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With a growing speaking Spanish population in the USA, it is necessary to help meet their healthcare needs. The Paul L. Foster School of Medicine is located in El Paso at the US–Mexico border. The medical Spanish curriculum is required for all medical students and begins on their first day of medical school, with conversational Spanish and medical Spanish through the preclerkship years. One of the key elements to the success of this course is the use of instructors with expertise in language instruction with an emphasis on task-based instruction. In addition to language instruction, this course also emphasizes instruction and experience in the culture of the US–Mexico border region. While taught medical Spanish, students are also prompted to understand when their skills are not adequate for the situation, in which case they need to enlist a skilled translator. Students report that, on a daily basis, they productively use what they learned in this preclerkship curriculum.

The new single-pixel TROPESS (TRopospheric Ozone and its Precursors from Earth System Sounding) profile retrievals of carbon monoxide (CO) from the Cross-track Infrared Sounder (CrIS) are evaluated using vertical profiles of in situ observations from the National Oceanic and Atmospheric Administration (NOAA) Global Monitoring Laboratory (GML) aircraft program and from the Atmospheric Tomography Mission (ATom) campaigns. The TROPESS optimal estimation retrievals are produced using the MUSES (MUlti-SpEctra, MUlti-SpEcies, MUlti-Sensors) algorithm, which has heritage from retrieval algorithms developed for the EOS/Aura Tropospheric Emission Spectrometer (TES). TROPESS products provide retrieval diagnostics and error covariance matrices that propagate instrument noise as well as the uncertainties from sequential retrievals of parameters such as temperature and water vapor that are required to estimate the carbon monoxide profiles. The validation approach used here evaluates biases in column and profile values as well as the validity of the retrieval error estimates using the mean and variance of the compared satellite and aircraft observations. CrIS–NOAA GML comparisons had biases of 0.6 % for partial column average volume mixing ratios (VMRs) and (2.3, 0.9, −4.5) % for VMRs at (750, 511, 287) hPa vertical levels, respectively, with standard deviations from 9 % to 14 %. CrIS–ATom comparisons had biases of −0.04 % for partial column and (2.2, 0.5, −3.0) % for (750, 511, 287) hPa vertical levels, respectively, with standard deviations from 6 % to 10 %. The reported observational errors for TROPESS/CrIS CO profiles have the expected behavior with respect to the vertical pattern in standard deviation of the comparisons. These comparison results give us confidence in the use of TROPESS/CrIS CO profiles and error characterization for continuing the multi-decadal record of satellite CO observations.

Context. Understanding the earliest stages of star formation, and setting it in the context of the general cycle of matter in the interstellar medium, is a central aspect of research with the James Webb Space Telescope (JWST). Aims. The JWST program JOYS (JWST Observations of Young protoStars) aims to characterize the physical and chemical properties of young high- and low-mass star-forming regions, in particular the unique mid-infrared diagnostics of the warmer gas and solid-state components. We present early results from the high-mass star formation region IRAS 23385+6053. Methods. The JOYS program uses the Mid-Infrared Instrument (MIRI) Medium Resolution Spectrometer (MRS) with its integral field unit (IFU) to investigate a sample of high- and low-mass star-forming protostellar systems. Results. The full 5-? 28 μm MIRI MRS spectrum of IRAS 23385+6053 shows a plethora of interesting features. While the general spectrum is typical for an embedded protostar, we see many atomic and molecular gas lines boosted by the higher spectral resolution and sensitivity compared to previous space missions. Furthermore, ice and dust absorption features are also present. Here, we focus on the continuum emission, outflow tracers such as the H2(0-? 0)S(7), [FeII](4F9/2-6D9/2), and [NeII](2P1/2-2P3/2) lines, and the potential accretion tracer Humphreys α H I(7-6). The short-wavelength MIRI data resolve two continuum sources, A and B; mid-infrared source A is associated with the main millimeter continuum peak. The combination of mid-infrared and millimeter data reveals a young cluster in the making. Combining the mid-infrared outflow tracers H2, [FeII], and [NeII] with millimeter SiO data reveals a complex interplay of at least three molecular outflows driven by protostars in the forming cluster. Furthermore, the Humphreys α line is detected at a 3-?4σ? level toward the mid-infrared sources A and B. One can roughly estimate both accretion luminosities and corresponding accretion rates to be between ∼2.6 × 10-6 and ∼0.9 × 10-4 Mo yr-1. This is discussed in the context of the observed outflow rates. Conclusions. The analysis of the MIRI MRS observations for this young high-mass star-forming region reveals connected outflow and accretion signatures, as well as the enormous potential of JWST to boost our understanding of the physical and chemical processes at play during star formation., Astronomy & Astrophysics, 673, ISSN:0004-6361, ISSN:1432-0746

