Patient interest in and clinician reservations on polygenic embryo screening: a qualitative study of stakeholder perspectives.

PURPOSE: We explored and compared perspectives of reproductive endocrinology and infertility specialists (REIs) and in vitro fertilization (IVF) patients regarding polygenic embryo screening (PES), a new type of preimplantation screening that estimates the genetic chances of developing polygenic conditions and traits in the future. METHODS: Qualitative thematic analysis of semi-structured interviews with US-based REIs and IVF patients. RESULTS: Clinicians and patients often held favorable views of screening embryos for physical or psychiatric conditions, though clinicians tended to temper their positive attitudes with specific caveats. Clinicians also expressed negative views about screening embryos for traits more frequently than patients, who generally held more positive views. Most clinicians were either unwilling to discuss or offer PES to patients or were willing to do so only under certain circumstances, while many patients expressed interest in PES. Both stakeholder groups envisioned multiple potential benefits or uses of PES and raised multiple potential, interrelated concerns about PES. CONCLUSION: A gap exists between clinician and patient attitudes toward PES; clinicians generally maintained reservations about such screening and patients indicated interest in it. Clinicians and patients sometimes imagined using PES to prepare for the birth of a predisposed or "affected" individual-a rationale that is often associated with prenatal testing. Many clinicians and patients held different attitudes depending on what is specifically screened, despite the sometimes blurry distinction between conditions and traits. Considerations raised by clinicians and patients may help guide professional societies in developing guidelines to navigate the uncertain terrain of PES.

Cardiovascular magnetic resonance in autoimmune rheumatic diseases: a clinical consensus document by the European Association of Cardiovascular Imaging.

Autoimmune rheumatic diseases (ARDs) involve multiple organs including the heart and vasculature. Despite novel treatments, patients with ARDs still experience a reduced life expectancy, partly caused by the higher prevalence of cardiovascular disease (CVD). This includes CV inflammation, rhythm disturbances, perfusion abnormalities (ischaemia/infarction), dysregulation of vasoreactivity, myocardial fibrosis, coagulation abnormalities, pulmonary hypertension, valvular disease, and side-effects of immunomodulatory therapy. Currently, the evaluation of CV involvement in patients with ARDs is based on the assessment of cardiac symptoms, coupled with electrocardiography, blood testing, and echocardiography. However, CVD may not become overt until late in the course of the disease, thus potentially limiting the therapeutic window for intervention. More recently, cardiovascular magnetic resonance (CMR) has allowed for the early identification of pathophysiologic structural/functional alterations that take place before the onset of clinically overt CVD. CMR allows for detailed evaluation of biventricular function together with tissue characterization of vessels/myocardium in the same examination, yielding a reliable assessment of disease activity that might not be mirrored by blood biomarkers and other imaging modalities. Therefore, CMR provides diagnostic information that enables timely clinical decision-making and facilitates the tailoring of treatment to individual patients. Here we review the role of CMR in the early and accurate diagnosis of CVD in patients with ARDs compared with other non-invasive imaging modalities. Furthermore, we present a consensus-based decision algorithm for when a CMR study could be considered in patients with ARDs, together with a standardized study protocol. Lastly, we discuss the clinical implications of findings from a CMR examination.

Polygenic embryo screening: four clinical considerations warrant further attention.

Recent advances in developing polygenic scores have made it possible to screen embryos for common, complex conditions and traits. Polygenic embryo screening (PES) is currently offered commercially, and though there has been much recent media and academic coverage, reproductive specialists' points of view have not yet been prominent in these discussions. We convened a roundtable of multidisciplinary experts, including reproductive specialists to discuss PES and its implications. In this Opinion, we describe four clinically relevant issues associated with the use of PES that have not yet been discussed in the literature and warrant consideration.

Health Impact of Street Sweeps from the Perspective of Healthcare Providers.

BACKGROUND: Homeless street sweeps are frequent operations in many cities in the USA in which government agencies move unhoused people living in public outdoor areas. Little research exists on the health impact of street sweeps operations. OBJECTIVE: This study was created at the request of community advocacy groups to investigate and document the health impacts of street sweeps from the perspective of healthcare providers. DESIGN: This is a qualitative study using data gathered from open-ended questions. PARTICIPANTS: We recruited 39 healthcare providers who provided health and wellness services in San Francisco for people experiencing homelessness (PEH) between January 2018 and January 2020. INTERVENTIONS: We administered a qualitative, open-ended questionnaire to healthcare providers using Qualtrics surveying their perspectives on the health impact of street sweeps. APPROACH: We conducted qualitative thematic analysis on questionnaire results. KEY RESULTS: Street sweeps may negatively impact health through two outcomes. The first outcome is material loss, including belongings and medical items. The second outcome is instability, including geographic displacement, community fragmentation, and loss to follow-up. These outcomes may contribute to less effective management of chronic health conditions, infectious diseases, and substance use disorders, and may increase physical injuries and worsen mental health. Providers also reported that sweeps may negatively impact the healthcare system by promoting increased usage of emergency departments and inpatient hospital care. CONCLUSIONS: Sweeps may have several negative consequences for the physical and mental health of the PEH community and for the healthcare system.

