bluuebunny/crossref_metadata_2025 huggingface dataset:
DOTS-Plus
Authors: Garg Tushar
Published: July 2023

Multidrug-resistant tuberculosis (TB) is a major issue in global health, prompting concerns from multilateral agencies and donor organizations about the ability of low- and middle-income countries (LMICs) to effectively treat patients with this disease as a result of poor health infrastructure and the perceived inability to ensure that patients receive and take their specialized antibiotic regimens. The DOTS-Plus program for patients with drug-resistant TB described in this study provides individualized, patient-centered care in a community-based, outpatient, and low-resource environment. With this program, 83% of the patients completing at least 4 months of treatment achieved a probable cure. This study catalyzed changes to guidelines and practice of treating every drug-resistant case in an in-patient hospital setting and highlighted the limits of the standardized short-course approach to TB treatment.
Economic Growth and Child Undernourishment
Authors: Gun Arkaprabha
Published: July 2023

Nutrition is essential to survival, and malnutrition is a large contributor to under-5 mortality globally. This study examines the effect that state-level economic growth has on nutritional outcomes in children in India. The authors estimated the odds ratio of the children being underweight, stunted, or suffering from wasting, given a 5000 Indian rupees (INR) increase in the state per capita income. The authors found that the likelihood of a child experiencing undernourishment does not vary as a result of state-level economic growth. This implies that increased GDP/economic growth is insufficient to improve childhood nutrition status, but instead that targeted policies and interventions may be necessary.
Implicit Bias in Pain Management
Authors: Huang Kuang-Ning , Carpenter Cristina Rivera
Published: July 2023

Implicit biases involve associations outside conscious awareness that lead to a negative outcome based on race, class, or sexual orientation. In this study, Hispanic patients with long bone fractures were twice as likely as non-Hispanic white patients to receive no pain medications in the emergency room, and when they did receive pain medications, the doses were smaller. Multiple studies have documented similar phenomena, and unfortunately this study is just one of many examples in healthcare that shows patients may be treated differently as a result of implicit bias.
Race-Based Medicine—Is It Biological or Profit Driven?
Authors: Crawford Nadra
Published: July 2023

The African-American Heart Failure Trial (A-HeFT) was performed after retrospective subgroup analyses of Vasodilator Heart Failure Trial (V-HeFT) I and II trial data showed a significant improvement in mortality in Blacks using ISDN combined with hydralazine. A-HeFT is a randomized, placebo-controlled, double-blind trial of 161 sites throughout the United States, whose aim was to determine if there is a survival benefit with the addition of ISDN and hydralazine to standard therapy in a single ethnic group—Blacks—with advanced heart failure. The study found that the addition of isosorbide dinitrate (ISDN) and hydralazine (BiDil) to standard therapy improved survival, reduced hospitalization, and enhanced quality of life in participants.
How Do Locals Feel about Expats in Global Health?
Authors: Fukushima Jack , Jumbe Arnold
Published: July 2023

There are an abundance of short-term medical trips, including global health training programs that send partially trained or untrained learners to “help” in the medical field; other programs include medium- to longer-term healthcare providers from high-income countries (HICs) who travel to low- and middle-income countries (LMICs) to work in healthcare. Each program has varying levels of preparation, cultural sensitivity training, and partnerships with the host country or facility. The visiting provider(s) and their services may or may not have been specifically requested by the host country. These providers may not adhere to the same credentialing standards they adhere to in their own country, and may not have a full understanding of the health system into which they are traveling. This study aims to understand how the healthcare professionals in the LMICs perceive those who are coming from the HICs. In doing so, the study authors bring up ethical considerations around the themes of medical colonialism, recognizing and understanding power dynamics, cultural competency, and sustainability.
Isoniazid for Preventing TB in HIV-Positive People
Authors: Laux Timothy S.
Published: July 2023

Tuberculosis (TB) is a major cause of morbidity and mortality in patients with HIV. This study looked at patients with HIV-1 infection who were starting or continuing antiretroviral therapy (ART) and the use of 12 months of isoniazid to prevent active TB disease. They found that isoniazid preventive therapy (IPT) provided protection against active TB with a number needed to treat (NNT) of 25. This shows that in moderate- or high-burden TB settings, HIV-1 positive individuals on ART should receive 12 months of IPT for prevention of incident TB with few exceptions.
A National Program to Introduce Impregnated Bednets to Address Malaria in Gambia
Authors: Parker Jessica C.
Published: July 2023

The Gambia initiated a National Insecticide Impregnated Bednet Programme (NIBP) after a controlled trial of insecticide-treated bednets was found to lower child mortality. The goal of the study was to determine if implementation of insecticide-treated bednets at a national level would result in a significant reduction in child mortality and would be cost-effective. Five geographic areas were selected, and the authors compared childhood mortality in populations using insecticide-treated bednets to those using untreated nets. Despite poor compliance in some of the groups, the authors found an overall reduction in childhood mortality in populations using insecticide-treated nets, albeit with a significant and likely prohibitive cost.
Solidarity Trial
Authors: Agarwal Anup
Published: July 2023

