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We present results from the KMOS Lens-Amplified Spectroscopic Survey (KLASS), an ESO Very Large Telescope (VLT) large program using gravitational lensing to study the spatially resolved kinematics of 44 star-forming galaxies at 0.6 < z < 2.3 with a stellar mass of 8.1 < log(M⋆/M⊙) < 11.0. These galaxies are located behind six galaxy clusters selected from the Hubble Space Telescope Grism Lens-Amplified Survey from Space (GLASS). We find that the majority of the galaxies show a rotating disc, but most of the rotation-dominated galaxies only have a low υ rot/σ0 ratio (median of υrot/σ0 ∼2.5). We explore the Tully-Fisher relation by adopting the circular velocity, $V_{\mathrm{ circ}}=(\upsilon _{\mathrm{ rot}}^2+3.4\sigma _0^2)^{1/2}$, to account for pressure support. We find that our sample follows a Tully-Fisher relation with a positive zero-point offset of +0.18 dex compared to the local relation, consistent with more gas-rich galaxies that still have to convert most of their gas into stars. We find a strong correlation between the velocity dispersion and stellar mass in the KLASS sample. When combining our data to other surveys from the literature, we see an increase of the velocity dispersion with stellar mass at all redshift. We obtain an increase of υrot/σ0 with stellar mass at 0.5 < z < 1.0. This could indicate that massive galaxies settle into regular rotating discs before the low-mass galaxies. For higher redshift (z > 1), we find a weak increase or flat trend. We find no clear trend between the rest-frame UV clumpiness and the velocity dispersion and υrot/σ0. This could suggest that the kinematic properties of galaxies evolve after the clumps formed in the galaxy disc or that the clumps can form in different physical conditions.

Detections and non-detections of Lyman alpha (Lyα) emission from z > 6 galaxies ( 7, where Lyα redshifts to near infra-red wavelengths. Here we present a search for z > 7.2 Lyα emission in 53 intrinsically faint Lyman Break Galaxy candidates, gravitationally lensed by massive galaxy clusters, in the KMOS Lens-Amplified Spectroscopic Survey (KLASS). With integration times of ∼7-10 h, we detect no Lyα emission with signal-to-noise ratio (S/N) > 5 in our sample. We determine our observations to be 80 per cent complete for 5σ spatially and spectrally unresolved emission lines with integrated line flux >5.7 × 10−18 erg s−1 cm−2. We define a photometrically selected sub-sample of 29 targets at z = 7.9 ± 0.6, with a median 5σ Lyα EW limit of 58 Å. We perform a Bayesian inference of the average intergalactic medium (IGM) neutral hydrogen fraction using their spectra. Our inference accounts for the wavelength sensitivity and incomplete redshift coverage of our observations, and the photometric redshift probability distribution of each target. These observations, combined with samples from the literature, enable us to place a lower limit on the average IGM neutral hydrogen fraction of > 0.76 (68 per cent), > 0.46 (95 per cent) at z ∼ 8, providing further evidence of rapid reionization at z ∼ 6-8. We show that this is consistent with reionization history models extending the galaxy luminosity function to MUV −12, with low ionizing photon escape fractions, fesc 15 per cent.

We present deep spectroscopic observations of a Lyman break galaxy (LBG) candidate (hereafter MACS1149-JD) at z ∼ 9.5 with the Hubble Space Telescope (HST) WFC3/IR grisms. The grism observations were taken at four distinct position angles, totaling 34 orbits with the G141 grism, although only 19 of the orbits are relatively uncontaminated along the trace of MACS1149-JD. We fit a three-parameter (z, F160W mag, and Lyα equivalent width [EW]) LBG template to the three least contaminated grism position angles using a Markov chain Monte Carlo approach. The grism data alone are best fit with a redshift of (68% confidence), in good agreement with our photometric estimate of (68% confidence). Our analysis rules out Lyα emission from MACS1149-JD above a 3σ EW of 21 Å, consistent with a highly neutral IGM. We explore a scenario where the red Spitzer/IRAC [3.6]-[4.5] color of the galaxy previously pointed out in the literature is due to strong rest-frame optical emission lines from a very young stellar population rather than a 4000 Å break. We find that while this can provide an explanation for the observed IRAC color, it requires a lower redshift (z ≲ 9.1), which is less preferred by the HST imaging data. The grism data are consistent with both scenarios, indicating that the red IRAC color can still be explained by a 4000 Å break, characteristic of a relatively evolved stellar population. In this interpretation, the photometry indicates that a Myr stellar population is already present in this galaxy only ∼500 Myr after the big bang.

