bluuebunny/crossref_metadata_2025 huggingface dataset:
Spanish and Portuguese Commerce and Contraband in the Amazonian Borderlands
Authors: Gómez-González Juan Sebastián
Published: November 2022

Legal, illicit, and clandestine trade was fundamental for the social, political, and economic development of the Amazon basin during the colonial period. Since the second half of the 16th century, Spanish and Portuguese establishments in this tropical region needed agriculture, livestock, and mining, but also exchanges of goods to ensure the stability and growth of missions and cities founded in their vast jurisdictions. Encomenderos, Indians, slaves, soldiers, bandeirantes, and Jesuits invigorated the illegal trade by establishing contacts through roads and tributary rivers of the Amazon River that linked different spaces through navigation. The scarce military presence in the border jurisdictions, especially between the province of Maynas and the captaincy of Rio Negro, in addition to the existence of gold mines, trafficking of manufactured goods, food, firearms, and other trade goods coming from both domestic and Atlantic markets, served as constant stimuli to strengthen the fraudulent business until the last decades of the 18th century. The prohibitions and monopolies decreed in the Luso-Hispanic laws, especially those stipulated in the treaties of limits, peace, and friendship verified in Tordesillas, Lisbon, Madrid, San Ildefonso, and Badajoz (from 1494 to 1802), were decisive to try to ensure the sovereignty and sociopolitical control in the Amazonian domains. However, the persistence of smuggling, as a complement to authorized trade and an indispensable resource for the Luso-Hispanic economies, would not have been possible without the complicity of governors, military, and astute Jesuit and Franciscan missionaries who took advantage of corruption by encouraging participation in the illegal trade. This demonstrates that trade, smuggling, and fraud in those imperial margins were inseparable aspects of settlement and the defense of territories mutually stalked by Spanish and Portuguese vassals to the first decades of the 19th century.
Chicle Gum and Popular Culture in the Americas
Authors: Mathews Jennifer P.
Published: November 2022

Chicle is a thick and odorless natural latex that comes from the Chicozapote tree (Manilkara sapota), which is indigenous in Mexico and Central America. When the sapodilla tree is cut into with a blade or infested with insects, it produces latex as a protective response. The ancient Maya and Aztec used this latex as chewing gum, a habit that Mexican president General Antonio López de Santa Anna continued in the 19th century. While in the United States, he introduced chicle to US inventor Thomas Adams, Sr., who in the 1870s produced the first mass-produced chicle chewing gum. However, it was William Wrigley, Jr. who in the 1890s entered a highly competitive gum market and innovated new marketing campaigns that appealed to a broad audience. These advertisements often proclaimed the benefits of gum chewing for digestion, dental hygiene, and the ability to improve mental focus. Wrigley used these qualities to encourage the US military to adopt chewing gum into rations starting in World War I. As military personnel shared chewing gum with children in war zones, this “American habit” spread around the world. Public officials complained about the expense of cleaning up gum-littered sidewalks, the Women’s Temperance Union even argued that chewing gum was a slippery slope that could lead to smoking, gambling, or drinking, and many cultures have strong social norms regarding gum chewing in public. Despite these challenges, William Wrigley spent millions of dollars promoting a favorable image for gum and the habit of gum chewing, and other marketers launched collectables such as baseball cards to encourage sales. Chicle-based chewing gum ultimately became a victim of its own popularity, and while researchers sought out other sources of latex, such as jelutong, balata, and gutta-percha, US manufacturers ultimately resorted to synthetic substitutes. Although the chewing gum industry of today is dominated by the use of a synthetic gum chewing base, it is worth more than $25 billion annually.
Regina and Roma: Women at the 1968 and 1971 Political Crossroads
Authors: Anderson Sarah
Published: November 2022

The female protagonists of the Mexican novel Regina (1987) and film Roma (2018), Regina and Cleo, find themselves at the crossroads of two politically charged protests and massacres in the nation: the Tlatelolco Massacre and the Corpus Christi massacre. Both Regina and Cleo face many challenges and share archetypal characteristics of hero or savior. In the film and novel, both protagonists overcome many obstacles to better understand themselves and in turn their nation. The lives of both women are woven into a narrative where their role as hero is to metaphorically rescue or save the nation from its long history of authoritarian rule and corruption. Each narrative reads as a form of historical fiction, which highlights in Regina the years up to and including 1968 and in Roma the years 1970 and 1971. The two artistic creations remember the Mexico of these tumultuous years while also challenging the narrative of the Mexico of the 21st century. In both the novel and the film, nature becomes a vehicle to enable and assist the protagonists on their journey to overcome a myriad of challenges. As such, both present a nostalgic yet critical analysis of Mexico’s past and provide insight on creating a new path for the future.
The Language of Science and Technology in the Romance Languages
Authors: Weber Anne , Fetzer Bettina , Atayan Vahram
Published: November 2022

Discussing the language of science and technology in the Romance languages is highly complex and challenging for several reasons. On the one hand, there are different fields to be included, namely computer sciences, engineering, mathematics, as well as physics and astronomy. On the other hand, English has become (or even has always been in the case of computer sciences) the lingua franca in all these fields, so there seems to be rather little to analyze from a synchronic perspective as far as the Romance languages are concerned, and accordingly there is rather little up-to-date linguistic research on it. In the beginning, that is, during the late 1980s, the focus was on specific phenomena, while modern research often deals with didactic aspects and language teaching.

