bluuebunny/crossref_metadata_2025 huggingface dataset:
Access to postpartum tubal ligation services in Cape Town, South Africa – an observational study
Authors: Vorster M , Petro G , Patel M
Published: December 2022

Background. Many women receiving antenatal care in public health services in Cape Town choose bilateral tubal ligation as their preferred method of postpartum contraception during their antenatal course. If the sterilisation does not occur immediately, these women are discharged on an alternative form of contraception and, ideally, an interval date for bilateral tubal ligation is arranged.Objectives. To assess the access to tubal ligation services in the Metro West area of Cape Town, South Africa, in women who requestpermanent contraception following delivery, looking specifically at the number of women requesting bilateral tubal ligation who receive the procedure intrapartum, immediately postpartum or as an interval procedure. Other objectives included determining the reproductive outcomes if bilateral tubal ligation was not performed, investigating the alternative forms of contraception provided and to study the demographics of the population requesting bilateral tubal ligation as a form of contraception.Methods. The study was conducted as a cross-sectional observational study collecting data over a period of 3 months, from June 2019 to August 2019. Maternity case records for deliveries between June 2019 and August 2019 from four facilities were reviewed. The facilities, representing all levels of care, were Vanguard Midwife Obstetric Unit, Wesfleur Hospital (district hospital), New Somerset Hospital (regional hospital), Groote Schuur Hospital (tertiary hospital).Results. There were 260 women who requested tubal ligation as their choice of contraception. Only 50% of these received a tubal ligation. Of the 131 tubal ligations performed, 2 were interval sterilisations. Ninety-one percent (120/131) of the tubal ligations were done at the time of caesarean section. Of the 129 women who received alternative forms of contraception, 13 women had a recurrent pregnancy.Conclusion. The study suggests that only 50% of women requesting tubal ligation as form of contraception actually end up receiving the procedure. Alternative forms of contraception are widely used and relied upon, but not without risks of recurrent pregnancy. Interval tubal ligation was not easily accessed by those women who were referred for the procedure.
On the Need to Expand the Legal Regulation of Surrogacy Relations in Russia
Authors: Purge Anna Rolandovna , Murtazozoda Dzhamshed Saidali
Published: December 2022

The subject of the study is the regulatory and legal provisions of the Institute of surrogacy in the Russian Federation. The object of this research is the concept and essence of surrogacy as a method of assisted reproductive technologies in accordance with the current legislation of the Russian Federation. The methodological basis is represented by a set of methods of scientific cognition of objective legal reality applied in the course of preparation and writing: comparative analysis (also known as the comparative legal method), as well as the formal legal method. In addition, the methods of scientific cognition of objective legal reality used by the author also include the logical method, system-structural analysis, and the method of legal modeling. The sharp drop in the birth rate in Russia in 2022 exacerbates the issue of the early legislative establishment of legal mechanisms that have not yet been used by the Russian state, but which are quite capable of assisting Russian citizens in the use of assisted reproductive technologies, overcoming infertility and, ultimately, in the exercise of their conventional and legal rights to create a family and procreation. The author conducted a sociological observation based on the materials of websites specializing in informing citizens about assisted reproductive technologies, identified the most typical problematic and conflict situations in the relationship of potential biological parents and potential surrogate mothers, made conclusions and suggestions to eliminate the identified problems from social practice. In particular, it is concluded that it is necessary to organize departments at maternity hospitals specializing in monitoring the condition of surrogate mothers and their implementation of medical recommendations, including compliance with the pregnancy preservation regime.
On the Diversity of "Pure" Doctrines of Law
Authors: Gorban Vladimir Sergeevich , Gruzdev Vladimir Sergeevich
Published: December 2022

The subject of the study is one of the epistemological problems in the history of political and legal thought, as well as the modern theory of state and law. We are talking about the attempts of the authors of various historical periods, at least over the past two centuries, to construct a model of the study of law as a "pure" phenomenon, or call for the "purity" of the methods of its cognition. There is a strong opinion in the modern legal literature that the "pure doctrine of law" is the creative result of the Austrian lawyer G. Kelsen. His teaching is often a variant of logical positivism, in which an interpretive model of law was created, in which one subject corresponds to a special and only method – legal, and all the others were declared superfluous. In fact, in the history of legal thought, attempts have been made more than once to write "pure" doctrines about law, and long before G. Kelsen. The scientific novelty of the research lies in the analysis and illumination of new facets of the history of political and legal thought, which previously remained completely unexplored in both domestic and foreign political and legal thought. The article analyzes both well-known and previously virtually unknown scientists and thinkers who have developed original concepts of "pure doctrines of law". In this regard, G. Kelsen's teaching is justifiably considered as one of the many variants of this kind of teaching, the uniqueness of which is connected only with the idea of interpretation as a philosophical paradigm, which allowed him to combine well-known legal concepts and techniques within the framework of the methodological doctrine of law.
[The “Pozzo del Merro” drowned sinkhole: 20 years of exploration and study]
Authors: Caramanna Giorgio , Argentieri Alessio , Buonfiglio Vincenzo
Published: December 2022

[In Italian]
Lotte e problemi sociali in Cassio Dione
Authors: Urso Gianpaolo
Published: December 2022

