Companion Article Research Articles

Pharmacotherapy of acute ST-elevation myocardial infarction and the pharmacist's role, part 1: Patient presentation through revascularization.

In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. Key pharmacotherapeutic modalities and considerations for the patient with ST-elevation myocardial infarction (STEMI) across the critical initial phases of care are reviewed. Despite established value in the emergency department (ED), cardiac care, and intensive care settings, there is currently little published literature describing or supporting clinical pharmacist roles in the acute management of STEMI. The high-risk period from hospital presentation through revascularization and stabilization involves complex pharmacotherapeutic decision points, many operational medication needs, and multiple layers of quality oversight. While rife with opportunities for pharmacists to optimize care, this timeframe appears inconsistently targeted by clinical pharmacy services, which may halt after ED evaluation and then resume upon postcatheterization cardiac unit admission. Herein we review the key pharmacotherapeutic modalities and considerations for the patient with STEMI across the critical initial phases of care. These include supportive therapies prior to revascularization, the host of antithrombotics involved in revascularization by percutaneous coronary intervention and/or fibrinolysis, and other periprocedural medications. Important practice guidelines and clinical resources are summarized from the clinical pharmacist perspective, and roles and responsibilities of the responding pharmacist are suggested. A companion article will extend the review to periprocedural adverse event management, key early decision-making regarding long-term risk reduction, and pharmacist involvement in institutional quality improvement efforts. We aim to support inpatient pharmacy departments in advancing clinical services for this critical patient population, and we call for further research delineating pharmacist impact on patient and institutional STEMI outcomes. Patients presenting with STEMI rapidly traverse multiple phases of care and receive a host of antithrombotic and supportive medications during acute management, presenting many important pharmacotherapeutic decision points and roles for pharmacists.

Pharmacotherapy of acute ST-elevation myocardial infarction and the pharmacist's role, part 2: Complications, postrevascularization care, and quality improvement.

In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. Key pharmacotherapeutic modalities and considerations for the patient with ST-elevation myocardial infarction (STEMI) across the later phases of inpatient care are reviewed. Published descriptions and validation of clinical pharmacist roles specific to the acute management of STEMI are limited. This high-risk period from presentation through revascularization, stabilization, and hospital discharge involves complex pharmacotherapeutic decision points, many operational medication needs, and multiple layers of quality oversight. A companion article reviewed STEMI pharmacotherapy from emergency department presentation through revascularization. Herein we complete the pharmacotherapy review for the STEMI patient across the inpatient phases of care, including the management of peri-infarction complications with vasoactive and antiarrhythmic agents, considerations for postrevascularization antithrombotics, and assessments of supportive therapies and secondary prevention. Key guideline recommendations and literature developments are summarized from the clinical pharmacist's perspective alongside suggested pharmacist roles and responsibilities. Considerations for successful hospital discharge after STEMI and pharmacist involvement in associated institutional quality improvement efforts are also provided. We aim to support inpatient pharmacy departments in advancing clinical services for this critical patient population and call for further research delineating pharmacists' impact on patient and institutional STEMI outcomes.

A New Model to Advance a Collaborative Clinical Education Placement Process: A Consortium Core Network.

