Determining the Impact of Roller Compaction Processing Conditions on Granulate and API Properties: Impact of Formulation API Load.

Previous work demonstrated that roller compaction of a 40%w/w theophylline-loaded formulation resulted in granulate consisting of un-compacted fractions which were shown to constitute between 34 and 48%v/v of the granulate dependent on processing conditions. The active pharmaceutical ingredient (API) primary particle size within the un-compacted fraction was also shown to have undergone notable size reduction. The aim of the current work was to test the hypothesis that the observations may be more indicative of the relative compactability of the API due to the formulation being above the percolation threshold. This was done by assessing the impact of varied API loads in the formulation on the non-granulated fraction of the final granulate and the extent of attrition of API particles within the non-granulated fraction. The influence of processing conditions for all formulations was also investigated. The results verify that the observations, both of this study and the previous work, are not a consequence of exceeding the percolation threshold. The volume of un-compacted material within the granulate samples was observed to range between 34.7 and 65.5% depending on the API load and roll pressure, whilst the API attrition was equivalent across all conditions.

Large increases in methane emissions expected from North America's largest wetland complex.

Natural methane (CH4) emissions from aquatic ecosystems may rise because of human-induced climate warming, although the magnitude of increase is highly uncertain. Using an exceptionally large CH4 flux dataset (~19,000 chamber measurements) and remotely sensed information, we modeled plot- and landscape-scale wetland CH4 emissions from the Prairie Pothole Region (PPR), North America's largest wetland complex. Plot-scale CH4 emissions were driven by hydrology, temperature, vegetation, and wetland size. Historically, landscape-scale PPR wetland CH4 emissions were largely dependent on total wetland extent. However, regardless of future wetland extent, PPR CH4 emissions are predicted to increase by two- or threefold by 2100 under moderate or severe warming scenarios, respectively. Our findings suggest that international efforts to decrease atmospheric CH4 concentrations should jointly account for anthropogenic and natural emissions to maintain climate mitigation targets to the end of the century.

Decreasing the Incidence of Hypoxia and Airway Maneuvers During GI Procedures.

Many outpatient gastrointestinal procedures are completed with propofol anesthesia. A side effect of propofol is airway obstruction and subsequent hypoxia. This study was designed to determine whether the use of a high-flow nasal cannula is associated with a decreased incidence of hypoxia or airway obstruction in patients undergoing propofol sedation in the gastrointestinal laboratory with a STOP-BANG score ≥5. High-flow nasal cannula was administered at 70 L/min on 27 patients with a STOP-BANG score ≥5 receiving monitored anesthesia care sedation for an esophagogastroduodenoscopy, endoscopic ultrasound, or colonoscopy procedure. Patients were compared to a group from a previous project without the use of high-flow nasal cannula assessing whether hypoxia, apnea, or the need for airway maneuvers occurred. The non-high-flow nasal cannula group required an airway maneuver 53.3% (n = 8) whereas the high-flow nasal cannula group required an airway maneuver 18.5% (n = 5) (p = .021). High-flow nasal cannula was associated with a reduced need for airway maneuvers in patients with a high risk of obstructive sleep apnea undergoing propofol-assisted procedures.

The Psychology of Coronavirus Behavioral Health Mindset, Vaccination Receptivity, Customer Orientation and Community Public Service.

Three studies were conducted to explore the psychological determinants of COVID-deterrent behaviors. In Study 1, using data collected and analyzed both before and after the release of COVID-19 vaccines, mask-wearing, other preventative behaviors like social distancing, and vaccination intentions were positively related to assessments of the Coronavirus Behavioral Health Mindset (CVBHM); belief in the credibility of science; progressive political orientation; less use of repressive and more use of sensitization coping; and the attribution of COVID-19 safety to effort rather than ability, powerful forces, fate, or luck. In Study 2, favorable COVID-19 vaccination intentions were related to greater willingness to work, lower emotional distress, and greater customer experience mindset. Study 3 examined the personality and motives of individuals who volunteered to help deliver COVID-19 inoculations to the local community. The vaccine-giving volunteers, especially those with prosocial motives, had high CVBHM scores, belief in the credibility of science, low use of repressive coping, greater attribution of COVID-19 protection to effort, low likelihood of voting conservative, were older, and had more education than others. The majority of public health volunteers expressed prosocial motives to help people or join a cause (60.7%), but many (39.3%) expressed the personal motives of getting the COVID-19 vaccination for themselves, conveying a public image of compassion, or structuring time. Based on the three research studies, a COVID-19 Mindset Hierarchy model is proposed to integrate the results.