This paper presents a procedure for estimating the systems state when considerable Information and Communication Technology (ICT) component outages occur, leaving entire system areas un-observable. For this task, a novel method for analyzing system observability is proposed based on the Manifold Boundary Ap-proximation Method (MBAM). By utilizing information geome-try, MBAM analyzes boundaries of models in data space, thus detecting unidentifiable system parameters and states based on available data. This approach extends local, matrix-based meth-ods to a global perspective, making it capable of detecting both structurally unidentifiable parameters as well as practically uni-dentifiable parameters (i.e., identifiable with low accuracy). Be-yond partitioning identifiable/unidentifiable states, MBAM also reduces the model to remove reference to the unidentifiable state variables. To test this procedure, cyber-physical system (CPS) simulation environments are constructed by co-simulating the physical and cyber system layers.

Two experiments were conducted to investigate the effects of feeding kernel processed corn silage to growing calves at 65% inclusion (dry matter [DM] basis; Exp. 1] and finishing beef steers at 20% inclusion (DM basis; Exp. 2). In Exp. 1, steers (n = 184; initial shrunk body weight [BW] = 388 ± 22.3 kg) were used to evaluate the influence that kernel processing of corn silage has on production responses when fed at 65% diet inclusion (DM basis) during a 46-d growing period. Steers were allotted to 1 of 24 pens (12 replicate pens/treatment). Treatments were based upon corn silage that was either kernel processed or not. In Exp. 2, steers (n = 192; initial shrunk BW = 446 ± 28.3 kg) were used in a 112-d finishing experiment. Treatments were grouped in a 2 × 2 factorial arrangement (24 pens total; 8 steers/pen) to evaluate corn silage harvest maturity (1/2 to 2/3 milk line or black layer) and kernel processing (processed or not) at time of corn silage harvest on finishing steer growth performance and carcass traits when corn silage is fed at a dietary DM inclusion of 20%. Both experiments were analyzed as a randomized completed block design with pen as experimental unit. In Exp. 1, final BW tended (P = 0.07) to be increased by 3 kg in kernel processed corn silage. Daily weight gain and DM intake were increased (P ≤ 0.04) by 6% and 2%, respectively, in steers fed kernel processed corn silage compared to controls; however, gain efficiency was not appreciably influenced by treatment (P = 0.15). In Exp. 2, there were no harvest maturity × kernel processing interactions (P ≥ 0.26) for any growth performance measures or any parameters related to efficiency of dietary NE utilization. No harvest maturity × kernel processing interactions (P ≥ 0.08) were observed for any carcass traits except for the distribution of USDA Prime carcasses (P = 0.04). Steers fed 2/3 milk line and unprocessed corn silage had a lower (P = 0.05) proportion of carcasses grade USDA Prime (0.0%) compared to all other treatments (12.0%). Harvest time (P ≥ 0.07) and kernel processing (P ≥ 0.07) of corn silage had no appreciable influence on any other carcass trait measures. These data indicate that kernel processed corn silage fed to growing calves at 65% diet inclusion (DM basis) enhances intake and daily gain, while kernel processed corn silage fed to finishing steers at 20% diet inclusion (DM basis) does not appreciably influence daily gain, efficiency of gain, or carcass parameters.Kernel processing of corn silage has yielded inconsistent results on diet digestibility and growth performance in beef cattle. These are likely a function of a variety of factors such as differing dry matter concentration of corn silage at harvest, diet inclusion levels, and length of cut. Two experiments were conducted to determine the effect that kernel processing of corn silage has on production responses in growing (65% dietary dry matter inclusion) and finishing beef steers (20% dietary dry matter inclusion). Data from the growing steer experiment when corn silage was included in the diet at 65% (dry matter basis) indicate that kernel processing of corn silage enhances dry matter intake and daily weight gain of beef steers with no appreciable influence on DM conversion efficiency. Data from the finishing steer experiment indicate that harvest maturity and kernel processing of corn silage have minimal effects on animal growth performance and carcass traits in finishing steers when corn silage is fed at 20% inclusion (dry matter basis). Variable responses could be related to differences in inclusion level, differences in effective roughage level fed, and a variety of other factors. Overall, these results suggest that corn silage fed to growing calves should be kernel processed to enhance dry matter intake and daily weight gain, while kernel processed corn silage fed to finishing steers does not appreciably influence daily gain, efficiency of gain, or carcass parameters.

