bluuebunny/crossref_metadata_2025 huggingface dataset:
Benjamin Graham Revisited
Authors: Balik Robert , Mehran Jamshid
Published: February 2023

Warren Buffett read the first edition of Benjamin Graham’s book, The Intelligent Investor, in 1950. According to Buffett (Graham, Revised, 2003) “I thought then that it was by far the best book about investing ever written. I still think it is.” Can a buy and hold defensive investor use this stock selection criteria and earn a positive abnormal risk adjusted rate of return? To test this hypothesis data for 2000 and prior years are used to select stocks that meet the defensive investor criteria. Nine stocks from an original list of more than 9,000 satisfy the criteria. Buy and hold is the investment strategy and these stocks are held from the end of June 2001 until the end of December 2007. The performance measure is the time-series regression intercept, or alpha, for the four-factor model. The estimated alpha is negative but not statistically significant.
Case Study of Firm Valuation Measures and the Reversal of Fortune Among 7 Rivers Equity Index Firms
Authors: Krueger Thomas
Published: February 2023

This article represents an attempt to provide readers with insight regarding common valuation metrics and how these can be applied to real companies. The same analysis could be applied in alternative settings and results compared to those presented here.
Indications of Risk: Standard Deviation of Returns or VaR of Terminal Wealth?
Authors: Bouzouita Raja , Young Arthur
Published: February 2023

Investors with long time horizons are more concerned with the dispersion of their terminal wealth than with within-period volatility of asset returns. The risk of terminal wealth will indicate whether the liquidated value of the portfolio will be sufficient to finance liabilities. In this paper we apply three different strategies to construct portfolios using the historical returns of five asset classes and report their performance over several time horizons. These three investment strategies are: mean-variance optimized portfolios, Roy’s safety first rule, and Value at Risk, VaR to minimize the impact of downsize risk when selecting portfolios. The distributions of terminal wealth generated from these portfolios are used to compare these investment strategies.
Effect of Subprime Lending on Residential Housing Investment: Evidence from the 2006 HMDA Loan Access Register
Authors: Sung Jane , Bosworth Steve
Published: February 2023

This paper empirically examined the effects of economic variables on the residential housing transaction with more emphasis on the subprime issues. The results support the easiness of lending will lead to more housing transaction.
Five Year Low as a Trading Strategy: The Kitchin Cycle Revisited
Authors: Ary Eddie , Horton Marshall
Published: February 2023

Consistent with the Kitchin inventory cycle, MSN Money routinely reports the five-year low stock price as a standard investment parameter. This paper analyzes quarterly returns to the strategy of buying a stock at its five-year low price and compares them with comparable returns to investing in either the S&P 500 Index or NASDAQ Composite Index. Consistent with the weak form of the Efficient Markets Hypothesis, the authors find no value in using the five-year low as a buying strategy. However, the five-year low appears to have considerable merit as a tool for short sellers.
Geometric or Arithmetic Mean: A Reevaluation
Authors: Bouzouita Raja , Saini Amandeep , Young Arthur
Published: February 2023

This study evaluates two competing forecasting models of rates of returns and recommends the preferable model for academicians and practitioners. In the first model, which was developed by Jacquier, Kane, and Marcus (2002), the forecast is a weighted mean between the geometric mean and the sum of the geometric mean and half the variance, where the weights are determined by the relative importance of the estimation period and the forecasting period. The second model, which is an adaption by Bodie, Kane, and Marcus (2008) of the first model, where the arithmetic mean is substituted for the sum of the geometric mean and half the variance. This substitution is not explained or justified in any way. The purpose of this paper is to explore the statistical significance and impact on forecasts of this substitution. In theory, these two models could be the same in large samples generated from normally distributed returns. However, the relative ability of these two competing models to forecast for small samples of actual returns is unknown. We find statistically significant differences in the inputs and the forecasts, but no meaningful difference in the models’ performance of forecasts as indicated by forecasting errors. In light of these results, despite the statistical differences, we find no economic difference between the forecasting errors of the two models and recommend the simpler of the two models which uses the arithmetic mean.
Study of Framing Effects in a New Risk Aversion Experiment
Authors: Lawson Larry , Lawson Catherine
Published: February 2023

Risk aversion experiments such as those by Holt and Laury (2002 and 2005) measure risk aversion by examining responses of experimental subjects who are confronted with single-sheet paper displays of probability-ordered arrays of choices in which “real” money is at risk. As an alternative to this approach, the findings reported in this paper were obtained using a modified adventure-type video game to offer the choices presented by the HL experiment embedded in a more realistic scenario. The decisions are confronted first by our experimental subjects in a sequential and unordered manner. Then, later in the experiment, subjects are instructed to examine the results of their decisions in an array that shares the simultaneous and probability-ordered characteristics of the standard laboratory protocol. Subjects then had the option of altering their decisions before their payment was determined. The results indicate that decisions made in a sequential and unordered manner exhibit less risk aversion and higher degrees of decision inconsistency.
Fundamental Stock Investment Strategies for Bull and Bear Markets
Authors: Johnston Charles
Published: February 2023