This article studies the way in which Dio deals with social issues in his Roman History. In particular, it examines the rise of the parvenus in Severan Rome, the problem of indebtedness of individual citizens and the state, the recurring phenomenon of banditry, famines and ‘hunger revolts’. The impression of the historian’s insensitivity to the needs of the most disadvantaged social classes is diminished by the analysis of his narrative concerning the struggle between patricians and plebeians in the archaic age, which Dio re-examines also in light of the problems of his time, and in which an unexpected attention to the motives of the poor emerges.
Die Familie des Aristoteles und die zwei Fassungen seines Testaments
Authors: Schorn Stefan
Published: December 2022

This article compares the Greek and the Arabic versions of Aristotle’s last will and argues that the differences between them are not to be explained as paraphrases and mistakes by the translator(s), as has recently been stated. Rather, the Greek text which constituted the basis of the translation was a manipulated version of the original last will and meant to support the view that Herpyllis was not Aristotle’s mistress and that Nikomachos was not her but Pythias’ son. Although the Greek version in Diogenes Laertios is to be regarded as the original version of this document, it lacks one authentic sentence preserved by the Arabic tradition. A reading of the Greek version of the will before the background of Athenian law makes it probable that Herpyllis was Aristotle’s legal wife and the mother of Nikomachos. In addition, it is shown that Ptolemy’s Life of Aristotle was not, as is assumed in its editio princeps, an epitome of Hermippos’ On Aristotle.
Research on air quality prediction based on improved long short-term memory network algorithm
Authors: Huang Wenchao , Cao Yu , Cheng Xu , Guo Zongkai
Published: December 2022

Air quality is changing due to the influence of industry, agriculture, people’s living activities and other factors. Traditional machine learning methods generally do not consider the time series of the data itself and cannot handle long-range dependencies, thus ignoring information relevant to the predicted items and affecting the accuracy of air quality predictions. Therefore, an attention mechanism is introduced based on the long short term memory network model (LSTM), which attenuates unimportant information by controlling the proportion of the weight distribution. Finally, an integrated lightGBM+LSTM-attention model was constructed based on the light gradient boosting machine (lightGBM), and the prediction results were compared with those of 11 models. The experimental results show that the integrated model constructed in this article performs better, with the coefficient of determination (R2) of prediction accuracy reaching 0.969 and the root mean square error (RMSE) improving by 5.09, 4.94, 4.85 and 4.0 respectively compared to other models, verifying the superiority of the model.
Convergências e divergências entre os conceitos de custos de transação e de agência
Authors: Abreu Emmanuel Sousa de
Published: December 2022

O objetivo desse ensaio é avaliar as convergências e divergências entre os conceitos de custos de transação e de agência, os quais são utilizados em diferentes teorias, abordagens e contextos, fato que acaba por dificultar a coerência nas suas respectivas utilizações teóricas e interpretativas. São avaliadas as dimensões teóricas dos custos, como unidade de análise, pressupostos comportamentais dos indivíduos e fatos geradores. Três conclusões são alcançadas. Em primeiro lugar, verifica-se que os termos custos de transação e de agência podem ser adotados em sentido amplo ou estrito. Em segundo lugar, adotando-se os conceitos estritos, é possível distanciar os custos de transação dos de agência. Por último, adotando-se os conceitos amplos, é possível estabelecer o custo de agência como uma espécie de custo transacional.
A critical pedagogy approach for teaching adult English language learners
Authors: Floyd Joel
Published: December 2022

Critical pedagogy as an instructional approach to teaching and learning focuses on democracy, freedom, and the opportunity to challenge oppressive power structures founded upon hegemonic ideologies. This article presents a critical pedagogy approach to support the instruction of adult English language learners. Such an approach should adopt the following components: Building community, addressing implicit biases, dialogic instruction, reflective teaching, and critical thinking. Implementing a critical pedagogy approach to teaching in the adult English as a second language classroom will prepare the learners to become critical thinkers and learners for life.
Task‐based language teaching and rigorous instruction in beginning English as a second language classrooms
Authors: Huang Jiuhan
Published: December 2022

Learning an additional language as well as acquiring skills for careers and educational opportunities are lifelong learning endeavors. Adult English language learners (ELLs), particularly those at the beginning English proficiency levels, require instruction offering opportunities to meet their goals in life. Using tasks in English as a second language classrooms might respond to this tall order. This article discusses task‐based language teaching, outlines the benefits of using tasks, provides guidelines for implementing tasks in beginning English as a second language classrooms, and suggests ways on how to adapt textbook materials into tasks.
Language and culture learning needs of adult refugees
Authors: Ugurel Kamışlı Merih
Published: December 2022

Refugees suddenly face life transitions and challenges such as the need to learn a new language, learn the rules of a new culture, endure traumatic situations, and loss; all of these are factors that impact their integration. This article describes the language and culture learning needs of adult refugees resettling in the United States suggests best teaching practices to meet their unique learning needs.
Practical implications from teaching adult English as a second language in faith‐based programs
Authors: Anumudu Chinedu
Published: December 2022

