We use high‐resolution data from dayside passes of the Magnetospheric Multiscale (MMS) mission to create for the first time a comprehensive listing of encounters with the electron diffusion region ...(EDR), as evidenced by electron agyrotropy, ion jet reversals, and j • E′ > 0. We present an overview of these 32 EDR or near‐EDR events, which demonstrate a wide variety of observed plasma behavior inside and surrounding the reconnection site. We analyze in detail three of the 21 new EDR encounters, which occurred within a 1‐min‐long interval on 23 November 2016. The three events, which resulted from a relatively low and oscillating magnetopause velocity, exhibited large electric fields (up to ~100 mV/m), crescent‐shaped electron velocity phase space densities, large currents (≥2 μA/m2), and Ohmic heating of the plasma (~10 nW/m3). We include an Ohm's law analysis, in which we show that the divergence of the electron pressure term usually dominates the nonideal terms and is much more turbulent on the magnetosphere versus the magnetosheath side of the EDR.
Plain Language Summary
NASA's Magnetospheric Multiscale (MMS) mission was designed to study magnetic reconnection, a process in which oppositely directed magnetic fields embedded within two neighboring plasma populations annihilate, dumping magnetic energy into the plasmas. Previous missions studying reconnection in space were not fully equipped to analyze how the electrons in the plasma behave near the core of a reconnection site. This study provides MMS researchers with many new reconnection events to dissect, and calls special attention to three events that occurred back to back. Each event included is very unique and helps to fill in another piece of the reconnection puzzle. Perhaps the ultimate goal of these studies is to provide insight into methods of shutting down the reconnection process, which is known to impede attempts toward a stable nuclear fusion engine. A blueprint for stable nuclear fusion could solve mankind's energy needs forever.
Key Points
MMS mapped the EDR and near‐EDR several times during a sequence of new dayside encounters
Turbulence in Ohm's law terms is greatest on the magnetospheric‐side EDR, near the plane containing the X line and boundary normal vector
Thirty‐two EDR or near‐EDR encounters show crescent‐like enhancements in electron velocity space perpendicular to the local magnetic field
As a generalization of the optimal mass transport (OMT) approach of Benamou and Brenier's, the regularized optimal mass transport (rOMT) formulates a transport problem from an initial mass ...configuration to another with the optimality defined by the total kinetic energy, but subject to an advection-diffusion constraint equation. Both rOMT and the Benamou and Brenier's formulation require the total initial and final masses to be equal; mass is preserved during the entire transport process. However, for many applications, e.g., in dynamic image tracking, this constraint is rarely if ever satisfied. Therefore, we propose to employ an unbalanced version of rOMT to remove this constraint together with a detailed numerical solution procedure and applications to analyzing fluid flows in the brain.
•No-shows were associated with certain patient and appointment characteristics.•Younger age was associated with a higher likelihood of no-show.•Lower socioeconomic status was associated with a higher ...likelihood of no-show.•Black and other races were associated with a higher likelihood of no-show.•Longer lead times were associated with a higher likelihood of no-show.
This study aimed to identify patient and appointment characteristics associated with no-shows to new patient appointments at a US academic ophthalmology department.
Cross-sectional study.
This was a study of all adult patients with new patient appointments scheduled with an attending ophthalmologist at Penn State Eye Center between January 1st and December 31st of 2019. A multiple logistic regression model was used to assess the association between characteristics and no-show status.
Of 4,628 patients, 759 (16.4%) were no-shows. From the multiple logistic regression model, characteristics associated with no-shows were age (Odds Ratio (OR) for 18-40 years vs. >60 years: 3.41, 95% Confidence Interval (CI) 2.57, 4.51, p <0.001 and OR for 41-60 years vs. >60 years: 2.14, 95% CI 1.67, 2.74, p<0.001), median household income (OR for <$35,667 vs. >$59,445: 1.59, 95% CI 1.08, 2.34, p<0.001), insurance (OR for None vs. Medicare: 6.92, 95% CI 4.41, 10.86, p<0.001 and OR for Medicaid vs. Medicare: 1.54, 95% CI 1.18, 2.01, p=0.002), race (OR for Black vs. White: 2.62, 95% CI 2.00, 3.43, p<0.001 and OR for Other vs. White: 2.02, 95% CI 1.58, 2.59, p<0.001), and commute distance (OR for 5-10 mi vs. ≤5 mi: 1.73, 95% CI 1.17, 2.55, p=0.006). Appointments with longer lead times and scheduled with glaucoma or retina specialists were also significantly associated with greater no-shows.