This research paper provides a stock investment model using both value and growth strategies for bull and bear markets. The model is based on fundamental principles of finance and can be efficiently used by individual investors and professional stock portfolio managers, in markets with high or low volatility, in the U.S. and internationally. The author initially developed the model primarily as a teaching tool, to demonstrate a profitable use of financial ratio analysis. The model and other findings of this research paper could also be useful to finance teachers of stock investing and their students.
Financial Meltdown – Crisis and Challenges
Authors: Hoque Monzurul
Published: February 2023

This paper looks at the current financial crisis in the light of the preceding major bubbles in the United States. We observe that history of bubbles is history of asset bubbles with attendant easy money. We posit that solution to these bubble crashes do not have to lead to deflation or inflation. If we go back to the basic of credit creation through real savings, the solution will not likely to set the stage for another bubble. An example of back to basic credit creation is provided.
Do Changes in Corporate Reputation Impact Subsequent Stock Price Performance?
Authors: Krueger Thomas , Wrolstad Mark , Dalsem Shane
Published: February 2023

This study of firm reputations finds that firms with improved reputations, as measured by Harris Interactive, provide higher average rates of return on the announcement date than those firms with diminished reputations. Somewhat surprisingly, firms with improved reputations earned an 8.3% return over the following year whereas firms with diminished returns earned a higher 15.4 % return. One can only speculate that firms with diminished reputations might be making management decisions that enhanced profitability at the expense of positive public perceptions of the firm. Sharpe and Treynor measures, based on median returns, were significantly greater for those firms with above average changes in reputation.
Does the Ruling to Break Up Microsoft Add Value to Its Competitors and Other High-Tech Companies?
Authors: Yip Yewmun , Lou Cathy
Published: February 2023

In this study, we examine the impact of the announcements of the ruling to break up Microsoft into two independent companies on the market values of Microsoft, Microsoft’s competitors and other firms operating in computer related industry. Our empirical results show that the stock price of Microsoft declined substantially on the day when the Department of Justice proposed to break up the company. In addition, significant negative abnormal returns are also observed for Microsoft’s competitors and other firms operating in the computer industry. This result contradicts the belief that a stricter enforcement of the antitrust laws will benefit Microsoft’s competitors. Although significant negative abnormal returns are also observed on the final hearing day, the abnormal negative returns on the ruling day is not statistically significant. This is perhaps an indication that the market has already factored in a high likelihood that the judge will rule to break up Microsoft as a remedy.
Assessing Alternative Equal-Weight Asset Re-Balancing Rules
Authors: DePrince Albert , Morris Pamela
Published: February 2023

This paper evaluates a hypothetical portfolio based on an equal-weight investment rule involving four asset classes: domestics, industrialized countries excluding the U.S., emerging market countries, and global bonds. Portfolio results using three alternative re-balancing rules are compared with a composite benchmark index. The simulation period runs from July 1996 through January 2010, which is dictated by the availability of data on the underlying asset classes. The equal-weight investment strategy is superior to investing the composite benchmark index in all three rules examined. The first involves no rebalancing over the simulation period. This provides the best performance versus the composite benchmark. The second rule collects and rebalances dividends according to the equal-weight investment rule. The third collects both dividends and capital gains and reallocates them among the four asset classes using the same equal-weight investment rule. Of these rules, there is a slight surrendering of return as one moves to more complex rebalancing rules. Additionally, the variability of portfolio return increases marginally as one moves from the baseline rule through the two rebalancing rules. Thus, a good case could be made to following a fixed investment rule and allowing the market to rebalance the portfolio.
Maximizing IRA Returns Using FLP/LLC Discounting Techniques
Authors: Maas William , Bahr Kevin , Carey Sean
Published: February 2023

The purpose of this paper is to demonstrate the potential investment benefits of holding real estate inside an IRA and utilizing Family Limited Partnership (FLP) or family Limited Liability Company (LLC) discounting techniques. Statutory authority, administrative authority, and judicial authority was researched to support the conclusion that an IRA may own real estate and the Individual Retirement Account (IRA) value may be discounted for tax and minimum required distribution (MRD) purposes by using properly structured techniques.
INFLUENCE OF FLAIR FACTORS ON COMPENSATION – BALANCING CONTRIBUTIONS AND PAY EQUITY
Authors:   Faculty of Management, Sremski Karlovci, University UNION Nikola Tesla, Belgrade, Runić-Ristić Marija , Savić-Tot Tijana ,   Faculty of Management, Sremski Karlovci, University UNION Nikola Tesla, Belgrade, Arsić Milica
Published: February 2023

The utmost priority of every organization in today’s competitive environment is to attract and retain top talents. The aim of this paper is to emphasize the importance of “flair factors” those greatly valued personal qualities that enable an organization to accomplish its mission. The paper links insights about flair factors, as critical elements of organizational success, with the development of a compensation philosophy that can help organizations to recruit, attract, and retain top talented employees. Moreover, nine often-repeated errors made in developing and administering an effective compensation system are outlined. Finally, the paper benefits to both scholars and practitioners by suggesting how to solve the problem of identifying and hiring the right people for successful performance in organizations.
Topografiske infiltrationer:
Authors: Hastrup Kirsten
Published: February 2023