When it comes to the state of research in the different Romance languages, it turns out that it is mainly Canadians who are noted for playing a major role in the analysis of French technolectes. Numerous studies, some of which were conducted by German Romanists, center on the lexis and terminology of specific fields in French. As for Portuguese, most works have been published in Brazil, and lately the focal point seems to have primarily been placed on computer science and mathematics. Studies regarding Italian typically reveal a major interest in the general structure of terminology and its relation to everyday language use. Moreover, special emphasis is often placed on historical matters, especially the role of Galileo. Finally, the influence of specific text types as well as didactic aspects of special languages at different levels of education is also a subject of interest. With regard to Spanish, it should first be pointed out that, due to diatopic variation, it is hardly possible to talk about one single concept of the language of science and technology. Only a few comprehensive works on this area of research exist, yet many individual studies have been published in the last few decades, primarily on information science, especially the influence of English on Spanish, as well as on terminology in different fields. In Catalan, specialized languages emerged rather early, and their development has been systematically encouraged since the 20th century; the center of interest in current research is mainly on information science.
Functional Word Acquisition in Mandarin Chinese
Authors: Yang Xiaolu
Published: November 2022

Functional categories carry little or no semantic content by themselves and contribute crucially to sentence structure. In the generative framework, they are assumed to mark and head functional projections in the basic hierarchical structure underlying each phrase or sentence. Given their intertwining with grammar, child language researchers have long been attracted by the development of functional categories. To a child, it is important to differentiate functional categories from lexical categories and relate each of them to the hidden hierarchical structure of the phrase or sentence. The learning of a functional category is no easy task and implies the development of different dimensions of linguistic knowledge, including the lexical realization of the functional category in the ambient language, the specific grammatical function it serves, the abstract underlying structure, and the semantic properties of the associated structure. A central issue in the acquisition of functional categories concerns whether children have access to functional categories early in language development. Differing accounts have been proposed. According to the maturational view, functional categories are absent in children’s initial grammar and mature later. In contrast to the maturational view is the continuity view, which assumes children’s continuous access to functional categories throughout language development. Cross-linguistic evidence from production and experimental studies has been accumulated in support of the continuity hypothesis.

Mandarin Chinese has a rich inventory of function words, though it lacks overt inflectional markers. De, aspect markers, ba, and sentence final particles are among the most commonly used function words and play a fundamental role in sentence structure in Mandarin Chinese in that they are functional categories that head various functional projections in the hierarchical structure. Acquisition studies show that these function words emerge early in development and children’s use of these function words is mostly target-like, offering evidence for the continuity view of functional categories as well as insights into child grammar in Mandarin Chinese.
Economics of Gender in Resource Dependent Communities
Authors: Ray Biswajit , Mukherjee Promita
Published: November 2022

Gender inequalities exist within commons-dependent communities in developing countries regarding the role of society’s overall attitudes to women as decision-makers. While, in forestry, women have some access to resources and decision-making, in other community resources like fisheries and irrigation water, women are absent and males entirely dominate. Different theories on gender and environment suggest that women’s inclusion is an important step toward reducing their economic marginalization and argue that in reality women’s economic advancement/empowerment may not get carried into home and community spaces as durable empowerment if society holds negative attitudes toward women’s needs, contribution and deservedness in families and beyond.

Due to society’s negative attitudes toward women, women remain trapped in a vicious cycle of exclusion. Breaking this vicious cycle requires combining household assets and income to assess women’s true poverty type. A flat implementation of economic policies toward women’s pathway out of poverty may not yield the desired results and may even be counterproductive if society’s negative attitudes and the poverty characteristics of women or female-headed households are not taken into account. Since all women are not homogeneous and that a few communities hold pro-women attitudes, to promote women’s economic empowerment, the role of society’s attitudes toward women’s participation as decision-makers cannot be ignored as women’s relations to their social, economic, political, and natural environments are itself a culturally and historically specific process, which can be understood only through identifying and understanding gender-specific attitudes and actions toward those environments.
Economic Development and Groundwater Sustainability
Authors: Tortajada Cecilia , González-Gómez Francisco
Published: November 2022

An analysis is made of the relationship between economic development and water sustainability in Campo de Dalías, in southeastern Spain. What used to be a poor, deserted region based on traditional agriculture has become one of the most prosperous regions in Spain. Economic development has been based on highly productive greenhouse agriculture, but this has resulted in the overexploitation of the aquifer that supplies water to different users in the region. Contradictions are considered between economic development and water sustainability in the area, as well as the plans and policies that have been put in place to improve the status of the aquifer but that have had limited success so far.
Developing a Culturally Competent Neuropsychological Assessment Battery for Farsi-speaking Patients with Suspected Dementia
Authors: Henry Samantha K , Talavari Donna , York Michele K , Stinson Jennifer M , Strutt Adriana M , McCauley Stephen R
Published: November 2022

Objective

To assemble a comprehensive neuropsychological battery appropriate for differential diagnosis of dementia in Farsi-speaking Iranian adults in the United States.