Refractive Error Findings in Students Who Failed School-based Vision Screening.

PURPOSE: To report refractive error findings in Baltimore City schoolchildren who failed school-based vision screenings. METHODS: In this cross-sectional analysis, students pre-kindergarten through 8th grade who failed screenings during school years 2016-2019 received an eye examination, including non-cycloplegic autorefraction and visual acuity (VA) measurements. Refractive error was identified when there was at least: -0.50 diopter (D) spherical equivalent (SE) myopia, +0.50D SE hyperopia, 1.00D astigmatism, or 1.00D anisometropia in either eye. Generalized estimating equation models were used to identify factors associated with clinically significant refractive error, defined as decreased VA and more severe refractive error. RESULTS: Of 7520 students who failed screening, 6627 (88%) were analyzed. Clinically significant refractive error and any refractive error were found in 2352 (35.5%) and 5952 (89.8%) students, respectively. Mild myopia (45%, -0.50 D to <-3.00 D SE) and low astigmatism (47%, 1.00 D to <3.00 D cylinder) were the most prevalent types of refractive error. Proportions of students with myopia increased with higher grade levels (Ptrend<0.001). Myopia and astigmatism were more common in black and Latinx. Risk factors for clinically significant refractive error included higher grades (odds ratios [OR] ranged from 1.30 to 2.19 compared with 1st grade, P < .05) and Latinx ethnicity (OR = 1.31, 95%CI: 1.08-1.59). CONCLUSION: A Baltimore school-based vision program identified a substantial number of students with refractive error in a high-poverty urban community. Over 1/3 students who failed vision screening had clinically significant refractive error, with black and Latinx students at higher risk of having myopia and astigmatism.

Teacher and school staff perspectives on their role in school-based vision programs.

OBJECTIVE: School-based vision programs (SBVPs) are one approach to increase access to vision care by providing vision screenings, eye examinations, and eyeglasses directly in schools. Few studies report on the perspectives of teachers and staff, who are important stakeholders, on SBVPs. We examined teacher and staff perspectives on their involvement in SBVPs. DESIGN: Qualitative study using focus groups. PARTICIPANTS: Teachers and staff at Baltimore and Chicago public schools served by SBVPs between 2016 and 2018. METHODS: We conducted 21 semistructured focus groups with 117 teachers and staff in 10 Baltimore and 11 Chicago public preK-12 schools that participated in SBVPs. Sessions were recorded, transcribed, and coded using inductive thematic analysis. RESULTS: Participants identified 2 main themes regarding teacher and staff involvement in SBVPs: (i) program outreach, including using multiple communication modalities to engage parents, explaining program details to families, and helping with program consent form return and (ii) promoting vision health, including identifying vision problems in the classroom, encouraging eyeglasses wear, and supporting eyeglasses maintenance. Participants also discussed limitations in capacity to partake in these activities. CONCLUSION: Teachers interact with parents and students throughout the SBVP process, undertaking important roles in outreach and health promotion to ensure uptake of SBVP services. SBVPs and other school-based health programs should explore strategies to support teachers in the roles they fill to optimize program impact.

Stakeholders' Perceptions of a School-Based Eye Care Programme in Baltimore, MD.

PURPOSE: To explore stakeholders' perceptions of a school-based vision programme (SBVP). METHODS: We conducted 20 focus groups with 105 parents and teachers at schools in Baltimore, MD, that participated in a SBVP. Facilitators used a semi-structured interview guide to discuss participants' perceptions of the SBVP. Focus groups were audio-recorded, transcribed, and coded using inductive thematic analysis. RESULTS: Participant perceptions fell into three categories: benefits of school-based eye care, limitations of school-based eye care, and observation of impact. The majority of participants had positive comments about the programme; benefits included convenience (location, time, and cost), the comprehensive nature of the programme, the quality of the eyeglasses and ability to receive replacements, and a positive screening/exam experience. Limitations of programme impact were related to communication and organisation, the time to receive the glasses, missed instructional time, and uncertainty about screenings. Observations of impact included academic and classroom improvements, as well as visual and other health improvements. CONCLUSION: Parents and teachers reported mostly positive perceptions regarding the SBVP. Their appreciation for the convenience underscores that location, cost, time, and comprehensive services are crucial aspects for implementing a successful programme. To maximize impact, programs must also implement robust communication campaigns that integrate into the schools' workflow to help parents and teachers stay engaged in the process from start to finish.