The COVID-19 pandemic highlighted inequities in technology literacy and access for students with extensive support needs (ESN) in k-12 settings. Technology is critical for students with ESN to continue lifelong learning after graduation. The unprecedented level of funds from the American Relief Plan provides schools opportunities to invest in sustainable and accessible technology which benefits all students. The Universal Design for Learning (UDL) framework is used to increase access to learning for all students, and should be applied to decision making surrounding technology investment and purchasing. This essay provides three considerations for schools to reflect on when spending ARP Act funds: (a) use UD to purchase technology, (b) provide UDL professional development to teach technology literacy skills, and (c) provide learning opportunities aimed at technology use among students with ESN.

Stiff Person Syndrome (SPS), a rare autoimmune neurologic disorder characterized by fluctuating muscle spasms and rigidity, is mediated by autoantibodies to glutamic acid decarboxylase (GAD) antibodies. Symptoms of SPS have been shown to improve after administration of intravenous immunoglobulin (IVIG) however, there is a paucity of information regarding use of SCIg in SPS. Four patients with Stiff Person Syndrome were treated with SCIgPro20 for a period between 31 to 101 months. Most reactions were local and mild. All patients reported improvement in spasticity, and 2 patients reported improvement in seizure frequency. SCIgPro20 was well tolerated in patients with SPS and was associated with improvement in symptoms.

T cell based immunotherapies can be applicable to acute myeloid leukemia (AML). Therefore, the selection of optimal T cells, cell manufacturing, and therapeutic T cell engineering are essential for the development of effective adoptive T cell therapies for AML. Autologous tumor-infiltrating lymphocytes (TILs) have been in clinical trials to treat solid malignancies. Herein, we assessed whether TILs can be isolated from the bone marrow (BM) of AML patients, expanded ex vivo and utilized as a novel therapeutic strategy for AML. To this end, firstly we analyzed the immunophenotypes of a series of primary BM samples from AML patients (N = 10) by flow cytometry. We observed a variable amount of CD3+ TILs (range ∼2.3–∼32.6% of mononuclear cells) among BM samples. We then developed a novel protocol that produced a three-log ex vivo expansion of TILs isolated from AML patient BM (N = 10) and peripheral blood (PB) (N = 10), including from patients with a low number of CD3+ T cells, within 3, 4 weeks. Further, we identified previously described naïve T cells (CCR7+CD95-/or CD62L+CD45RA+) in AML BM and PB samples, which seemed to be required for a successful TILs ex vivo expansion. Finally, we showed that the expanded TILs could: (1) cause cytotoxicity to autologous AML blasts ex vivo (90.6% in control without T cell treatment vs. 1.89% in experimental groups with PB derived T cells and 1.77% in experimental groups with BM derived TILs, p