We present the first results of the K-band Multi-Object Spectrometer (KMOS) Lens-Amplified Spectroscopic Survey, a new ESO Very Large Telescope large program, doing multi-object integral field spectroscopy of galaxies gravitationally lensed behind seven galaxy clusters selected from the Hubble Space Telescope (HST) Grism Lens-Amplified Survey from Space. Using the power of the cluster magnification, we are able to reveal the kinematic structure of 25 galaxies at 0.7 z 2.3, in four cluster fields, with stellar masses 7.8log;(M∗/Mo) 10.5. This sample includes five sources at Z > 1 with lower stellar masses than in any previous kinematic integral field unit (IFU) surveys. Our sample displays a diversity in kinematic structure over this mass and redshift range. The majority of our kinematically resolved sample is rotationally supported, but with a lower ratio of rotational velocity to velocity dispersion than in the local universe, indicating the fraction of dynamically hot disks changes with cosmic time. We find that no galaxies with stellar mass

We combine deep Hubble Space Telescope grism spectroscopy with a new Bayesian method to derive maps of gas-phase metallicity for 10 star-forming galaxies at high redshift (). Exploiting lensing magnification by the foreground cluster MACS1149.6+2223, we reach sub-kiloparsec spatial resolution and push the limit of stellar mass associated with such high-z spatially resolved measurements below for the first time. Our maps exhibit diverse morphologies, indicative of various effects such as efficient radial mixing from tidal torques, rapid accretion of low-metallicity gas, and other physical processes that can affect the gas and metallicity distributions in individual galaxies. Based upon an exhaustive sample of all existing sub-kiloparesec resolution metallicity gradient measurements at high z, we find that predictions given by analytical chemical evolution models assuming a relatively extended star-formation profile in the early disk-formation phase can explain the majority of observed metallicity gradients, without involving galactic feedback or radial outflows. We observe a tentative correlation between stellar mass and metallicity gradients, consistent with the "downsizing" galaxy formation picture that more massive galaxies are more evolved into a later phase of disk growth, where they experience more coherent mass assembly at all radii and thus show shallower metallicity gradients. In addition to the spatially resolved analysis, we compile a sample of homogeneously cross-calibrated integrated metallicity measurements spanning three orders of magnitude in stellar mass at z ∼ 1.8. We use this sample to study the mass-metallicity relation (MZR) and find that the slope of the observed MZR can rule out the momentum-driven wind model at a 3σ confidence level.

We present a model for the evolution of the galaxy ultraviolet (UV) luminosity function (LF) across cosmic time where star formation is linked to the assembly of dark matter halos under the assumption of a mass-dependent, but redshift-independent, efficiency. We introduce a new self-consistent treatment of the halo star formation history, which allows us to make predictions at z > 10 (lookback time ≲500 Myr), when growth is rapid. With a calibration at a single redshift to set the stellar-to-halo mass ratio, and no further degrees of freedom, our model captures the evolution of the UV LF over all available observations (0 ≲ z ≲ 10). The significant drop in luminosity density of currently detectable galaxies beyond z ∼ 8 is explained by a shift of star formation toward less massive, fainter galaxies. Assuming that star formation proceeds down to atomic cooling halos, we derive a reionization optical depth T = 0.056+0.007-0.010, fully consistent with the latest Planck measurement, implying that the universe is fully reionized at z = 7.84+0.65-0.98. In addition, our model naturally produces smoothly rising star formation histories for galaxies with L ≲ L∗ in agreement with observations and hydrodynamical simulations. Before the epoch of reionization at z > 10 we predict the LF to remain well-described by a Schechter function, but with an increasingly steep faint-end slope (α ∼ -3.5 at z ∼ 16). Finally, we construct forecasts for surveys with James Webb Space Telescope (JWST) and Wide-field Infrared Survey Telescope (WFIRST) and predict that galaxies out to z ∼ 14 will be observed. Galaxies at z > 15 will likely be accessible to JWST and WFIRST only through the assistance of strong lensing magnification.