Drawing from the pillars of lifelong learning, this article takes a look at two church‐based English as a Second Language programs. While one of the settings has been in existence for over 20 years, the second setting has only been in existence for a few months. This article will identify what works in both settings and suggest recommendations for practice.
An Array of Light‐Stimulated Two‐Terminal Synaptic Devices with the Modulation of Electric Polarity
Authors: Liu Xiao , Huang Shijie , Wang Kun , Wang Yue , Yin Lei , Yang Deren , Pi Xiaodong
Published: December 2022

Neuromorphic visual systems based on optoelectronic synaptic devices have been recently studied to simulate the retina and visual cortex of a human being. Now it is shown that an array of optoelectronic synaptic devices based on the two‐terminal structure of Si/perovskite/Au may mimic the functionalities of lateral geniculate nucleus (LGN) cells. Benefiting from the photovoltaic effect, the devices can work under a self‐powered mode. Diverse synaptic functionalities such as postsynaptic current, paired‐pulse facilitation/depression, spike duration‐dependent plasticity, spike number‐dependent plasticity, and spike rate‐dependent plasticity have been simulated. By modulating the electric bias of the devices in the array the simulation of the positional and orientational recognition of the LGN cells is demonstrated.
Peripheral Microneedle Patch for First‐Aid Hemostasis
Authors: Lee Jungho , Park Sebin , Le Phuong Thao , Lee Geunho , Lee Hyoun Wook , Yun Gaeun , Jeon Juhyeong , Park Jeongwoo , Pham Duy Tho , Park Young Sook , Lim Hoon , Kim Chulhong , Hwang Tae Sik , Kim Seung Whan , Lim Geunbae
Published: December 2022

Despite the minimized puncture sizes and high efficiency, microneedle (MN) patches have not been used to inject hemostatic drugs into bleeding wounds because they easily destroy capillaries when a tissue is pierced. In this study, a shelf‐stable dissolving MN patch is developed to prevent rebleeding during an emergency treatment. A minimally and site‐selectively invasive hemostatic drug delivery system is established by using a peripheral MN (p‐MN) patch that does not directly intrude the wound site but enables topical drug absorption in the damaged capillaries. The invasiveness of MNs is histologically examined by using a bleeding liver of a Sprague–Dawley (SD) rat as an extreme wound model in vivo. The skin penetration force is quantified to demonstrate that the administration of the p‐MN patch is milder than that of the conventional MN patch. Hemostatic performance is systematically studied by analyzing bleeding weight and time and comparing them with that of conventional hemostasis methods. The superior performance of a p‐MN for the heparin‐pretreated SD rat model is demonstrated by intravenous injection in vivo.
A Multifunctional Reconfigurable Absorber Enabled by Graphene and Shape Memory Alloy
Authors: Peng Jinqiang , She Ying , Su He , Ji Chen , Huang Cheng , Luo Xiangang
Published: December 2022

Reconfigurable absorbers have attracted much interest owing to their dynamic reflection manipulation property. In this work, a novel multifunctional reconfigurable absorber, which can be flexibly switched among wideband absorption mode, frequency‐reconfigurable narrowband absorption mode, and amplitude‐controllable absorption mode, is proposed and demonstrated. This absorber employs the graphene layer for tuning its reflection magnitude, while the springs‐using shape memory alloy (SMA) is adopted to support the whole absorber for dynamically controlling absorption frequency through height regulation. The above functionality switching is realized by the bias voltage applied to the graphene layer and the loaded SMA springs. The reconfigurable absorption performance is experimentally verified, and the corresponding results show that such an absorber can generate wideband absorption in the range of 3.6–18 GHz. By tuning the height of the loaded SMA springs, it will be switched to the narrowband absorption state and its absorption peak frequency can be dynamically tuned from 8.7 to 13.5 GHz. When further changing the graphene resistance, the reflection amplitude can be also controlled in both wide‐ and narrow‐band absorption modes. In addition, the absorber also performs well under circumstances of different polarizations, which may have promising prospects in electromagnetic protection and camouflage fields.
Establishing consensus‐based high‐acuity low‐occurrence skills forEMSphysicians: A pilot survey ofEMSfellowship faculty
Authors: Hack Kaytlin E. , Levy Matthew J. , Garfinkel Eric , Margolis Asa M.
Published: December 2022

Background

The specialty of emergency medical services (EMS) medicine focuses on providing out‐of‐hospital patient care, including initial stabilization, treatment, and transport in specially equipped vehicles including ambulances and airframe platforms to hospitals and better‐resourced destinations. The Core Content of EMS Medicine outlines the knowledge, procedures, and psychomotor skills relevant to prehospital patient care. However, this document does not specify the high‐consequence skills that are infrequently performed and that carry high levels of complexity as well as potential morbidity. We refer to these as high‐acuity low‐occurrence (HALO) skills. Additionally, there is no consensus definition of what meets the criteria for a HALO skill. The goals of this pilot study were twofold: (1) to determine a consensus definition for a HALO skill and (2) to survey EMS fellowship faculty to identify an initial set of EMS physician trainee skills that meet the HALO definition.

Methods

Using a modified Delphi method, we established a consensus definition of a HALO skill as well as skills that met this definition for EMS physicians. Demographic information was collected from the experts.

