Boat encounter with the 2019 Java bioluminescent milky sea: Views from on-deck confirm satellite detection.

"Milky seas" are massive swaths of uniformly and steadily glowing ocean seen at night. The phenomenon is thought to be caused by luminous bacteria, but details of milky sea composition, structure, cause, and implications in nature remain largely uncertain. Between late July and early September 2019, specialized low-light satellite sensors detected a possible bioluminescent milky sea south of Java, Indonesia, spanning >100,000 km2. Upon learning of these findings, crew members of the yacht Ganesha reached out to confirm and share details of their personal encounter with this same event. Here, we document Ganesha's experience as recalled by the crew, compare their course to satellite data, and assess their photography of this milky sea.

The 21st Century CURES Act in Pediatric Gastroenterology: Problems, Solutions, and Preliminary Guidance.

ABSTRACT: The information blocking (IB) prohibition component of the 21st Century CURES Act (21CCA) comes into effect April 5, 2021, which gives patients and their families near-instant access to almost all clinical notes, lab results, and health data. Exceptions to IB prohibition include risk of harm and patient privacy, but violations can be punished by a fine of up to $1,000,000.00. A committee of pediatric gastroenterologists reviewed the 21CCA regulation and compared local practice policies. Pediatric practitioners need to understand how age will affect local information release policies and to know which note types are released, paying special consideration to trainee notes and confidential information. Extraneous detail should be removed from notes, emotional labeling be avoided, and objective statements be made when referring to the care of other providers. Awareness of the 21CCA provides pediatric gastroenterologists with the opportunity to adapt their medical documentation practices to accommodate the new law.

Upper atmospheric gravity wave details revealed in nightglow satellite imagery.

Gravity waves (disturbances to the density structure of the atmosphere whose restoring forces are gravity and buoyancy) comprise the principal form of energy exchange between the lower and upper atmosphere. Wave breaking drives the mean upper atmospheric circulation, determining boundary conditions to stratospheric processes, which in turn influence tropospheric weather and climate patterns on various spatial and temporal scales. Despite their recognized importance, very little is known about upper-level gravity wave characteristics. The knowledge gap is mainly due to lack of global, high-resolution observations from currently available satellite observing systems. Consequently, representations of wave-related processes in global models are crude, highly parameterized, and poorly constrained, limiting the description of various processes influenced by them. Here we highlight, through a series of examples, the unanticipated ability of the Day/Night Band (DNB) on the NOAA/NASA Suomi National Polar-orbiting Partnership environmental satellite to resolve gravity structures near the mesopause via nightglow emissions at unprecedented subkilometric detail. On moonless nights, the Day/Night Band observations provide all-weather viewing of waves as they modulate the nightglow layer located near the mesopause (∼ 90 km above mean sea level). These waves are launched by a variety of physical mechanisms, ranging from orography to convection, intensifying fronts, and even seismic and volcanic events. Cross-referencing the Day/Night Band imagery with conventional thermal infrared imagery also available helps to discern nightglow structures and in some cases to attribute their sources. The capability stands to advance our basic understanding of a critical yet poorly constrained driver of the atmospheric circulation.

ER Chaperone BiP/GRP78 Is Required for Myelinating Cell Survival and Provides Protection during Experimental Autoimmune Encephalomyelitis.

Myelinating cells synthesize large amounts of membrane protein through the secretory pathway, which makes these cells particularly sensitive to perturbations of the endoplasmic reticulum (ER). Ig binding protein (BiP), also known as glucose-regulated protein 78 (GRP78), is a critical ER chaperone that also plays a pivotal role in controlling the cellular response to ER stress. To examine the potential importance of BiP to myelinating cells, we used a conditional knock-out approach to BiP gene inactivation in oligodendrocytes during development, in adulthood, and in response to experimental autoimmune encephalomyelitis (EAE), an animal model of the inflammatory demyelinating disorder multiple sclerosis (MS). During development, mice lacking functional BiP gene expression in oligodendrocytes developed tremors and ataxia and died before reaching maturity. When BiP gene inactivation in oligodendrocytes was initiated in adulthood, the mice displayed severe neurological symptoms including tremors and hind-limb paralysis. The inactivation of BiP in oligodendrocytes during development or in adulthood resulted in oligodendrocyte loss and corresponding severe myelin abnormalities. Mice heterozygous for the oligodendrocyte-specific inactivation of BiP, which were phenotypically normal without evidence of neuropathology, displayed an exacerbated response to EAE that correlated with an increased loss of oligodendrocytes. Furthermore, mice in which the BiP gene was specifically inactivated in developing Schwann cells displayed tremor that progressed to hindlimb paralysis, which correlated with diminished numbers of myelinating Schwann cells and severe PNS hypomyelination. These studies demonstrate that BiP is critical for myelinating cell survival and contributes to the protective response of oligodendrocyte against inflammatory demyelination.

