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Up to 80% of Parkinson's disease patients develop dementia, but time to dementia varies widely from motor symptom onset. Dementia with Lewy bodies presents with clinical features similar to Parkinson's disease dementia, but cognitive impairment precedes or coincides with motor onset. It remains controversial whether dementia with Lewy bodies and Parkinson's disease dementia are distinct conditions or represent part of a disease spectrum. The biological mechanisms underlying disease heterogeneity, in particular the development of dementia, remain poorly understood, but will likely be the key to understanding disease pathways and, ultimately, therapy development. Previous genome-wide association studies in Parkinson's disease and dementia with Lewy bodies/Parkinson's disease dementia have identified risk loci differentiating patients from controls. We collated data for 7804 patients of European ancestry from Tracking Parkinson's, The Oxford Discovery Cohort, and Accelerating Medicine Partnership-Parkinson's Disease Initiative. We conducted a discrete phenotype genome-wide association study comparing Lewy body diseases with and without dementia to decode disease heterogeneity by investigating the genetic drivers of dementia in Lewy body diseases. We found that risk allele rs429358 tagging APOEe4 increases the odds of developing dementia, and that rs7668531 near the MMRN1 and SNCA-AS1 genes and an intronic variant rs17442721 tagging LRRK2 G2019S on chromosome 12 are protective against dementia. These results should be validated in autopsy-confirmed cases in future studies.

Natural gas combustion to serve space heating hot water systems causes approximately one third of large commercial building energy use in California. This project evaluated an innovative set of non-proprietary, cost-effective methods to reduce energy consumption and associated emissions from these systems. The project demonstrated 70% natural gas savings and substantial electricity savings in two large office buildings, yielding total utility cost savings of approximately $110,000 (or $0.5/ft²) per year. The project also conducted detailed studies on distribution losses and boiler efficiency in several buildings; measured performance of key components in laboratory tests; gathered and analyzed data from hundreds of buildings to evaluate actual performance of these systems; and provided a public dataset to inform future retrofits, research, and code development. The research also highlighted characteristics that make a building a good candidate for retrofit so these results can be scaled. Market transformation activities included 10 journal and conference publications, policy recommendations and a design guide. Based on these findings and other recent work, the opportunity for similarly large emissions reductions appears to be common within the existing large commercial building stock. The resources provided by this project can aid stakeholders in achieving California’s goals to decarbonize buildings.

Background: Interstitial lung disease (ILD) is a significant cause of morbidity and mortality in patients with systemic sclerosis (SSc). To date, clinical practice guidelines regarding treatment for patients with SSc-ILD are primarily consensus based. Methods: An international expert guideline committee composed of 24 individuals with expertise in rheumatology, SSc, pulmonology, ILD, or methodology, and with personal experience with SSc-ILD, discussed systematic reviews of the published evidence assessed using the Grading of Recommendations, Assessment, Development, and Evaluation approach. Predetermined conflict-of-interest management strategies were applied, and recommendations were made for or against specific treatment interventions exclusively by the nonconflicted panelists. The confidence in effect estimates, importance of outcomes studied, balance of desirable and undesirable consequences of treatment, cost, feasibility, acceptability of the intervention, and implications for health equity were all considered in making the recommendations. This was in accordance with the American Thoracic Society guideline development process, which is in compliance with the Institute of Medicine standards for trustworthy guidelines. Results: For treatment of patients with SSc-ILD, the committee: 1) recommends the use of mycophenolate; 2) recommends further research into the safety and efficacy of (a) pirfenidone and (b) the combination of pirfenidone plus mycophenolate; and 3) suggests the use of (a) cyclophosphamide, (b) rituximab, (c) tocilizumab, (d) nintedanib, and (e) the combination of nintedanib plus mycophenolate. Conclusions: The recommendations herein provide an evidence-based clinical practice guideline for the treatment of patients with SSc-ILD and are intended to serve as the basis for informed and shared decision making by clinicians and patients.