Abstract Research has been published regarding the effects of sublethal dicamba rates applied at different growth stages in soybean [Glycine max (L.) Merr.]; however, there is limited research on the effect of dicamba on reproductive growth in corn (Zea mays L.) and rice (Oryza sativa L.). Experiments were conducted in 2018 and 2019 to determine the potential consequences of dicamba exposure to reproductive stages of corn and rice. Dicamba was applied at 0.56, 5.6, 56, and 560 g ae ha–1, with a 1X rate being 560 g ae ha–1. Each rate was applied at three reproductive growth stages (corn: pretassel, tassel, and green silk; rice: late boot, panicle exertion, and anthesis). Visible injury to corn was negligible; however, rice treated with dicamba at 56 and 560 g ae ha–1 had noticeably greater injury (3 and 12%, respectively) relative to the nontreated. For rice, visible injury associated with dicamba at 56 and 560 g ae ha–1 appeared in the form of upright panicles, which reduced panicle weight and seeds per panicle, ultimately decreasing yields by 2,120 (22%) and 4,140 kg ha–1 (43%). A yield loss in corn could be detected only when dicamba was applied at 560 g ae ha–1 at the pretassel growth stage despite dicamba at 560 g ae ha–1 reducing seeds per row and total seeds per ear. With severe consequences being observed only at high dicamba rates, the threat of off‐target movement to corn and rice is far less severe than in soybean.

ABSTRACT: Introduction: The frequency of adverse outcomes after revision ACLR emphasizes the importance of the primary reconstruction regarding intra-articular graft healing and tunnel osteointegration. Objectives: The objective was to generate a functionalized suture based on peptide attachments that spatially recruits VEGFs and BMPs for graft healing. It was hypothesized that the suture would capture cytokines with favorable graft-bone integration in an ACLR rabbit model. Methods: Suture functionalization with established peptides was tested by immunofluorescence (IF) for recombinant VEGFA and BMP2. Three rabbit groups (n = 12/group) underwent ACLR using either a dual functionalized, plain suture (DF vs suture groups) or no suture (tendon group). Outcomes were assessed by μCT, molecular analysis, histology, and biomechanics at 4 to 12 weeks postoperatively. Results: Adequate functionalization was verified by IF for both growth factors. In vivo, the bone mineral density trended towards an increase at 4 weeks in the DF group (P > .194) but not at 12 weeks. Healing was better in the mid-section bone tunnel areas of the tendon group at 12 weeks compared to the suture (P = .026), or DF group (P = .011). Molecular analysis was inconclusive. Accumulation of growth factors was not evident by immunohistochemistry. Biomechanics showed no intergroup difference. Conclusions: The study established the development of a suture capable of capturing BMP2 and VEGFA by a peptide-binding strategy. This technology did not show superior tissue response or changes in biological parameters of ingrowth in vivo but seems to be interfering with bone tunnel closure at 12 weeks. The current model and technology should be further optimized.

BACKGROUND: Research on contextual and neighborhood effects increasingly includes the built (physical) environment's influences on health and social well-being. A population-based study examined whether architectural features of the built environment theorized to promote observations and social interactions (e.g., porches, windows) predict Hispanic elders' psychological distress. METHODS: Coding of built environment features of all 3,857 lots across 403 blocks in East Little Havana, Florida, and enumeration of elders in 16,000 households was followed by assessments of perceived social support and psychological distress in a representative sample of 273 low socioeconomic status (SES) Hispanic elders. Structural-equation modeling was used to assess relationships between block-level built environment features, elders' perceived social support, and psychological distress. RESULTS: Architectural features of the front entrance such as porches that promote visibility from a building's exterior were positively associated with perceived social support. In contrast, architectural features such as window areas that promote visibility from a building's interior were negatively associated with perceived social support. Perceived social support in turn was associated with reduced psychological distress after controlling for demographics. Additionally, perceived social support mediated the relationship of built environment variables to psychological distress. CONCLUSIONS: Architectural features that facilitate direct, in-person interactions may be beneficial for Hispanic elders' mental health. [ABSTRACT FROM AUTHOR]

This study documents a 35% prevalence of clinically relevant depressive symptoms in a population-based sample of mostly Cuban older adults residing in a low-income, urban Miami neighborhood. This rate is comparable to, or higher than, prevalence rates reported by most other population-based samples of U.S. older adults. Logistic regression analyses indicate that perceived financial strain was the only sociodemographic factor associated with greater odds of clinically relevant symptoms when other sociodemographic factors were statistically controlled. Gender, age, and marital status were not related to elevated depressive symptoms. A case study illustrates the impact of financial strain on older adults' mental health. Findings highlight the need for mental health screening and case management services among these older adults, particularly those who experience financial strain. [ABSTRACT FROM AUTHOR]

Ethnic diversity in the former Yugoslavia, measured as informational entropy increased in most regions at the level of the naselje, the opština, and the region, 1961-1991 (no useful data for Slovenia, Macedonia, and Kosovo in 1991). Vojvodina is the most diverse region, Slovenia the least. An exception to the increase is Kosovo-Metohija, where diversity decreased 1961-1981 driven by already serious interethnic conflict. There is some diminution of the increase in diversity in some regions in 1991, possibly because of refugee flows in anticipation of the impending violence. This rather broad and steady increase in diversity leads to questions about the view that pre-existing ethnic hatreds among broad segments of the population led to the ethnic fracturing and collapse of Yugoslavia. Instead it suggests that this fracturing may instead have been the result of competition between political leaders, stimulated by serious economic difficulties, leading them to emphasize ethnicity in their search for popular support. From this the authors support the view that the collapse of Yugoslavia was from the top downward, not from the bottom upward.