Results

There was 100% agreement in the definition provided of a HALO skill. No additional proposed definitions were provided. Thirteen HALO skills were suggested by the panel from the originally proposed 56 skills, requiring three rounds to establish consensus. Final skill domains emphasized by the expert panel include airway management, obstetric emergencies, and shock management.

Conclusions

We present an initial consensus definition of a HALO skill and a recommended list of HALO skills for EMS physicians in training. Opportunity exists for further research to validate the definition and list of HALO skills through the sampling of a broader group of EMS physicians.
Comparison of two validated evidence‐based medicine assessments: Do they correlate?
Authors: Kenney Adam , Yu Catherine , Sena Ariel , Ghafoor Naila , Moffett Shannon
Published: December 2022

Evidence‐based medicine (EBM) has been defined as a process involving five actions: asking, acquiring, appraising, applying, and assessing. Several attempts have been made to create and validate tools to assess EBM aptitude. The newest testing instrument, the ACE tool, which is a 15‐question true/false exam, has not been directly compared to the more established Fresno test, which is composed of 12 in‐depth short‐answer questions. Although both were designed to test Steps 1–4 of the five‐step EBM process, it is unclear whether they examine the same things or whether one is superior. To our knowledge there is not a widely used standard for EBM assessment despite the broad requirements for inclusion of EBM in both undergraduate and graduate medical education.

Hypotheses

It was hypothesized that these instruments do not correlate between one another, based on inherent differences between them, including assessment format, grading method, and scoring range. The authors sought to examine whether a correlation between the results of these two instruments exists in a population of U.S. medical students.

Methods

A retrospective cohort study of 158 fourth‐year U.S. medical students in academic year 2018–2019 was conducted. All students were exposed to a focused EBM curriculum, consisting of three guided discussions of separate journal articles clinically relevant to the practice of emergency medicine. Outcomes measured included scores on both the ACE tool and Fresno test using descriptive statistics. Spearman's rho was used to determine the correlation between the ACE and Fresno scores for each student among the entire group. A subgroup analysis was performed to assess for correlations at more extreme data points.

Results

The median scores on the ACE tool and Fresno test were 66.7% and 62.7%. There was no statistically significant correlation between the results of these two assessments (Spearman's rho 0.023, p = 0.774) in our population. The scores from the subgroup of advanced performers on the Fresno test showed a weak statistically significant positive correlation (p = 0.045) to advanced scores on the ACE tool. No other subgroups showed statistically significant correlation.

Conclusions

In our population of U.S. medical students, the results of two known EBM assessment instruments do not correlate with one another. The assessments may differ in what categories of learning they measure or in generalizability or perhaps in what depth of understanding they test overall. Further study is needed to determine what each instrument is measuring and whether there is demonstrable variation across populations.
C‐reactive protein, APOE status, and cognitive impairment in older adults
Authors: Hooshmand Babak , Sindi Shireen , Rusanen Minna , Leiviska Jaan , Soininen Hilkka , Kivipelto Miia
Published: December 2022

Background

The aim of this study was to investigate the impact of Apolipoprotein ε4 (APOEε4) on the possible relationship between high sensitive serum CRP (hsCRP) and risk of incident dementia, Alzheimer’s disease (AD), and cognitive impairment over seven years in a longitudinal, population based study of community dwelling older adults.

Method

Serum hsCRP was measured at baseline in 304 dementia‐free individuals aged 65‐79 years derived from the Cardiovascular Risk Factors, Aging, and Dementia (CAIDE) study. Participants were re‐examined seven years later, and global cognition, episodic memory, executive functioning, verbal expression, and psychomotor speed were assessed both at baseline and at follow‐up. Incident dementia was diagnosed using DSM‐IV criteria. Multiple linear regression and logistic‐regression models were used to investigate the association of serum hsCRP and its interaction with APOEε4 status on cognitive performance and incident dementia at follow‐up, after adjusting for several potential confounders, including common vascular risk factors.

Result

After adjustment for age, sex, education, duration of follow‐up, systolic blood pressure, diastolic blood pressure, body mass index, prevalent stroke, and smoking status, odds ratio (95% confidence intervals (CI)) was 3.02 (1.18 – 7.73) for those who had at least one alle of APOEε4 compared to those who did not. The odds ratio (95%CI) for incident dementia was 1.00 (0.96 – 1.04) oer unit increase in hsCRP. No associations between hsCRP and cognitive impairment seven years later was detected. However, raised hsCRP values were related to worse performance in episodic memory seven years later in participants who had at least one allele of APOEε4 (β (standard error): ‐0.005 (0.002); p = 0.025).

Conclusion

Raised values of hsCRP is associated with higher risk of cognitive impairment seven years later among individuals who carry at least one allele of APOEε4. Randomized controlled trials are needed to determine this issue.
Epigenetic signatures of insulin resistance associated with Alzheimer’s Disease and related traits
Authors: Sarnowski Chloé , Hivert Marie‐France , Liu Chunyu , Satizabal Claudia L , Lin Honghuang , Beiser Alexa S , DeCarli Charles S. , DeStefano Anita L. , Dupuis Josée , Morrison Alanna C , Seshadri Sudha
Published: December 2022

Background

Insulin resistance (IR) is a major risk factor for Alzheimer’s disease (AD) and is primarily driven by obesity, another AD risk factor. The mechanism by which IR predisposes to AD is unknown. Epigenetic studies may help identify molecular signatures of IR associated with AD, thus contributing to an improved understanding of the biological and regulatory mechanisms of IR in AD.