Excessively high minimum airflow setpoints for Variable Air Volume (VAV) boxes, caused by outdated energy codes stipulating they should be 30% or higher of the maximum airflow, led to significant energy waste. Lower setpoints meet the ventilation code requirements while minimizing recirculation and reheat energy waste. ASHRAE RP-1515 showcased this by correcting VAV minimums in 1,000,000 ft2 (92903 m2) of California office space which yielded 10-30% HVAC energy savings and improved thermal comfort. Consequently, the Title 24 Energy Standards and ASHRAE 90.1 were updated to mandate minimum airflows match ventilation requirements. Beyond increased reheat energy waste caused by elevated VAV minimums, boiler operation issues can also contribute to avoidable energy waste. Despite energy codes mandating low VAV minimums for several years, these issues remain common in new construction and existing buildings. Our goal is to simplify retrofit decision-making for owners and operators by developing a screening method to assess extensive or small-scale building portfolios, using easily accessible data encompassing building type, age, size, and monthly gas consumption. The method entails applying a series of filters to a list of potential buildings to identify those with heating system challenges that should be prioritized for system upgrades. The main filter highlights buildings with elevated summertime gas consumption, as well-functioning systems lacking a major gas end-user should exhibit minimal gas usage during the cooling season. This filter employs a threshold for summer gas consumption we calculated based on standard design parameters, assumptions, and past case studies to serve as a benchmark and pinpoint problematic buildings. We applied this filter, among others, to over a decade of gas consumption data for 22 buildings at California State Polytechnic University, Humboldt. Collaborating with operators enabled us to identify 2 high priority buildings from the data set and validate the filtering process by cross-referencing floor plans and schedules to verify that these issues do in fact exist. Additionally, we applied this methodology to monthly gas data for 3318 buildings in Washington, DC to gauge its applicability on a larger scale. This process prioritized 30 potential buildings that could significantly reduce fossil fuel consumption, elevate thermal comfort, and realize gas bill savings through economical retrofits. While the screening method does not identify all buildings needing heating system upgrades, the results demonstrate how effective they are at highlighting buildings which should be prioritized to see the largest savings from the lowest cost interventions.

Abstract In this work, we aim at disentangling the theoretical contribution through mathematical modeling approach to advance the understanding of rabies dynamics and control in livestock population. A fractional order model of rabies, using Atangana–Baleanu fractional operator is created. The analysis of suggested system and its application are both conducted. The capacity of proposed model to forecast the disease can help researchers and livestock health care agencies to take preventive actions.

Abstract This research explores the challenges posed by variations in cystic duct anatomy during laparoscopic cholecystectomy and the potential use of stapler devices to address such complexities. It aims to assess the safety and efficacy of stapler devices, particularly in cases involving short, and wide cystic duct. The study, conducted at King Abdulaziz Medical City in Riyadh, Saudi Arabia, between 2021 and 2023. The study design involved a retrospective cohort approach, and the sample size encompassed all cases meeting the inclusion criteria during the study period. Data was analyzed using SPSS program. The study involving 568 patients, with the predominant technique for ligation being clipping (89.3%). The primary indication for using the Endo GIA stapler was a wide cystic duct (6.2%). Analysis revealed a significant association between stapler device use and hypertension (p = 0.042), diabetes (p = 0.001), CKD (p = 0.011), and obstructive jaundice (p = 0.006). Multivariate regression demonstrated that older patients were 2.1 times more likely to use stapler devices (AOR = 2.125; p = 0.039), while those with obstructive jaundice had a 2.2 times higher likelihood (AOR = 2.168; p = 0.049). Throughout the years, metal clips have shown the best prognosis compared to any other method for securing the cystic duct during closure in laparoscopic cholecystectomy. However, to avoid incomplete sealing of wide, short, or inflamed ducts, other instruments have emerged as possible alternatives for such conditions. Use of Endo-GIA is a safe and effective method for patients with wide, short cystic duct. Selective usage of endo-GIA is considered cost effective and may add a positive impact in decreasing post operative biliary leak.