Forfatteren argumenterer for den topografiske vending ved at tage udgangspunkt i, at men- nesker og landskaber gensidigt konstituerer hinanden. Det indebærer, at topografien infil- trerer samfundet, og at mennesker orienterer sig i overensstemmelse med en konkret erfa- ring med landskabet. Vendingen har metodo- logiske konsekvenser, idet den indebærer en reel grænseløshed i forståelsen af menneskers sociale forbindelser til nære og fjerne dele i deres omverden og stiller nye krav til en ar- gumenteret analytisk lukning af det studerede. Den sociale kompleksitet er en konsekvens af en bottom-up proces i en bevægelig verden, hvorfor analytikerens position og interesse altid bidrager til tilskæringen og skaleringen af feltet. Det udfordrer i næste omgang fore- stillingen om realisme, der nu må inkludere forskerens position. Der må argumenteres for fremstillingens rigtighed på baggrund af et engagement i den virkelige verden, og ikke mindst med henvisning til fortolkningens in- tersubjektive kvalitet.
Kvantefysiske subjekter?
Authors: Juelskjær Malou
Published: February 2023

Artiklens ambition er at integrere komponen- terne tid og rum i et socialpsykologisk studie af subjektivering. Inspirationen trækkes fra Ka- ren Barads abstrakte arbejde med at tænke ma- terialisering gennem kvantefysikken, et arbejde som præsenterer en gentænkning af tid-rum langs med kvantefysikkens forståelse af disse komponenter. Artiklen bruger et empirisk stu- die af elevers skoleskift som afsæt til at tænke tid-rum som aktive transformative agenter i subjektets tilblivelse. Her rejses teoretiske, me- todologiske og analysestrategiske spørgsmål i forhold til, hvordan man kan studere tid og rum i subjekt konstituering. Artiklen under- søger endvidere hvilken status man kan give til interviews i studiet af materialiseringspro- cesser og processer af konstituering af tid og rum i forlængelse af ‘den materielle vending’.
Organizacje pacjentów a ochrona zdrowia w Polsce
Authors:   Wydział Zarządzania Uniwersytetu Warszawskiego, Stasiewicz-Swinney Agnieszka
Published: February 2023

Patients and patient organizations are becoming increasingly involved in health policy and operations of health care. The value of such activity plays a particularly important role in the area of chronic diseases such as cancer or rare diseases, where patients suffer from limited access to effective therapies due to lengthy clinical trials, complex regulatory procedures of drug registration and reimbursement. It has been suggested that input of patient organizations has a significant impact on reducing uncertainty and decision risk, throughout the entire process, beginning from the clinical trials, through engagement as experts in their diseases in registration and reimbursement, up to routine clinical practice applications. This comprehensive review examines the areas of patient organizations involvement at crucial stages of public healthcare operations. At present, activities of patient organizations seem to be closely related to the lifecycle of a medical product on the health care market and coverings following areas: psychological and emotional support, financial and non-financial assistance to patients, knowledge gathering and sharing, raising public awareness of their disease, participation in the design and conduct of clinical trials, early access programs, engaging in reimbursement decision making and advocacy aimed at regulatory changes. All inputs of patient organizations listed above generate significant impact on the health care system and shaping of drug policies. The findings demonstrate that involvement of patients, their families and patient organizations exist at many levels of the health care system. Due to study limitations, the extent and effectiveness of patient’s organization various initiatives have yet to be explicitly explored. Moreover, the existing input requires further studies to evaluate the level of engagement.
Socio-Economic Approach to Health in the European Union Chemicals Regulation Policy
Authors:   Health Care Management and Logistic Unit, Rydlewska-Liszkowska Izabela
Published: February 2023

Socio-economic analysis (SEA) of health safety is the approach to describing and analysing all relevant impacts – positive and negative – of restricting or non-restricting and granting or refusing authorisation for chemicals in the European Union (EU) market. SEA provides the evidence and documents on whether the socio-economic benefits of continued use or restricted use of chemicals outweigh or not the risk of chemicals for human health and the environment. The aim of SEA as a method of weighing up the arguments of action for society is to play the crucial role in restrictions and authorisations of the chemicals under the Registration, Evaluation, Authorisation and Restriction of Chemicals Act (REACH) in the EU. Regarding the restrictions proposals, such regulations contain a description of the risks, health and environmental benefits, associated costs and other socio-economic impacts. An application for chemicals authorisation should answer the question if the socio-economic benefits outweigh the risks to human health and the environment arising from the use of the substance. The aim of the paper is to present the methods developed by the European Chemicals Agency (ECHA) in cooperation with its Committee for Socio-economic Analysis (SEAC) in order to evaluate the impact of costs and effects of different alternative uses of chemicals on the EU population health. The paper will also show the main limitations of the analysis at the EU member countries level.
Peculiarities of Perception of Sounds by Children with Speech Disorders and Children with Autism Spectrum Disorder
Authors: Efimova Viktoriya Leonidovna , Nikolaeva Elena Ivanovna , Frolovskaia Ol'ga Vladimirovna
Published: February 2023

In this study, an attempt was made to find prognostic parameters that allow finding diagnostic differences between the two most common speech disorders (SD) and autism spectrum disorders (ASD). The aim of the study was to compare the characteristics of the conduction of an audio signal at the level of the cerebral trunk (results of ABR) and the loss in the frequencies of the spoken range of 500-1000-2000-4000 Hz (multi ASSR) of the children with ASD and children with SD. The study involved 495 children aged 2 to 11 years. The experimental group included children with ASD in the amount of 245 people, as well as children with speech disorders 250 people. All children were examined at the Prognoz clinic and, according to the conclusion of the audiologists, had no hearing impairment. The data obtained revealed similarities and differences in the functioning of the auditory pathways in children with ASD and SD. The question of whether this information can be used for differential diagnosis needs further study. It is important that the structures of the brainstem, which determine the quality of the conduction of bioelectrical impulses along the auditory pathways, are formed even before the birth of a child. Thus, already in the first weeks of life, it is possible to identify children at risk, who subsequently have a high probability of developing ASD or SD.
When cancer strikes (twice)
Authors: Swann Nicole
Published: February 2023