Cytokine receptor-like factor 2 B-cell acute lymphoblastic leukemia (CRLF2 B-ALL) is a high-risk subtype characterized by CRLF2 overexpression with poor survival rates in children and adults. CRLF2 and interleukin-7 receptor alpha (IL-7Rα) form a receptor for the cytokine thymic stromal lymphopoietin (TSLP), which induces JAK/STAT and PI3K/AKT/mTOR pathway signals. Previous studies from our group showed that low TSLP doses increased STAT5, AKT, and S6 phosphorylation and contributed to CRLF2 B-ALL cell survival. Here we investigated the role of TSLP in the survival and proliferation of CRLF2 B-ALL cells in vitro and in vivo. We hypothesized that high doses of TSLP increase CRLF2 signals and contribute to increased proliferation of CRLF2 B-ALL cells in vitro and in vivo. Interestingly, we observed the opposite effect. Specifically, high doses of TSLP induced apoptosis in human CRLF2 B-ALL cell lines in vitro, prevented engraftment of CRLF2 B-ALL cells, and prolonged the survival of +TSLP patient-derived-xenograft mice. Mechanistically, we showed that high doses of TSLP induced loss of its receptor and loss of CRLF2 signals in vitro. These results suggest that high doses of TSLP could be further investigated as a potential therapy for the treatment of CRLF2 B-ALL.

OBJECTIVE The objective of this study was to evaluate the relationship between vaginal mesh exposure and vaginal bacterial community composition. METHODS Vaginal swab samples were collected from 13 women undergoing excision of vaginal mesh with vaginal mesh exposure. Samples were collected at the midvagina, site of exposure, and underneath the vaginal epithelium at the exposure. Control samples were collected vaginally during 15 new patient examinations. For all samples, we extracted genomic DNA and polymerase chain reaction amplified and sequenced the 16S rRNA gene V4 region. We tested for differences in the microbiota among control and exposure samples with PERMANOVA tests of beta diversity measures (Morisita-Horn dissimilarity) and Wilcoxon rank sum tests of Lactobacillus distribution. RESULTS Vaginal bacterial communities in both control and case groups were divided into 2 primary community types, one characterized by Lactobacillus dominance (>50% of community) and the other by low Lactobacillus and a high diversity of vaginal anaerobes. In 10 of 13 case women, bacterial communities were highly similar between the 3 vaginal sites (adonis R2 = 0.86, P = 0.0099). In the 3 women with community divergence, all 3 were characterized by decreased Lactobacillus abundance at the exposure site. Overall, Lactobacillus abundance was lower at the site of mesh exposure and under the epithelium than in the experimental control (W = 137, P = 0.072, r = 0.41; W = 146, P = 0.025, r = 0.50). Common putative pathogenic mesh colonizing bacteria were common (in 51 of 54 samples), but generally not abundant (median relative abundance = 0.014%). CONCLUSIONS In vaginal mesh exposure cases, a woman is more likely to have a diverse, non-Lactobacillus-dominant community.

Monoclonal antibodies with neutralizing activity against SARS-CoV-2 have demonstrated clinical benefits in cases of mild-to-moderate SARS-CoV-2 infection, substantially reducing the risk for hospitalization and severe disease1–4. Treatment generally requires the administration of high doses of these monoclonal antibodies and has limited efficacy in preventing disease complications or mortality among hospitalized patients with COVID-195. Here we report the development and evaluation of anti-SARS-CoV-2 monoclonal antibodies with optimized Fc domains that show superior potency for prevention or treatment of COVID-19. Using several animal disease models of COVID-196,7, we demonstrate that selective engagement of activating Fcγ receptors results in improved efficacy in both preventing and treating disease-induced weight loss and mortality, significantly reducing the dose required to confer full protection against SARS-CoV-2 challenge and for treatment of pre-infected animals. Our results highlight the importance of Fcγ receptor pathways in driving antibody-mediated antiviral immunity and exclude the possibility of pathogenic or disease-enhancing effects of Fcγ receptor engagement of anti-SARS-CoV-2 antibodies upon infection. These findings have important implications for the development of Fc-engineered monoclonal antibodies with optimal Fc-effector function and improved clinical efficacy against COVID-19 disease. Optimization of monoclonal antibodies against SARS-CoV-2 for enhanced Fc-effector function increase their effectiveness for prevention and treatment of COVID-19 in multiple animal models of SARS-CoV-2 infection.