Earth-viewing satellite perspectives on the Chelyabinsk meteor event.

Large meteors (or superbolides [Ceplecha Z, et al. (1999) Meteoroids 1998:37-54]), although rare in recorded history, give sobering testimony to civilization's inherent vulnerability. A not-so-subtle reminder came on the morning of February 15, 2013, when a large meteoroid hurtled into the Earth's atmosphere, forming a superbolide near the city of Chelyabinsnk, Russia, ∼1,500 km east of Moscow, Russia [Ivanova MA, et al. (2013) Abstracts of the 76th Annual Meeting of the Meteoritical Society, 5366]. The object exploded in the stratosphere, and the ensuing shock wave blasted the city of Chelyabinsk, damaging structures and injuring hundreds. Details of trajectory are important for determining its specific source, the likelihood of future events, and potential mitigation measures. Earth-viewing environmental satellites can assist in these assessments. Here we examine satellite observations of the Chelyabinsk superbolide debris trail, collected within minutes of its entry. Estimates of trajectory are derived from differential views of the significantly parallax-displaced [e.g., Hasler AF (1981) Bull Am Meteor Soc 52:194-212] debris trail. The 282.7 ± 2.3° azimuth of trajectory, 18.5 ± 3.8° slope to the horizontal, and 17.7 ± 0.5 km/s velocity derived from these satellites agree well with parameters inferred from the wealth of surface-based photographs and amateur videos. More importantly, the results demonstrate the general ability of Earth-viewing satellites to provide valuable insight on trajectory reconstruction in the more likely scenario of sparse or nonexistent surface observations.

Fertility preservation in patients receiving cyclophosphamide therapy for renal disease.

Cyclophosphamide continues to have an important role in the treatment of renal disease, including nephrotic syndrome and lupus nephritis, despite known complications of gonadotoxicity and potential infertility in both male and female patients. It is important that the physician recommending this therapy mitigates the effect of the drug on fertility by adhering to recommendations on dosing limits and offering fertility-preserving strategies. In addition to well-established methods, such as sperm banking and embryo cryopreservation, advances in reproductive technology have yielded strategies such as oocyte cryopreservation, resulting in more fertility-preserving options for the pediatric patient. Despite these advances, there continues to be a significant barrier to referral and access to sperm banks and fertility specialists. These issues are further complicated by ethical issues associated with the treatment of pediatric patients. In this review we explore the development of recommended dosing limits and include a discussion of the available fertility-preserving methods, strategies for increasing access to fertility specialists, and the ethical considerations facing the pediatric healthcare provider.

Suomi satellite brings to light a unique frontier of nighttime environmental sensing capabilities.

Most environmental satellite radiometers use solar reflectance information when it is available during the day but must resort at night to emission signals from infrared bands, which offer poor sensitivity to low-level clouds and surface features. A few sensors can take advantage of moonlight, but the inconsistent availability of the lunar source limits measurement utility. Here we show that the Day/Night Band (DNB) low-light visible sensor on the recently launched Suomi National Polar-orbiting Partnership (NPP) satellite has the unique ability to image cloud and surface features by way of reflected airglow, starlight, and zodiacal light illumination. Examples collected during new moon reveal not only meteorological and surface features, but also the direct emission of airglow structures in the mesosphere, including expansive regions of diffuse glow and wave patterns forced by tropospheric convection. The ability to leverage diffuse illumination sources for nocturnal environmental sensing applications extends the advantages of visible-light information to moonless nights.

CryoEM structures of the human CLC-2 voltage-gated chloride channel reveal a ball-and-chain gating mechanism.

