medical Center, Boston, MA, USA; 3Touro Osteopathic School of Medicine, Touro University, New York, NY, USA&ast;These authors contributed equally to this workCorrespondence: Shani Reich, Tel +1 305 984 7785, Fax + 1 305 570 2642, Email Shani.reich@gmail.comPurpose: To compare clinical outcomes and patient preference for the dexamethasone intracanalicular insert (DEX) versus topical loteprednol (LOT) or olopatadine (OLO) for the treatment of allergic conjunctivitis in a real-world model of allergen exposure.Methods: This was a prospective comparative trial. Adults with testing-confirmed bilateral allergic conjunctivitis received DEX in the more symptomatic eye and either LOT 2 times daily or OLO once daily for 30 days in the fellow eye. The primary outcome was patient preference for treatment. Clinical outcomes included ocular itching and hyperemia, lid swelling, and watering/tearing. Safety outcomes included intraocular pressure (IOP).Results: Thirty patients participated and completed the study. All received DEX in the eye with worse symptoms and 15 received LOT and the other 15 received OLO in the other eye. Patients preferred DEX (10/15; 66.7%) over LOT (4/15; 26.7%), with one patient having no preference (p = 0.0103). Patients had no preference between DEX (8/15; 53.3%) and OLO (6/15; 40%), with one patient having no preference (p = 0.1044). In the DEX/LOT cohort, ocular itching and hyperemia improved more with DEX than LOT (p ≤ 0.009), while in the DEX/OLO cohort, the DEX eyes showed greater improvement in conjunctival hyperemia (p < 0.0001) but not itching (p = 0.074). No between-group differences were seen in eyelid swelling or tearing/watering in either cohort. Mean change in IOP was similar between the DEX and LOT eyes (p = 0.4921), and mean IOP rose more in the DEX eyes than the OLO eyes (by < 1 mmHg; p = 0.0403).Conclusion: Overall, this real-world study demonstrated that the dexamethasone intracanalicular insert was as effective as a topical antihistamine/mast cell stabilizer and more effective than topical steroids in relieving the signs and symptoms of allergic conjunctivitis. This insert should be considered as an alternative to topical therapy for the treatment of allergic conjunctivitis.Keywords: dexamethasone, dextenza, allergic conjunctivitis

Background/Objectives: Products from various parts of Crataegus species are traditionally applied as a cardiotonic. In Europe and the USA, mainly Crataegus monogyna Jacq. (Lindm.) and Crataegus laevigata (Poir.) DC (synonym Crataegus oxyacantha L.) are used, but worldwide, other Crataegus species are also used. Phytotherapeutic preparations with a standardised content of flavonoids and/or oligomeric procyanidins are commercially available. The products are generally considered as safe and are at most associated with minor and atypical adverse reactions. The aim of this study was to critically assess the information about the safety of Crataegus-containing products in humans. Methods: A scoping review of the literature about adverse reactions associated with Crataegus-containing products was performed. Next, individual case safety reports (ICSRs) were assessed, which were included in VigiBase (the World Health Organisation’s global database of adverse event reports for medicines and vaccines) and in the database of the Netherlands Pharmacovigilance Centre Lareb. The findings are discussed in relation to the literature. Results: The scoping review yielded 23 clinical studies with single-herb and 14 with multi-herb preparations, from which only a few minor gastrointestinal and cardiac events had been reported. A total of 1527 reports from VigiBase, from 1970 to 2023, were analysed, as well as 13 reports from Lareb. The most frequently reported adverse reactions belonged to the system organ classes ‘gastrointestinal disorders’, ‘skin and subcutaneous tissue disorders’, ‘general disorders and administration site conditions’, ‘cardiac disorders’ or ‘nervous system disorders’. In 277 reports of VigiBase, a single-herb product was the only suspect for causing the adverse reaction(s). Of these, 12.6% were graded as serious. Conclusions: The results of our study provide deeper insight in the adverse reaction profile of Crataegus-containing products and should contribute to their safe application in the treatment of less severe forms of cardiac failure.