In February 2020, when the COVID-19 pandemic started, there was no known therapy for COVID-19 but multiple repurposed drugs were being considered as potential treatments. To study these drugs in a fast-tracked manner, the World Health Organization (WHO) initiated a multi-center, international, simple adaptive trial of 4 potential therapies including remdesivir, hydroxychloroquine, lopinavir, and interferon with the primary outcome of mortality reduction. The trial was completed within 7 months to conclusively answer that none of the 4 drugs was found to have any benefit on mortality reduction, or on initiation of ventilation among non-ventilated patients. These results would help government and policymakers in low- and middle-income countries to streamline resources for COVID-19 away from these 4 drugs.
Oral Maintenance Therapy for Cholera in Adults
Authors: Chatterjee Pranab
Published: July 2023

Cholera and non-cholera diarrheal illnesses are an important cause of morbidity and mortality in low- and middle-income countries (LMICs). The major challenge in management of diarrheal illness is treatment of dehydration. In resource-denied settings, where supplies for intravenous (IV) fluid administration can be scarce, an oral substitute can be a lifesaving modality. This study administered oral fluids in one group in addition to giving IV fluids, compared with IV fluid administration only in another group. There was a difference of nearly 15.5 L of total IV fluids needed between the oral therapy group and the IV fluid group, with the oral therapy group having a significantly smaller IV fluid requirement. This study, conducted in the infancy of clinical trials, was instrumental in identifying the reduction in need for IV fluid support with the addition of oral fluids to the management strategy for cholera.
Does Helping Babies Breathe Training Help Reduce Neonatal Mortality?
Authors: Sikder Shegufta Shefa
Published: July 2023

The first hour of life is critical to newborn survival. This study conducted at 8 hospital in Tanzania highlights the effectiveness of a training and education curricula on neonatal mortality in settings that have previously failed to initiate resuscitative steps in a timely manner. This study shows that successful implementation of this program results in 47% reduction in early neonatal mortality (ENM) within 24 hours of training and 24% reduction in fresh still births after 2 years. The Helping Babies Breathe approach is simple and can be implemented readily at all deliveries, including those in low-resource settings, as it emphasizes low-cost interventions, including immediate drying and stimulation.
Sickle Cell Anemia in Children in Sub-Saharan Africa—What Is the Best Medicine?
Authors: Laux Timothy S.
Published: July 2023

Hydroxyurea is a myelosuppressive agent that raises the level of fetal hemoglobin in red blood cells and is well known to significantly reduce the frequency of sickle cell crises, chronic organ damage, and prolong survival. It is on the WHO list of essential medicines for the treatment of hemoglobinopathies. However, in areas where malaria and malnutrition are endemic there were concerns over whether toxicity risks may outweigh benefits. The REACH trial looked at the benefits versus risks of hydroxyurea in sickle cell patients in children in sub-Saharan Africa and found that hydroxyurea treatment reduced the rates of painful events, infection, transfusion and death with no increase in adverse events and in fact had a protective effect against malaria with a rate reduction of more than 50%.
Can Tranexamic Acid Stop Postpartum Hemorrhage?
Authors: Lindley Alexa , Montano Mariana , Molina Rose L.
Published: July 2023

Postpartum hemorrhage is the leading cause of maternal mortality worldwide. This chapter reviews the World Maternal Antifibrinolytic (WOMAN) trial that tested whether the administration of tranexamic acid prevents death and other adverse events from postpartum hemorrhage. The study found a statistically significant decrease in death from postpartum hemorrhage in patients who received tranexamic acid compared to those who received placebo, but with a large number needed to treat of 250. However, given that there were no complications associated with tranexamic acid treatment, this trial supports its use in postpartum hemorrhage, which is the leading cause of maternal mortality worldwide.
Magnesium Sulphate for Seizure Prophylaxis in Women with Preeclampsia
Authors: Walker Andrea
Published: July 2023

The article “Do women with pre-eclampsia, and their babies, benefit from magnesium sulphate? The Magpie Trial: A randomized placebo-controlled trial” describes the first randomized trial that objectively evaluates the utility of magnesium sulphate therapy as prophylaxis against progression to eclamptic convulsions in a high-risk cohort of women. It specifically evaluates the effect of magnesium sulphate given before and after delivery on maternal progression to eclampsia and fetal/neonatal death. It also evaluates secondary outcomes such as maternal morbidity, magnesium toxicity, side effects of magnesium sulphate, and for those who received magnesium sulphate prior to delivery, it evaluates complications of the labor process.
Effects of Partograms on Birthing Outcomes in Developing Nations
Authors: Dean Nakyda
Published: July 2023

A partogram is a graphic representation of labor and was established as the gold standard of monitoring labor in the low-resource setting by the World Health Organization (WHO) in 1994. Obstructed labor is still a major cause of maternal and neonatal morbidity and mortality and can be prevented with the aid of the partogram. The careful use of the partogram, and the value of the alert and action line, can improve maternal-child health outcomes by early detection of abnormal progression of labor. Healthcare workers must receive continuing education to utilize this tool in real time to greatly impact maternal-child health outcomes.
Can Community Health Workers Effectively Provide Cognitive Behavioral Therapy–Based Services?
Authors: White Rebecca
Published: July 2023