Method

Systematic searches of PubMed, PsychInfo, and Google Scholar databases were conducted to obtain test instruments relevant to Farsi speakers in consultation with a Farsi-speaking cultural broker.

Results

A proposed battery assessing the domains of attention, executive function, verbal and visual episodic memory, language, visuospatial/visuoconstruction abilities, and mood/anxiety was assembled that includes core measures developed, either specifically for a Farsi-speaking Iranian population or validated/normed with a Farsi-speaking Iranian sample. Though not ideal, additional measures were selected that can be administered using translated instructions with English normative data to supplement the limited tests available for use in this population. The rationale for test selection and caveats for their clinical use are presented along with a case study.

Conclusions

The number of neuropsychological measures available in Farsi and/or with normative data for Farsi speakers is extremely limited. Cognitive tests either developed for or validated with a bilingual Farsi-English sample also represent a significant gap in the literature. Appropriate measures for these populations are urgently needed to provide a culturally competent assessment of a growing older adult segment of an underserved community.
Deep earthquake study still resonant at 100
Authors: Kennett Brian
Published: November 2022

A century on from the first dedicated geophysical publication by the RAS, Brian Kennett reflects on its first article, presenting evidence for deep earthquakes.
Direct electrical brain stimulation of human memory: lessons learnt and future perspectives
Authors: Kucewicz Michal T , Worrell Gregory A , Axmacher Nikolai
Published: November 2022

Modulation of cognitive functions supporting human declarative memory is one of the grand challenges of neuroscience, and of vast importance for a variety of neuropsychiatric, neurodegenerative and neurodevelopmental diseases. Despite a recent surge of successful attempts at improving performance in a range of memory tasks, the optimal approaches and parameters for memory enhancement have yet to be determined. On a more fundamental level, it remains elusive as to how delivering electrical current in a given brain area leads to enhanced memory processing. Starting from the local and distal physiological effects on neural populations, the mechanisms of enhanced memory encoding, maintenance, consolidation or recall in response to direct electrical stimulation are only now being unravelled. With the advent of innovative neurotechnologies for concurrent recording and stimulation intracranially in the human brain, it becomes possible to study both acute and chronic effects of stimulation on memory performance and the underlying neural activities. In this review, we summarize the effects of various invasive stimulation approaches for modulating memory functions. We first outline the challenges that were faced in the initial studies of memory enhancement and the lessons learnt. Electrophysiological biomarkers are then reviewed as more objective measures of the stimulation effects than behavioural outcomes. Finally, we classify the various stimulation approaches into continuous and phasic modulation with an open or closed loop for responsive stimulation based on analysis of the recorded neural activities. Although the potential advantage of closed-loop responsive stimulation over the classic open-loop approaches is inconclusive, we foresee the emerging results from ongoing longitudinal studies and clinical trials will shed light on both the mechanisms and optimal strategies for improving declarative memory. Adaptive stimulation based on the biomarker analysis over extended periods of time is proposed as a future direction for obtaining lasting effects on memory functions. Chronic tracking and modulation of neural activities intracranially through adaptive stimulation opens tantalizing new avenues to continually monitor and treat memory and cognitive deficits in a range of brain disorders. Brain co-processors created with machine-learning tools and wireless bi-directional connectivity to seamlessly integrate implanted devices with smartphones and cloud computing are poised to enable real-time automated analysis of large data volumes and adaptively tune electrical stimulation based on electrophysiological biomarkers of behavioural states. Next-generation implantable devices for high-density recording and stimulation of electrophysiological activities, and technologies for distributed brain–computer interfaces are presented as selected future perspectives for modulating human memory and associated mental processes.
Predictive models for starting antiseizure medication withdrawal following epilepsy surgery in adults
Authors: Ferreira-Atuesta Carolina , de Tisi Jane , McEvoy Andrew W , Miserocchi Anna , Khoury Jean , Yardi Ruta , Vegh Deborah T , Butler James , Lee Hamin J , Deli-Peri Victoria , Yao Yi , Wang Feng-Peng , Zhang Xiao-Bin , Shakhatreh Lubna , Siriratnam Pakeeran , Neal Andrew , Sen Arjune , Tristram Maggie , Varghese Elizabeth , Biney Wendy , Gray William P , Peralta Ana Rita , Rainha-Campos Alexandre , Gonçalves-Ferreira António J C , Pimentel José , Arias Juan Fernando , Terman Samuel , Terziev Robert , Lamberink Herm J , Braun Kees P J , Otte Willem M , Rugg-Gunn Fergus J , Gonzalez Walter , Bentes Carla , Hamandi Khalid , O’Brien Terence J , Perucca Piero , Yao Chen , Burman Richard J , Jehi Lara , Duncan John S , Sander Josemir W , Koepp Matthias , Galovic Marian
Published: November 2022

More than half of adults with epilepsy undergoing resective epilepsy surgery achieve long-term seizure freedom and might consider withdrawing antiseizure medications. We aimed to identify predictors of seizure recurrence after starting postoperative antiseizure medication withdrawal and develop and validate predictive models.