This study investigated whether and how medication reviews (MRs) conducted by pharmacists and general practitioners (GPs) with patient involvement can be performed on the island of Aruba (Dutch Caribbean). In this mixed-methods pilot study (both qualitative and quantitative), constructive and observational methodologies were combined. Healthcare providers’ and patients’ views on MRs and aspects of Aruban healthcare and culture relevant to MRs were examined. These insights were used to develop a protocol for conducting and implementing MRs in Aruba. Surveys were distributed and semi-structured interviews were held among Aruban community pharmacists and GPs, and a pilot program was created in which MRs were carried out with four Aruban patients and their GPs. According to the included healthcare providers, the main purpose of MRs is to optimize the patient experience and achieve concordance. Even though pharmacists and GPs consider their partnership equal, they have different views as to who should bear which responsibility in the MR process in matters regarding patient selection and follow-up. Common Aruban themes that were mentioned by the healthcare providers and deemed relevant for conducting MRs included behaviour/culture, healthcare, lifestyle, and therapy compliance. Anamnesis should be concise during the MR, and questions about medication storage, concerns, beliefs, and practical problems, as well as checks for limited health literacy, were considered important. In the pilot, at least three to, maximally, eight pharmacotherapy-related problems (PRPs) were detected per MR consultation, such as an incorrect dosage of acetylsalicylic acid, an inappropriate combination tablet for blood pressure regulation, and the absence of important laboratory values. All patients considered their consultation to be positive and of added value. In addition, it was observed that an MR can potentially generate cost savings. The information obtained from the healthcare providers and patients, together with the basic principles for MRs, as applied in the Netherlands, led to a definitive and promising MR format with practical recommendations for community pharmacists in Aruba: in comparison with the Dutch MR approach, GPs and pharmacists in Aruba could collaborate more on patient selection for MRs and their follow-up, because of their specific knowledge regarding the medications patients are taking chronically (pharmacists), and possible low levels of health literacy (GPs). Taking into account the Aruban culture, pharmacists could ask extra questions during MRs, referring to lifestyle (high prevalence of obesity), readability of medication labels (limited literacy), and herbal product use (Latin American culture). GPs and medical specialists sometimes experience miscommunication regarding the prescription of medication, which means that pharmacists must carefully take into account possible duplicate medications or interactions.

Even though, nowadays, most medicines are manufactured industrially, patients may have medical needs that can only be met by a tailor-made approach. This requires the availability of pharmacy preparations made under Good Manufacturing Practice (GMP) conditions. An efficient hand hygiene practice is essential herewith, especially if sterile products that are prepared in a cleanroom are concerned. The effectiveness of hand washing and hand disinfection procedures greatly relies on adequate training. We carried out an observational cross-sectional pilot study aimed at optimizing hand hygiene training with objective and measurable quality assessments using an ultraviolet (UV) dye. Practical acceptance criteria for qualifying personnel through this method were set and evaluated. In total, 25 GMP-qualified cleanroom operators washed and disinfected their hands with UV dye hand wash lotion and UV dye hand alcohol, respectively. To obtain a proof-of-concept, the results were judged based on adherence to the WHO six-step protocol and associated acceptance criteria. Commonly missed areas were brought to light, and the influence of procedure duration was investigated. UV-dye-based assessments appeared to be more valuable in hand disinfection than in hand washing. In both procedures, the back of the hands and the thumbs were frequently missed. This underpins the need for enhanced and repeated education on hand washing and disinfection. Additionally, a dry skin gave rise to extra cleaning challenges. From this pharmacy practice pilot study with a focus on pharmaceutical product care, it may be concluded that the application of UV-dye-based assessments offers valuable insights for pharmacists to optimize hand hygiene, thereby increasing the safety of tailor-made medicines and on-site preparations.