Method

We conducted an epigenome‐wide association study of IR, quantified using the homeostasis model assessment of IR, in 3,167 Framingham Heart Study (FHS) participants without diabetes. We selected epigenetic markers (outcome) associated with IR at the genome‐wide level (P<10‐7: 0.05/450,000) and evaluated their association with AD, vascular dementia, dementia, and brain volumes (hippocampal, total brain‐TBV, intracranial‐ICV, and lateral ventricular) in up to 3,040 FHS participants. We defined significant associations using P<0.002 (0.05/3/7). All analyses were performed using blood DNA methylation measured using the Illumina HumanMethylation450 BeadChip and linear mixed‐effects models adjusted for age, sex, and batch, while allowing for heterogeneous variance across batches and accounting for familial relatedness. Models including IR or brain volume as a covariate were additionally adjusted for body mass index or ICV respectively.

Result

We confirmed the association of blood DNA methylation with IR at three loci (1p32:cg17901584‐DHCR24, 11q13:cg17058475‐CPT1A, and 21q22:cg06500161‐ABCG1). Blood DNA methylation at cg17058475‐CPT1A was significantly associated with TBV (P=0.0007). The carnitine palmitoyl transferase (CPT) system, crucial for the mitochondrial beta‐oxidation of long‐chain fatty acids, is involved in metabolic syndrome, type 2 diabetes, cardiovascular and neurological diseases including AD. Blood DNA methylation levels at cg17901584‐DHCR24 and cg06500161‐ABCG1 were nominally associated with AD (P=0.03) or vascular dementia (P=0.04) respectively. Both DHCR24 and ABCG1 are involved in cholesterol synthesis or transport. Reduced expression of DHCR24 occurs in AD patient’s temporal cortex while CSF capacity to promote cell cholesterol efflux via ABCG1 is specifically impaired in AD and this impairment correlates with the main AD neurobiochemical markers.

Conclusion

Our methylation analysis has shed light on genes potentially implicated in both IR and AD. Future work includes association analyses using brain omics from the AD Knowledge Portal.
Neuropsychiatric symptoms, Alzheimer’s Disease and Cerebrospinal Fluid Cortisol and Dehydroepiandrosterone Sulfate: a Prospective Study
Authors: Ouanes Sami , Clark Christopher , Richiardi Jonas , Maréchal Bénédicte , Lewczuk Piotr , Kornhuber Johannes , Kirschbaum Clemens , Popp Julius
Published: December 2022

Background

Neuropsychiatric symptoms (NPS) are important treatment targets in the management of dementia, can be present at very early stages of neurodegeneration, and are associated with more rapid clinical disease progression. Increased cortisol has been reported in Alzheimer’s disease (AD), and has been associated with cognitive decline. At the same time, cortisol is often referred to as the “stress hormone” and elevated cortisol output has been observed in association with depression and delirium. Dehydroepiandrosterone sulfate (DHEAS) has known anti‐glucocorticoid effects and may counter the effects of cortisol.

Methods

One hundred and twenty‐three participants with cognitive impairment (mild cognitive impairment or dementia, N=78) and with normal cognition (N=53) were included in a prospective study in a memory clinic setting. NPS were assessed using the Neuropsychiatric Inventory (NPI), CSF cortisol and DHEAS, as well as CSF AD biomarkers were obtained at baseline. NPS and cognitive performance were re‐assessed at follow‐up visits 18 and 36 months from baseline. We constructed linear regression models to examine the links between baseline NPS, AD pathology, and CSF cortisol and DHEA. We used repeated‐measures mixed ANCOVA models to examine the associations between the NPS changes over time, baseline CSF cortisol and DHEA, and AD pathology.

Results

Higher CSF cortisol was associated with more common (p<0.001) and more severe NPS at baseline after controlling for covariates (B=0.091[0.031;0.150], p=0.003; r=0.309), in particular with depression, anxiety, apathy/indifference. Elevated CSF cortisol was also associated with NPS worsening over time regardless of AD pathology (p=0.036, η2=0.207). Both associations remained significant after controlling for AD pathology status. CSF DHEAS was neither associated with NPS at baseline nor with their change over time.

Conclusion

Elevated CSF cortisol is associated with more severe NPS at baseline, as well as with more pronounced worsening over three years, independently of AD pathology status. Cortisol may predict the course of NPS in individuals with cognitive impairment. Our findings also suggest that interventions targeting the HPA axis may be helpful to treat neuropsychiatric symptoms of dementia.
Structuring multi‐stakeholder participation to increase the impact of dementia research
Authors: Weidner Wendy S
Published: December 2022

Background

Effective translation of knowledge from research into practice requires effective communication, collaboration, and meaningful engagement across diverse stakeholders. Developing this expertise is a multi‐faceted process that takes time and effort; requiring a range of techniques to engage a wide variety of stakeholders extending from people living with dementia all the way to government policy makers. Here, we select key methods used in pioneer projects to help build capacity in structuring and implementing effective multi‐stakeholder participation.