We performed an international multicentre observational cohort study in nine tertiary epilepsy referral centres. We included 850 adults who started antiseizure medication withdrawal following resective epilepsy surgery and were free of seizures other than focal non-motor aware seizures before starting antiseizure medication withdrawal. We developed a model predicting recurrent seizures, other than focal non-motor aware seizures, using Cox proportional hazards regression in a derivation cohort (n = 231). Independent predictors of seizure recurrence, other than focal non-motor aware seizures, following the start of antiseizure medication withdrawal were focal non-motor aware seizures after surgery and before withdrawal [adjusted hazard ratio (aHR) 5.5, 95% confidence interval (CI) 2.7–11.1], history of focal to bilateral tonic-clonic seizures before surgery (aHR 1.6, 95% CI 0.9–2.8), time from surgery to the start of antiseizure medication withdrawal (aHR 0.9, 95% CI 0.8–0.9) and number of antiseizure medications at time of surgery (aHR 1.2, 95% CI 0.9–1.6). Model discrimination showed a concordance statistic of 0.67 (95% CI 0.63–0.71) in the external validation cohorts (n = 500). A secondary model predicting recurrence of any seizures (including focal non-motor aware seizures) was developed and validated in a subgroup that did not have focal non-motor aware seizures before withdrawal (n = 639), showing a concordance statistic of 0.68 (95% CI 0.64–0.72). Calibration plots indicated high agreement of predicted and observed outcomes for both models.

We show that simple algorithms, available as graphical nomograms and online tools (predictepilepsy.github.io), can provide probabilities of seizure outcomes after starting postoperative antiseizure medication withdrawal. These multicentre-validated models may assist clinicians when discussing antiseizure medication withdrawal after surgery with their patients.
Cell-free DNA-based liquid biopsies in neurology
Authors: Gaitsch Hallie , Franklin Robin J M , Reich Daniel S
Published: November 2022

This article reviews recent developments in the application of cell-free DNA-based liquid biopsies to neurological diseases.

Over the past few decades, an explosion of interest in the use of accessible biofluids to identify and track molecular disease has revolutionized the fields of oncology, prenatal medicine and others. More recently, technological advances in signal detection have allowed for informative analysis of biofluids that are typically sparse in cells and other circulating components, such as CSF. In parallel, advancements in epigenetic profiling have allowed for novel applications of liquid biopsies to diseases without characteristic mutational profiles, including many degenerative, autoimmune, inflammatory, ischaemic and infectious disorders. These events have paved the way for a wide array of neurological conditions to benefit from enhanced diagnostic, prognostic, and treatment abilities through the use of liquid biomarkers: a ‘liquid biopsy’ approach.

This review includes an overview of types of liquid biopsy targets with a focus on circulating cell-free DNA, methods used to identify and probe potential liquid biomarkers, and recent applications of such biomarkers to a variety of complex neurological conditions including CNS tumours, stroke, traumatic brain injury, Alzheimer’s disease, epilepsy, multiple sclerosis and neuroinfectious disease. Finally, the challenges of translating liquid biopsies to use in clinical neurology settings—and the opportunities for improvement in disease management that such translation may provide—are discussed.
Effects of hypertension and aging on brain function in spontaneously hypertensive rats: a longitudinal resting-state functional magnetic resonance imaging study
Authors: Yang Yingying , Zhu Qingfeng , Wang Lixin , Gao Duo , Wang Zhanqiu , Geng Zuojun
Published: November 2022

To investigate the dynamic evolution of brain function under the comorbidities of hypertension and aging. Resting-state functional magnetic resonance imaging scans were longitudinally acquired at 10, 24, and 52 weeks in spontaneously hypertensive rats (SHRs) and Wistar-Kyoto rats. We computed the mean amplitude of low-frequency fluctuation (mALFF), mean regional homogeneity (mReHo), and functional connectivity (FC). There was no interaction between hypertension and aging on brain function. The main effect of aging reflects primarily the cumulative increase of brain activity, especially the increase of mALFF in amygdala and mReHo in cingulate cortex, accompanied by the decrease of brain activity. The main effect of hypertension reflects primarily decreased brain activity in default modal network, accompanied by increased brain activity. The main effect of aging shows reduced brain FC as early as 24 weeks, and the main effect of hypertension shows higher brain FC in SHRs. The novel discovery is that 1 brain FC network increased linearly with age in SHRs, in addition to the linearly decreasing FC. Hypertension and aging independently contribute to spatiotemporal alterations in brain function in SHRs following ongoing progression and compensation. This study provides new insight into the dynamic characteristics of brain function.
Potential Impact of Long-Acting Products on the Control of Tuberculosis: Preclinical Advancements and Translational Tools in Preventive Treatment
Authors: Ammerman Nicole C , Nuermberger Eric L , Owen Andrew , Rannard Steve P , Meyers Caren Freel , Swindells Susan
Published: November 2022