Conventional therapy is commonly used for the treatment of inflammatory skin conditions, but undesirable effects, such as erythema, dryness, skin thinning, and resistance to treatment, may cause poor patient compliance. Therefore, patients may seek complementary treatment with herbal plant products including essential oils (EOs). This scoping review aims to generate a broad overview of the EOs used to treat inflammatory skin conditions, namely, acne vulgaris, dermatitis and eczema, psoriasis, and rosacea, in a clinical setting. The quality, efficacy, and safety of various EOs, as well as the way in which they are prepared, are reviewed, and the potential, as well as the limitations, of EOs for the treatment of inflammatory skin conditions are discussed. Twenty-nine eligible studies (case studies, uncontrolled clinical studies, and randomized clinical studies) on the applications of EOs for inflammatory skin conditions were retrieved from scientific electronic databases (PubMed, Embase, Scopus, and the Cochrane Library). As an initial result, tea tree (Melaleuca alternifolia) oil emerged as the most studied EO. The clinical studies with tea tree oil gel for acne treatment showed an efficacy with fewer adverse reactions compared to conventional treatments. The uncontrolled studies indicated the potential efficacy of ajwain (Trachyspermum ammi) oil, eucalyptus (Eucalyptus globulus) oil, and cedarwood (Cedrus libani) oil in the treatment of acne, but further research is required to reach conclusive evidence. The placebo-controlled studies revealed the positive effects of kānuka (Kunzea ericoides) oil and frankincense (Boswellia spp.) oil in the treatment of psoriasis and eczema. The quality verification of the EO products was inconsistent, with some studies lacking analyses and transparency. The quality limitations of some studies included a small sample size, a short duration, and the absence of a control group. This present review underscores the need for extended, well-designed clinical studies to further assess the efficacy and safety of EOs for treating inflammatory skin conditions with products of assured quality and to further elucidate the mechanisms of action involved.

In this study, a variety of ZnO-based heterojunctions with disparate wt.% doping of WO3 and BiOI have been prepared for the photodestruction of methyl orange (MO) dye in aqueous solution. The composites were analysed by scanning electron microscopy, energy-dispersive X-ray spectroscopy, X-ray diffraction, optical studies, and nitrogen adsorption-desorption isotherms. The SEM images revealed non-uniform surfaces of the ZnO–BiOI based composites while mostly nodular morphology was observed for all three samples of ZnO-WO3. As the WO3 loading increased, more clustering was detected. The analysed samples exhibited characteristic peaks representative of the triclinic phase of WO3 and the hexagonal wurtzite structure of ZnO, while the diffractogram observed from the materials displayed distinct peaks corresponding to the crystalline phases of both BiOI and ZnO in their pure forms. Further evidence of the samples' characteristics includes the presence of distinct crystalline patterns without any impurity peaks, a red shift in the absorption spectra of the heterostructure, the detection of only the reference elements, and mostly Type IV isotherm adsorption. This study identified the ZnO-[10%]BiOI and ZnO-[10%]WO3 heterojunctions as the best performing photocatalysts, as MO was completely destroyed in 120 and 90 min, respectively. Thus, confirming 10% wt. as the optimal doping concentration for the best photo-activity in this study. The impact of varying process parameters demonstrates that at an elevated photocatalyst mass of 40 mg, both heterojunctions effectively degraded MO. The photodegradation efficiency of MO was more pronounced in strong acidic conditions (pH 2) when compared to high alkaline conditions (pH 11) for the ZnO-[10%]BiOI heterostructure. However, a decrease in performance was observed for both strong acidic and high alkaline pH values when the ZnO-[10%]WO3 heterostructure was applied. The kinetic analysis of the photodegradation study reveals that all the photodegradation experiments can be represented by the pseudo-first-order kinetic model. The findings from this investigation propose that the ZnO-[10%]BiOI heterojunction photocatalyst holds significant potential for the effective treatment of dye-contaminated wastewater.