Method

We reviewed 3 projects focusing on policy or system change that used multi‐stakeholder participation in key areas: engagement, consultation, and implementation. We explored methods employed to achieve effective participation, by reviewing both peer review and project‐related grey literature. We then cross‐compared the methods to establish effectiveness, ease of replication, and impact.

Result

All identified methods used a Knowledge Exchange (KE) framework. Specific methods fostering multi‐stakeholder participation included:

Engagement to help set project priorities: Stakeholder mapping, theory of change workshops, awareness raising campaigns

Consultation to seek views, sense‐check, validate findings: focus groups, situational analysis process (stakeholder interviews, vignettes)

Implementation to increase research impact: advocacy, policy change

Cross comparisons of the methods used in each project showed that these methods cover non‐overlapping and equally important aspects of stakeholder engagement.

Conclusion

Although there is still a long way to go, when methods of multi‐stakeholder participation are used independently or collectively, they help move research into policy impact. More research is needed as translational studies often remain academic and lack translation into impactful policy change. A key process to do this is through effective multi‐stakeholder participation. Systematic collection of different methods serving the same aim, hierarchical and flow chart definition of the use of such methods and related tools, indicators comparing effectiveness, guidelines for selection and to build capacity among translational research may be a roadmap for future development.
Anger expression moderates the effects of neighborhood disadvantage on cognitive decline among African‐Americans in the Jackson Heart Study and Atherosclerosis Risk in Communities study
Authors: Bey Ganga
Published: December 2022

Background

Previous research has identified neighborhoods and individual psychosocial characteristics such as anger expression as important contributors to cognitive health. However, less is known about whether neighborhood environments interact with individual psychosocial characteristics to confer increased susceptibility to adverse cognitive outcomes such as accelerated cognitive decline. We tested the hypothesis that internalized anger will strengthen the associations between neighborhood disadvantage and faster rates of cognitive decline.

Method

Among 1,314 African Americans dually enrolled in two community‐based cohorts in Jackson, Mississippi—the ARIC and JHS cohort studies—a factor score of global cognitive function was calculated based on ten cognitive tests of working memory, language, and executive function administered repeatedly from 1996 to 2019. Age‐ and sex‐adjusted linear mixed effects models were used to examine whether individual‐level anger expression moderated the associations of four measures of census tract‐level neighborhood socioeconomic and social environment characteristics (the national Area Deprivation Index (ADI), a JHS neighborhood disadvantage score, racial residential segregation, and perceived physical disorder) with individual‐level cognitive decline.

Result

Of the four neighborhood characteristics, greater JHS neighborhood disadvantage and racial residential segregation were associated with faster rates of 10‐year cognitive decline. Among those with high inward anger expression (>1 SD above the mean), there was a 33% and 35% faster rate of decline in global cognition associated with higher neighborhood disadvantage (as measured by the JHS score) and segregation, respectively (Table).

Conclusion

Dispositional inward anger expression may increase susceptibility to the detrimental impacts of neighborhood disadvantage on cognitive health.
Anti‐ulcer drug teprenone clinical trial
Authors: Matsuzaki Juntaro , Yokoyama Shunichi , Suzuki Hidekazu
Published: December 2022

Background

Teprenone (geranylgeranylacetone), a gastric mucosal protective agent, has been reported to inhibit the accumulation of coagulated amyloid‐β by increasing heat shock protein 70 (HSP70) in mice.

Objective

We conducted a randomized, double‐blind, placebo‐controlled study to ascertain teprenone’s therapeutic ability for AD.

Methods

Patients with mild to moderate AD, with a Mini‐Mental State Examination (MMSE) score of 13 to 26, were randomly allocated into two groups depending on the administered drug: donepezil + placebo (placebo group) and donepezil + teprenone (teprenone group). The primary and secondary endpoints included changes in scores of the Japanese version of the AD Assessment Scale‐cognitive subscale (ADAS‐J cog) and other evaluations, respectively, including MMSE scores, during a 12‐month period after the first administration.

Results

Forty‐two and thirty‐seven patients were allocated to the teprenone and placebo groups, respectively. ADAS‐J cog score changes were not different between groups (placebo, 0.6±0.8; teprenone, 0.4±0.8; p = 0.861). However, MMSE scores significantly improved in the teprenone group (placebo, ‐ 1.2±0.5; teprenone, 0.2±0.5; p = 0.044). Subgroup analysis considering the severity of medial temporal area atrophy revealed that this improvement by teprenone was significant in patients with mild (p = 0.013) but not with severe atrophy (p = 0.611). Adverse events were observed in 17.8 and 10.4% of patients in the placebo and teprenone group, respectively.

Conclusion

Teprenone may be effective for AD when administered before atrophy progression in the medial temporal areas. (J Alzheimers Dis. 2019;71:1187‐1199)
A Placebo‐Controlled Phase I Study in Healthy Subjects Assessing NVG‐291, which Targets CNS Receptor Protein Tyrosine Phosphatase Sigma (PTPσ)
Authors: Mikol Daniel D , DePaul Marc , Lawrence Betty , Toews Judy , Collett Nana , Lukashev Matvey
Published: December 2022

Background

Substantial data from animal models of spinal cord injury (SCI), multiple sclerosis (MS) and Alzheimer’s disease (AD) indicate that accumulation of chondroitin sulfate proteoglycans (CSPGs) at sites of CNS damage can lead to inhibition of CNS repair. A CSPG receptor termed protein tyrosine phosphatase sigma (PTPσ) has been implicated in mediating the inhibitory effect of CSPGs. NervGen is developing a first‐in‐class PTPσ modulator NVG‐291, a systemically administered therapeutic peptide derived from the cytoplasmic domain of PTPs, for treatment of nervous system damage. A rodent analogue of NVG‐291 was found to improve functional outcomes, axonal regeneration, remyelination and neuroplasticity in animal models of CNS damage.