This chapter examines the effectiveness of using non-specialists to provide mental health services. Trained mental health workers are a scarce resource globally, and task sharing has been implemented in primary care settings to improve access to evidence-based mental health treatment. This cluster randomized controlled trial conducted across 40 sites in rural Pakistan assesses the efficacy of non-specialists to provide cognitive behavioral therapy–based services for mothers with perinatal depression and outcomes for both mothers and infants 12 months post-delivery. Depression and disability were nearly 50% lower in the intervention group compared to the control group. Nutritional indicators of infants were same in both groups at 6 and 12 months. It concludes with a case study to examine concrete ways to implement recommendations from the study.
Improving Mental Health Access Where There Is No Psychiatrist
Authors: Chandrashekhar Riti , Walker Andrea
Published: July 2023

There is a dearth of mental health professionals globally. This shortage is disproportionally pronounced in low- and middle-income countries (LMICs). To address the shortage, collaborative care models (CoCM) have been proposed which consider primary care providers (PCP) and behavioral health providers (such as social workers) as mental health professional substitutes who operate under the guidance of a psychiatrist. This study is among the first to evaluate CoCM implementation in LMICs. It reviews the impact of the intervention on PCP behaviors to screen, diagnose, and treat mental illness, as well as clinical outcomes in patients with depression, showing a 49% improvement in clinical response to depression.
Aspirin in Acute Stroke
Authors: Bender Jessica
Published: July 2023

According to a 2013 Global Burden of Disease study, stroke was the second largest contributor to age-adjusted disability-adjusted life years (DALYs) in developing countries. Access to thrombolytic therapy for stroke within 4.5 hours of symptom onset remains a major logistical challenge in most parts of the Global South. This study was done to assess the efficacy of aspirin in the setting of acute ischemic stroke in preventing short term death and disability. The study results suggest that aspirin results in modest reduction in death and disability when given in the acute period after presumed ischemic stroke. The increased burden of stroke and subsequent loss of DALYs in the Global South suggests that aspirin use in acute stroke is a worthwhile intervention.
Introduction: Some Context
Authors: Weiner Saul J. , Schwartz Alan
Published: July 2023

The introduction to the second edition is designed to provide the reader who is not familiar with research on contextual error with an overview of the fundamental concepts and terms, followed by a brief description of each chapter, laying out a rationale for the body of work and placing it in a historical context. For instance, studies on contextualization of care build on the work of George Engel’s biopsychosocial model by introducing an empirical framework and set of tools for characterizing and measuring a dimension of quality that has previously been sidelined with non-specific terms like “art of medicine” and “humanistic care.” The authors argue that contextualizing care to prevent contextual error is a clinician competency that should be systematically taught, assessed, and then reinforced in clinical practice.
Measuring the Problem
Authors: Weiner Saul J. , Schwartz Alan
Published: July 2023

Chapter 2, “Measuring the Problem,” transitions from anecdotes and hypotheses to systematic inquiry. Contextual error is characterized as a subtype of medical error that has been overlooked because it is not detectable utilizing conventional methods for detecting error. The authors describe observing physician decision-making directly by sending unannounced standardized patients (USPs) into doctors’ practices to portray cases that challenge physicians to think contextually. Doing so is methodologically challenging as it entails training actors to adopt the personae of real patients while adhering to a script, creating fake medical records, and gaining the trust of physicians who consent not to know when a USP is recording them. The work demonstrates that when patients drop hints that there are life factors interfering with their care, doctors often miss them, instead sending them out with plans that look appropriate on paper but, in fact, are not if one takes into account the context.
The Problem Is Everywhere
Authors: Weiner Saul J. , Schwartz Alan
Published: July 2023

Chapter 3, “The Problem Is Everywhere,” describes the next phase of work, in which hundreds of actual patients, carrying concealed audio recorders, recorded their visits with their physicians. This approach captures how often context matters in actual practice and how often effective care really hinges on a personalized approach in which individual life circumstances are a key factor in planning. The chapter describes the development of a coding system, termed “Content Coding for Contextualization of Care” or “4C,” designed to study actual patient interactions and their outcomes. It also delves into the complex process of conducting the research itself, including the legal and ethical implications of covert audio recording as well as the potential concerns of participants, clinicians, and patients alike.
What We Hear That Physicians Don’t
Authors: Weiner Saul J. , Schwartz Alan
Published: July 2023

Chapter 4, “What We Hear That Physicians Don’t,” is a technical breakdown of how to analyze contextualization of care using data collected from audio-recorded encounters and the medical record. In particular, it describes in detail the “4C” content coding system introduced in the previous chapter. Coding content, in contrast to coding of process, requires following the thread and logic of a conversation. 4C identifies contextual red flags (clues that there may be relevant context), contextual probes (attempts to explore the clues), contextual factors (discovered by probes or revealed by the patient), and contextualized care plans (responsive to patient context). This chapter also explains the need for 4C, which is that other approaches to assessing communication in doctor–patient communication research do not capture information on whether clinicians are actually paying attention to and addressing key information that comes up during the medical encounter.
High versus Low Performers
Authors: Weiner Saul J. , Schwartz Alan
Published: July 2023