Indigenous fire stewardship enhances ecosystem diversity, assists with the management of complex resources, and reduces wildfire risk by lessening fuel loads. Although Indigenous Peoples have maintained fire stewardship practices for millennia and continue to be keepers of fire knowledge, significant barriers exist for re-engaging in cultural burning. Indigenous communities in Canada have unique vulnerabilities to large and high-intensity wildfires as they are predominately located in remote, forested regions and lack financial support at federal and provincial levels to mitigate wildfire risk. Therefore, it is critical to uphold Indigenous expertise in leading effective and socially just fire stewardship. In this perspective, we demonstrate the benefits of cultural burning and identify five key barriers to advancing Indigenous fire stewardship in Canada. We also provide calls to action to assist with reducing preconceptions and misinformation and focus on creating space and respect for different knowledges and experiences. Despite growing concerns over wildfire risk and agency-stated intentions to establish Indigenous Peoples as partners in wildfire management, power imbalances still exist. The future and coexistence with fire in Canada needs to be a shared responsibility and led by Indigenous Peoples within their territories.

The feruloyl esterase B gene (faeB) is specifically induced by hydroxycinnamic acids (e.g. ferulic acid, caffeic acid and coumaric acid) but the transcriptional regulation network involved in faeB induction and ferulic acid metabolism has only been partially addressed. To identify transcription factors involved in ferulic acid metabolism we constructed and screened a transcription factor knockout library of 239 Aspergillus niger strains for mutants unable to utilize ferulic acid as a carbon source. The ΔfarA transcription factor mutant, already known to be involved in fatty acid metabolism, could not utilize ferulic acid and other hydroxycinnamic acids. In addition to screening the transcription factor mutant collection, a forward genetic screen was performed to isolate mutants unable to express faeB. For this screen a PfaeB-amdS and PfaeB-lux613 dual reporter strain was engineered. The rationale of the screen is that in this reporter strain ferulic acid induces amdS (acetamidase) expression via the faeB promoter resulting in lethality on fluoro-acetamide. Conidia of this reporter strain were UV-mutagenized and plated on fluoro-acetamide medium in the presence of ferulic acid. Mutants unable to induce faeB are expected to be fluoro-acetamide resistant and can be positively selected for. Using this screen, six fluoro-acetamide resistant mutants were obtained and phenotypically characterized. Three mutants had a phenotype identical to the farA mutant and sequencing the farA gene in these mutants indeed showed mutations in FarA which resulted in inability to growth on ferulic acid as well as on short and long chain fatty acids. The growth phenotype of the other three mutants was similar to the farA mutants in terms of the inability to grow on ferulic acid, but these mutants grew normally on short and long chain fatty acids. The genomes of these three mutants were sequenced and allelic mutations in one particular gene (NRRL3_09145) were found. The protein encoded by NRRL3_09145 shows similarity to the FarA and FarB transcription factors. However, whereas FarA and FarB contain both the Zn(II)2Cys6 domain and a fungal-specific transcription factor domain, the protein encoded by NRRL3_09145 (FarD) lacks the canonical Zn(II)2Cys6 domain and possesses only the fungal specific transcription factor domain.

Phytoestrogens (PEs) are plant-based compounds that can interact with estrogen receptors and are mainly used to treat menopausal complaints. However, the safety of products with assumed phytoestrogenic activity is not fully understood. This study aimed to identify plant species with assumed phytoestrogenic activity, review existing literature on their use and safety, and critically evaluate adverse reaction (AR) reports of single-herb, multi-herb, and mixed-multiple products, as submitted to the Netherlands Pharmacovigilance Centre Lareb and to VigiBase of the World Health Organization (WHO). In the Lareb database, the most commonly reported plant species to cause ARs (total of 67 reports) were Actaea racemosa L. (black cohosh) (47.8%), Humulus lupulus L. (hops) (32.8%), and Glycine max (L.) Merr. (soybean) (22.4%). In the VigiBase database (total of 21,944 reports), the top three consisted of Glycine max (L.) Merr. (71.4%), Actaea racemosa L. (11.6%), and Vitex agnus-castus L. (chaste tree) (6.4%). In the scoping review (total of 73 articles), Actaea racemosa L. (30.1%), Glycine max (L.) Merr. (28.8%), and Trifolium pratense L. (13.7%) were the most frequently mentioned plant species. ARs were most frequently reported in the system organ classes “gastrointestinal disorders”, “skin and subcutaneous tissue disorders”, “reproductive system and breast disorders”, and “general disorders and administration site conditions”. Furthermore, from the scoping review, it appeared that the use of products with assumed phytoestrogenic activity was associated with postmenopausal bleeding. It was concluded that, while the potential benefits of products with assumed phytoestrogenic activity have been extensively pursued, the potential occurrence of ARs after using these products is less well understood. This study highlights the need for further investigation and careful monitoring of these products to better understand their effects and ensure the safety and well-being of individuals using them.