Although an extensive literature focuses on gender and water, fewer studies focus explicitly on intrahousehold power dynamics and their consequences. This paper aims to understand the intrahousehold power dynamics that influence decisions such as who collects water from what source and how water is allocated across activities. Drawing on the rich intrahousehold literature from economics, we demonstrate how it would strengthen our understanding of the impacts of water policy and interventions. A review of intrahousehold bargaining models suggests that it is important to consider how policies and interventions in the water sector may affect the outside options of household members and thus shape their bargaining power. Social norms, property rights and water infrastructure all influence household members’ bargaining power and shape the context within which household decisions are made. Analysing intrahousehold dynamics for water needs to go beyond just considering the dynamic between the spouses; it also needs to consider others in the household who may provide labour for fetching water and who require water for their personal care and productive livelihoods.

Abstract Objective This study aimed to investigate the normal volumetric space and variations in the measurements of different landmarks in adults with different skeletal relations of the maxilla and the mandible based on CBCT data. The study also analyses these landmarks to locate any correlations. Background Numerous studies in orthodontics have found a relationship between orthodontic treatment and changes in the anatomy and function of the airway. Severe changes in airway morphology can cause breathing difficulties, lower quality of life, and even result in life-threatening conditions such as obstructive sleep apnoea. Consequently, orthodontic diagnosis and treatment planning require a thorough understanding of the airway space and its function. Methods The present retrospective study was conducted using CBCT records of 120 adult patients, containing 40 samples of each skeletal class (20 males and 20 females). The boundaries were defined for the 3 major regions: the nasopharynx, the oropharynx, and the hypopharynx. Various measurements were recorded across these regions, as well as selective cephalometric landmarks. The obtained data was used to calculate average and standard deviation, while regression analysis was used to evaluate correlations and t-test was used to test statistical significance of gender differences. Results The results demonstrate that skeletal Class III individuals exhibit a reduced airway volume in the nasopharynx compared to other groups, whereas skeletal Class II individuals displayed a diminished airway volume in the hypopharynx. A strong correlation was observed for Sella turcica parameters. There were no significant differences in skeletal parameters across genders. Nasopharynx cavity volume demonstrated significant differences between skeletal Class I–Class III as well as between skeletal Class II–Class III. Hypopharynx cavity volume also demonstrated significant differences between skeletal Class I–Class II and between skeletal Class II–Class III. Conclusion The major findings are the presence of a reduced nasopharyngeal volume in skeletal Class III malocclusions while skeletal Class II individuals displayed a diminished hypopharyngeal volume, making these critical areas to consider during the diagnostic and orthodontic treatment planning stages. This study also revealed a consistent correlation between Sella turcica parameters across various facial skeletal profiles, with skeletal Class II patients exhibiting a distinct pattern and skeletal Class I and Class III demonstrating an average relationship.

Abstract Objective This study aimed to develop a deep learning model to predict skeletal malocclusions with an acceptable level of accuracy using airway and cephalometric landmark values obtained from analyzing different CBCT images. Background In orthodontics, multitudinous studies have reported the correlation between orthodontic treatment and changes in the anatomy as well as the functioning of the airway. Typically, the values obtained from various measurements of cephalometric landmarks are used to determine skeletal class based on the interpretation an orthodontist experiences, which sometimes may not be accurate. Methods Samples of skeletal anatomical data were retrospectively obtained and recorded in Digital Imaging and Communications in Medicine (DICOM) file format. The DICOM files were used to reconstruct 3D models using 3DSlicer (slicer.org) by thresholding airway regions to build up 3D polygon models of airway regions for each sample. The 3D models were measured for different landmarks that included measurements across the nasopharynx, the oropharynx, and the hypopharynx. Male and female subjects were combined as one data set to develop supervised learning models. These measurements were utilized to build 7 artificial intelligence-based supervised learning models. Results The supervised learning model with the best accuracy was Random Forest, with a value of 0.74. All the other models were lower in terms of their accuracy. The recall scores for Class I, II, and III malocclusions were 0.71, 0.69, and 0.77, respectively, which represented the total number of actual positive cases predicted correctly, making the sensitivity of the model high. Conclusion In this study, it is observed that the Random Forest model was the most accurate model for predicting the skeletal malocclusion based on various airway and cephalometric landmarks.