A key component of global tuberculosis (TB) control is the treatment of latent TB infection. The use of long-acting technologies to administer TB preventive treatment has the potential to significantly improve the delivery and impact of this important public health intervention. For example, an ideal long-acting treatment could consist of a single dose that could be administered in the clinic (ie, a “1-shot cure” for latent TB). Interest in long-acting formulations for TB preventive therapy has gained considerable traction in recent years. This article presents an overview of the specific considerations and current preclinical advancements relevant for the development of long-acting technologies of TB drugs for treatment of latent infection, including attributes of target product profiles, suitability of drugs for long-acting formulations, ongoing research efforts, and translation to clinical studies.
Prospects for Long-Acting Treatments for Hepatitis C
Authors: Thomas David L , Owen Andrew , Kiser Jennifer J
Published: November 2022

In 2019, more than 4 years after the widespread availability of safe, oral, curative treatments, an estimated 58 million people were living with hepatitis C virus infections (PLWHC). Additional tools may enable those not yet reached to be treated. One such tool could be long-acting parenteral formulations of HCV treatments, which may allow PLWHC to be diagnosed and cured in a single encounter. Although existing highly effective oral medications might be formulated as long-acting parenteral treatments, pharmacological, regulatory, patent, and medical challenges have to be overcome; this requires the concerted efforts of PLWHC, researchers, funding agencies, industry, the World Health Organization, and other stakeholders.
Barriers to Uptake of Long-Acting Antiretroviral Products for Treatment and Prevention of Human Immunodeficiency Virus (HIV) in High-Income Countries
Authors: Cooper Stanley E , Rosenblatt Joshua , Gulick Roy M
Published: November 2022

Long-acting injectable antiretroviral therapy (LAI-ART) for the treatment and prevention of human immunodeficiency virus (HIV) holds great potential to shift treatment paradigms by offering an alternative to daily oral medication. However, significant challenges at the drug, patient, and system levels risk impeding the uptake and implementation of LAI-ART. This review aims to describe the known and anticipated barriers to uptake of LAI-ART in high-income countries, as well as the ongoing research addressing some of these barriers to improve the delivery and uptake of LAI-ART products.
What Clinicians Need to Know About the Development of Long-Acting Formulations
Authors: Flexner Charles , Thomas David L , Clayden Polly , Swindells Susan
Published: November 2022

We encourage readers of this Supplement to find articles that are relevant to the current and future practice of infectious diseases medicine. Access to long-acting products and formulations in low- and middle-income countries remains a key determinant of the impact of these advances on global health.
The LEAP Process: Streamlining the Development of Long-Acting Products and Formulations for Infectious Diseases
Authors: Flexner Charles , Siccardi Marco , Bunglawala Fazila , Owen Andrew
Published: November 2022

Developing long-acting products and formulations for infectious diseases is a nontrivial undertaking that is frequently classified as high risk and low reward by the pharmaceutical industry. The Long-Acting/Extended Release Antiretroviral Research Resource Program (LEAP) was founded in 2015 with the support of the National Institutes of Health to encourage, promote, and accelerate the development of such products. Assessment methodology for any new proposal brought to this group is part of a framework—the LEAP Process—that includes a landscape analysis of what is currently available in the public domain. This is followed by in silico modeling and simulation offered as a service to the relevant scientific community. A variety of preclinical and clinical outcome metrics are applied to each new agent as part of a continuous feedback loop to improve product characteristics. This allows us to catalog knowledge gaps and barriers that can be addressed by engaged stakeholders. Results are communicated in scientific articles, reviews, and position papers. This undertaking serves to de-risk discovery, development, and implementation by bridging the gaps between academic, regulatory, and industrial investigators, and by engaging those in the community who will be the eventual users of these medicines. The LEAP Process has supported formulations now approved for human immunodeficiency virus, as well as products in clinical and preclinical development for tuberculosis and hepatitis viruses B and C.
Barriers to Uptake of Long-Acting Antiretroviral Products for Treatment and Prevention of HIV in Low- and Middle-Income Countries (LMICs)
Authors: Kityo Cissy , Cortes Claudia P , Phanuphak Nittaya , Grinsztejn Beatriz , Venter Francois
Published: November 2022