A young group leader reflects on academic culture and working while going through cancer treatments.
Comparative chloroplast genomics of three species of Bulbophyllum section Cirrhopetalum (Orchidaceae), with an emphasis on the description of a new species from Eastern Himalaya
Authors: Li Mengkai , Tang Lu , Deng Jianping , Tang Hanqing , Shao Shicheng , Xing Zhen , Luo Yan
Published: February 2023

Background

Chloroplast (cp) genomes are useful and informative molecular markers used for species determination and phylogenetic analysis. Bulbophyllum is one of the most taxonomically complex taxa in Orchidaceae. However, the genome characteristics of Bulbophyllum are poorly understood.

Methods

Based on comparative morphological and genomic analysis, a new species Bulbophyllum pilopetalum from eastern Himalaya belonging to section Cirrhopetalum is described and illustrated. This study used chloroplast genomic sequences and ribosomal DNA (nrDNA) analysis to distinguish the new Bulbophyllum species and determine its phylogenetic position. An additional phylogenetic analysis was conducted using 74 coding sequences from 15 complete chloroplast genomes from the genus Bulbophyllum, as well as nrDNA sequences and two chloroplast DNA sequences from 33 Bulbophyllun species.

Results

The new species is morphologically similar to B. pingnanense, B. albociliatum, and B. brevipedunculatum in vegetative and floral morphology, but it can be distinguished by its ovate-triangle dorsal sepal without a marginal ciliate. The chloroplast genome of the new Bulbophyllum species is 151,148 bp in length, and includes a pair of inverted repeats (IRs) of 25,833 bp, a large single-copy region (LSC) of 86,138 bp, and a small single-copy region (SSC) of 13,300 bp. The chloroplast genome includes 108 unique genes encoding 75 proteins, 30 tRNAs, and four rRNAs. Compared with the cp genomes of its two most closely-related species, B. pingnanense and B. albociliatum, this chloroplast genome exhibited great interspecific divergence and contained several Indels that were specific to the new species. The plastid tree showed that B. pilopetalum is most closely-related to B. pingnanense. The phylogenetic tree based on combined nrDNA and chloroplast DNA sequences indicated that section Cirrhopetalum was monophyletic and B. pilopetalum was a member of this section.

Discussion

The taxonomic status of the new species is strongly supported by cp genome data. Our study highlights the importance of using the complete cp genome to identify species, elucidate the taxonomy, and reconstruct the phylogeny of plant groups with complicated taxonomic problems.
Multifaceted COVID-19 Associated Coagulopathy
Authors: Bhardwaj Manisha , Himral Pratibha , Aggarwal Deepak
Published: February 2023

The pathophysiology behind Coronavirus Disease-2019 (COVID-19) has remained blur even after more than two years of onset of the pandemic. Apart from pulmonary parenchymal involvement, widespread vascular thrombosis affecting both pulmonary and extra-pulmonary systems has also been seen to contribute to COVID-19 associated morbidity. This vascular manifestation often remains undiagnosed due to non specific and varied symptoms that range from asymptomatic detection to life threatening presentations. A series of six COVID-19 positive (three male and three female) cases who presented with thrombosis of pulmonary, coronary and cerebral vessels despite being on thromboprophylaxis are reported herein. The age of patients ranged from 32 to 80 years. Out of six patients, three had comorbidities. The most common complication was Pulmonary Thromboembolism (PTE, n=4) followed by Myocardial Infarction (MI, n=1) and cerebellar infarct (n=1). Out of three patients with PTE, one patient had concurrent Deep Vein Thrombosis (DVT). All patients were managed as per guidelines issued by the Ministry of Health and Family Welfare for severe COVID-19 disease. Out of six patients, three patients died and three were discharged. The series highlights the need for high index of suspicion on the part of the treating physician that could aid in early detection and successful management of this potentially fatal condition.
Case Study of Patients Using Injectable Trancinolone Acetonide with Neurological Complications
Authors: Qi E. , Jiayi Peng , Ziyin Zhou , Xianjie Wen
Published: February 2023

Aim: Through the analysis of two cases of serious neurological complications after triamcinolone acetonide use, this case study warns that the risk of serious neurological complications should be paid attention to when triamcinolone acetonide is used clinically.

Presentation of Case: In this paper, we reported two cases of severe neurological complications caused by triamcinolone acetonide. One case was severe hearing loss on the same side after triamcinolone acetonide was injected around the ear to treat scars. After 2 months of treatment, the patient's nausea, vomiting and vertigo improved, but the hearing damage did not improve. The other case was severe complications of lower limb paralysis after triamcinolone acetonide was injected into the spinal canal. Two hours after the injection of the drug, the patient developed paraplegia of both lower limbs. After three months of treatment, it still did not improve.