Chapter 5, “High versus Low Performers,” asks and answers the question “What makes a clinician good at this?” From an analysis of high, medium, and low performers, the authors have identified six attributes that lead a physician either to overlook context or to recognize and incorporate it. The archetype of a clinician who exemplifies all of the skills for attending to the complexity of context in decision-making is an individual who is flexible rather than rigid in conversation, does not let checklists get in the way of building and testing theories about what might be going on, avoids drawing conclusions prematurely in the face of conflicting evidence, looks for opportunities in every visit to provide some level of care to the patient right now, manages rather than is managed by electronic medical record technology, and is capable of seeing the linkages between patients’ life situations and their clinical care.
Is Lasting Change Possible?
Authors: Weiner Saul J. , Schwartz Alan
Published: July 2023

Chapter 7, “Is Lasting Change Possible?,” describes three different interventions designed to reduce contextual error rates, improving contextualization of care. In the first, termed “audit and feedback,” physicians and other health-care professionals receive ongoing data on their performance at contextualizing care, based on analysis of audio recordings of encounters with their patients. In the second, the feedback is based on data collected by unannounced standardized patients. These interventions are like “holding a mirror up” to the clinician so that they can see what their care looks like, both the good (contextualized care) and the bad (contextual errors), and adapt accordingly. In the third intervention, clinical decision support tools in the electronic medical record guide physicians to contextualize care, drawing on data provided by patients before the visits and from their medical record.
What We Can’t Measure That Matters
Authors: Weiner Saul J. , Schwartz Alan
Published: July 2023

Chapter 8, “What We Can’t Measure That Matters,” addresses the limitations of the measures described in this book for capturing what they are designed to measure. In an effort not to overreach and to retain high levels of inter-rater agreement and strong evidence for validity of the construct of contextual error, the coding methodology “4C” applies the term only to the most straightforward instances during clinical encounters where it applies. The benefit of the approach is that the system is highly specific in identifying contextual errors but not particularly sensitive. The concepts of engagement and boundary clarity are introduced to describe ideal clinician behaviors that result in highly contextualized care, beyond the bounds of what is currently measurable.
Bringing Context Back into Care
Authors: Weiner Saul J. , Schwartz Alan
Published: July 2023

Chapter 9, “Bringing Context Back into Care,” reviews the core findings of research on contextualizing of care—that contextual errors are measurable, pervasive, diminish health-care outcomes, increase costs, and are preventable. Addressing the problem will require a broader appreciation of its significance and a commitment to change. Stakeholders, particularly payers and regulators, must hold physicians and all providers accountable for improved attention to patient context in care planning. Doing so will likely require widespread audit and feedback methods, including the use of unannounced standardized patients and real patients who are comfortable audio-recording their care. Medical schools and medical educators must also address a deficit in contextual reasoning skills by revising curricula to include attention to patient context in all clinical case-based instruction.
Introduction
Authors: Navin Mark C. , Attwell Katie
Published: July 2023

In 2015, California eliminated nonmedical exemptions to school vaccine mandates. Unvaccinated children were excluded from school if they did not have medical reasons not to be vaccinated. California’s new mandatory vaccination policy was a watershed moment in the history of American public health. It replaced efforts to persuade and nudge parents to vaccinate with potentially coercive threats: Either vaccinate your children or miss out on school. California’s elimination of nonmedical exemptions—and the political battles that preceded and followed that policy change—heralded a new kind of partisan politics for childhood immunization policy. Immunization policy changes in California illustrate the emergence of national and international trends in immunization governance that precede and will likely extend past the COVID-19 pandemic.
The Mandates & Exemptions Regime
Authors: Navin Mark C. , Attwell Katie
Published: July 2023

Every state in the United States has had school vaccine mandates for decades, but until recently, almost all states offered nonmedical exemptions (NMEs). The widespread availability of NMEs helped state vaccine mandates to be objects of political consensus. Recent efforts to eliminate nonmedical exemptions therefore aim to transform America’s immunization governance. This chapter identifies the origins of the “mandates & exemptions” regime in the United States and traces the recent history of school vaccine requirements. It explains why schools were natural locations for immunization governance, and it reviews the history, law, and ethics of religious and philosophical exemptions to vaccine mandates.
Mobilizing for the Nonmedical Exemptions Bill
Authors: Navin Mark C. , Attwell Katie
Published: July 2023

This chapter explains how a network of California parents and civil society organizations worked with elected officials to eliminate nonmedical exemptions. Parent activists responded to outbreaks in their communities by mobilizing against the permissive attitude that California’s government took toward vaccine refusal. After the Disneyland measles outbreak of 2014, pro-vaccine parents contacted Dr. Richard Pan, a California state senator who had led successful efforts to limit California’s nonmedical exemptions in 2012. Pan encouraged parents to be the public face of his new campaign to eliminate nonmedical exemptions. Their organization, Vaccinate California, lobbied for Pan’s new bill and recruited other parents to their movement. Along with health and medical civil society organizations, Vaccinate California shepherded a bill to eliminate nonmedical exemptions, Senate Bill 277, through California’s legislature.
Drawing the Wrong Lessons from the History of Mandates
Authors: Navin Mark C. , Attwell Katie
Published: July 2023