Long-acting injectable antiretroviral therapy (LA ART) has been found to be non-inferior to daily oral ART in phase 3 clinical trials and is poised to soon enter routine clinical care. This treatment modality has the potential to address many barriers to daily oral ART adherence among people living with human immunodeficiency virus (HIV) and for HIV Pre-Exposure prevention. Data from the Patient Reported Outcomes (PROs) showed high rates of satisfaction, acceptability, tolerability and preference for the LA regimen, compared with the daily oral treatment. Once LA ART is available, access and uptake will be limited because of current knowledge gaps in the use of these agents and multiple challenges many specific to low-income and middle-income countries, where the epidemic is most concentrated and HIV prevention and treatment options are limited. These gaps will lead to multiple systems-level and individual-level barriers to implementation. Anticipating and addressing these gaps and barriers will help fulfill the promise of these agents against the pandemic.
Transitioning Long-Acting Products to a Generic Marketplace: What's Missing?
Authors: Brown Ripin David H , Catlin Kelly , Lewis Linda , Resar Danielle , Amole Carolyn , Bollinger Robert C , Flexner Charles
Published: November 2022

Development of and increased access to generic oral medications to treat high-burden diseases including human immunodeficiency virus (HIV), tuberculosis, viral hepatitis, and malaria have had a major impact on reducing global morbidity and mortality. However, access and adherence to these life-saving treatments remains limited for some of the most vulnerable and underserved populations, for whom stigma, control, and discretion are critical to decisions around care. Current efforts to develop long-acting formulations to treat and prevent these conditions could overcome many of these barriers. However, generic manufacturing of these innovative products will be required to ensure affordable access to the communities and patients in greatest need. Strategic investments in new infrastructure will be required even before markets and manufacturing costs are clear, to ensure that access to these new products is not delayed, particularly for patients in low- and middle-income countries. Unlike conventional oral medications, long-acting products require greater investment for formulation, packaging, and delivery. The requirement for long-term bioequivalence studies will introduce additional delays in regulatory approval of generic long-acting products, and expedited approval pathways must be developed. Lessons learned from the development of long-acting hormonal contraceptives and long-acting antiretroviral products may provide a way forward.
Manage Risk with a Software Bill of Materials
Authors: Harrison Anthony
Published: November 2022

Open source software (OSS) is everywhere, driving businesses as well as many of our smart devices. But do we know what software is being used and, more importantly, do we know if it is secure? Anthony Harrison CEng FBCS explains.
Revealing stromal and lymphoid sources of Col3a1-expression during inflammation using a novel reporter mouse
Authors: da Rosa Larissa C , Scales Hannah E , Makhija Sangeet , Sutherland Katie , Benson Robert A , Brewer James M , Garside Paul
Published: November 2022

One of the earliest signs of dysregulation of the homeostatic process of fibrosis, associated with pathology in chronic conditions such as rheumatoid arthritis, is the overexpression of collagen type III (COL-3). Critically, there is still relatively little known regarding the identity of the cell types expressing the gene encoding COL-3 (Col3a1). Identifying and characterizing Col3a1-expressing cells during the development of fibrosis could reveal new targets for the diagnosis and treatment of fibrosis-related pathologies. As such, a reporter mouse expressing concomitantly Col3a1 and mKate-2, a fluorescent protein, was generated. Using models of footpad inflammation, we demonstrated its effectiveness as a tool to measure the expression of COL-3 during the repair process and provided an initial characterization of some of the stromal and immune cells responsible for Col3a1 expression.
Disparities in the treatment of cardiogenic shock: does sex matter?
Authors: Wang Amy S , Nemeth Samantha , Vinogradsky Alice , Kurlansky Paul , Brodie Daniel , Fried Justin , Takeda Koji
Published: November 2022

OBJECTIVES

The use of extracorporeal life support for cardiogenic shock has significantly increased over the past decade. However, there are insufficient data for the presence of sex-associated outcomes differences. Our study assesses differences between male and female patients placed on venoarterial extracorporeal life support (VA-ECLS) for cardiogenic shock from an international database.

METHODS

This is a multicentre, retrospective study on 9888 adult patients on VA-ECLS for cardiogenic shock from the Extracorporeal Life Support Organization registry from 2011 to 2019. The 1:1 nearest neighbour propensity score matching was performed. The primary end point was in-hospital mortality. Secondary end points include bleeding, infection and other complications.

RESULTS

There were 6747 (68%) male patients and 3141 (32%) female patients. Male patients were more likely to have history of myocardial infarction, coronary artery disease, diabetes, chronic kidney disease and congestive heart failure. Female patients were more likely to be centrally cannulated. After propensity score matching, there was no difference seen in in-hospital mortality. In regards to complications, female patients were more likely to experience limb ischaemia, whereas males were more likely to receive renal replacement therapy and have longer hospital stays. Multivariable logistic regression confirmed sex was not independently associated with mortality.