Discussion and Conclusion: Triamcinolone acetonide is a suspension, insoluble in water, with a large number of particles gathering, and the largest particle is greater than 500μm. It has been reported that the medium-sized particles of adrenocortical hormone with a diameter of 51-1000μm can easily block the blood vessels, especially the anterior spinal artery. In clinical practice, we should pay attention to the disastrous neurological complications caused by triamcinolone acetonide hydrochloride, and take relevant preventive and coping measures.
The Effect of Using Digital Marketing Platforms, Optimizing Potential Assets on the Inclusive and Sustainable Economy Improvement
Authors: Yuniarta Gede Adi , Purnamawati I Gusti Ayu , Suwena Kadek Rai
Published: February 2023

This study aims to analyze the role of the green economy and digitalization for sustainable rural economic development. This research is quantitative descriptive research. The research was conducted in Manistutu Village, Jembrana Regency, Bali Province. Research data using primary sources were collected using a questionnaire with a Likert scale. Respondents in this study were the community and village officials who carried out activities using technical assistance in government activities, tourism, agriculture, and plantations. The research sample amounted to 70 people using purposive sampling. Data were analyzed using Structural Equation Modeling. The results of the research were conducted to explain the importance of maintaining sustainable economic growth in the tourism, agriculture, and plantation sectors in the Jembrana Regency by using technology. Digital marketing platforms and optimizing the potential of village assets have a significant influence on growth in the inclusive and sustainable economic and financial sectors.
Identification of Biochemical Composition and Pesticides Residue in Ten Rose Cultivars Leaves Using FT-IR Spectroscopy
Authors: Cantor Maria , Buta Erzsebet , Conţiu Ioana , Ştefan Răzvan , Crișan Ioana , Buru Timea
Published: February 2023

In order to optimize the application of nutritive solutions and the phytosanitary treatments with direct influence on the quality of cut roses from hydroponic culture (soilless culture), it is necessary to study the biochemical composition of the different organs of the plant (leaves). By FT-IR spectroscopy using the standard KBr pellet technique; it was possible to differentiate between 10 Rosa cultivars based on the chemical composition of the leaves and also to identify the pesticide residue within the leaf tissues and some of its effects. Thus, it was observed that the intensity of the bands corresponding to amide I (proteins) and aromatic compounds were weaker in leaf sheath and petiole compared with the leaf lamina. Aldehydes were present only in leaf sheath and petiole and not in the leaf lamina. As for the six pesticides tested, simple bond vibration C–H corresponding to aromatic compounds has been detected at 817 cm-1 and 805 cm-1 in the samples treated with penconazole based pesticide (Topas) and a triadimenol with folpet pesticide (Shavit). Also, application of penconazole increases the concentration of polisaccharides in the treated leaves, while a strong intensity band that could be attributed to the presence of halogenated compounds (chlorinated) C-Cl can be observed at 715 cm-1 for the samples treated with the triadimenol and folpet pesticide. The overall results of the present study could provide helpful information for the development of pesticides that have a shorter persistence and a lower biochemical influence on the plant tissues.
Changes in plant species diversity as affected by shading conditions and continuous agricultural practices in kiwifruit orchards
Authors: Triantafyllidis Vassilios , Zotos Anastasios , Kosma Chariklia , Kehayias George , Pittaras Antonios , Drougas Panagiotis
Published: February 2023

The environmental impact of commercial Mediterranean kiwifruit 'Hayward’ orchards was assessed after ten years of continuous cultivation. Species diversity seems to be influenced both by the subcanopy photosynthetically active radiation (PAR) budget, and the usual agricultural practices in conventional orchards. The largest reduction of species diversity (~64%) was observed in kiwifruit orchards with pergola canopy structure followed by that in T-bar canopy structure (~34%) in comparison with new installed kiwifruit orchards. In excessive shading conditions and particularly in well irrigated kiwifruit orchards with the synergistic effect of the above variables, the highest reduction of plant species has occurred. The continuous herbicides application and the soil compaction are strongly correlated with the reduction of taxa, while the long-term agricultural practices, such as inorganic fertilizers and Cu-fungicides application, have a negative impact on plant species diversity in kiwifruit orchards.
Trends in Out-of-Pocket Costs for and Characteristics of Pharmacy-Dispensed Buprenorphine Medications for Opioid Use Disorder Treatment by Type of Payer, 2015 to 2020
Authors: Strahan Andrea E. , Desai Shaina , Zhang Kun , Guy Gery P.
Published: February 2023

Importance

Buprenorphine has been approved for opioid use disorder treatment, yet remains underutilized. Cost may present a barrier; little is known about how out-of-pocket costs vary.

Objective

To determine if out-of-pocket costs and prescription characteristics for buprenorphine varied by type of payer.

Design, Setting, and Participants

This cross-sectional study used all-payer data on retail pharmacy–dispensed buprenorphine prescriptions from January 1, 2015, through December 31, 2020, for adults (aged ≥18 years) in the US, excluding formulations primarily used to treat pain. Data were analyzed from July 2021 to June 2022.

Exposures

Type of payer (private and commercial, self-pay, Medicaid, Medicare, assistance, and unknown) for dispensed prescription.

Main Outcomes and Measures

All outcomes are prescription-level. Mean and median daily out-of-pocket costs were calculated overall and by payer type. Prescription characteristics (days supplied, patient age and sex, generic vs name brand formulations, and prescriber’s location) were examined by payer type.