The extracellular matrix (ECM) of the brain is comprised of unique glycan “sulfation codes” that influence neurological function. Perineuronal nets (PNNs) are chondroitin sulfate-glycosaminoglycan (CS-GAG) containing matrices that enmesh neural networks involved in memory and cognition, and loss of PNN matrices are reported in patients with neurocognitive and neuropsychiatric disorders including Alzheimer’s disease (AD). Using liquid hromatography tandem mass spectrometry (LC-MS/MS), we show that patients with a clinical diagnosis of AD-related dementia undergo a re-coding of their PNN-associated CS-GAGs that correlates to Braak stage progression, hyperphosphorylated tau (P-tau) accumulation, and cognitive impairment. As these CS-GAG sulfation changes are detectable prior to the regional onset of classical AD pathology, they may contribute to the initiation and/or progression of the underlying degenerative processes and implicate the brain matrix sulfation code as a key player in the development of AD clinicopathology.

Participation in the Congregate Nutrition Program (CNP) is declining. This study examined CNP participation motivators, barriers, menu preferences, desired facility attributes, and educational programming to help identify strategies to increase participation. Four focus groups were held (3 = CNP participants only, n = 21; 1 = non-CNP participants, n = 11). They were audio-recorded, transcribed, and analyzed for common themes. All participants were White and food secure (93.8%). The majority were educated (75.8%), female (72.2%), and aged 71-80 years old (53.1%). CNP participation motivators were affordability, healthy meals, socialization, and location convenience. CNP participation barriers were limited awareness, the low perceived need for attending the CNP, and transportation. Ideal CNP characteristics were menu choice, variety of activities, and a welcoming ambiance. Preferred marketing strategies were print advertising and word of mouth. These findings provide insight as to how the CNP may be modified to be more appealing for the older adult population.

Background: Bacille Calmette-Guérin (BCG) vaccine could play a role in counteracting the rising prevalence of atopic diseases, through its beneficial off-target effects. We aimed to determine whether neonatal BCG vaccination reduces the incidence of eczema in infants.Methods: Randomized controlled trial with 1272 infants allocated to receive BCG-Denmark or no BCG at birth. The primary outcome was the 12-month incidence of eczema based on 3-monthly questionnaires. Eczema was also assessed at a 12-month clinic visit. ClinicalTrial.gov: NCT01906853.Results: The 12-month eczema incidence was 32.2% in the BCG group compared with 36.6% in the control group (adjusted risk difference (aRD) -4.3%, 95% CI -9.9% to 1.3%, multiple imputation model). In addition, comparing infants in the BCG group with the control group, 15.7% vs. 19.2% had eczema lesions at the 12-month visit (aRD -3.5%, 95% CI -8.0% to 1.0%); 35.7% vs. 39.0% reported using topical steroids (aRD -3.3, 95% CI -9.2 to 2.7); and 7.3% vs. 10.2% had severe eczema scores (aRD -3.0%, 95% CI -8.8% to 2.7%). In 344 high-risk infants (two atopic parents), the 12-month eczema incidence was 35.3% in the BCG group compared with 46.8% in the control group (aRD -11.5%, 95% CI -21.9% to -1.2%; number needed to treat 8.7, 95% CI 4.6 to 83.3).Conclusion: There is insufficient evidence to recommend neonatal BCG vaccination in all infants for the prevention of eczema in the first year of life; however, a modest beneficial effect was observed among high-risk infants. A single dose of BCG-Denmark soon after birth could reduce the incidence of eczema in infants with two atopic parents.