Contemporary advocates of eliminating nonmedical exemptions—or of otherwise tightening vaccine mandates—often invoke historical examples to support their cause. However, previous eras’ more coercive vaccine mandates were enforced against populations whose ethical and political sensibilities were very different from those of today. Recent decades have witnessed the institutionalization of many limits on public health powers, including resistance to coercive interventions on the bodies of America’s most vulnerable members, institutional protections of individual liberty, and the promotion of informed consent. Furthermore, previous instances of coercive vaccine mandates sometimes caused popular backlashes against immunization governance, as in the case of late-19th-century England. Current efforts to introduce greater coercion into vaccine policy risk similar kinds of political backlash.
The Ethics and Public Acceptability of Mandates
Authors: Navin Mark C. , Attwell Katie
Published: July 2023

This chapter evaluates efforts to eliminate nonmedical exemptions to school entry vaccinate mandates from an ethical and pragmatic standpoint. It examines three arguments that critics often raise against coercive vaccine mandates for daycare or school: parents’ rights, informed consent, and children’s rights to care and education. Then it evaluates four arguments that proponents offer in defense of such policies: children’s right to receive vaccines, preventing disease transmission, the duty to contribute to herd immunity, and the overall social benefits associated with high rates of vaccination. Finally, it expresses skepticism about the potential for today’s coercive vaccine mandates to eradicate or eliminate disease (or even to achieve stable disease control). Accordingly, today’s vaccine mandates need to be justified by their short-term and often more moderate benefits, and their potential harms must be given greater comparative weight.
Simulation of polarized emission from recollimation shocks in relativistic jets
Authors: Kaye C , Cawthorne T V , Marti J-M , Hughes P A
Published: July 2023

This paper presents a method for obtaining synthetic images of linearly polarized synchrotron radiation from steady-state numerical simulations of relativistic jets, in which the magnetic field is assumed to be initially either partially or completely disordered. The method is based on the earlier work which characterized the deformation of the fluid using infinitessimal fluid elements that are initially cubic, and which evolve into parallelepipeds. The method is described for a range of models for the initial magnetic field, including ordered components that are axial, helical, and toroidal with a bi-directional axial component. The method is then applied to steady, axisymmetric simulations of initially overpressured jets and the initial results are discussed. Some characteristic patterns and trends in polarization angle are identified. Although the recollimation shocks that form in these jets are not clearly visible in the total intensity images presented here, arcs of strongly polarized emission associated with radial velocity gradients in the vicinity of the shock waves are seen, and might prove to be a useful diagnostic feature of this model.
Diagnosis of 3D magnetic field and mode composition in MHD turbulence with Y-parameter
Authors: Malik Sunil , Yuen Ka Ho , Yan Huirong
Published: July 2023

Magnetic fields are crucial in numerous astrophysical processes within the interstellar medium (ISM). However, the detailed determination of magnetic field geometry is notoriously challenging. Based on the modern magnetohydrodynamic (MHD) turbulence theory, we introduce a novel statistical technique, the ‘Y-parameter’, to decipher the magnetic field inclination in the ISM and identify dominant turbulence modes. The Y-parameter, calculated as the ratio of anisotropies of different Stokes parameter combinations, displays contrasting trends with the mean-field inclination angle in Alfvénic and compressible turbulence modes. A Y-parameter value around 1.5 ± 0.5 provide a statistical boundary to determine the dominant MHD turbulence modes. We have discovered specific correlations between the Y-parameter value and the inclination angle that unveil the dominant turbulence mode. This methodology, when applied to future radio polarization surveys such as LOFAR and SKA, promises to significantly enhance our knowledge of 3D magnetic field in the ISM and improve our understanding of interstellar turbulence.
Non-Equilibrium Abundances Treated Holistically (NEATH): the molecular composition of star-forming clouds
Authors: Priestley F D , Clark P C , Glover S C O , Ragan S E , Fehér O , Prole L R , Klessen R S
Published: July 2023

Much of what we know about molecular clouds, and by extension star formation, comes from molecular line observations. Interpreting these correctly requires knowledge of the underlying molecular abundances. Simulations of molecular clouds typically only model species that are important for the gas thermodynamics, which tend to be poor tracers of the denser material where stars form. We construct a framework for post-processing these simulations with a full time-dependent chemical network, allowing us to model the behaviour of observationally important species not present in the reduced network used for the thermodynamics. We use this to investigate the chemical evolution of molecular gas under realistic physical conditions. We find that molecules can be divided into those that reach peak abundances at moderate densities ($10^3 \, {\rm cm}^{-3}$) and decline sharply thereafter (such as CO and HCN), and those that peak at higher densities and then remain roughly constant (e.g. NH3, N2H+). Evolving the chemistry with physical properties held constant at their final values results in a significant overestimation of gas-phase abundances for all molecules, and does not capture the drastic variations in abundance caused by different evolutionary histories. The dynamical evolution of molecular gas cannot be neglected when modelling its chemistry.
On the pollution of white dwarfs by exo-Oort cloud comets
Authors: O’Connor Christopher E , Lai Dong , Seligman Darryl Z
Published: July 2023