Results

Although mean daily out-of-pocket costs decreased overall from $4.79 (95% CI, $4.79-$4.80) in 2015 (7 375 508 prescriptions) to $1.91 (95% CI, $1.90-$1.91) in 2020 (13 486 822 prescriptions), out-of-pocket costs continued to vary by payer in 2020. Medicaid had the lowest mean daily out-of-pocket cost across all years—$0.18 (95% CI, $0.18-$0.18) in 2015, and $0.10 (95% CI, $0.10-$0.10) in 2020. Private and commercial paid prescriptions fell from $4.80 (95% CI, $4.79-$4.81) per day in 2015 to $1.82 (95% CI, $1.82-$1.83) in 2020. Self-pay and assistance categories had the highest mean daily out-of-pocket costs across study years ($9.76 [95% CI, $9.74-$9.78] and $8.72 [95% CI, $8.71-$8.73], respectively, in 2015; $8.44 [95% CI, $8.43-$8.46] and $6.31 [95% CI, $6.30-$6.31], respectively, in 2020). Medicaid paid prescriptions had a mean supply of 15.59 days (95% CI, 15.58-15.59 days) and the lowest percentage of generic prescriptions (57.88%; 95% CI, 57.84%-57.92%). Out-of-pocket cost varied by prescriber location and patient characteristics; mean costs were highest for prescriptions written in the South ($2.91; 95% CI, $2.90-$2.91), metropolitan counties ($1.93; 95% CI, $1.93-$1.93), and for individuals aged 35 to 44 years ($2.10; 95% CI, $2.09-$2.10).

Conclusions and Relevance

This cross-sectional study found that mean daily out-of-pocket costs for buprenorphine were lower in 2020 than in 2015, but variation by payer existed in all study years. Financial barriers to accessing and maintaining buprenorphine for opioid use disorder treatment may exist and differ by type of prescription coverage. Future research could monitor costs and identify potential barriers that may impact access and retention in care.
Trends in In-Hospital Cardiac Arrest and Mortality Among Children With Cardiac Disease in the Intensive Care Unit
Authors: Sperotto Francesca , Daverio Marco , Amigoni Angela , Gregori Dario , Dorste Anna , Allan Catherine , Thiagarajan Ravi R.
Published: February 2023

Importance

Data on trends in incidence and mortality for in-hospital cardiac arrest (IHCA) in children with cardiac disease in the intensive care unit (ICU) are lacking. Additionally, there is limited information on factors associated with IHCA and mortality in this population.

Objective

To investigate incidence, trends, and factors associated with IHCA and mortality in children with cardiac disease in the ICU.

Data Sources

A systematic review was conducted using PubMed, Web of Science, EMBASE, and CINAHL, from inception to September 2021.

Study Selection

Observational studies on IHCA in pediatric ICU patients with cardiac disease were selected (age cutoffs in studies varied from age ≤18 y to age ≤21 y).

Data Extraction and Synthesis

Quality of studies was assessed using the National Institutes of Health Quality Assessment Tools. Data on incidence, mortality, and factors associated with IHCA or mortality were extracted by 2 independent observers. Random-effects meta-analysis was used to compute pooled proportions and pooled ORs. Metaregression, adjusted for type of study and diagnostic category, was used to evaluate trends in incidence and mortality.

Main Outcomes and Measures

Primary outcomes were incidence of IHCA and in-hospital mortality. Secondary outcomes were proportions of patients who underwent extracorporeal membrane oxygenation (ECMO) cardiopulmonary resuscitation (ECPR) and those who did not achieve return of spontaneous circulation (ROSC).

Results

Of the 2574 studies identified, 25 were included in the systematic review (131 724 patients) and 18 in the meta-analysis. Five percent (95% CI, 4%-6%) of children with cardiac disease in the ICU experienced IHCA. The pooled in-hospital mortality among children who experienced IHCA was 51% (95% CI, 42%-59%). Thirty-nine percent (95% CI, 29%-51%) did not achieve ROSC; in centers with ECMO, 22% (95% CI, 14%-33%) underwent ECPR, whereas 22% (95% CI, 12%-38%) were unable to be resuscitated. Both incidence of IHCA and associated in-hospital mortality decreased significantly in the last 20 years (both P for trend < .001), whereas the proportion of patients not achieving ROSC did not significantly change (P for trend = .90). Neonatal age, prematurity, comorbidities, univentricular physiology, arrhythmias, prearrest mechanical ventilation or ECMO, and higher surgical complexity were associated with increased incidence of IHCA and mortality odds.

Conclusions and Relevance

This systematic review and meta-analysis found that 5% of children with cardiac disease in the ICU experienced IHCA. Decreasing trends in IHCA incidence and mortality suggest that education on preventive interventions, use of ECMO, and post-arrest care may have been effective; however, there remains a crucial need for developing resuscitation strategies specific to children with cardiac disease.
Long‐term clinical, imaging and cognitive outcomes association with MS immunopathology
Authors: Kalinowska‐Lyszczarz Alicja , Tillema Jan‐Mendelt , Tobin William Oliver , Guo Yong , Weigand Stephen D. , Metz Imke , Brück Wolfgang , Lassmann Hans , Giraldo‐Chica Monica , Port John D. , Lucchinetti Claudia F.
Published: February 2023

Objective

In this observational study on a cohort of biopsy‐proven central nervous system demyelinating disease consistent with MS, we examined the relationship between early‐active demyelinating lesion immunopattern (IP) with subsequent clinical course, radiographic progression, and cognitive function.