Determining the Impact of Roller Compaction Processing Conditions on Granule and API Properties.

The attrition of drug particles during the process of dry granulation, which may (or may not) be incorporated into granules, could be an important factor in determining the subsequent performance of that granulation, including key factors such as sticking to punches and bio-performance of the dosage form. It has previously been demonstrated that such attrition occurs in one common dry granulation process train; however, the fate of these comminuted particles in granules was not determined. An understanding of the phenomena of attrition and incorporation into granule will improve our ability to understand the performance of granulated systems, ultimately leading to an improvement in our ability to optimize and model the process. Unique feeding mechanisms, geometry, and milling systems of roller compaction equipment mean that attrition could be more or less substantial for any given equipment train. In this work, we examined attrition of API particles and their incorporation into granule in an equipment train from Gerteis, a commonly used equipment train for dry granulation. The results demonstrate that comminuted drug particles can exist free in post-milling blends of roller compaction equipment trains. This information can help better understand the performance of the granulations, and be incorporated into mechanistic models to optimize such processes.

Isolating Anthropogenic Wetland Loss by Concurrently Tracking Inundation and Land Cover Disturbance across the Mid-Atlantic Region, U.S.

Global trends in wetland degradation and loss have created an urgency to monitor wetland extent, as well as track the distribution and causes of wetland loss. Satellite imagery can be used to monitor wetlands over time, but few efforts have attempted to distinguish anthropogenic wetland loss from climate-driven variability in wetland extent. We present an approach to concurrently track land cover disturbance and inundation extent across the Mid-Atlantic region, United States, using the Landsat archive in Google Earth Engine. Disturbance was identified as a change in greenness, using a harmonic linear regression approach, or as a change in growing season brightness. Inundation extent was mapped using a modified version of the U.S. Geological Survey's Dynamic Surface Water Extent (DSWE) algorithm. Annual (2015-2018) disturbance averaged 0.32% (1095 km2 year-1) of the study area per year and was most common in forested areas. While inundation extent showed substantial interannual variability, the co-occurrence of disturbance and declines in inundation extent represented a minority of both change types, totaling 109 km2 over the four-year period, and 186 km2, using the National Wetland Inventory dataset in place of the Landsat-derived inundation extent. When the annual products were evaluated with permitted wetland and stream fill points, 95% of the fill points were detected, with most found by the disturbance product (89%) and fewer found by the inundation decline product (25%). The results suggest that mapping inundation alone is unlikely to be adequate to find and track anthropogenic wetland loss. Alternatively, remotely tracking both disturbance and inundation can potentially focus efforts to protect, manage, and restore wetlands.

Monitoring of multiple solvent induced form changes during high shear wet granulation and drying processes using online Raman spectroscopy.

Form changes during drug product processing can be a risk to the final product quality in terms of chemical stability and bioavailability. In this study, online Raman spectroscopy was used to monitor the form changes in real time during high shear wet granulation of Compound A, a highly soluble drug present at a high drug load in an extended release formulation. The effect of water content, temperature, wet massing time and drying technique on the degree of drug transformation were examined. A designed set of calibration standards were employed to develop quantitative partial least square regression models to predict the concentration of each drug form during both wet granulation and the drying process. Throughout all our experiments we observed complex changes of the drug form during granulation, manifest as conversions between the initial non-solvated form of Compound A, the hemi-hydrate form and the "apparent" amorphous form (dissolved drug). The online Raman data demonstrate that the non-solvated form converts to an "apparent" amorphous form (dissolved drug) due to drug dissolution with no appearance of the hemi-hydrate form during water addition stage. The extent of conversion of the non-solvated form was governed by the amount of water added and the rate of conversion was accelerated at higher temperatures. Interestingly, in the wet massing zone, the formation of the hemi-hydrate form was observed at a rate equivalent to the rate of depletion of the non-solvated form with no change in the level of the "apparent amorphous" form generated. The level of hemi-hydrate increased with an increase in wet massing time. The drying process had a significant effect on the proportion of each form. During tray drying, changes in drug form continued for hours. In contrast fluid bed drying appeared to lock the final proportions of drug form product attained during granulation, with comparatively small changes observed during drying. In conclusion, it was possible to simultaneously monitor the three forms in real time during wet granulation and drying using online Raman spectroscopy. The results regarding the effect of process parameters on the degree of transformation are critical for designing a robust process that ensures a consistent form in the final drug product.