A large fraction of white dwarfs (WDs) have metal-polluted atmospheres, which are produced by accreting material from remnant planetary systems. The composition of the accreted debris broadly resembles that of rocky Solar system objects. Volatile-enriched debris with compositions similar to long-period comets (LPCs) is rarely observed. We attempt to reconcile this dearth of volatiles with the premise that exo-Oort clouds (XOCs) occur around a large fraction of planet-hosting stars. We estimate the comet accretion rate from an XOC analytically, adapting the ‘loss cone’ theory of LPC delivery in the Solar system. We investigate the dynamical evolution of an XOC during late stellar evolution. Using numerical simulations, we show that 1–30 per cent of XOC objects remain bound after anisotropic stellar mass-loss imparting a WD natal kick of ${\sim}1 \, {\rm km \, s^{-1}}$. We also characterize the surviving comets’ distribution function. Surviving planets orbiting a WD can prevent the accretion of XOC comets by the star. A planet’s ‘dynamical barrier’ is effective at preventing comet accretion if the energy kick imparted by the planet exceeds the comet’s orbital binding energy. By modifying the loss cone theory, we calculate the amount by which a planet reduces the WD’s accretion rate. We suggest that the scarcity of volatile-enriched debris in polluted WDs is caused by an unseen population of 10–$100 \, \mathrm{au}$ scale giant planets acting as barriers to incoming LPCs. Finally, we constrain the amount of volatiles delivered to a planet in the habitable zone of an old, cool WD.
Apical fibrobullous lung disease in spondyloarthritis patients with biologic DMARDs indication
Authors: Ozsoy Zehra , Ayan Gizem , Durhan Gamze , Kalyoncu Umut
Published: July 2023

Objective

The rate of pleuroparenchymal involvement in patients with SpA varies widely, from 0% to 85%. The most common form is apical fibrobullous disease (AFLD). The aim of this study was to determine the incidence of AFLD and associated factors in SpA patients under and/or planned to start biologic DMARDs (bDMARDs) therapy.

Methods

The records of 3021 SPA patients registered with HUR-BIO who had indication of bDMARDs between 2010 and 2021 were scanned. The study included 2489 patients with at least one chest radiograph (X-ray). Patient demographics, comorbidities, laboratory data, bDMARDs used, baseline DASs, and purified protein derivative and/or QuantiFERON test results before initiation of bDMARDs were recorded.

Results

Of the 2489 patients, 36 (1.4%) were found to have AFLD by X-ray and/or CT. The mean disease duration was 11.7 (7.1) years. Patients with AFLD were more likely to be male [28 (77.8%) vs 1321 (53.9%), P = 0.004], older [56.3 (10.5) years vs 44.8 (11.4) years, P < 0.001], heavy smokers [27 (79.4%) vs 1468 (60.9%), P = 0.028] and have had longer disease duration [17. 7 (9.7) years vs 11.6 (7) years, P = 0.001]. QuantiFERON positivity was higher in the AFLD group [9 (36%) vs 309 (16.1%), P = 0.013]. While treatment with adalimumab was less preferred in those with AFLD, treatment with etanercept was more frequently preferred.

Conclusion

As the radiological findings of AFLD can be confused with those of tuberculosis, special attention should be paid to differentiating between tuberculosis and the disease in males and in patients who have had long disease duration.
Human cell-based in vitro systems to assess respiratory toxicity: a case study using silanes
Authors: Sharma Monita , Stucki Andreas O , Verstraelen Sandra , Stedeford Todd J , Jacobs An , Maes Frederick , Poelmans David , Van Laer Jo , Remy Sylvie , Frijns Evelien , Allen David G , Clippinger Amy J
Published: July 2023

Inhalation is a major route by which human exposure to substances can occur. Resources have therefore been dedicated to optimize human-relevant in vitro approaches that can accurately and efficiently predict the toxicity of inhaled chemicals for robust risk assessment and management. In this study—the IN vitro Systems to PredIct REspiratory toxicity Initiative—2 cell-based systems were used to predict the ability of chemicals to cause portal-of-entry effects on the human respiratory tract. A human bronchial epithelial cell line (BEAS-2B) and a reconstructed human tissue model (MucilAir, Epithelix) were exposed to triethoxysilane (TES) and trimethoxysilane (TMS) as vapor (mixed with N2 gas) at the air-liquid interface. Cell viability, cytotoxicity, and secretion of inflammatory markers were assessed in both cell systems and, for MucilAir tissues, morphology, barrier integrity, cilia beating frequency, and recovery after 7 days were also examined. The results show that both cell systems provide valuable information; the BEAS-2B cells were more sensitive in terms of cell viability and inflammatory markers, whereas MucilAir tissues allowed for the assessment of additional cellular effects and time points. As a proof of concept, the data were also used to calculate human equivalent concentrations. As expected, based on chemical properties and existing data, the silanes demonstrated toxicity in both systems with TMS being generally more toxic than TES. Overall, the results demonstrate that these in vitro test systems can provide valuable information relevant to predicting the likelihood of toxicity following inhalation exposure to chemicals in humans.
New Host Plant Species of Grapevine Virus A Identified with Vector-Mediated Infections
Authors: Vončina Darko , Jagunić Martin , De Stradis Angelo , Diaz-Lara Alfredo , Al Rwahnih Maher , Šćepanović Maja , Almeida Rodrigo P. P.
Published: July 2023