The 2014 Clinical Education (CE) Summit and subsequent scholarly work prompted development of collaborative, mutually beneficial, innovative processes to mitigate CE challenges and inefficiencies. Contemporary practice advocates for collaboration among physical therapist (PT) academic programs (Programs) and clinical partners (Partners) to create a sustainable placement process with mutual benefits for stakeholders. The purpose of this article is to describe the design and implementation of the Ohio Kentucky Consortium of Physical Therapy Educators (Consortium) Consortium Core Network's (CCN) centralized PT CE Placement Process (PT-CEPP) model and share participants' experience perspectives. The Consortium established the CCN and a Steering Committee, representing stakeholders, and designed a novel 5-phase centralized PT-CEPP model, in Exxat, an educational management platform. The phases included Request, Offer, Placement, Reallocation, and Confirmation and Release. A postimplementation Qualtrics survey was disseminated to obtain participant perspectives. Open-text survey responses were compiled, reviewed, thematically analyzed, and presented in this article (part 1). The resulting quantitative CCN PT-CEPP analyses were deferred to a companion article (part 2). The CCN participation included invited Partners (n = 101/364; 28%) and Programs (n = 14/14; 100%). During initial PT-CEPP implementation, 1,005 offers resulted in 549 CE placements. Participant perspectives from 20 of 101 SCCEs (20%) and eight of 14 DCEs (57%) were dichotomized into "Benefits and What Worked Well" and "Challenges and What Did Not Work Well." Perspectives were unique to participant roles, with partners valuing "centralization" and Programs "process." Lessons gleaned from the PT-CEPP paradigm shift to a CCN-centralized model may optimize processes and improve sustainability with future iterations.

Within Thermal Scales: The Kinetic and Energetic Pull of Chemical Entropy.

Biological systems are fundamentally containers of thermally fluctuating atoms that through unknown mechanisms are structurally layered across many thermal scales from atoms to amino acids to primary, secondary, and tertiary structures to functional proteins to functional macromolecular assemblies and up. Understanding how the irreversible kinetics (i.e., the arrow of time) of biological systems emerge from the equilibrium kinetics of constituent structures defined on smaller thermal scales is central to describing biological function. Muscle's irreversible power stroke - with its mechanochemistry defined on both the thermal scale of muscle and the thermal scale of myosin motors - provides a clear solution to this problem. Individual myosin motors function as reversible force-generating switches induced by actin binding and gated by the release of inorganic phosphate, P i . As shown in a companion article, when N individual switches thermally scale up to an ensemble of N switches in muscle, the entropy of a binary system of switches is created. We have shown in muscle that a change in state of this binary system of switches entropically drives actin-myosin binding (the switch) and muscle's irreversible power stroke, and that this simple two-state model accurately accounts for most key aspects of muscle contraction. Extending this observation beyond muscle, here I show that the chemical kinetics of an ensemble of N molecules differs fundamentally from a conventional chemical analysis of N individual molecules, describing irreversible chemical reactions as being pulled into the future by the a priori defined entropy of a binary system rather than being pushed forward by the physical occupancy of chemical states (e.g., mass action).

MultIHeaTS: A Fast and Stable Thermal Solver for Multilayered Planetary Surfaces

A fully implicit scheme is proposed for solving the heat equation in 1D heterogeneous media, available as a computationally efficient open-source Python code. The algorithm uses finite differences on an irregular grid and is unconditionally stable due to the implicit formulation. The thermal solver is validated against a stiff analytical solution, demonstrating its robustness in handling stiff initial conditions. Its general applicability for heterogeneous cases is demonstrated through its use in a planetary surface scenario with nonlinear boundary conditions induced by blackbody thermal emission. MultIHeaTS's advantageous stability allows for computation times up to 100 times faster than Spencer’s explicit solver, making it ideal for simulating processes on large timescales. This solver is used to compare the thermal signatures of homogeneous and bilayer profiles on Europa. Results show that homogeneous materials cannot reproduce the thermal signature observed in bilayer profiles, emphasizing the need for multilayer solvers. In order to optimize the scientific return of a space mission, we propose a strategy made of three local time observations that is enough to identify bilayer media, for instance, for the next missions to the Jovian system. A second application of the solver is the estimation of the temperature profile of Europa’s near surface (first 10s m) throughout a 1 million yr simulation with varying orbital parameters. The probability distribution of temperature through depth is obtained. Among its various applications, MultIHeaTS serves as the core thermal solver in a multiphysics simulation model detailed in the companion article by C. Mergny & F. Schmidt.

PH-independent effects of acid suppressants in dogs and cats: a One Health perspective and case for further investigation.