CLC-2 is a voltage-gated chloride channel that contributes to electrical excitability and ion homeostasis in many different tissues. Among the nine mammalian CLC homologs, CLC-2 is uniquely activated by hyperpolarization, rather than depolarization, of the plasma membrane. The molecular basis for the divergence in polarity of voltage gating among closely related homologs has been a long-standing mystery, in part because few CLC channel structures are available. Here, we report cryoEM structures of human CLC-2 at 2.46 - 2.76 Å, in the presence and absence of the selective inhibitor AK-42. AK-42 binds within the extracellular entryway of the Cl--permeation pathway, occupying a pocket previously proposed through computational docking studies. In the apo structure, we observed two distinct conformations involving rotation of one of the cytoplasmic C-terminal domains (CTDs). In the absence of CTD rotation, an intracellular N-terminal 15-residue hairpin peptide nestles against the TM domain to physically occlude the Cl--permeation pathway. This peptide is highly conserved among species variants of CLC-2 but is not present in other CLC homologs. Previous studies suggested that the N-terminal domain of CLC-2 influences channel properties via a "ball-and-chain" gating mechanism, but conflicting data cast doubt on such a mechanism, and thus the structure of the N-terminal domain and its interaction with the channel has been uncertain. Through electrophysiological studies of an N-terminal deletion mutant lacking the 15-residue hairpin peptide, we support a model in which the N-terminal hairpin of CLC-2 stabilizes a closed state of the channel by blocking the cytoplasmic Cl--permeation pathway.

Data Science as a Core Competency in Undergraduate Medical Education in the Age of Artificial Intelligence in Health Care.

The increasingly sophisticated and rapidly evolving application of artificial intelligence in medicine is transforming how health care is delivered, highlighting a need for current and future physicians to develop basic competency in the data science that underlies this topic. Medical educators must consider how to incorporate central concepts in data science into their core curricula to train physicians of the future. Similar to how the advent of diagnostic imaging required the physician to understand, interpret, and explain the relevant results to patients, physicians of the future should be able to explain to patients the benefits and limitations of management plans guided by artificial intelligence. We outline major content domains and associated learning outcomes in data science applicable to medical student curricula, suggest ways to incorporate these themes into existing curricula, and note potential implementation barriers and solutions to optimize the integration of this content.

Tobacco use in Crohn's disease patients and association with disease outcomes in the United States Medicaid population, 2010-2019.

Background and Aim: To identify demographic factors associated with tobacco use in Crohn's disease (CD) patients in the US Medicaid population and examine how tobacco use affects disease outcomes. Methods: We included Medicaid-eligible patients who had ≥1 ICD code for CD, and 1 year of eligibility before and after the initial encounter. We used ICD codes to identify tobacco use with respect to the time of diagnosis and used logistic regression to identify the association between age, sex, and race with tobacco use at any point before diagnosis and after diagnosis, and determine the association of tobacco use before and after diagnosis on disease outcomes. Results: We identified 98 176 eligible patients; 74.5% had no documented use of tobacco and 25.5% used tobacco at some point; 21.1% had used tobacco before their CD diagnosis and 11.8% had used tobacco after diagnosis. The population that used tobacco had a higher proportion of women, those who were White, non-Hispanic, and those in their middle ages (21-60) than the group that did not use tobacco. Tobacco use before diagnosis resulted in higher risk of hospitalization and surgery (OR: 1.85 and 1.36, respectively). Conclusion: Within the CD Medicaid population, tobacco use is more common in women than men, which differs from the general population, which is possibly a result of using diagnostic codes rather than survey data. Smoking cessation efforts should especially be directed at younger people who are at risk for CD, due to increased risk for more adverse outcomes among those who use tobacco before diagnosis.

Substance Use Among Patients With Incident Crohn's Disease in the United States, 2010 to 2019: A Medicaid Observational Study.

BACKGROUND AND AIMS: Substance use among persons with Crohn's disease (CD) is associated with symptomatic exacerbation and poorer quality of life. However, data on the prevalence of substance use among individuals with CD are limited. Therefore, our study aimed to estimate the burden of alcohol and drug use among individuals with incident CD in the United States. We also assessed the associations between CD-related interventions and substance use after CD diagnosis. METHODS: Our retrospective cohort study of the national Medicaid databases from 2010 to 2019 identified participants with newly diagnosed CD and defined substance use (ie, alcohol, opioids, cocaine, amphetamine, and cannabis) using diagnosis codes. Multivariable logistic regression models assessed the associations between CD-related interventions and substance use after CD diagnosis. RESULTS: Overall, 16.3% of Medicaid enrollees with incident CD had substance ever-use, most commonly alcohol or opioids (each 8.0%). Any substance use saw an absolute decrease of 3.8% after CD diagnosis, but changes were less than 1% in either direction for each substance. CD-related hospitalization was associated with increased alcohol or opioid use post-CD diagnosis. Surgery was associated with lower use post-CD of opioids but not alcohol. CD medications (except steroids) were generally associated with decreased post-CD alcohol or opioid use. CONCLUSION: Among Medicaid enrollees with incident CD, alcohol and opioid use were more frequent than previously published estimates for the general US population (6% and 4%, respectively, in 2019). Consequently, medical communities must be more aware of substance use by patients with CD to provide quality patient-centered care.