Quasi-periodic eruptions (QPEs) are luminous bursts of soft X-rays from the nuclei of galaxies, repeating on timescales of hours to weeks1-5. The mechanism behind these rare systems is uncertain, but most theories involve accretion disks around supermassive black holes (SMBHs) undergoing instabilities6-8 or interacting with a stellar object in a close orbit9-11. It has been suggested that this disk could be created when the SMBH disrupts a passing star8,11, implying that many QPEs should be preceded by observable tidal disruption events (TDEs). Two known QPE sources show long-term decays in quiescent luminosity consistent with TDEs4,12 and two observed TDEs have exhibited X-ray flares consistent with individual eruptions13,14. TDEs and QPEs also occur preferentially in similar galaxies15. However, no confirmed repeating QPEs have been associated with a spectroscopically confirmed TDE or an optical TDE observed at peak brightness. Here we report the detection of nine X-ray QPEs with a mean recurrence time of approximately 48 h from AT2019qiz, a nearby and extensively studied optically selected TDE16. We detect and model the X-ray, ultraviolet (UV) and optical emission from the accretion disk and show that an orbiting body colliding with this disk provides a plausible explanation for the QPEs.

Objective: Hyperthermic Intraperitoneal Chemotherapy (HIPEC) is standard of care in the Netherlands in patients with stage III epithelial ovarian cancer following interval cytoreductive surgery (CRS). Differences in patient selection, technical aspects, and perioperative management exist between centers performing HIPEC. Standardization aims to reduce unwanted variation in clinical practice. As part of an implementation process, we aimed to standardize perioperative care for patients treated with CRS and HIPEC using a Delphi-based consensus approach. Methods: We performed a two-phase modified Delphi method involving a multidisciplinary panel of 40 experts who completed a survey on CRS and HIPEC. During a consensus meeting, survey outcomes and available scientific evidence was discussed. Items without consensus (

Cine-MRI for adhesion detection is a promising novel modality that can help the large group of patients developing pain after abdominal surgery. Few studies into its diagnostic accuracy are available, and none address observer variability. This retrospective study explores the inter- and intra-observer variability, diagnostic accuracy, and the effect of experience. A total of 15 observers with a variety of experience reviewed 61 sagittal cine-MRI slices, placing box annotations with a confidence score at locations suspect for adhesions. Five observers reviewed the slices again one year later. Inter- and intra-observer variability are quantified using Fleiss’ (inter) and Cohen’s (intra) κ and percentage agreement. Diagnostic accuracy is quantified with receiver operating characteristic (ROC) analysis based on a consensus standard. Inter-observer Fleiss’ κ values range from 0.04 to 0.34, showing poor to fair agreement. High general and cine-MRI experience led to significantly (p < 0.001) better agreement among observers. The intra-observer results show Cohen’s κ values between 0.37 and 0.53 for all observers, except one with a low κ of −0.11. Group AUC scores lie between 0.66 and 0.72, with individual observers reaching 0.78. This study confirms that cine-MRI can diagnose adhesions, with respect to a radiologist consensus panel and shows that experience improves reading cine-MRI. Observers without specific experience adapt to this modality quickly after a short online tutorial. Observer agreement is fair at best and area under the receiver operating characteristic curve (AUC) scores leave room for improvement. Consistently interpreting this novel modality needs further research, for instance, by developing reporting guidelines or artificial intelligence-based methods.