Abstract Background Campylobacter jejuni, a gram-negative bacterium, is a frequent cause of gastrointestinal food-borne illness in humans throughout the world. There are several reports that the virulence of C. jejuni might be modulated by non-flagellar proteins that are secreted through the filament. Recently, FspA (Flagella secreted proteins) have been described. Two alleles of fspA (fspA1 and fspA2) based on sequence analysis were previously reported and only the fspA2 allele was found in Thai isolates. The aim of this study is to analyze the deduced amino acid sequences fspA and the adjacent putative integral membrane protein from 103 Thai C. jejuni isolates. Results A total of 103 representative C. jejuni isolates were amplified by PCR for the fspA gene and the adjacent integral membrane protein gene. Two PCR product sizes were amplified using the same primers, an approximately 1600-bp PCR product from 19 strains that contained fspA and integral membrane protein genes and an approximately 800-bp PCR product from 84 strains that contained only the fspA gene. DNA sequencing was performed on the amplified products. The deduced amino acid sequences of both genes were analyzed separately using CLC Free Workbench 4 software. The analysis revealed three groups of FspA. Only FspA group 1 sequences (19/103) (corresponding to fspA1) consisting of 5 subgroups were associated with the adjacent gene encoding the integral membrane protein. FspA group 2 was the largest group (67/103) consisting of 9 subgroups. FspA group 2p (17/103) consisting of 7 subgroups was found to contain stop codons at a position before the terminal 142 position. Conclusions This study reveals greater heterogeneity of FspA (group 1, 2 and 2p) among Thai C. jejuni isolates than previously reported. Furthermore, the subgroups of FspA groups 1 were associated with groups of integral membrane protein. The significance of these different FspA variants to virulence requires further study.

Abstract Background Shigella is a frequent cause of bacterial dysentery in the developing world. Treatment with effective antibiotics is recommended for shigellosis, but options become limited due to globally emerging resistance. One of the mechanisms for the development of resistance utilizes integrons. This study described the antibiotic susceptibility and the presence of class 1 and 2 integrons in S. flexneri and S. sonnei isolated in Uzbekistan. Results We studied 31 isolates of S. flexneri and 21 isolates of S. sonnei isolated in Uzbekistan between 1992 and 2007 for the susceptibility or resistance to ampicillin (Am), chloramphenicol (Cl), tetracycline (Te), co-trimoxazole (Sxt), kanamycin (Km), streptomycin (Str), gentamicin (Gm), cefazolin (Czn), cefoperazone (Cpr), cefuroxime (Cur), ceftazidime (Ctz), nalidixic acid (NA) and ciprofloxacin (Cip). Am/Str/Cl/Te and Am/Str/Cl/Te/Sxt resistance patterns were found most frequently in S. flexneri. Single isolates were resistant to aminoglycoside, quinolones and cephalosporins. The resistance patterns were different in the two species. Integrons were detected in 93.5% of S. flexneri (29/31) and 81.0% of S. sonnei (17/21) isolates. In addition, 61.3% of S. flexneri (19/31) isolates and 19.0% of S. sonnei (4/21) isolates carried both classes of integrons. In 29.0% of S. flexneri (9/31) isolates, only class 1 integrons were identified. In S. flexneri isolates, the presence of class 1 integrons was associated with resistance to ampicillin and chloramphenicol. Only Class 2 integrons were present in 61.9% of S. sonnei (13/21) isolates. Conclusions Our study documents antibiotic resistance among Shigella spp. in Uzbekistan. Ninety percent of Shigella strains were resistant to previously used antibiotics. Differences among S. flexneri and S. sonnei isolates in patterns of antimicrobial resistance to routinely used shigellosis antibiotics were observed. The majority of S. flexneri were resistant to ampicillin, chloramphenicol, tetracycline and streptomycin. Class 1 and 2 integrons were widely present in these Shigella strains. Resistance to ampicillin/chloramphenicol was associated with the presence of class 1 integrons. Though several mechanisms are possible, the resistance of Shigella isolates to ampicillin/chloramphenicol may be associated with the expression of genes within class 1 integrons.