Educators and administrators in secondary and higher education in Kazakhstan have experienced significant reforms since 2010. New policies, curricula, pedagogy, assessment practices, accountability mechanisms, and legislation were implemented in an education revolution, to modernize Kazakh education and build human capital for economic prosperity. The development and use of educational research is a component of these reforms but little is known about practitioners' understanding of and engagement with educational research. This qualitative study employed individual in-depth interviews with ten educational practitioners in secondary and higher education to address the knowledge gap. The findings suggest that practitioner understandings of research remain underdeveloped. While some practitioners both consume and produce research to improve practice and institutional decision-making, issues of access to research, the challenge of time within workload and perceptions of the limited relevance of externally produced research continue to be barriers to more extensive utilization of research. Further research is being undertaken to explore this issue with policymakers and researchers. The findings may be used to improve the mobilization of research to policy and practice, especially in other post-soviet contexts.

Abstract Fentanyl test strips (FTS) are lateral flow immunoassays that were originally designed and validated for detecting low concentrations of fentanyl in urine. Some FTS are now being marketed for the harm reduction purpose of testing street drugs for the presence of fentanyl. This manuscript provides a simple protocol to assess whether different brands and lots of fentanyl test strips perform adequately for use in drug checking. The results gathered from this protocol will document problems with particular lots or brands of FTS, help buyers choose from among the array of products, provide feedback to manufacturers to improve their products, and serve as an early warning system for ineffective products.

The symbiosis of blockchain technology with human creativity has given rise to what we now call crypto art, marking a new frontier in digital artistic expression. This development has profoundly altered our understanding of digital artifacts and ownership in this domain. Once easily accessible to all, digital art poses a unique challenge in the realm of collecting: how does one collect something that can be effortlessly replicated and shared? This paper explores the role of non-fungible tokens (NFTs) as authentication mechanisms and proof of authorship for digital artworks. Initially designed for decentralized financial transactions, blockchain technology has become instrumental in validating authorship and enabling the monetization of digital artworks through NFTs. Although digital artists now benefit from the validation of their work as legitimate investment assets through NFT technology, challenges persist due to the absence of copyright verification during token creation. For example, many artists have discovered their creations being used by third parties to mint tokens without their consent. The study demonstrates the transformative impact of NFTs on the digital art landscape while addressing the ongoing challenges and the imperative for enhanced copyright protection mechanisms.

Abstract Background Bouveret syndrome is a rare etiology of gastric outlet obstruction, presenting with clinical manifestations that resemble those of several gastric pathologies. Timely diagnosis is imperative to mitigate potentially fatal consequences associated with this condition. Case presentation This case report involves a male patient, aged 35, who exhibited symptoms of intense abdominal discomfort, nausea, and vomiting over a 24-h period. The individual experienced identical symptoms of lesser intensity on three separate occasions throughout the preceding 4-month period, during which they resorted to analgesic medication for temporary relief. A contrast-enhanced computed tomography (CT) scan of the abdomen was performed, which identified the presence of the Rigler triad, characterized by pneumobilia, a cholecysto-antral fistula, and an ectopic gallstone lodged in the gastric antrum resulting in an obstruction. The patient’s diagnosis of Bouveret syndrome was determined based on the imaging findings. A surgical procedure known as cholecystectomy was conducted, which confirmed the existence of the sizable cholecystoduodenal fistula that was previously detected in the computed tomography (CT) scan. The surgical procedures that were conducted included a partial duodenectomy, a gastrojejunostomy, a cholecystectomy, and a common bile duct exploration with the removal of common bile duct stones. After examining the bile duct, a t-tube was inserted into the bile duct. Conclusion This case demonstrates a distinctive occurrence of a condition in a young man, typically observed in elderly females. There is a lack of established treatment guidelines for this particular entity. The appropriate course of action depends on various factors, including the patient’s condition, CT scan results, medical history, presence of co-existing illnesses, and intraoperative circumstances. These considerations are taken into account when determining whether a single-step surgical strategy or a multi-step approach should be pursued in order to minimize complications in patients. In this case, due to favorable conditions, a single-step approach was taken that yielded promising results.