Grapevine virus A (GVA) is an economically important virus and a member of the genus Vitivirus (family Betaflexiviridae) that causes a range of symptoms with qualitative and quantitative effects on grape production. Wild and domesticated species of Vitis, including hybrids used as rootstocks, are considered important natural hosts of GVA. Mechanical transmission to some herbaceous plant species, graft transmission, and vector transmission from grape to grape by various mealybugs and soft scale insects have been reported. Under laboratory and greenhouse conditions, this study demonstrates the transmission of GVA from grapes to alternative hosts by the vine mealybug (Planococcus ficus). Results of ELISA, end-point one-step RT-PCR, and real-time RT-PCR, and in some cases electron microscopy and genome sequencing, confirmed successful transmission to three new plant species commonly found in Croatian vineyards: velvetleaf (Abutilon theophrasti), redroot pigweed (Amaranthus retroflexus), and field poppy (Papaver rhoeas), along with Chenopodium murale and the previously known host Nicotiana benthamiana, with variable infection rates. Depending on the host species, symptoms in the form of leaf reddening, yellow spots, reduced growth of lateral shoots, systemic vein clearing, foliar deformation and rugosity, and dwarfism were observed in GVA-infected plants, whereas no symptoms were observed in infected plants of A. theophrasti. Reverse transmission from these new hosts to grapevines by Pl. ficus was not successful. These results confirm four new GVA host species and open new research venues.
Longitudinal dose patterns among patients newly initiated on long-term opioid therapy in the United States, 2018 to 2019: an observational cohort study and time-series cluster analysis
Authors: Rikard S. Michaela , Nataraj Nisha , Zhang Kun , Strahan Andrea E. , Mikosz Christina A. , Guy Gery P.
Published: July 2023

Opioid prescribing varies widely, and prescribed opioid dosages for an individual can fluctuate over time. Patterns in daily opioid dosage among patients prescribed long-term opioid therapy have not been previously examined. This study uses a novel application of time-series cluster analysis to characterize and visualize daily opioid dosage trajectories and associated demographic characteristics of patients newly initiated on long-term opioid therapy. We used 2018 to 2019 data from the IQVIA Longitudinal Prescription (LRx) all-payer pharmacy database, which covers 92% of retail pharmacy prescriptions dispensed in the United States. We identified a cohort of 277,967 patients newly initiated on long-term opioid therapy during 2018. Patients were stratified into 4 categories based on their mean daily dosage during a 90-day baseline period (<50, 50-89, 90-149, and ≥150 morphine milligram equivalent [MME]) and followed for a 270-day follow-up period. Time-series cluster analysis identified 2 clusters for each of the 3 baseline dosage categories <150 MME and 3 clusters for the baseline dosage category ≥150 MME. One cluster in each baseline dosage category comprised opioid dosage trajectories with decreases in dosage at the end of the follow-up period (80.7%, 98.7%, 98.7%, and 99.0%, respectively), discontinuation (58.5%, 80.0%, 79.3%, and 81.7%, respectively), and rapid tapering (50.8%, 85.8%, 87.5%, and 92.9%, respectively). These findings indicate multiple clusters of patients newly initiated on long-term opioid therapy who experience discontinuation and rapid tapering and highlight potential areas for clinician training to advance evidence-based guideline-concordant opioid prescribing, including strategies to minimize sudden dosage changes, discontinuation, or rapid tapering, and the importance of shared decision-making.
Treatment of neurogenic detrusor overactivity and overactive bladder with Botox (onabotulinumtoxinA): Development, insights, and impact
Authors: Nitti Victor , Haag-Molkenteller Cornelia , Kennelly Michael , Chancellor Michael , Jenkins Brenda , Schurch Brigitte
Published: July 2023

Neurogenic detrusor overactivity (NDO) is a complication of multiple sclerosis, spinal cord injury (SCI), stroke, head injury, and other conditions characterized by damage to the upper motor neuronal system. NDO often leads to high bladder pressure that may cause upper urinary tract damage and urinary incontinence (UI). Prior to the use of onabotulinumtoxinA, oral anticholinergics and surgical augmentation cystoplasty were the treatment options. Overactive bladder (OAB) is non-neurogenic and affects a much larger population than NDO. Both NDO and OAB negatively impact patients’ quality of life (QOL) and confer high health care utilization burdens. Early positive results from pioneering investigators who injected onabotulinumtoxinA into the detrusor of patients with SCI caught the interest of Allergan, which then initiated collaborative clinical trials that resulted in FDA approval of onabotulinumtoxinA 200U in 2011 for NDO and 100U in 2013 for patients with OAB who inadequately respond to or are intolerant of an anticholinergic. These randomized, double-blind, placebo-controlled trials for NDO showed significant improvements in UI episodes, urodynamic parameters, and QOL; the most frequent adverse events were urinary tract infection (UTI) and urinary retention. Similarly, randomized, double-blind, placebo-controlled trials of onabotulinumtoxinA 100U for OAB found significant improvements in UI episodes, treatment benefit, and QOL; UTI and dysuria were the most common adverse events. Long-term studies in NDO and OAB showed sustained effectiveness and safety with repeat injections of onabotulinumtoxinA, the use of which has profoundly improved the QOL of patients failing anticholinergic therapy and has expanded the utilization of onabotulinumtoxinA into smooth muscle.
Botulinum neurotoxins: Future innovations
Authors: Brideau-Andersen Amy , Dolly J. Oliver , Brin Mitchell F.
Published: July 2023