CONCLUSIONS

There was no difference in-hospital mortality between male and female patients receiving VA-ECLS for cardiogenic shock. Female patients were more likely to have limb ischaemia as a complication. Varying cannulation approaches for female patients should be further investigated.
Interruptions during general practice consultations: negative impact on physicians, and patients’ indifference
Authors: Santos Catarina Neves , Pedrosa Bruno Ferreira , Martins Marília , Gouveia Fábio , Franco Fátima , Vardasca Margarida João , Pedro Bernardo , Nogueira Jorge Domingues
Published: November 2022

Background

Interruptions can impact consultation duration, doctors and patients’ satisfaction, and quality of care provided. Although most of them seem to have a negative impact, affecting doctor–patient relationship and interfering with clinical reasoning, which increases the risk of error, there is still no evidence on their global impact on consultations.

Objectives

To evaluate the number and duration of interruptions during general practice consultations. To compare physicians and patients’ perceptions of their urgency and impact, as well as the overall satisfaction with the consultation.

Methods

Cross-sectional study of a representative sample of annual face-to-face general practice consultations at a Health Centre. Between January and March 2022, anonymous questionnaires were given to physicians and patients after consultation. We performed a descriptive and inferential statistical analysis.

Results

A total of 403 consultations were included. Physicians reported more interruptions than patients (108 vs. 87, P < 0.001). From patients’ perspective those interruptions were more urgent (34.5%) compared with physicians’ perspective (20.6%; P = 0.029). Patients undervalued their impact on consultations (7.1% of interruptions with a negative impact among patients vs. 24.7% among doctors; P < 0.001). Interruptions did not interfere with patients’ satisfaction with consultation (P = 0.135) but were associated with lower physicians’ satisfaction with consultation (P = 0.003).

Conclusion

Physicians are more critical regarding consultations interruptions, being more aware of their incidence and reporting more often a negative impact, which translates into lower satisfaction with interrupted consultations. Patients devalue the occurrence of interruptions, showing no concern about their impact on security or privacy, and their satisfaction is not affected by them.
Deciphering the community structure and the functional potential of a hypersaline marsh microbial mat community
Authors: Pavloudi Christina , Zafeiropoulos Haris
Published: November 2022

Microbial mats are vertically stratified communities of microorganisms characterized by pronounced physiochemical gradients allowing for high species diversity and a wide range of metabolic capabilities. High Throughput Sequencing has the potential to reveal the biodiversity and function of such ecosystems in the cycling of elements. The present study combines 16S rRNA amplicon sequencing and shotgun metagenomics on a hypersaline marsh in Tristomo bay (Karpathos, Greece). Samples were collected in July 2018 and November 2019 from microbial mats, deeper sediment, aggregates observed in the water overlying the sediment, as well as sediment samples with no apparent layering. Metagenomic samples’ coassembly and binning revealed 250 bacterial and 39 archaeal metagenome-assembled genomes, with completeness estimates higher than 70% and contamination less than 5%. All MAGs had KEGG Orthology terms related to osmoadaptation, with the ‘salt in’ strategy ones being prominent. Halobacteria and Bacteroidetes were the most abundant taxa in the mats. Photosynthesis was most likely performed by purple sulphur and nonsulphur bacteria. All samples had the capacity for sulphate reduction, dissimilatory arsenic reduction, and conversion of pyruvate to oxaloacetate. Overall, both sequencing methodologies resulted in similar taxonomic compositions and revealed that the formation of the microbial mat in this marsh exhibits seasonal variation.
Tropical stream microcosms of isolated fungal species suggest nutrient enrichment does not accelerate decomposition but might inhibit fungal biomass production
Authors: Camelo Flávio Roque Bernardes , Tonin Alan M , Salgueiro Laís , Sena Guilherme , Braga Isabela , Medeiros Adriana Oliveira , Gonçalves Júnior José Francisco
Published: November 2022

Terrestrial leaf litter is an essential energy source in forest streams and in many tropical streams, including Cerrado, litter undergoes biological decomposition mainly by fungi. However, there is a limited understanding of the contribution of isolated fungal species to in-stream litter decomposition in the tropics. Here we set a full factorial microcosms experiment using four fungal species (Aquanectria penicillioides, Lunulospora curvula, Pestalotiopsis submerses, and Pestalotiopsis sp.) incubated in isolation, two litter types (rapid and slow decomposing litter) and two nutrient levels (natural and enriched), all characteristics of Cerrado streams, to elucidate the role of isolated fungal species on litter decomposition. We found that all fungal species promoted litter mass loss but with contributions that varied from 1% to 8% of the initial mass. The fungal species decomposed 1.5 times more the slow decomposing litter and water nutrient enrichment had no effect on their contribution to mass loss. In contrast, fungal biomass was reduced by nutrient enrichment and was different among fungal species. We showed fungal contribution to decomposition depends on fungal identity and litter type, but not on water nutrients. These findings suggest that the identity of fungal species and litter types may have more important repercussions to in-stream decomposition than moderate nutrient enrichment in the tropics.
Conceptualizing and Operationalizing Collaboration Among Multiple Caregivers of Older Adults
Authors: Ellis Katrina R , Koumoutzis Athena , Lewis Jordan P , Lin Zhiyong , Zhou Yuanjin , Chopik William J , Gonzalez Richard
Published: November 2022

Objectives

In many families, multiple caregivers support older adults living with dementia. Studying collaboration among caregivers requires consideration of conceptual and methodological issues that have not been fully explored. This study presents a framework for conceptualizing caregiver collaboration and an index that captures variation in collaboration among multiple caregivers within care networks.