CryoEM structures of the human CLC-2 voltage gated chloride channel reveal a ball and chain gating mechanism.

CLC-2 is a voltage-gated chloride channel that contributes to electrical excitability and ion homeostasis in many different mammalian tissues and cell types. Among the nine mammalian CLC homologs, CLC-2 is uniquely activated by hyperpolarization, rather than depolarization, of the plasma membrane. The molecular basis for the divergence in polarity of voltage gating mechanisms among closely related CLC homologs has been a long-standing mystery, in part because few CLC channel structures are available, and those that exist exhibit high conformational similarity. Here, we report cryoEM structures of human CLC-2 at 2.46 - 2.76 Å, in the presence and absence of the potent and selective inhibitor AK-42. AK-42 binds within the extracellular entryway of the Cl--permeation pathway, occupying a pocket previously proposed through computational docking studies. In the apo structure, we observed two distinct apo conformations of CLC-2 involving rotation of one of the cytoplasmic C-terminal domains (CTDs). In the absence of CTD rotation, an intracellular N-terminal 15-residue hairpin peptide nestles against the TM domain to physically occlude the Cl--permeation pathway from the intracellular side. This peptide is highly conserved among species variants of CLC-2 but is not present in any other CLC homologs. Previous studies suggested that the N-terminal domain of CLC-2 influences channel properties via a "ball-and-chain" gating mechanism, but conflicting data cast doubt on such a mechanism, and thus the structure of the N-terminal domain and its interaction with the channel has been uncertain. Through electrophysiological studies of an N-terminal deletion mutant lacking the 15-residue hairpin peptide, we show that loss of this short sequence increases the magnitude and decreases the rectification of CLC-2 currents expressed in mammalian cells. Furthermore, we show that with repetitive hyperpolarization WT CLC-2 currents increase in resemblance to the hairpin-deleted CLC-2 currents. These functional results combined with our structural data support a model in which the N-terminal hairpin of CLC-2 stabilizes a closed state of the channel by blocking the cytoplasmic Cl--permeation pathway.

Human-Centered Design of a Clinical Decision Support for Anemia Screening in Children with Inflammatory Bowel Disease.

BACKGROUND: Inflammatory bowel disease (IBD) commonly leads to iron deficiency anemia (IDA). Rates of screening and treatment of IDA are often low. A clinical decision support system (CDSS) embedded in an electronic health record could improve adherence to evidence-based care. Rates of CDSS adoption are often low due to poor usability and fit with work processes. One solution is to use human-centered design (HCD), which designs CDSS based on identified user needs and context of use and evaluates prototypes for usefulness and usability. OBJECTIVES: this study aimed to use HCD to design a CDSS tool called the IBD Anemia Diagnosis Tool, IADx. METHODS: Interviews with IBD practitioners informed creation of a process map of anemia care that was used by an interdisciplinary team that used HCD principles to create a prototype CDSS. The prototype was iteratively tested with "Think Aloud" usability evaluation with clinicians as well as semi-structured interviews, a survey, and observations. Feedback was coded and informed redesign. RESULTS: Process mapping showed that IADx should function at in-person encounters and asynchronous laboratory review. Clinicians desired full automation of clinical information acquisition such as laboratory trends and analysis such as calculation of iron deficit, less automation of clinical decision selection such as laboratory ordering, and no automation of action implementation such as signing medication orders. Providers preferred an interruptive alert over a noninterruptive reminder. CONCLUSION: Providers preferred an interruptive alert, perhaps due to the low likelihood of noticing a noninterruptive advisory. High levels of desire for automation of information acquisition and analysis with less automation of decision selection and action may be generalizable to other CDSSs designed for chronic disease management. This underlines the ways in which CDSSs have the potential to augment rather than replace provider cognitive work.