Methods

Seventy‐five patients had at least one early‐active lesion on biopsy and were pathologically classified into three immunopatterns based on published criteria. The median time from biopsy at follow‐up was 11 years, median age at biopsy ‐ 41, EDSS ‐ 4.0. At last follow‐up, the median age was 50, EDSS ‐ 3.0. Clinical examination, cognitive assessment (CogState battery), and 3‐Tesla‐MRI (MPRAGE/FLAIR/T2/DIR/PSIR/DTI) were obtained.

Results

IP‐I was identified in 14/75 (19%), IP‐II was identified in 41/75 (56%), and IP‐III was identified in 18/75 (25%) patients. Patients did not differ significantly by immunopattern in clinical measures at onset or last follow‐up. The proportions of disease courses after a median of 11 years were similar across immunopatterns, relapsing–remitting being most common (63%), followed by monophasic (32%). No differences in volumetric or DTI measures were found. CogState performance was similar for most tasks. A slight yet statistically significant difference was identified for episodic memory scores, with IP‐III patients recalling one word less on average.

Interpretation

In this study, immunopathological heterogeneity of early‐active MS lesions identified at biopsy does not correlate with different long‐term clinical, neuroimaging or cognitive outcomes. This could be explained by the fact that while active white matter lesions are pathological substrates for relapses, MS progression is driven by mechanisms converging across immunopatterns, regardless of pathogenic mechanisms driving the acute demyelinated plaque.
MRI and fluid biomarkers reveal determinants of myelin and axonal loss with aging
Authors: Walker Keenan A. , Duggan Michael R. , Gong Zhaoyuan , Dark Heather E. , Laporte John P. , Faulkner Mary E. , An Yang , Lewis Alexandria , Moghekar Abhay R. , Resnick Susan M. , Bouhrara Mustapha
Published: February 2023

Objective

White matter damage is a feature of Alzheimer's disease, yet little is known about how facets of the Alzheimer's disease process relate to key features of white matter structure. We examined the association of Alzheimer's disease (Aß42/40 ratio; pTau181), neuronal injury (NfL), and reactive astrogliosis (GFAP) biomarkers with MRI measures of myelin content and axonal density.

Methods

Among cognitively normal participants in the BLSA and GESTALT studies who received MRI measures of myelin content (defined by myelin water fraction [MWF]) and axonal density (defined by neurite density index [NDI]), we quantified plasma levels of Aβ42, Aβ40, pTau181, NfL, and GFAP. Linear regression models adjusted for demographic variables were used to relate these plasma biomarker levels to the MRI measures.

Results

In total, 119 participants received MWF imaging (age: 56 [SD 21]), of which 43 received NDI imaging (age: 50 [SD 18]). We found no relationship between plasma biomarkers and total brain myelin content. However, secondary analysis found higher GFAP was associated with lower MWF in the temporal lobes (ß = −0.13; P = 0.049). Further, higher levels of NfL (ß = −0.22; P = 0.009) and GFAP (ß = −0.29; P = 0.002) were associated with lower total brain axonal density. Secondary analyses found lower Aβ42/40 ratio and higher pTau181 were also associated with lower axonal density, but only in select brain regions. These results remained similar after additionally adjusting for cardiovascular risk factors.

Interpretation

Plasma biomarkers of neuronal injury and astrogliosis are associated with reduced axonal density and region‐specific myelin content. Axonal loss and demyelination may co‐occur with neurodegeneration and astrogliosis ahead of clinically meaningful cognitive decline.
Appellate court overturns judgment for health plan members in Wit case
Authors: Enos Gary
Published: February 2023

The news continues to be deeply disappointing for advocates who had believed the original decision in the Wit v. United Behavioral Health case represented a landmark moment for the rights of insured individuals. Following an appellate panel's 2022 reversal of the ruling for plan members in 2019, the full Ninth Circuit Court of Appeals last month reversed the U.S. District Court's original judgment that the managed behavioral health care company had wrongfully denied benefits to plan members.
Additive Manufacturing of Carbon Using Commodity Polypropylene
Authors: Smith Paul , Obando Alejandro Guillen , Griffin Anthony , Robertson Mark , Bounds Ethan , Qiang Zhe
Published: February 2023

Carbon materials are essential to the development of modern society with indispensable use in various applications, such as energy storage and high‐performance composites. Despite great progress, on‐demand carbon manufacturing with control over 3D macroscopic configuration is still an intractable challenge, hindering their direct use in many areas requiring structured materials and products. This work introduces a simple and scalable method to generate complex, large‐scale carbon structures using easily accessible materials and technologies. 3D‐printed, commercial polypropylene (PP) parts can be thermally stabilized through cracking‐facilitated diffusion and crosslinking. The newly elucidated mechanism from this work allows thick PP parts to yield carbonaceous products with complex structures through a subsequent pyrolysis step. The approach for enabling PP‐to‐carbon conversion has consistent product yield and controlled dimensional shrinkage. Under optimized processing conditions, these PP‐derived carbons exhibit robust mechanical properties and excellent joule heating performance, demonstrated by their versatile use as heating elements. Furthermore, this process can be extended to recycled PP, enabling the conversion of waste plastic materials to value‐added products. This work provides an innovative approach to create structured carbon materials with direct access to complex geometry, which can be transformative to, and broadly benefit, many important technological applications.
Designed Concave Octahedron Heterostructures Decode Distinct Metabolic Patterns of Epithelial Ovarian Tumors
Authors: Pei Congcong , Wang You , Ding Yajie , Li Rongxin , Shu Weikang , Zeng Yu , Yin Xia , Wan Jingjing
Published: February 2023