Analysis of vision screening failures in a school-based vision program (2016-19).

BACKGROUND: Vision screenings of a school-based program were conducted in state-mandated grades (pre-kindergarten [pre-K] or kindergarten [K], 1st and 8th grade), and nonmandated grades (2nd to 7th). METHODS: During school years 2016-19, 51,593 pre-K to 8th grade students from 123 Baltimore City Public Schools underwent vision screenings, with 85% of the schools qualifying for Free and Reduced Price Meals. Assessments included distance visual acuity, Spot photoscreening, stereopsis, and cover testing. Screening failures were analyzed by grade using aggregate data. Failure rates for mandated and nonmandated grades were compared using a logistic regression model, and visual acuity distributions were analyzed using individual data. RESULTS: Over the 3-year period, 17,414 (34%) of students failed vision screening. Failure rates by grade ranged from 28% to 38%. Children in kindergarten and 3rd grade and higher were statistically more likely to fail screening than those in 1st grade. Reduced visual acuity was the most common reason for failure (91%). Failure rates were significantly higher in nonmandated grades than in state-mandated testing grades (34.7% vs 32.5% [P < 0.001]). Mean visual acuity of all students who failed vision screening was 20/50 in the worse-seeing eye and was 20/40 in the better-seeing eye. CONCLUSIONS: One-third of students failed vision screening. High screening failure rates across all grades suggest that screening in select grade levels, as currently mandated in Maryland schools, is inadequate for detecting vision problems in the low-income communities served by this program.

Exacerbations of Severe Asthma While on Anti-IL-5 Biologics.

Anti-interleukin 5 (IL-5) and anti-IL-5 receptor α monoclonal antibodies markedly decrease airway and peripheral blood eosinophil numbers and are thus highly effective in reducing asthma exacerbations. Nonetheless, these biologics do not completely resolve exacerbations. There is very little information on the cellular nature of exacerbations during treatment with biologics. Using illustrative clinical case scenarios, we highlight the importance of carefully characterizing asthmatics at the time of exacerbation and recognizing neutrophilic causes of exacerbations to ensure optimal management. While an eosinophilic exacerbation may improve with more corticosteroids or by switching to another anti-IL-5 monoclonal antibody, a noneosinophilic exacerbation will likely not. An infective exacerbation needs to be recognized, and the pathogen must be identified and treated with the appropriate antimicrobial agent.

Parent and Teacher Perspectives on Factors Decreasing Participation in School-Based Vision Programs.

Purpose: To examine factors decreasing participation in school-based vision programs from parent and teacher perspectives.Methods: We conducted 41 semi-structured focus groups (20 parent groups, 21 teacher/staff groups), at 10 Baltimore and 11 Chicago public elementary and middle schools offering school-based vision programs. School-based vision programs provided vision screening, eye exams, and eyeglasses if needed. Focus groups ranged in size from 2-9 participants (median = 5). Sessions were recorded, transcribed, and coded through an iterative process to develop themes using inductive analysis.Results: Ninety parents and 117 teachers/staff participated. Participants identified five major factors decreasing participation in school-based vision programs: (1) challenges with the consent form, including distribution, collection, and literacy and language barriers; (2) having existing eye care; (3) misunderstandings about the program, especially related to cost and insurance; (4) difficulty raising parental awareness of the program; and (5) certain attitudes towards vision, eye care, and school-based programs, including low prioritization of eye care, mistrust of the program, fear of sharing private information, not believing their child needs glasses, and reluctance accepting 'subsidized' services.Conclusion: Parents and teachers identified important structural barriers to participation (i.e., consent form challenges and low parental awareness) and specific reasons for non-participation (i.e., attitudes, misunderstanding of the program, existing eye care) in school-based vision programs. Effective strategies are needed to facilitate return of consent forms and promote awareness of school-based vision programs among parents. Programs should also target services towards those currently without access to eye care and increase awareness about paediatric vision needs.

Status of pesticide residues in water, sediment, and fishes of Chilika Lake, India.