Implementation and cost validation of a real-time benefit tool.

OBJECTIVES: To assess the accuracy of a real-time benefit tool (RTBT) that is compliant with the standards of the National Council for Prescription Drug Programs (NCPDP) in a large academic medical center. STUDY DESIGN: Observational study of electronic health records and pharmacy records from July 14, 2019, through January 14, 2020, across all ambulatory clinics and outpatient pharmacies in the health system. METHODS: Main assessments included (1) demographic characteristics of patients in whom the RTBT was used and those in whom it was not used, (2) types of changes most frequently made to medication orders upon reviewing the RTBT, and (3) comparison of the out-of-pocket costs for prescriptions vs the RTBT-generated estimates. RESULTS: The most common modifications made to prescriptions due to RTBT use were changes in days' supply (44%) and the quantity of medication (69%). In more than 98% of prescription orders, patients' out-of-pocket costs were either equivalent to or lower than the estimates generated by the RTBT. CONCLUSIONS: Current standards established by NCPDP yield accurate patient out-of-pocket estimates and could serve as a national standard for all Part D sponsors.

Honing in on bioluminescent milky seas from space.

Milky seas are a rare form of marine bioluminescence where the nocturnal ocean surface produces a widespread, uniform and steady whitish glow. Mariners have compared their appearance to a daylit snowfield that extends to all horizons. Encountered most often in remote waters of the northwest Indian Ocean and the Maritime Continent, milky seas have eluded rigorous scientific inquiry, and thus little is known about their composition, formation mechanism, and role within the marine ecosystem. The Day/Night Band (DNB), a new-generation spaceborne low-light imager, holds potential to detect milky seas, but the capability has yet to be demonstrated. Here, we show initial examples of DNB-detected milky seas based on a multi-year (2012-2021) search. The massive bodies of glowing ocean, sometimes exceeding 100,000 km2 in size, persist for days to weeks, drift within doldrums amidst the prevailing sea surface currents, and align with narrow ranges of sea surface temperature and biomass in a way that suggests water mass isolation. These findings show how spaceborne assets can now help guide research vessels toward active milky seas to learn more about them.

Telemedicine Expansion in Pediatric Gastroenterology in Response to COVID-19: Early Results of an International Physician Survey.

The COVID-19 pandemic triggered an unprecedented expansion of telemedicine, leading to development of new workflows. We conducted a survey of telemedicine practice among pediatric gastroenterology practitioners on March 26, 2020. Responses were coded and analyzed. The survey garnered 33 responses. Most centers were 3 weeks into the implementation. The most commonly used telemedicine software was Zoom followed by FaceTime, telephone, and Epic software. Provider education was through online meetings, webinars, and tip sheets. Patient education was by nonclinical staff at the time of visit scheduling or tip sheets. A major barrier was the need for patients to enroll in an electronic portal. Two thirds of practices offered telemedicine to both new and return patients. Most sites billed based on time. This represents a record of the very early response of the pediatric gastroenterology community to the COVID-19 telemedicine expansion and can inform follow-up studies.

Assessment of cost and health resource utilization for elderly patients with heart failure and diabetes mellitus.

BACKGROUND: Our aim was to examine the health resource utilization and cost of care associated with heart failure (HF) and diabetes mellitus (DM) for elderly Medicare enrollees. METHODS AND RESULTS: A retrospective case-control design was used to identify 4 groups of elderly patients with HF and DM (n = 498), HF only (n = 1089), DM only (n = 971), and no-HF and no-DM (n = 5438) using an administrative database of a large urban academic health care system. Demographic, diagnostic, health resource utilization, and cost (reimbursement) data were obtained from the Medicare claims database for the years 2000 and 2001. Disease states were identified by ICD-9 codes. Costs and health resource utilization were compared across the groups. The mean total costs were highest for the group with HF and DM ($32,676), and second highest for the HF only group ($22,230). In multivariable models that adjusted for potentially influential covariates, the group with HF and DM had a 3-fold increase in total cost compared with the group without DM and HF (relative total cost = 4.51, 95% confidence interval 3.82-5.31). CONCLUSIONS: The presence of DM has a substantial influence on the costs for managing older patients with HF. An integrated approach to management may be needed.