Background and study aim The clinical impact of eosinophilic esophagitis (EoE) limited to the distal esophagus (Lim-EE) vs. diffuse involvement (Dif-EE) is unknown. This study compared clinical characteristics and outcomes of Lim-EE vs. Dif-EE. Patients and methods This retrospective, single-center study of patients with EoE between December 2011 and December 2019 evaluated treatment response based on repeated pathology and/or clinical improvement using comparative statistics. Results 479 patients were identified (126 Lim-EE, 353 Dif-EE). Lim-EE patients had a higher incidence of endoscopically identified esophagitis (23.0 % vs. 14.7 %; P = 0.04), were older (50.8 [SD 16.2] vs. 46.4 [SD 15.3] years; P = 0.007), and were more likely to present with iron deficiency anemia (5.6 % vs. 1.7 %; P = 0.05), dyspepsia (15.1 % vs. 8.8 %; P = 0.06) or for Barrett’s surveillance (10.3 % vs. 3.7 %; P = 0.02). Patients with Dif-EE presented more frequently with dysphagia (57.2 % vs. 45.2 %; P = 0.02). Both groups had similar proton pump inhibitor (87.2 % vs. 83.3 %; P = 0.37) and steroid (12.8 % vs. 21.4 %; P = 0.14) use. Patients with Lim-EE had a better clinicopathologic response (61.5 % vs. 44.8 %; P = 0.009). On multivariate analysis, EoE extent predicted treatment response with an odds ratio of 1.89 (95 % confidence interval 1.13–3.20; P = 0.02). However, treatment response based only on repeat biopsy results showed no statistical difference between Lim-EE (52.5 %) and Dif-EE (39.7 %; P = 0.15). Conclusions Lim-EE may represent a distinct phenotype separate from Dif-EE, with more overlap with gastroesophageal reflux disease and better treatment response.

We used experience sampling to examine perceptions of empathy in the everyday lives of a group of 246 U.S. adults who were quota sampled to represent the population on key demographics. Participants reported an average of about nine opportunities to empathize per day; these experiences were positively associated with prosocial behavior, a relationship not found with trait measures. Although much of the literature focuses on the distress of strangers, in everyday life, people mostly empathize with very close others, and they empathize with positive emotions 3 times as frequently as with negative emotions. Although trait empathy was negatively associated only with well-being, empathy in daily life was generally associated with increased well-being. Theoretically distinct components of empathy—emotion sharing, perspective taking, and compassion—typically co-occur in everyday empathy experiences. Finally, empathy in everyday life was higher for women and the religious but not significantly lower for conservatives and the wealthy.

Background: Regular physical activity is crucial for healthy aging, but older adults are the least active age group. This study explored the feasibility, acceptability, and efficacy of a multilevel mHealth intervention for increasing physical activity of older adults living in a retirement community. Methods: Participants included 54 older adults (mean age = 81.2 y, 77.8% female, 98.1% white) living in a retirement community. Participants received a Fitbit Zip and access to a multilevel mHealth physical activity intervention (MapTrek Residential) for 8 weeks. Physical activity (in steps per day) and intervention compliance (days worn) were measured objectively with the Fitbit for 12 weeks (8-wk intervention plus 4-wk follow-up). Psychosocial outcomes (social support, self-efficacy, and outcome expectations) were assessed at baseline and 8 weeks. Acceptability outcomes were assessed with an open-ended process evaluation survey and focus groups. Descriptive statistics and linear mixed models were used to examine intervention effects. Results: Participants increased daily steps from 5438 steps per day at baseline (95% CI, 4620 to 6256) to 6201 steps per day (95% CI, 5359 to 7042) at week 8 (P P = .92). Conclusions: Our multilevel mHealth physical activity intervention was effective for increasing physical activity older adults over 8 weeks. Additional research focused on maintaining physical activity gains with this approach is warranted.

A series of 1-benzyloxy-5-phenyltetrazole derivatives and similar compounds were synthesized and evaluated for their in vitro inhibitory activity against androgen-receptor-dependent (22Rv1) and androgen-receptor independent (PC3) prostate cancer cells. The most active compounds had in vitro IC

This four-month study evaluated the virtual delivery of