Monitoring adverse drug reactions is a vital issue to ensure drug safety and to protect the general public from medication-related harmful effects. In order to properly monitor drug safety, a regulatory system needs to be in place as well as an infrastructure that allows for analyzing national and international safety data. In Mongolia, adverse drug reaction (ADR) reporting activities have been implemented in the past decade. During this period, the basic structure and legal basis of an adverse drug reaction monitoring system was established. Because of the fragmented but growing healthcare system and the complexity of pharmaceutical issues in Mongolia, a sustainable process for the development of the adverse drug reaction reporting system is a key issue. The aim of this article is to disclose the Mongolian situation for the rest of the world and to share experiences on how an ADR reporting system can be developed towards a higher and more advanced level to contribute to both national and international drug safety issues. In this article, we review the features of the Mongolian health care and pharmaceutical systems, as well as the current development of the adverse drug reaction reporting system.

The effects of stress may be alleviated when its impact or a decreased stress-resilience are detected early. This study explores whether wearable-measured sleep and resting HRV in police officers can be predicted by stress-related Ecological Momentary Assessment (EMA) measures in preceding days and predict stress-related EMA outcomes in subsequent days. Eight police officers used an Oura ring to collect daily Total Sleep Time (TST) and resting Heart Rate Variability (HRV) and an EMA app for measuring demands, stress, mental exhaustion, and vigor during 15–55 weeks. Vector Autoregression (VAR) models were created and complemented by Granger causation tests and Impulse Response Function visualizations. Demands negatively predicted TST and HRV in one participant. TST negatively predicted demands, stress, and mental exhaustion in two, three, and five participants, respectively, and positively predicted vigor in five participants. HRV negatively predicted demands in two participants, and stress and mental exhaustion in one participant. Changes in HRV lasted longer than those in TST. Bidirectional associations of TST and resting HRV with stress-related outcomes were observed at a weak-to-moderate strength, but not consistently across participants. TST and resting HRV are more consistent predictors of stress-resilience in upcoming days than indicators of stress-related measures in prior days.

In the compounding facilities of hospital pharmacies, extemporaneous preparations for parenteral administration are produced using aseptic handling. The designated environment for this practice is a clean area, such as a laminar airflow (LAF) cabinet placed in a classified cleanroom complying with good manufacturing practices (GMP) and International Organization for Standardization (ISO) 14644-1 guidelines. The European GMP Annex 1 (Revision 2020) and United States Pharmacopeia (USP) monograph state that airflow visualization studies (“smoke” studies) should be performed to substantiate the cleanroom and LAF cabinet performance and their qualification status. Even though smoke studies are required by these guidelines, current literature does not describe detailed practical protocols and acceptance criteria. The objective of this study was to develop and implement a practical smoke study protocol to ensure compliance with aseptic handling guidelines in hospital pharmacies. First, a literature search was performed to collect information about smoke study protocols and acceptance criteria. Subsequently, a smoke study protocol was developed for a downflow and crossflow LAF cabinet as well as for grade C/B cleanroom areas. As a proof of concept, the smoke study protocol for the downflow LAF cabinet was executed in the at-rest and in-operation states. Video recordings of the smoke studies were analyzed to assess the performance of the cabinet. Finally, the video recordings obtained from the smoke studies were used in a training program for hospital pharmacy operators, which showed that smoke studies might aid in operators’ aseptic handling awareness. To the best of our knowledge, the present study provides for the first time a practical approach for the development of smoke study protocols in a hospital pharmacy setting and shows potential for training operators, process optimization, and continuous quality improvement.

Swallowing problems and the required dose adaptations needed to obtain optimal pharmacotherapy may be a hurdle in the use of tablets in daily clinical practice. Tablet splitting, crushing, or grinding is often applied to personalise medication, especially for the elderly and children. In this study, the performance of different types of (commercially available) devices was studied. Included were splitters, screwcap crushers, manual grinders, and electric grinders. Unscored tablets without active ingredient were prepared, with a diameter of 9 and 13 mm and a hardness of 100–220 N. Tablets were split into two parts and the difference in weight was measured. The time needed to pulverise the tablets (crush time) was recorded. The residue remaining in the device (loss) was measured. The powder was sieved to obtain a particle fraction >600 µm and