Methods

We used data from the 2015 waves of the National Health and Aging Trends Study and National Study of Caregiving (NSOC) to operationalize collaboration among multiple caregivers (N = 1,298) of 552 care recipients (Mage = 83.69, SD = 7.73; 71.6% women; 47.9% possible/probable dementia; 38.9% people of color).

Results

The care collaboration index considered individual and overlapping contributions while controlling for the size of the care network (caregivers in network responding to NSOC survey) and total network size (number of caregivers in network) in the statistical model. Larger care networks enabled more collaboration, both in general and across most types of tasks (βs > 0.38). Collaboration was greater among those caring for a Black or Hispanic care recipient, both in general and for household and medical/health tasks specifically (βs > 0.11). Collaboration was also greater among those caring for recipients with probable dementia, both in general and for most tasks (βs > 0.11) but not transportation-related tasks (p = .219).

Discussion

Results are examined in the context of care network dynamics and proposed mechanisms linking care collaboration to outcomes for caregivers and recipients. Strengths and limitations of our conceptualization and operationalization of collaboration are discussed.
A simple algorithm for optimal design in distributed fibre-optic sensing
Authors: Fichtner Andreas , Hofstede Coen
Published: November 2022

We present a basic algorithm for optimal experimental design in distributed fibre-optic sensing. It is based on the fast random generation of fibre-optic cable layouts that can be tested for their cost-benefit ratio. The algorithm accounts for the maximum available cable length, lets the cable pass through pre-defined points of interest, avoids obstacles that the cable must not traverse, permits the adaptation of geometric complexity of different cable segments and allows for the incorporation of topography. Furthermore, the algorithm can be combined with arbitrary measures of the cost-benefit ratio, and its simplicity enables easy adaptations to the needs of specific applications. In addition to a description of the basic concept, we provide examples that illustrate the circumnavigation of obstacles, the steering of geometric complexity and the cable layout optimization in the presence of topographic variations.
Burden of mental distress in the US associated with trust in media for COVID-19 information
Authors: Jalan Madhu , Riehm Kira , Agarwal Smisha , Gibson Dustin , Labrique Alain , Thrul Johannes
Published: November 2022

During the COVID-19 pandemic, news and social media outlets have played a major role in dissemination of information. This analysis aimed to study the association between trust in social and traditional media and experiences of mental distress among a representative sample of US adults. Data for this study came from National Pandemic Pulse, a cross-sectional, nationally representative survey that sampled participants on the Dynata platform. Participants included 6435 adults surveyed between 15–23 December 2020. Ordinal logistic regression analyses examined the associations of trust in (i) social media, (ii) print media, (iii) broadcast TV and (iv) cable TV, for COVID-19-related information with self-reported mental distress (4-item Patient Health Questionnaire), controlling for sociodemographics and census region. Compared with those who distrusted social media, those who trusted social media had 2.09 times (95% CI = 1.84–2.37) greater adjusted odds of being in a more severe category of mental distress. In contrast, compared with those who distrusted print media, those who trusted print media had 0.80 times (95% CI = 0.69–0.93) lower adjusted odds of being in a more severe category of mental distress. No significant associations were found between mental distress and trust in broadcast or cable TV for accessing news about COVID-19. Trust in different news outlets may be associated with mental distress during public health emergencies like the COVID-19 pandemic. Future studies should explore mechanisms behind these associations, including adherence to best practices for crisis reporting among different media sources and exposure of individuals to misinformation.
How not to learn from history
Authors: Khong Yuen Foong
Published: November 2022

This article attempts to answer two questions. First, what are the relevant ‘how not tos’ when it comes to learning from history? I argue that from existing accounts of how policy-makers (mis)learn the lessons of history, we can derive four ‘how not tos’: 1) do not settle or fixate on the first, or most ‘available’ or ‘representative’ analogy; 2) do not dismiss differences between your favoured analogy and the case in question; 3) do not neglect alternative analogies; and 4) do not shirk from ‘testing’ the observable implications of your preferred analogy. Second, do policy-makers show awareness of these ‘how not tos’ as they use historical analogies? An examination of how they are using the Cold War analogy to interpret the nature and trajectory of contemporary US–China relations suggest that they seem to have avoided the worst pitfalls of analogical reasoning in foreign affairs. The most prominent users of these historical analogies show awareness of the first three of the above proscriptions; all, however, shy away from the fourth proscription—testing the prognostications of their favoured analogy. Although this is far from perfect, the signs point to the Cold War analogy being used in ways that avoid the general pattern of superficial and poor use documented in existing analyses of analogical reasoning in foreign affairs.