Chilika Lake is the largest coastal lagoon in Asia and the second largest in the world covering an area of 1100 km2 and spread over three districts of Odisha state of India. It is the first Indian wetland designated as a wetland of international importance under the Ramsar Convention in 1981. The lake ecosystem sustains large and diversified resources of plants and animals including fisheries. Pollution of the ecosystem caused by residues of pesticides originating from different sources was assessed through multiple sampling from 2012 to 2016 from three potential sites of contamination, viz., Palur Bridge, Daya River Estuary, and Makara River. Incidence of organochlorinated (OC) pesticide residues was noticed in about 25% water samples. HCH (α, γ&δ), DDD (op|), DDE (op|&pp.|) and heptachlor were the OCs detected in concentration varying from 0.025 to 23.4 µg/l. None of the eight targeted synthetic pyrethroid (SP) pesticides was found in water, but among the organophosphates (OP), chlorpyrifos (0.019-2.73 µg/l), and dichlorvos (0.647 µg/l) were recorded. In sediment samples, residues of OC or OP pesticides were not present, but one SP pesticide was recorded. Fish samples were contaminated to the extent of 55%, mostly with residues of OCs and OPs and less with SPs. However, their concentrations were below the permissible limit, so there was no direct threat of health hazards to humans.

Exacerbations of severe asthma while on anti-IL-5 biologics

Anti-interleukin 5 (IL-5) and anti-IL-5 receptor alfa monoclonal antibodies markedly decrease airway and peripheral blood eosinophil numbers and are thus highly effective in reducing asthma exacerbations. Nonetheless, these biologics do not completely resolve exacerbations. There is very little information on the cellular nature of exacerbations during treatment with biologics. Using illustrative clinical case scenarios, we highlight the importance of carefully characterizing asthmatics at the time of exacerbation and recognizing neutrophilic causes of exacerbations to ensure optimal management. While an eosinophilic exacerbation may improve with more corticosteroids or by switching to another anti-IL-5 monoclonal antibody, a noneosinophilic exacerbation will likely not. An infective exacerbation needs to be recognized, and the pathogen must be identified and treated with the appropriate antimicrobial agent

Los anticuerpos monoclonales anti-interleucina 5 (IL5) y anti-receptor de IL5 son altamente efectivos en reducir las exacerbaciones del asma al disminuir notablemente el número de eosinófilos en las vías respiratorias y en sangre periférica. Sin embargo, aun estando bajo el tratamiento con estos biológicos, las descompensaciones asmáticas no desaparecen por completo. Disponemos de una modesta evidencia que señala la naturaleza de estas exacerbaciones, y los pacientes afectos de asma grave en estas terapias podrían tener exacerbaciones graves no eosinofílicas. Utilizando como escenarios ilustrativos varios casos clínicos, destacamos la importancia de caracterizar cuidadosamente al paciente asmático en el momento de la exacerbación y reconocer las causas neutrofílicas de las exacerbaciones, lo cual es de importancia a la hora de manejar estas exacerbaciones. Si bien una exacerbación eosinofílica puede beneficiarse con más glucocorticosteroides o al cambiar a otro mAb anti-IL5, una exacerbación no eosinofílica probablemente no lo hará. Es necesario reconocer una exacerbación infecciosa, identificar el patógeno y tratarlo con el agente antimicrobiano más apropiado

Poly(piperizinamide) with copper ion composite membranes: Application for mitigation of Hexaconazole from water and combat microbial contamination.

Thin film Poly(piperazine-amide) composite membranes using sequential interfacial polymerization with tuning by Cu2+ have brought significant findings in it. The hydrophobicity is relatively enhanced for the copper containing membranes. The membrane in which copper solution is applied prior to piperizine (Memb-III) exhibits higher hydrophobicity where as membrane (Memb-II) in which copper solution is applied following piperizine, possesses higher roughness compared to other two. Filtration experiments in terms of salts, mono/disaccharides and hexaconazole indicate that modified membranes are of different behaviours according to their sequence of preparative methods. Memb-III has shown lower SO4=/Cl- selectivity compared to Memb-II (i.e. 3.92), though they are in different range. The unmodified membrane (Memb-I) exhibits SO4=/Cl- selectivity 3.23 is in the same scale of Memb-III (2.27). Memb-III exhibits higher hexaconazole separation (91.5%) compared to Memb-II (i.e. 53.9%). The flux decline follows the order: field water > tap water > deionized water. The copper incorporated membrane (Memb-II) has shown a low flux decline compared to Memb-III as well as Memb-I. The antibacterial properties towards E. Coli and Bacillus subtilis are well reflected. The copper containing membranes have promising antibacterial properties and follows the order Memb-II > Memb-III > Memb-I.

High resolution spectroscopy on Te2: New lines for reference.