Our understanding of the use of acid-suppressant drugs (ASDs) in companion animals is largely centered around the treatment of acid-related disorders including gastroesophageal reflux and gastrointestinal ulceration. The companion article by Grady et al, JAVMA, October 2024, summarizes our current knowledge of the efficacy of and indications for ASDs for the treatment of acid-related disorders. Far less is understood about both the benefits of and potential for adverse effects of ASDs outside of the parietal cell including those directed toward inflammation and immunomodulation, tumorigenesis, fibrosis, and oxidative stress. In this Currents in One Health article, we summarize the pH-independent properties of ASDs as demonstrated in studies conducted largely in humans and rodents. The objective of this review is to highlight and increase awareness of the pH-independent effects of ASDs to elucidate the need for further veterinary research in this area.

Rational curvature invariants for 2-complexes

New invariants for two-dimensional cell complexes are defined, which can be interpreted as curvature bounds. These invariants are proved to be rational and computable in a companion article. This document is a survey that collects theorems about these invariants, computes examples and lays out a programme of conjectures.

Through the Looking Glass Darkly: How May AI Models Influence Future Underwriting?

Applications of Artificial Intelligence (AI) deep-learning models to screening for clinical conditions continue to evolve. Instances provided in this treatise include using a simple one-view PA chest radiograph to screen for Type 2 Diabetes Mellitus (T2DM), congestive heart failure, valvular heart disease, and to assess mortality in asymptomatic persons with respiratory diseases. This technology incorporates hundreds of thousands of CXRs into a convoluted neural network and is generally named AI CXR. As an example, the AUROC (Area Under Receiving Operator Characteristic) of screening for T2DM was 0.84, with sensitivity and specificities that exceed those of the United States Preventative Services Task Force (USPSTF) guidelines for screening with HBA1c or blood glucose studies. The AUROC's for diagnosing ejection fractions less than 40% was 0.92, and for detecting valvular heart diseases was 0.87. The potential implications for underwriting life and disability policies may be significant. A companion article in the Journal of Insurance Medicine addresses this same technology using a simple 12-lead ECG, generally named AI ECGs.

Beyond School Climate: Validating the School as a Protective Factor-Brief Survey.

The conceptual framework for School as a Protective Factorapproach was presented in a companion article in this issue of the journal. The current article describes the validation of the School as a Protective Factor-Brief (SPF-Brief), a 13-item survey measuring the 3 core constructs and 13 defining characteristics of this framework. The SPF-Brief was validated through 2 studies. The developmental study used a longitudinal design including 1349 participants who completed surveys over 5 semesters, while the validation study used a cross-sectional design with 2775 participants. Both studies included middle and high school students. Factor analysis, growth model analysis, criterion-related validation, and outcome analysis were employed. Analyses provided strong evidence supporting the reliability and validity of the instrument and conceptual framework. Higher SPF-Brief scores were associated with higher math grades, English grades, and quality of life, as well as lower rates of anxiety, depression, conduct disorder, alcohol, e-cigarette, tobacco, and cannabis use. Effect size estimates ranged from moderate to strong. These findings suggest the utility of the SPF-Brief instrument and the School as a Protective Factor framework. Together, they may offer advantages to the traditional school climate approach.

Survey Methodology for Data Collection and Analysis in Nutrition and Dietetics Research

This article is part of a series of articles in the Journal of the Academy of Nutrition and Dietetics exploring the importance of research design, epidemiological methods, and statistical analysis as applied to nutrition and dietetics research. The purpose of this ongoing statistical portfolio is to assist registered dietitian nutritionists and nutrition and dietetic technicians, registered with interpreting nutrition research and applying scientific principles to produce high-quality data analysis. A survey is a systematic method for collecting reportable information on a topic of interest. Developing, adapting, and conducting survey research is a complex process; its aim is to collect accurate and useful data for the intended purpose and context. This article, which accompanies a companion article on electronic survey research, is an overview of survey methodology for data collection and analysis in nutrition and dietetics research. Its purpose is to highlight the general principles and components of survey development and survey administration that would maximize the validity of the data obtained. The goal is to provide a practical guide on the design and implementation of a survey as a method for data collection. Supporting figures are provided for use in direct application by practitioners and students.