Method

Part 1 (SAD portion) enrolled 37 subjects randomly assigned into 6 dose cohorts of placebo or NVG‐291. The doses tested exceed the human equivalent doses that showed efficacy in several animal models including SCI and MS. Part 2 (MAD portion) will dose up to 18 subjects randomly assigned into 3 dose cohorts to receive NVG‐291 or placebo once‐daily for 14 days. CSF will be collected in additional subjects for analysis of NVG‐291 concentration and biomarker exploration.

Result

NVG‐291 has been safe and well‐tolerated through the 6 SAD cohorts (Part 1). Part 2 will complete in 2022. Part 1/2 results will be presented.

Conclusion

This Phase 1 study will establish the safety, tolerability, and pharmacokinetics of NVG‐291 to support advancement to a clinical trial in patients with AD in 2022.
Non‐Pharmacological Care, Behavior Change, MCI
Authors: Lam Linda Chiu Wa C.W. , Lee Allen TC
Published: December 2022

Background

Not applicable

Method

Not applicable

Result

Not applicable

Conclusion

Not applicable
Does the presence of type II Diabetes affect cognitive decline in Alzheimer’s Disease Dementia?
Authors: Davidson Skylar , Allenback Gayle , Decourt Boris , Sabbagh Marwan N.
Published: December 2022

Background

Alzheimer’s disease (AD) is sometimes referred to as Type 3 diabetes. While it is very likely that insulin dysregulation and resistance participate in the etiology of AD pathologies, little is known about the possible correlation between diabetes and the progression of cognitive decline in AD patients. Previous studies have shown an increased risk of developing AD in patients with type 2 diabetes mellitus (T2DM). The specific aim of our study was to determine whether differences exist in cognitive decline experienced by AD subjects with and without T2DM co‐morbidity.

Method

All cognitive performance data and the presence or absence of T2DM co‐morbidity in AD patients used in the present report were derived from the Uniform Data Set (UDS) of the database maintained by the National Alzheimer’s Coordinating Center (NACC), USA. The scanning of the UDS database identified 3055 participants with AD who had more than one epoch completed. The dataset culled clinically‐diagnosed AD patients who were assessed for diabetes type in form A5 or D2 during at least one visit. These patients were divided into two groups dependent upon the presence of a diagnosis of T2DM. The data from these groups was then analyzed for differences in cognitive decline based upon Neuropsychological Battery Scores and a Clinician Dementia Rating (CDR) using a general linear model.

Result

Cognitive function tests looked at language, cognitive executive function, and verbal and nonverbal memory. Comparison of the mean scores in 16 selected tests from the Neuropsychological Battery test showed no significant differences in baseline scores and scores at subsequent visits between the T2DM and non‐diabetic groups.

Conclusion

Using the NACC database, which receives longitudinal data from Alzheimer’s Disease research Centers (ADRCs), it was found that there were no differences in cognitive decline metrics over the course of 5 visits in either group. This supports the position that the presence of T2DM does not appear to increase the magnitude of cognitive decline in AD patients
Proteomic profiling of human brain coupled to functional assays for the identification of neurotoxic proteins
Authors: Hsieh Yi‐Chen , Negri Joseph , He Amy , II Richard V Pearse , Liu Lei , Duong Duc M. , Chibnik Lori B. , Bennett David A , Seyfried Nicholas T. , Young‐Pearse Tracy
Published: December 2022

Background

Alzheimer’s Disease (AD) affects millions globally, but therapy development is lagging. The dearth of new therapies requires a reconsideration of pre‐clinical models of AD to facilitate the discovery of efficacious treatments. Ideally, such models would allow for monitoring the functional behavior of neurons in conditions approximating the AD brain.

Methods

Towards the goal of developing more representative, pre‐clinical AD models, we employ multiple‐electrode arrays (MEAs) and live‐cell imaging for assessing neuronal firing and neurite integrity (NI), respectively. We use this system to examine changes in neuronal activity and neurite integrity following treatment with TBS‐soluble human brain extract from a panel of 43 individuals comprised of AD patients, unaffected persons not exhibiting AD pathology nor cognitively impaired, and individuals not cognitively impaired but exhibited AD‐related postmortem pathology. To determine the molecular etiology of these functional changes in an unbiased manner, we perform label‐free proteomic analyses on the panel of 43 brain extracts.