Abstract Mammalian hibernators survive prolonged periods of cold and resource scarcity by temporarily modulating normal physiological functions, but the mechanisms underlying these adaptations are poorly understood. The hibernation cycle of thirteen-lined ground squirrels (Ictidomys tridecemlineatus) lasts for 5–7 months and comprises weeks of hypometabolic, hypothermic torpor interspersed with 24–48-h periods of an active-like interbout arousal (IBA) state. We show that ground squirrels, who endure the entire hibernation season without food, have negligible hunger during IBAs. These squirrels exhibit reversible inhibition of the hypothalamic feeding center, such that hypothalamic arcuate nucleus neurons exhibit reduced sensitivity to the orexigenic and anorexigenic effects of ghrelin and leptin, respectively. However, hypothalamic infusion of thyroid hormone during an IBA is sufficient to rescue hibernation anorexia. Our results reveal that thyroid hormone deficiency underlies hibernation anorexia and demonstrate the functional flexibility of the hypothalamic feeding center.

Objective: To evaluate the infrazygomatic crest (IZC) bone and develop guidelines for the optimum placement of orthodontic miniscrew implants (OMSIs) along the distobuccal root of the permanent maxillary first molar. Methods: Bone thickness of the IZC region of 50 young adults (25 males and 25 females) aged 18-30 years were evaluated using cone-beam computed tomography images. The infrazygomatic bone thickness along the distobuccal root of the permanent maxillary first molar was assessed at various insertion angles (40° to 75° i.r.t the maxillary occlusal plane) with an increment of 5°. Student’s t-test was used to compare the IZC bone thickness and height at the orthodontic miniscrew insertion site for males and females on the right and left sides. Results: The bone thickness of the IZC region above the distobuccal root of the permanent maxillary first molar was estimated between 4.39±0.25 mm and 9.03±0.45 mm for insertion angles from 40° to 75° to the maxillary occlusal plane. The corresponding OMSI insertion heights were 17.71±0.61 mm to 13.69±0.75 mm, respectively, above the maxillary occlusal plane. There were statistically significant gender and side-wise variations in bone thickness at the IZC area and insertion height. Conclusion: The safe position for OMSI placement at the IZC was 13.69-16 mm from the maxillary occlusal plane with an insertion angle between 55° and 75°. These parameters provide the optimum placement of OMSIs along the distobuccal root of the permanent maxillary first molar.

Abstract Background Fentanyl test strips (FTS) are lateral flow immunoassay strips designed for detection of ng/mL levels of fentanyl in urine. In 2021, the US Centers for Disease Control and the Substance Abuse and Mental Health Administration stated that federal funds could be used for procurement of FTS for harm reduction strategies approved by the government such as drug checking. The market for FTS has expanded rapidly in the US and Canada. However, there is no regulatory oversight by either government to ensure proper function of FTS that are being marketed for drug checking. Main body Many brands of FTS have rapidly entered the harm reduction market, creating concerns about the reproducibility and accuracy of their performance from brand to brand and lot to lot. Some examples are provided in this Comment. Similar problems with product quality were observed in the mid 2000’s when lateral flow immunoassays for malaria were funded in many countries and again in 2020, when COVID-19 tests were in huge demand. The combination of high demand and low levels of regulation and enforcement led some manufacturers to join the goldrush without adequate field testing or quality assurance. We argue that the harm reduction community urgently needs to set a lot checking program in place. A set of simple protocols for conducting the tests and communicating the results have been developed, and are described in the following Perspectives paper in this issue. Conclusion In the absence of governmental regulation and enforcement, the harm reduction community should implement a FTS lot checking program. Based on previous experience with the malaria diagnostic lot checking program, this inexpensive effort could identify products that are not suitable for harm reduction applications and provide valuable feedback to manufacturers. Dissemination of the results will help harm reduction organizations to ensure that FTS they use for drug checking are fit for the purpose.