Modal algebra of multirelations

Abstract We formalize the modal operators from the concurrent dynamic logics of Peleg, Nerode and Wijesekera in a multirelational algebraic language based on relation algebras and power allegories, using relational approximation operators on multirelations developed in a companion article. We relate Nerode and Wijesekera’s box operator with a relational approximation operator for multirelations and two related operators that approximate multirelations by different kinds of deterministic multirelations. We provide an algebraic soundness proof of Goldblatt’s axioms for concurrent dynamic logic and one for a multirelational Hoare logic based on Nerode and Wijesekera’s box as applications.

Entropy and Thermodynamic Temperature in Nonequilibrium Classical Thermodynamics as Immediate Consequences of the Hahn–Banach Theorem: II Properties

In a companion article it was shown in a certain precise sense that, for any thermodynamical theory that respects the Kelvin–Planck second law, the Hahn–Banach theorem immediately ensures the existence of a pair of continuous functions of the local material state—a specific entropy (entropy per mass) and a thermodynamic temperature—that together satisfy the Clausius–Duhem inequality for every process. There was no requirement that the local states considered be states of equilibrium. This article addresses questions about properties of the entropy and thermodynamic temperature functions so obtained: To what extent do such temperature functions provide a faithful reflection of “hotness”? In precisely which Kelvin–Planck theories is such a temperature function essentially unique, and, among those theories, for which is the entropy function also essentially unique? What is a thermometer for a Kelvin–Planck theory, and, for the theory, what properties does the existence of a thermometer confer? In all of these questions, the Hahn–Banach Theorem again plays a crucial role.

The Doppler wind, temperature, and aerosol RMR lidar system at Kühlungsborn, Germany – Part 1: Technical specifications and capabilities

Abstract. This paper describes the technical specifications of the extensions made to the middle-atmospheric lidar facility at the Leibniz Institute of Atmospheric Physics in Kühlungsborn, Germany (54.12° N, 11.77° E). The upgrade complements the existing daylight-capable Rayleigh–Mie–Raman (RMR) temperature lidar with a nighttime-only RMR wind–temperature lidar. The new system comprises an independent lidar with laser, telescopes, and detectors, which is synchronized with and adapted to the (old) temperature lidar. As a result, with the combination of RMR lidars the atmosphere is probed with three (vertical and tilted) beams. This work intends to highlight the recent innovations in the construction of a Doppler–Rayleigh lidar system using the single-edge iodine-cell technique, which allows for the simultaneous measurement of wind, temperature, and aerosols. We will detail supporting subsystems that allow for a high degree of lidar automation and concisely provide key technical information about the system that will support readers in the development of additional RMR wind–temperature lidar systems. We show an example of time-resolved temperature and wind soundings reaching up to ∼ 90 km. These data agree well with ECMWF-IFS profiles between 35 and ∼ 50 km but show a much larger variability above. In the companion article, we will present the algorithm design and uncertainty budgets associated with the data processing chain.

Antiviral cellular therapy for enhancing T-cell reconstitution before or after hematopoietic stem cell transplantation (ACES): a two-arm, open label phase II interventional trial of pediatric patients with risk factor assessment