Certain patient and appointment characteristics were associated with no-show status. These findings may assist in the development of targeted interventions at the patient, practice, and health system levels to improve appointment attendance.
The Children's Oncology Group study AHOD0031, a randomized phase III study, was designed to evaluate the role of early chemotherapy response in tailoring subsequent therapy in pediatric ...intermediate-risk Hodgkin lymphoma. To avoid treatment-associated risks that compromise long-term health and to maintain high cure rates, dose-intensive chemotherapy with limited cumulative doses was used.
Patients received two cycles of doxorubicin, bleomycin, vincristine, etoposide, cyclophosphamide, and prednisone (ABVE-PC) followed by response evaluation. Rapid early responders (RERs) received two additional ABVE-PC cycles, followed by complete response (CR) evaluation. RERs with CR were randomly assigned to involved-field radiotherapy (IFRT) or no additional therapy; RERs with less than CR were nonrandomly assigned to IFRT. Slow early responders (SERs) were randomly assigned to receive two additional ABVE-PC cycles with or without two cycles of dexamethasone, etoposide, cisplatin, and cytarabine (DECA). All SERs were assigned to receive IFRT.
Among 1,712 eligible patients, 4-year event-free survival (EFS) was 85.0%: 86.9% for RERs and 77.4% for SERs (P < .001). Four-year overall survival was 97.8%: 98.5% for RERs and 95.3% for SERs (P < .001). Four-year EFS was 87.9% versus 84.3% (P = .11) for RERs with CR who were randomly assigned to IFRT versus no IFRT, and 86.7% versus 87.3% (P = .87) for RERs with positron emission tomography (PET) -negative results at response assessment. Four-year EFS was 79.3% versus 75.2% (P = .11) for SERs who were randomly assigned to DECA versus no DECA, and 70.7% versus 54.6% (P = .05) for SERs with PET-positive results at response assessment.
This trial demonstrated that early response assessment supported therapeutic titration (omitting radiotherapy in RERs with CR; augmenting chemotherapy in SERs with PET-positive disease). Strategies directed toward improved response assessment and risk stratification may enhance tailoring of treatment to patient characteristics and response.
Translation elongation is essential for maintaining cellular proteostasis, and alterations in the translational landscape are associated with a range of diseases. Ribosome profiling allows detailed ...measurements of translation at the genome scale. However, it remains unclear how to disentangle biological variations from technical artifacts in these data and identify sequence determinants of translation dysregulation. Here we present Riboformer, a deep learning-based framework for modeling context-dependent changes in translation dynamics. Riboformer leverages the transformer architecture to accurately predict ribosome densities at codon resolution. When trained on an unbiased dataset, Riboformer corrects experimental artifacts in previously unseen datasets, which reveals subtle differences in synonymous codon translation and uncovers a bottleneck in translation elongation. Further, we show that Riboformer can be combined with in silico mutagenesis to identify sequence motifs that contribute to ribosome stalling across various biological contexts, including aging and viral infection. Our tool offers a context-aware and interpretable approach for standardizing ribosome profiling datasets and elucidating the regulatory basis of translation kinetics.
Patients with CKD have abnormal vascular remodeling that is a risk factor for cardiovascular disease. MicroRNAs (miRNAs) control mRNA expression intracellularly and are secreted into the circulation; ...three miRNAs (miR-125b, miR-145 and miR-155) are known to alter vascular smooth muscle cell (VSMC) proliferation and differentiation. We measured these vascular miRNAs in blood from 90 patients with CKD and found decreased circulating levels with progressive loss of eGFR by multivariate analyses. Expression of these vascular miRNAs miR-125b, miR-145, and miR-155 was decreased in the thoracic aorta in CKD rats compared to normal rats, with concordant changes in target genes of RUNX2, angiotensin II type I receptor (AT1R), and myocardin. Furthermore, the expression of miR-155 was negatively correlated with the quantity of calcification in the aorta, a process known to be preceded by vascular de-differentiation in these animals. We then examined the mechanisms of miRNA regulation in primary VSMC and found decreased expression of miR-125b, 145, and 155 in VSMC from rats with CKD compared to normal littermates but no alteration in DROSHA or DICER, indicating that the low levels of expression is not due to altered intracellular processing. Finally, overexpression of miR-155 in VSMC from CKD rats inhibited AT1R expression and decreased cellular proliferation supporting a direct effect of miR-155 on VSMC. In conclusion, we have found ex vivo and in vitro evidence for decreased expression of these vascular miRNA in CKD, suggesting that alterations in miRNAs may lead to the synthetic state of VSMC found in CKD. The decreased levels in the circulation may reflect decreased vascular release but more studies are needed to confirm this relationship.