Epithelial ovarian cancer (EOC) is a polyfactorial process associated with alterations in metabolic pathways. A high‐performance screening tool for EOC is in high demand to improve prognostic outcome but is still missing. Here, a concave octahedron Mn2O3/(Co,Mn)(Co,Mn)2O4 (MO/CMO) composite with a heterojunction, rough surface, hollow interior, and sharp corners is developed to record metabolic patterns of ovarian tumors by laser desorption/ionization mass spectrometry (LDI‐MS). The MO/CMO composites with multiple physical effects induce enhanced light absorption, preferred charge transfer, increased photothermal conversion, and selective trapping of small molecules. The MO/CMO shows ≈2–5‐fold signal enhancement compared to mono‐ or dual‐enhancement counterparts, and ≈10–48‐fold compared to the commercialized products. Subsequently, serum metabolic fingerprints of ovarian tumors are revealed by MO/CMO‐assisted LDI‐MS, achieving high reproducibility of direct serum detection without treatment. Furthermore, machine learning of the metabolic fingerprints distinguishes malignant ovarian tumors from benign controls with the area under the curve value of 0.987. Finally, seven metabolites associated with the progression of ovarian tumors are screened as potential biomarkers. The approach guides the future depiction of the state‐of‐the‐art matrix for intensive MS detection and accelerates the growth of nanomaterials‐based platforms toward precision diagnosis scenarios.
The Blue‐LED‐Sensitive Naphthoquinone‐Imidazolyl Derivatives as Type II Photoinitiators of Free Radical Photopolymerization
Authors: Borjigin Timur , Schmitt Michael , Giacoletto Nicolas , Rico Alexandre , Bidotti Hugo , Nechab Malek , Zhang Yijun , Graff Bernadette , Morlet‐Savary Fabrice , Xiao Pu , Dumur Frédéric , Lalevée Jacques
Published: February 2023

In this work, new naphthoquinone‐based photoinitiators are synthesized and applied for the first time in free radical photopolymerization. In the presence of acrylate monomers, these PIs display excellent photoinitiation capabilities under blue‐light LED@405 nm irradiation in a two‐component photoinitiating system in which the additive is a common iodonium salt (bis‐(4‐tert‐butylphenyl)iodonium hexafluorophosphate ‐ Iod) or a tertiary amine (ethyl 4‐dimethylaminobenzoate ‐ EDB). In controlled tests, the polymerization performance of dye4/Iod is equal to or better than that of common commercial Type II photoinitiators (2‐isopropylthioxanthone and benzophenone). Meanwhile, only a trace amount of photoinitiator is required (as low as 0.05%) to initiate the photopolymerization. It is worth noting that some of these compounds can also be used in one‐component photoinitiating system (monocomponent Type II behavior) and exhibit high photoinitiation ability. A series of complementary characterization analyses of two new naphthoquinone dyes (i.e. dye 1 and dye 4) with very similar chemical structures are carried out to investigate the relevant photochemical mechanism. Finally, 3D printing experiments are carried out by a simple and convenient Direct Laser Write (DLW) technique.
Stereospecific Synthesis of Allenes from β‐Ketosulfones
Authors: Wasilewska‐Rosa Alicja , Kisiel Kacper , Tkaczyk Antoni , Loska Rafał
Published: February 2023

Enolates formed from 1‐phenyl‐5‐tetrazolyl β‐ketosulfones containing a tetrasubstituted α carbon centre undergo elimination to allenes with up to four substituents at the cumulene unit when treated with a weak base (phenolate) in DMSO at room temperature. The reaction is completely regioselective for allene vs diene formation in nearly all investigated cases and it proceeds with central‐to‐axial chirality transfer.

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A Bio‐Mimetic Leaf Wetness Sensor from Replica Molding of Leaves
Authors: Nguyen Brian H. , Gilbert Gregory S. , Rolandi Marco
Published: February 2023

Plant diseases cause hundreds of billions of dollars in global crop production each year. Many plant diseases develop when pathogens germinate and proliferate in the fertile environment of excess water on the leaf surfaces. Accurate measurement of how long a leaf stays wet is important to assess the risk of pathogen infestation and decide on appropriate management tactics. Commercial leaf wetness sensors estimate the duration of leaf wetness by monitoring the water accumulated on the sensor surface. However, this one‐size‐fits‐all sensor surface does not replicate the wetting behavior of specific leaves resulting in an imprecise measurement of leaf wetness. Here it is developed a leaf wetness sensor with replica molded surfaces that closely mimic the leaf of interest and provide a more accurate measurement of leaf wetness duration compared to commercial sensors. This simple approach allows for better prediction of leaf wetness duration for each plant species, affording individualized and more effective disease forecasting for the management of plant diseases.