Viral infections remain a major risk in immunocompromised pediatric patients, and virus-specific T cell (VST) therapy has been successful for treatment of refractory viral infections in prior studies. We performed a phase II multicenter study (NCT03475212) for the treatment of pediatric patients with inborn errors of immunity and/or post allogeneic hematopoietic stem cell transplant with refractory viral infections using partially-HLA matched VSTs targeting cytomegalovirus, Epstein-Barr virus, or adenovirus. Primary endpoints were feasibility, safety, and clinical responses (>1 log reduction in viremia at 28 days). Secondary endpoints were reconstitution of antiviral immunity and persistence of the infused VSTs. Suitable VST products were identified for 75 of 77 clinical queries. Clinical responses were achieved in 29 of 47 (62%) of patients post-HSCT including 73% of patients evaluable at 1-month post-infusion, meeting the primary efficacy endpoint (>52%). Secondary graft rejection occurred in one child following VST infusion as described in a companion article. Corticosteroids, graft-versus-host disease, transplant-associated thrombotic microangiopathy, and eculizumab treatment correlated with poor response, while uptrending absolute lymphocyte and CD8 T cell counts correlated with good response. This study highlights key clinical factors that impact response to VSTs and demonstrates the feasibility and efficacy of this therapy in pediatric HSCT.

A measles-vectored vaccine candidate expressing prefusion-stabilized SARS-CoV-2 spike protein brought to phase I/II clinical trials: candidate selection in a preclinical murine model.

In the early COVID-19 pandemic with urgent need for countermeasures, we aimed at developing a replicating viral vaccine using the highly efficacious measles vaccine as vector, a promising technology with prior clinical proof of concept. Building on our successful pre-clinical development of a measles virus (MV)-based vaccine candidate against the related SARS-CoV, we evaluated several recombinant MV expressing codon-optimized SARS-CoV-2 spike glycoprotein. Candidate V591 expressing a prefusion-stabilized spike through introduction of two proline residues in HR1 hinge loop, together with deleted S1/S2 furin cleavage site and additional inactivation of the endoplasmic reticulum retrieval signal, was the most potent in eliciting neutralizing antibodies in mice. After single immunization, V591 induced similar neutralization titers as observed in sera of convalescent patients. The cellular immune response was confirmed to be Th1 skewed. V591 conferred long-lasting protection against SARS-CoV-2 challenge in a murine model with marked decrease in viral RNA load, absence of detectable infectious virus loads, and reduced lesions in the lungs. V591 was furthermore efficacious in an established non-human primate model of disease (see companion article [S. Nambulli, N. Escriou, L. J. Rennick, M. J. Demers, N. L. Tilston-Lunel et al., J Virol 98:e01762-23, 2024, https://doi.org/10.1128/jvi.01762-23]). Thus, V591 was taken forward into phase I/II clinical trials in August 2020. Unexpected low immunogenicity in humans (O. Launay, C. Artaud, M. Lachâtre, M. Ait-Ahmed, J. Klein et al., eBioMedicine 75:103810, 2022, https://doi.org/10.1016/j.ebiom.2021.103810) revealed that the underlying mechanisms for resistance or sensitivity to pre-existing anti-measles immunity are not yet understood. Different hypotheses are discussed here, which will be important to investigate for further development of the measles-vectored vaccine platform.IMPORTANCESARS-CoV-2 emerged at the end of 2019 and rapidly spread worldwide causing the COVID-19 pandemic that urgently called for vaccines. We developed a vaccine candidate using the highly efficacious measles vaccine as vector, a technology which has proved highly promising in clinical trials for other pathogens. We report here and in the companion article by Nambulli et al. (J Virol 98:e01762-23, 2024, https://doi.org/10.1128/jvi.01762-23) the design, selection, and preclinical efficacy of the V591 vaccine candidate that was moved into clinical development in August 2020, 7 months after the identification of SARS-CoV-2 in Wuhan. These unique in-human trials of a measles vector-based COVID-19 vaccine revealed insufficient immunogenicity, which may be the consequence of previous exposure to the pediatric measles vaccine. The three studies together in mice, primates, and humans provide a unique insight into the measles-vectored vaccine platform, raising potential limitations of surrogate preclinical models and calling for further refinement of the platform.