Results

Amyloid‐β (Aβ) and tau accumulate in the AD brain, and specific forms of each of these proteins have shown neurotoxic properties. We observe associations between spontaneous activity and Aβ42:40 levels, and between neurite integrity and oligomeric Aβ or tau containing N inserts. Additionally, the proteomic analyses reveal several candidates whose expression correlated with changes in neuronal structure and activity. Proteins associated with neurotoxic activities in MEA and NI assays are enriched in proteins implicated in lysosomal storage disorders, while proteins associated with neuroprotective properties are enriched in proteins of the WAVE regulatory complex that are involved in the regulation of actin polymerization. We further show that elevated GM2A in the AD brain and AD CSF is associated with reductions in both neurite integrity and MEA activity. Applying cell derived GM2A in the absence of brain extract is sufficient to induce a subtle but significant loss of neurite integrity.

Conclusion

The techniques and data herein introduce a system for modeling neuronal vulnerability in response to factors present in the aged human brain and provide insights into proteins potentially contributing to AD pathogenesis.
Cardiovascular Risk and Ethnic Disparities in Cognition among Mexican Americans and Non‐Hispanic Whites: The Health and Aging Brain Study
Authors: Jiang Xiaqing , Peltz Carrie , Johnson Leigh , O'Bryant Sid E. , Yaffe Kristine
Published: December 2022

Background

Mexican Americans (MAs) may have increased risk for cognitive impairment and greater cardiovascular risk (CVR) compared to non‐Hispanic whites (NHWs). This disproportionate burden of CVR in MAs may be an important driver for ethnic differences in cognitive aging, although population‐based evidence is lacking. As part of the Health and Aging Brain Study, we investigated the contribution of CVR burden to ethnic differences in cognition.

Methods

We studied 1,320 MA and NHW participants without dementia (63% women, 57% MAs) aged 50‐74 years (2017‐2021, mean age 63.7±6.7 years) who underwent a cognitive battery of five tests: Trail Making Test Part A (attention) and B (executive function), Digit Symbol Substitution (processing speed), FAS and Animal Naming (verbal fluency), and Spanish English Verbal Learning Test 30‐minute delay (verbal memory). CVR burden was assessed using the Framingham Risk Score (FRS, range ‐2 to 25 in woman, ‐2 to 19 in men). We used linear regression to assess the association of CVR (intermediate/high: FRS ≥10 vs. low: FRS <10) with cognitive function (z‐standardized) and its contribution to ethnic differences in cognition.

Results

MAs were on average four years younger but have higher FRS (1.8 points; 95% CI 1.5 to 2.2) compared to NHWs. In unadjusted models, intermediate/high CVR was associated with lower cognition in all domains. After adjusting for ethnicity, age, sex, education, and APOE ε4, intermediate/high CVR remained associated with lower cognition in two domains: processing speed (‐0.13, 95% Cl ‐0.23 to ‐0.03) and verbal memory (‐0.13, 95% Cl ‐0.23 to ‐0.03). The strength of the association in MAs was similar to NHW (p >0.05 for interactions by ethnicity). In unadjusted models, intermediate/high CVR explained 4‐6% of ethnic differences in cognition in all domains. Results in multivariable‐adjusted models were similar, although FRS explained a greater portion of the ethnic differences in some domains: 10% in processing speed and 15% in verbal memory.

Conclusion

Compared to NHWs, MAs had greater CVR burden, which explained some of the ethnic differences in cognition. Efforts to lessen ethnic disparities in cognitive outcomes may benefit from a better understanding, prevention, and management of CVR in a population with growing number of ethnic minorities.
Higher Household Air Pollution Levels Correlate with Poorer Cognitive Function in the Longitudinal Aging Study in India (LASI)
Authors: Adar Sara , D'Souza Jennifer , Shaddick Gavin , Langa Kenneth M , Gross Alden L , Angrisani Marco , Khobragade Pranali , Banerjee Joyita , Chattopadhyay Aparajita , Dey A. B. , Sekher T.V. , Bloom David , Lee Jinkook
Published: December 2022

Background

Indians have some of the highest fine particulate matter (PM2.5) exposures in the world, not only due to high ambient air levels but also because of household combustion of biomass fuel. To understand the burdens of these exposures for older adults, we evaluated associations of indoor PM2.5 with cognitive function in India.

Method

We used data from the 2017‐2019 baseline survey of the nationally‐representative Longitudinal Aging Study in India (LASI) to derive a general cognition score for each participant. For indoor PM2.5 levels, we used an India‐specific prediction model informed by participant cooking and housing characteristics. We estimated associations between indoor PM2.5 with cognitive function using linear mixed‐effects models after adjustment for age, sex, individual and community‐level socioeconomic variables, region, clustering by village, and sample weights.

Result

We observed a population of 61,708 participants aged 45 and over. Many of these individuals (48%) used highly polluting fuel, resulting in average indoor PM2.5 concentrations of 205± 110 µg/m3. After adjustment for individual and area‐level confounders, we found that indoor PM2.5 was associated with poorer cognitive function. For each 100 µg/m3 of indoor PM2.5, we observed ‐0.027 (95% CI: ‐0.033, ‐0.02) lower cognition scores. These associations were strongest among women as well as among adults less than age 65 years. When scaling these associations to the observed interquartile range (150 µg/m3), household exposures resulted in cognitive differences comparable to those observed between people 2 years apart.

Conclusion

Among older adults living in India, household PM2.5 is associated with poorer cognition at older ages even after adjustment for individual sociodemographic characteristics and regional trends.