Determination of process variables affecting drug particle attrition withinmulti-component blends during powder feed transmission.

The aim of this study was to determine the location of attrition of formulated API particles within a powder feed system using a Morphologi G3-ID system, an image analyzer with integrated Raman capability enabling classification of particles with respect to their chemistry, to extract the API size distribution from the blended sample. The study also aimed to investigate the impact of other process variables, such as feed screw speed, on the extent of attrition observed. The study demonstrated that attrition occurs in two zones of the powder feed system, at the bottom of the hopper at the interface with the feed screw, and also within the feed screw itself. In the situation of the attrition at the bottom of the hopper variations in the hopper fill level were not observed to change the extent of attrition observed. Variation of the feed screw speed was observed to affect the extent of API attrition, with the particle size within the formulation observed to decrease with increasing speed. The findings highlight that an understanding of the impact of unit processes, and variations in the associated processing conditions, is vital in order to fully understand the behavior and performance of pharmaceutical dosage forms.

Bicyclo[6.3.0]undeca-1(11),2,4,6,8-pentaen-10-ylidene: An Aromatic Carbene with Ambiphilic Properties.

The title carbene (4) was generated as a highly reactive species in solution by photoirradiation of 10-diazobicyclo[6.3.0]undecapentaene (5) using a high-pressure mercury lamp. Carbene 4 reacts with benzene to afford two isomeric adducts, 10-phenylbicyclo[6.3.0]undecapentaene (10) and tricyclo[9.3.03, 10 .0]heptadeca-1,3(10),4,6,8,12,14,16-octaene (11). The reactivity toward benzene is a characteristic of an electrophilic aromatic carbene analogous to cyclopentadienylidene 1. In contrast, the reaction of 4 with methanol produces 7-methoxybicyclo[6.3.0]undeca-1,3,5,8,10-pentaene (15). When [D1 ]methanol was employed as a reactant, the 10-deuterated analogue was formed. The results clearly indicate the formation of bicyclo[6.3.0]undecapentaenyl cation (7) as a novel 10 π-electronic compound by protonation of 4. Theoretical calculations indicate that the 2- and 7-positions of the cation have the largest positive charge in the cation. Moreover, the carbene was generated in the presence of tert-butyl hydroperoxide in aqueous tetrahydrofuran to afford azulene through oxidation of 7, followed by decarbonylation. The nucleophilic property of carbene 3 is similar to that of cycloheptatrienylidene 2. Thus, 4 can be regarded as a novel ambiphilic aromatic carbene.

The use of in situ near infrared imaging and Raman mapping to study the disproportionation of a drug HCl salt during dissolution.

NIR imaging and Raman mapping of the dissolution of model pharmaceutical formulations containing the HCl salt of a developmental compound, were carried out using a custom designed flow through cell. The results of this work have shown that NIR imaging and Raman mapping are capable of monitoring the distribution of the components in a formulation during dissolution while also revealing any form changes which may occur in real time. The NIR and Raman data revealed that the drug underwent conversion to the free base when water was used as the dissolution medium. However, in 0.1M HCl this conversion was no longer seen as the medium was below the pHmax (the pH of saturation of both unionised and ionised species and above which the free base can form) of the drug. The data from both approaches broadly agreed demonstrating the applicability of these methods to studying and enhancing our understanding of the complex physical and chemical processes which occur during dissolution in real time.