Plasma and wave measurements from the NASA Magnetospheric Multiscale mission are presented for magnetotail reconnection events on 3 July and 11 July 2017. Linear dispersion analyses were performed ...using distribution functions comprising up to six drifting bi‐Maxwellian distributions. In both events electron crescent‐shaped distributions are shown to be responsible for upper hybrid waves near the X‐line. In an adjacent location within the 3 July event a monodirectional field‐aligned electron beam drove parallel‐propagating beam‐mode waves. In the 11 July event an electron distribution consisting of a drifting core and two crescents was shown to generate upper‐hybrid and beam‐mode waves at three different frequencies, explaining the observed broadband waves. Multiple harmonics of the upper hybrid waves were observed but cannot be explained by the linear dispersion analysis since they result from nonlinear beam interactions.
Plain Language Summary
Magnetic reconnection is a process that occurs throughout the universe in ionized gases (plasmas) containing embedded magnetic fields. This process converts magnetic energy to electron and ion energy, causing phenomena such as solar flares and auroras. The NASA Magnetospheric Multiscale mission has shown that in magnetic reconnection regions there are intense electric field oscillations or waves and that electrons form crescent and beam‐like populations propagating both along and perpendicular to the magnetic field. This study shows that the observed electron populations are responsible for high‐frequency waves including their propagation directions and frequency ranges.
Key Points
Electron crescent‐shaped distributions produce upper hybrid waves in magnetotail reconnection events
Field‐aligned electron beams generate parallel electrostatic waves through the beam‐mode
Multiple crescent and convecting core distributions act together to produce broad frequency spectra as observed by MMS
Few clinical options are available for the treatment of volumetric muscle loss (VML). An important consideration that needs to be addressed for the development of treatments for these injuries is the ...establishment of a vascular supply sufficient to support skeletal muscle regeneration. The objective of the current study was to evaluate the potential for microvascular fragments (MVFs) harvested from adipose tissue to support tissue perfusion for VML. Tibialis anterior muscle defects in rats were replaced with constructs that were created on the day of surgery containing either (1) collagen only (COL), (2) freshly isolated microvascular fragments in collagen (MVF), or (3) adipose tissue derived stem cells (ASCs) in collagen. Muscles were harvested 7 and 14 days after surgery. Defects treated with MVFs had a vessel density higher than the other groups at both 7 and 14 days, and those treated with ASCs had a higher vessel density than COL by day 14 (p < 0.05). Perfused vessels were observed in both the ASC and MVF treated defects at day 14, as well as at day 7 in the MVF. This study supports the use of MVFs as a platform to improve tissue perfusion to treat large VML defects. The use of freshly isolated MVFs on the day of surgery supports their clinical use and application.
BACKGROUND Telomere syndromes have their most common manifestation in idiopathic pulmonary fibrosis and emphysema. The short telomere defect in these patients may manifest systemically as bone marrow ...failure and liver disease. We sought to understand the causes of dyspnea in telomerase and telomere gene mutation carriers who have no parenchymal lung disease. METHODS Clinical and pathologic data were reviewed as part of a Johns Hopkins-based natural history study of short telomere syndromes including dyskeratosis congenita. RESULTS Hepatopulmonary syndrome (HPS) was diagnosed in nine of 42 cases (21%). Their age at presentation was significantly younger than that of cases initially presenting with pulmonary fibrosis and emphysema (median, 25 years vs 55 years; P « .001). Cases had evidence of intra- and extrapulmonary arteriovascular malformations that caused shunt physiology. Nodular regenerative hyperplasia was the most frequent histopathologic abnormality, and it was seen in the absence of cirrhosis. Dyspnea and portal hypertension were progressive, and the median time to death or liver transplantation was 6 years (range, 4-10 years; n = 6). In cases that underwent liver transplantation, dyspnea and hypoxia improved, but pulmonary fibrosis subsequently developed. CONCLUSIONS This report identifies HPS as a frequent cause of dyspnea in telomerase and telomere gene mutation carriers. While it usually precedes the development of parenchymal lung disease, HPS may also co-occur with pulmonary fibrosis and emphysema. Recognizing this genetic diagnosis is critical for management, especially in the lung and liver transplantation setting.
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