Critical thinking ability and character education seem to be interesting educational topics that are being discussed in the digital era of 21st century. It is necessary to optimize the character education in the learning process earlier using various learning media. The aim of this study is to investigate the influence learning process of legend story the theme of "obligation and right me" using the a character-based media of "wayang beber" (the legend of "Wasis Joyokusumo") on the students' critical thinking ability. This study is quasi experimental research using post-test only non-equivalent. The samples or participants are two classes in Pati city, namely SD Ngepungrejo 01 Pati as the control class with 36 students and SD Payang 2 Pati as the experimental class with 38 students. Cluster sampling is a technique used to determine the research subject. The data then collected using several techniques, namely observations, interviews, tests, and document analysis. In analyzing the data, descriptive and inferential statistical analysis methods are implemented. In this case, the content validity and construct validity are utilized to test the internal validity. The external validity is tested using try out test of instruments on the sample of study. The validity and reliability tests are implemented. After that, the questions are eligible to be used to obtain the data. The conclusion of study is that the implementation of "wayang beber" as a character-based learning media influences the students' critical thinking ability because the significance value is less than 0,01.

John Lachs considers his major philosophical contributions to be his work on mediation, the love of life, and his explication of George Santayana's philosophical and literary outlooks. All three are undergirded by Lachs's effort to make philosophy relevant to people's lives. This article examines these three contributions with both a critical eye and an admiration for Lachs's efforts. The conclusion provides an assessment often missed in critiques of Lachs's work. Keywords: John Lachs, George Santayana, Wallace Stevens, Consciousness, Education, Immediacy, Living Well, Love of Life, Mediation, Naturalism, Neuroscience, Non-reductive Materialism, Preface John Lachs considers his major philosophical contributions to be his work on mediation, the love of life, and his explication of George Santayana's outlook. He notes that the foundation [...]

The threat that climate change poses to water resource systems has led to a substantial and growing number of impact studies. These studies follow two approaches: (a) top‐down studies are driven by projections of future climate change provided by downscaled general circulation models (GCMs); and (b) bottom‐up studies are driven by the systematic evaluation of exploratory scenarios. Top‐down approaches produce realistic scenarios rooted in the simulation of thermodynamic and dynamic processes represented in GCMs, but the internal resolution of these processes make it difficult to link vulnerabilities to discrete components of change. Bottom‐up approaches link vulnerabilities to discrete components of change through the structured evaluation of exploratory scenarios, but the lack of insight rooted in climate change processes can lead to the development of implausible scenarios. This paper evaluates exploratory scenarios developed through thermodynamic and dynamical guided perturbations motivated by GCM‐bound insights. The result is a hybrid approach that bridges a gap between top‐down and bottom‐up approaches. This yields several advantages. First, emerging vulnerabilities are linked to distinct thermodynamic and dynamic processes that are modeled in GCMs with differential likelihoods and plausible ranges of change. Second, the structured evaluation of process‐informed exploratory scenarios link system vulnerabilities to distinct components of climate change. An illustrative case study demonstrates perturbations linked to thermodynamic and dynamical processes have a large impact on stakeholder‐defined flood and drought performance, and the structured evaluation of process‐informed exploratory scenarios find nuanced infrastructure‐specific vulnerabilities that would be difficult to identify using an alternative approach. Plain Language Summary: This paper addresses the threat climate change poses to water resource systems. Existing studies mainly use top‐down and bottom‐up methods. Top‐down studies rely upon climate models but struggle to assess local concerns. Bottom‐up studies assess local concerns but struggle to link those concerns to ways the climate is changing. This paper introduces a hybrid approach that combines the strengths of both methods. It evaluates local vulnerabilities using variables that drive impacts and are represented in climate models. A case study shows that this hybrid approach identifies local flood and drought vulnerabilities that would be difficult to find with traditional top‐down and bottom‐up methods. This paper aims to enhance our understanding of how climate change impacts water resource systems. Key Points: Exploratory scenarios rooted in processes represented in climate model simulations enhance bottom‐up climate vulnerability assessmentsSystematic exploration of climate drivers with uncertain futures enhance top‐down climate impact assessmentsExploratory scenarios linked to specific climate change insights identify nuanced system‐centric vulnerabilities [ABSTRACT FROM AUTHOR]