BackgroundNontargeted analysis (NTA) methods identify novel exposures; however, few chemicals have been quantified and interrogated with pregnancy complications.ObjectivesWe characterized levels of nine exogenous and endogenous chemicals in maternal and cord blood identified, selected, and confirmed in prior NTA steps, including linear and branched isomers perfluorooctane sulfonate (PFOS), perfluorohexane sulfonate (PFHxS), monoethylhexyl phthalate, 4-nitrophenol, tetraethylene glycol, tridecanedioic acid, octadecanedioic acid, and deoxycholic acid. We evaluated relationships between maternal and cord levels and between gestational diabetes mellitus (GDM) and hypertensive disorders of pregnancy in a diverse pregnancy cohort in San Francisco.MethodsWe collected matched maternal and cord serum samples at delivery from 302 pregnant study participants from the Chemicals in Our Bodies cohort in San Francisco. Chemicals were identified via NTA and quantified using targeted approaches. We calculated distributions and Spearman correlation coefficients testing the relationship of chemicals within and between the maternal and cord blood matrices. We used adjusted logistic regression to calculate the odds of GDM and hypertensive disorders of pregnancy associated with an interquartile range increase in maternal chemical exposures.ResultsWe detected linear PFOS, PFHxS, octadecanedioic acid, and deoxycholic acid in at least 97% of maternal samples. Correlations ranged between -0.1 and 0.9. We observed strong correlations between cord and maternal levels of PFHxS, linear PFOS, and branched PFOS (coefficient=0.9, 0.8, and 0.8, respectively). An interquartile range increase in linear and branched PFOS, tridecanedioic acid, octadecanedioic acid, and deoxycholic acid was associated with increased odds ratio (OR) of GDM [OR=1.33 (95% CI: 0.89, 2.01), 1.24 (95% CI: 0.86, 1.80), 1.26 (95% CI: 0.93, 1.73), 1.24 (95% CI: 0.86, 1.80), and 1.23 (95% CI: 0.87, 1.75), respectively]. Tridecanedioic acid was positively associated with hypertensive disorders of pregnancy [OR=1.28 (95% CI: 0.90, 1.86)].DiscussionWe identified both exogenous and endogenous chemicals seldom quantified in pregnant study participants that were also related to pregnancy complications and demonstrated the utility of NTA to identify chemical exposures of concern. https://doi.org/10.1289/EHP11546.

BackgroundDifferential risks for adverse pregnancy outcomes may be influenced by prenatal chemical exposures, but current exposure methods may not fully capture data to identify harms and differences.MethodsWe collected maternal and cord sera from pregnant people in Fresno and San Francisco, and screened for over 2420 chemicals using LC-QTOF/MS. We matched San Francisco participants to Fresno participants (N = 150) and compared detection frequencies. Twenty-six Fresno participants wore silicone wristbands evaluated for over 1500 chemicals using quantitative chemical analysis. We assessed whether living in tracts with higher levels of pollution according to CalEnviroScreen correlated with higher numbers of chemicals detected in sera.ResultsWe detected 2167 suspect chemical features across maternal and cord sera. The number of suspect chemical features was not different by city, but a higher number of suspect chemicals in cosmetics or fragrances was detected in the Fresno versus San Francisco participants' sera. We also found high levels of chemicals used in fragrances measured in the silicone wristbands. Fresno participants living in tracts with higher pesticide scores had higher numbers of suspect pesticides in their sera.ConclusionsMultiple exposure-assessment approaches can identify exposure to many chemicals during pregnancy that have not been well-studied for health effects.