The effect of antimicrobial photodynamic therapy on human ciliated respiratory mucosa.

BACKGROUND: Chronic recurrent sinusitis (CRS) is one of the most common chronic conditions in the United States. There is a significant subpopulation of CRS patients who remain resistant to cure despite rigorous treatment regimens including surgery, allergy therapy, and prolonged antibiotic therapy. Antimicrobial photodynamic therapy (aPDT) is a noninvasive nonantibiotic broad spectrum antimicrobial treatment. Our previous in vitro studies demonstrated that aPDT reduced CRS polymicrobial biofilm and planktonic bacteria and fungi by > 99.9% after a single treatment. Prior to human treatment however, aPDT treatment must be demonstrated to not result in histologic damage to the sinus ciliated respiratory epithelium. The objective of this study was to demonstrate the safety of aPDT treatment on a living human ciliated respiratory mucosal model (EpiAirway). METHODS: A study of aPDT treatment of EpiAirway was performed. Treatment groups included a nontreatment control, laser light alone, photosensitizer alone, and therapeutic photosensitizer and light combination (aPDT). At completion of treatment, the EpiAirway tissue was fixed in 10% formalin, paraffin-embedded, sectioned, H&E stained and mounted. All samples were blinded and microscopically examined by a human pathologist to assess any effect of aPDT on the tissue, cilia, or mucosal glands. The results were correlated with the treatment parameters. RESULTS: The EpiAirway histologic study demonstrated no histologic alteration of the respiratory cilia or mucosal epithelium in any of the treatment groups. CONCLUSIONS: aPDT is a safe treatment for CRS resulting in no histologic alteration of human ciliated respiratory mucosa as is found in the human sinuses.

Test publishers' perspective on "an updated meta-analysis": comment on Van Iddekinge, Roth, Raymark, and Odle-Dusseau (2012).

Van Iddekinge, Roth, Raymark, and Odle-Dusseau's (2012) meta-analysis of pre-employment integrity test results confirmed that such tests are meaningfully related to counterproductive work behavior. The article also offered some cautionary conclusions, which appear to stem from the limited scope of the authors' focus and the specific research procedures used. Issues discussed in this commentary include the following: (a) test publishers' provision of studies for meta-analytic consideration; (b) errors and questions in the coding of statistics from past studies; (c) debatable corrections for unreliable criterion measures; (d) exclusion of laboratory, contrasted-groups, unit-level, and time-series studies of counterproductive behavior; (e) under-emphasis on the prediction of counterproductive workplace behaviors compared with job performance, training outcomes, and turnover; (f) overlooking the industry practice of deploying integrity scales with other valid predictors of employee outcomes; (g) implication that integrity test publishers produce biased research results; (h) incomplete presentation of integrity tests' resistance to faking; and (i) omission of data indicating applicants' favorable response to integrity tests, the tests' lack of adverse impact, and the positive business impact of integrity testing. This commentary, therefore, offers an alternate perspective, addresses omissions and apparent inaccuracies, and urges a return to the use of diverse methodologies to evaluate the validity of integrity tests and other psychometric instruments.

Multilocular thymic cyst with epithelioid granulomata of unknown etiology: a radiologic and histopathologic correlation.

Thymic cysts (congenital or acquired) are believed to account for 3% to 5% of all mediastinal masses. Multilocular thymic cysts are an acquired reactive inflammatory process arising within the thymus gland and are less common than the congenital unilocular type. Multilocular cysts have been reported in association with a variety of neoplastic, autoimmune, and infectious conditions. We report a case of a 23-year-old white man who presented with a 2-week history of progressive right-sided shoulder and chest pain. He was found to have an anterior mediastinal mass involving the thymus. This case of multilocular thymic cyst is particularly unique due to the presence of abundant epithelioid granulomata within the cyst, a finding that has not previously been emphasized as a histologic feature of these lesions, and one that expands the histopathologic differential diagnosis, warranting exclusion of infectious and autoimmune etiologies.