A measles-vectored vaccine candidate expressing prefusion-stabilized SARS-CoV-2 spike protein brought to phase I/II clinical trials: protection of African green monkeys from COVID-19 disease.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged at the end of 2019 and is responsible for the largest human pandemic in 100 years. Thirty-four vaccines are currently approved for use worldwide, and approximately 67% of the world population has received a complete primary series of one, yet countries are dealing with new waves of infections, variant viruses continue to emerge, and breakthrough infections are frequent secondary to waning immunity. Here, we evaluate a measles virus (MV)-vectored vaccine expressing a stabilized prefusion SARS-CoV-2 spike (S) protein (MV-ATU3-S2PΔF2A; V591) with demonstrated immunogenicity in mouse models (see companion article [J. Brunet, Z. Choucha, M. Gransagne, H. Tabbal, M.-W. Ku et al., J Virol 98:e01693-23, 2024, https://doi.org/10.1128/jvi.01693-23]) in an established African green monkey model of disease. Animals were vaccinated with V591 or the control vaccine (an equivalent MV-vectored vaccine with an irrelevant antigen) intramuscularly using a prime/boost schedule, followed by challenge with an early pandemic isolate of SARS-CoV-2 at 56 days post-vaccination. Pre-challenge, only V591-vaccinated animals developed S-specific antibodies that had virus-neutralizing activity as well as S-specific T cells. Following the challenge, V591-vaccinated animals had lower infectious virus and viral (v) RNA loads in mucosal secretions and stopped shedding virus in these secretions earlier. vRNA loads were lower in these animals in respiratory and gastrointestinal tract tissues at necropsy. This correlated with a lower disease burden in the lungs as quantified by PET/CT at early and late time points post-challenge and by pathological analysis at necropsy.IMPORTANCESevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the largest human pandemic in 100 years. Even though vaccines are currently available, countries are dealing with new waves of infections, variant viruses continue to emerge, breakthrough infections are frequent, and vaccine hesitancy persists. This study uses a safe and effective measles vaccine as a platform for vaccination against SARS-CoV-2. The candidate vaccine was used to vaccinate African green monkeys (AGMs). All vaccinated AGMs developed robust antigen-specific immune responses. After challenge, these AGMs produced less virus in mucosal secretions, for a shorter period, and had a reduced disease burden in the lungs compared to control animals. At necropsy, lower levels of viral RNA were detected in tissue samples from vaccinated animals, and the lungs of these animals lacked the histologic hallmarks of SARS-CoV-2 disease observed exclusively in the control AGMs.

Current challenges in school-based health center care: COVID, mental health care, immigrant youth, expansion of telemedicine

School based health centers (SBHCs) have been providing preventive, acute and chronic care in schools across the United States (US) for the past 40 years. A discussion of that care is provided in a companion article to this one. Several major societal issues of the 2020s, affecting the care provided in SBHCs, have taken place over the past 4 years. These issues, which will be discussed in this article, include the following: 1. The COVID pandemic had a major impact on utilization and services required at SBHCs, both at the peak of the pandemic, when schools were closed and since the peak of the pandemic, when schools reopened. 2. The transformation of mental health services, due both to increasing mental health needs of youth, as well as progression to new therapeutic modalities, has required expansion of services provided at SBHCs. 3. New immigrant health care needs and services have required a response by SBHCs to the substantial increase of new immigrants, most of whom are impacted by significant trauma, entering public schools nationally. 4. Telehealth integration into SBHC medical and mental health services, and its expansion to incorporate new technologies, have provided avenues for increased provision of services by SBHCs.

Pathologic maternal and neonatal outcomes associated with programmed embryo transfer.