Ro-vibrational spectra of different electronic states of molecules are often used as absolute wavelength or frequency standards. These standards are also used to mitigate any slow drift of laser frequency during an experiment. In the precision experiment, the two most commonly used molecular standards are iodine and tellurium, both are homo-nuclear diatomic molecules. The former is mostly used as standard for the long wavelength (600-900 nm) region, while the tellurium spectrum is widely used in short wavelength (400-550 nm) including near ultraviolet. A comprehensive data on tellurium spectra can be obtained from the tellurium atlas [1]. However near the 455 nm range where a number of important atomic resonance line, the atlas provides no significant data. We have performed high resolution modulation transfer spectroscopy (MTS) on tellurium molecule in a hot cell in the region close to 455 nm wavelength thereby obtained more than 100 new spectral lines which were not observed before. The linewidth of each of these peaks is about a few tens of MHz, making them suitable for laser frequency locking.

Electronic structure of twisted and planar rubrene molecules: a density functional study.

X-ray absorption spectra (XAS), the density of states (DOS) and the electron density distribution of the HOMO and LUMO for flat and twisted rubrene molecules have been calculated using density functional theory (DFT). The simulated XAS spectra are validated by experimental C K-edge near-edge X-ray absorption fine structure (NEXAFS) data. We demonstrate that the NEXAFS spectra of rubrene thin films of different thicknesses can be explained in terms of different combinations of spectral intensity from the twisted and the flat randomly oriented molecules. All the fine structure of the NEXAFS spectra is well reproduced and the energetic positions of the resonances agree within a window of ±0.3 eV with the calculated XAS. Our calculation reveals that the peak at lowest photon energy (α') of the NEXAFS spectra at the lower coverage of rubrene molecules appears only from the twisted molecules. Other peaks in the case of the flat molecules appear either from the backbone or the wings, whereas, for the twisted molecules, the backbone and the wings contribute somewhat equally. Lowering of the HOMO-LUMO gap, as well as redistribution of the electron density of both the frontier orbitals, is found to take place in the case of the twisted molecule. The redistribution explains the reduction in conductivity for the twisted molecule compared to the flat one despite the lower band gap for the former. This finding will further strengthen the progress of rubrene thin film based devices.

Lower limb joint angle variability and dimensionality are different in stairmill climbing and treadmill walking.

The present study tested if the quadratic relationship which exists between stepping frequency and gait dynamics in walking can be generalized to stairmill climbing. To accomplish this, we investigated the joint angle dynamics and variability during continuous stairmill climbing at stepping frequencies both above and below the preferred stepping frequency (PSF). Nine subjects performed stairmill climbing at 80, 90, 100, 110 and 120% PSF and treadmill walking at preferred walking speed during which sagittal hip, knee and ankle angles were extracted. Joint angle dynamics were quantified by the largest Lyapunov exponent (LyE) and correlation dimension (CoD). Joint angle variability was estimated by the mean ensemble standard deviation (meanSD). MeanSD and CoD for all joints were significantly higher during stairmill climbing but there were no task differences in LyE. Changes in stepping frequency had only limited effect on joint angle variability and did not affect joint angle dynamics. Thus, we concluded that the quadratic relationship between stepping frequency and gait dynamics observed in walking is not present in stairmill climbing based on the investigated parameters.

Cord blood NK cells engineered to express IL-15 and a CD19-targeted CAR show long-term persistence and potent antitumor activity.

Chimeric antigen receptors (CARs) have been used to redirect the specificity of autologous T cells against leukemia and lymphoma with promising clinical results. Extending this approach to allogeneic T cells is problematic as they carry a significant risk of graft-versus-host disease (GVHD). Natural killer (NK) cells are highly cytotoxic effectors, killing their targets in a non-antigen-specific manner without causing GVHD. Cord blood (CB) offers an attractive, allogeneic, off-the-self source of NK cells for immunotherapy. We transduced CB-derived NK cells with a retroviral vector incorporating the genes for CAR-CD19, IL-15 and inducible caspase-9-based suicide gene (iC9), and demonstrated efficient killing of CD19-expressing cell lines and primary leukemia cells in vitro, with marked prolongation of survival in a xenograft Raji lymphoma murine model. Interleukin-15 (IL-15) production by the transduced CB-NK cells critically improved their function. Moreover, iC9/CAR.19/IL-15 CB-NK cells were readily eliminated upon pharmacologic activation of the iC9 suicide gene. In conclusion, we have developed a novel approach to immunotherapy using engineered CB-derived NK cells, which are easy to produce, exhibit striking efficacy and incorporate safety measures to limit toxicity. This approach should greatly improve the logistics of delivering this therapy to large numbers of patients, a major limitation to current CAR-T-cell therapies.