Botulinum neurotoxins (BoNTs) are multi-domain proteins whose potent and selective actions on nerve endings have led to innovations in both basic and clinical science. The various BoNT domains are responsible for binding to gangliosides and proteins associated with nerve cell membranes, internalization into the cell, and cleavage of one or more SNARE (
s
oluble
N
-ethylmaleimide sensitive factor
a
ttachment protein
re
ceptor) proteins necessary for vesicle docking and fusion. Novel modifications to BoNT molecules, such as the creation of chimeras, helped identify the protein domains responsible for various aspects of BoNT action, such as localized effects. Other molecular modifications have been introduced in attempts to increase the specificity of BoNTs for autonomic or sensory neurons, with the ultimate goal of optimizing therapeutic selectivity. This research, in turn, has led to the development of BoNT-based proteins that can target non-SNARE substrates such as phosphatase and tensin homolog (PTEN). Still others are developing different BoNT serotypes, subtypes, or variants that are longer- or shorter-acting or have faster onset for various clinical purposes. New formulations of BoNTs that provide convenience for both patients and physicians are under investigation. Novel clinical uses are being evaluated for onabotulinumtoxinA, including in the prevention of post-operative atrial fibrillation. All these innovations capitalize on the unique properties of BoNTs, which continue to intrigue scientists and clinicians across numerous fields of study.
The effect of brace use on balance in individuals with adolescent idiopathic scoliosis
Authors: Yilmaz Kamil , Akkoyun Sert Ozlem , Bagcaci Sinan , Kimyongok Ozan
Published: July 2023

Background:

Patients with adolescent idiopathic scoliosis (AIS) have poorer standing balance compared with their healthy peers. However, the immediate effects of the braces used in the treatment on balance remain uncertain.

Objective:

To investigate the effect of brace use on balance and weight-bearing symmetry in patients with AIS and to compare the results of different brace designs.

Study design:

Observational.

Methods:

A total of 21 patients with AIS aged 10–17 years using 10 Boston and 11 Cheneau braces participated. Immediate balance and weight-bearing symmetries of patients with and without their own braces were evaluated. Balance assessment was performed using the Sensory Organization Test (SOT) on a computerized dynamic posturography device. Weight-bearing symmetry was evaluated on the computerized dynamic posturography device with the knees in full extension, with the knees flexed at 30°, 60°, and 90°.

Results:

Regardless of its design, it was found that brace use had no effect on immediate balance and weight-bearing symmetry (p > 0.05). Of the patients using a Boston brace, unbraced SOT condition 2, 3, and 5 and composite scores were found to be higher than their braced scores (p < 0.05). Braced SOT condition 3 scores of the patients using a Cheneau brace were higher than those using a Boston brace (p = 0.037). Brace use and brace types have no statistical effect on weight-bearing symmetry.

Conclusions:

It was observed that brace use in patients with AIS has no positive effect on immediate balance and weight-bearing symmetry, and the use of Boston brace negatively affects immediate balance scores and increases visual dependence.
Cardiovascular health among persons with HIV without existing atherosclerotic cardiovascular disease
Authors: Mclaughlin Megan M. , Durstenfeld Matthew S. , Gandhi Monica , Greene Meredith , Ma Yifei , Beatty Alexis L. , Hsue Priscilla Y.
Published: July 2023

Objectives:

We sought to characterize atherosclerotic cardiovascular disease (ASCVD) risk and metrics of CV health in persons with HIV (PWH) eligible for primary prevention of ASCVD.

Design:

Cross-sectional study of PWH 40 years and older without documented ASCVD who received care at three HIV clinics in San Francisco from 2019-2022.

Methods:

We used ICD-10 codes and electronic health record data to assess ASCVD risk and CV health, as defined by the American Heart Association's Life's Essential 8 (LE8) metrics for nicotine exposure, body mass index (BMI), lipids, glucose, and blood pressure (BP).

Results:

Among 2567 PWH eligible for primary prevention of ASCVD, the median age was 55 years, 14% were female, and 95% were on antiretroviral therapy. Seventy-seven percent had undergone complete assessment of ASCVD risk factors, and 50% of these patients had intermediate-high ASCVD risk (≥7.5%). Of those with hypertension, 39% were prescribed an anti-hypertensive. Among those eligible, 43% were prescribed a statin. The mean LE8 CV health score (0 to 100 [best health]) was 55.1 for nicotine exposure, 71.3 for BMI, 70.4 for lipids, 81.2 for blood glucose, 56.0 for BP, with an average score of 66.2 across the five metrics. Patients with Medicare insurance, Black patients, and those with sleep apnea and chronic kidney disease had on average lower CV health scores; patients with undetectable viral loads had higher CV health scores.

Conclusions:

We highlight opportunities for improving primary prevention of ASCVD among PWH, especially in the areas of guideline-based therapy, nicotine exposure, and BP control.