In this first of two companion papers, we critically review the evidence recently published in the primary literature, which addresses adverse maternal and neonatal pregnancy outcomes associated with programmed embryo transfer cycles. We next consider whether these pathological pregnancy outcomes might be attributable to traditional risk factors, unknown parental factors, embryo culture, culture duration, or cryopreservation. Finally, in the second companion article, we explore potential etiologies and suggest strategies for prevention. Comprehensive review of primary literature. The preponderance of retrospective and prospective observational studies suggests that increased risk for hypertensive disorders of pregnancy (HDP) and preeclampsia in assisted reproduction involving autologous embryo transfer is associated with programmed cycles. For autologous frozen embryo transfer (FET) and singleton live births, the risk of developing HDP and preeclampsia, respectively, was less for true or modified natural and stimulated cycles relative to programmed cycles: OR 0.63 [95% CI (0.57-0.070)] and 0.44 [95% CI (0.40-0.50)]. Though data are limited, the classification of preeclampsia associated with programmed autologous FET was predominantly late-onset or term disease. Other adverse pregnancy outcomes associated with autologous FET, especially programmed cycles, included increased prevalence of large for gestational age infants and macrosomia, as well as higher birth weights. In one large registry study, FET was associated with fetal overgrowth of a symmetrical nature. Postterm birth and placenta accreta not associated with prior cesarean section, uterine surgery, or concurrent placenta previa were also associated with autologous FET, particularly programmed cycles. The heightened risk of these pathologic pregnancy outcomes in programmed autologous FET does not appear to be attributable to traditional risk factors, unknown parental factors, embryo culture, culture duration, or cryopreservation, although the latter may contribute a modestdegree of increased risk for fetal overgrowth and perhaps HDP and preeclampsia in FET irrespective of the endometrial preparation. Programmed autologous FET is associated with an increased risk of several, seemingly diverse, pathologic pregnancy outcomes including HDP, preeclampsia, fetal overgrowth, postterm birth, and placenta accreta. Though the greater risk for preeclampsia specifically associated with programmed autologous FET appears to be well established, further research is needed to substantiate the limited data currently available suggesting that the classification of preeclampsia involved is predominately late-onset or term. If substantiated, then this knowledge could provide insight into placental pathogenesis, which has been proposed to differ between early- and late-onset or term preeclampsia (see companion paper for a discussion of potential mechanisms). If a higher prevalence of preeclampsia with severe features as suggested by some studies is corroborated in future investigations, then the danger to maternal and fetal/neonatal health is considerably greater with severe disease, thus increasing the urgency to find preventative measures. Presupposing significant overlap of these diverse pathologic pregnancy outcomes within subjects who conceive by programmed embryo transfer, there may be common etiologies.

Practical Tips on Epidermolysis Bullosa for Caregivers: Part 2.

The heritable condition epidermolysis bullosa (EB) is a rare but potentially devastating and life-threatening condition that is characterized primarily by cutaneous fragility, manifested when the dermis and epidermis fail to adhere properly. EB has no cure, and because of its rarity, few healthcare professionals have experience in treating it. Most families with an EB child are forced to rely on family caregiving which can be disruptive to family routines but, more importantly,place enormous time and emotional and financial burdens on the family. EB can be extremely painful, and families are often caught in the bind of trying to manage overwhelming financial burdens in an effort to help their children cope with excruciating pain. For many years, the nonprofit organization NoBabyBlisters.org has worked on five continents with families caring for EB children. Many of these families reside in under-developed nations with hot climates and limited healthcare resources. Over time, the healthcare professionals with NoBabyBlisters.org have worked with EB families both internationally and in the United States to develop a series of simple tips or "hacks" that may provide relief or great benefit to these children. The objective of this article is to share these field-tested tips with a wider audience. This is not a scientific study or a systematic review and is offered as a companion article to an earlier article on the same subject.

Proportionality in Causation, Part II: Applications and Challenges

AbstractIn ‘Proportionality in Causation, Part I: Theories’, I presented various ways of understanding the idea that causes which are ‘proportional’ to their effects are in some sense preferable. In this companion article, I discuss the principal applications of the resulting theories of proportionality, and the challenges they face.