Abstract Background Campylobacter jejuni is a major cause of gastroenteritis worldwide. In Thailand, several strains of C. jejuni have been isolated and identified as major diarrheal pathogens among adult travelers. To study the epidemiology of C. jejuni in adult travelers and U.S. military personnel with acute diarrhea in Thailand from 1998-2003, strains of C. jejuni were isolated and phenotypically identified, serotyped, tested for antimicrobial susceptibility, and characterized using pulsed-field gel electrophoresis (PFGE). Results A total of 312 C. jejuni isolates were obtained from travelers (n = 46) and U.S. military personnel (n = 266) in Thailand who were experiencing acute diarrhea. Nalidixic acid and ciprofloxacin resistance was observed in 94.9% and 93.0% of the isolates, respectively. From 2001-2003, resistance to tetracycline (81.9%), trimethoprim-sulfamethoxazole (57.9%), ampicillin (28.9%), kanamycin (5.9%), sulfisoxazole (3.9%), neomycin (2.0%), and streptomycin (0.7%) was observed. Combined PFGE analysis showed considerable genetic diversity among the C. jejuni isolates; however, four PFGE clusters included isolates from the major Lior serotypes (HL: 36, HL: 11, HL: 5, and HL: 28). The PFGE analysis linked individual C. jejuni clones that were obtained at U.S. military exercises with specific antimicrobial resistance patterns. Conclusions In summary, most human C. jejuni isolates from Thailand were multi-resistant to quinolones and tetracycline. PFGE detected spatial and temporal C. jejuni clonality responsible for the common sources of Campylobacter gastroenteritis.

Abstract Background Arcobacter spp. are a common contaminant of food and water, and some species, primarily A. butzleri and A. cryaerophilus, have been isolated increasingly from human diarrheal stool samples. Here, we describe the first Arcobacter multilocus sequence typing (MLST) method for A. butzleri, A. cryaerophilus, A. skirrowii, A. cibarius and A. thereius. Results A sample set of 374 arcobacters, including 275 A. butzleri, 72 A. cryaerophilus, 15 A. skirrowii and 8 A. cibarius isolates from a wide variety of geographic locations and sources, was typed in this study. Additionally, this sample set contained four strains representing a new Arcobacter species, A. thereius. The seven loci used in the four-species Arcobacter MLST method are the same as those employed previously in C. jejuni, C. coli, C. helveticus and C. fetus (i.e. aspA, atpA(uncA), glnA, gltA, glyA, pgm and tkt). A large number of alleles were identified at each locus with the majority of isolates containing a unique sequence type. All Arcobacter isolates typed in this study contain two glyA genes, one linked to lysS (glyA1) and the other linked to ada (glyA2). glyA1 was incorporated into the Arcobacter MLST method while glyA2 was not because it did not increase substantially the level of discrimination. Conclusion No association of MLST alleles or sequence types with host or geographical source was observed with this sample set. Nevertheless, the large number of identified alleles and sequence types indicate that this MLST method will prove useful in both Arcobacter strain discrimination and in epidemiological studies of sporadic Arcobacter-related gastroenteritis. A new Arcobacter MLST database was created http://pubmlst.org/arcobacter/; allele and ST data generated in this study were deposited in this database and are available online.

Abstract Background Subtype A is a major strain in the HIV-1 pandemic in eastern Europe, central Asia and in certain regions of east Africa, notably in rural Kenya. While considerable effort has been focused upon mapping and defining immunodominant CTL epitopes in HIV-1 subtype B and subtype C infections, few epitope mapping studies have focused upon subtype A. Results We have used the IFN-γ ELIspot assay and overlapping peptide pools to show that the pattern of CTL recognition of the Gag and Nef proteins in subtype A infection is similar to that seen in subtypes B and C. The p17 and p24 proteins of Gag and the central conserved region of Nef were targeted by CTL from HIV-1-infected Kenyans. Several epitope/HLA associations commonly seen in subtype B and C infection were also observed in subtype A infections. Notably, an immunodominant HLA-C restricted epitope (Gag 296–304; YL9) was observed, with 8/9 HLA-CW0304 subjects responding to this epitope. Screening the cohort with peptide sets representing subtypes A, C and D (the three most prevalent HIV-1 subtypes in east Africa), revealed that peptide sets based upon an homologous subtype (either isolate or consensus) only marginally improved the capacity to detect CTL responses. While the different peptide sets detected a similar number of responses (particularly in the Gag protein), each set was capable of detecting unique responses not identified with the other peptide sets. Conclusion Hence, screening with multiple peptide sets representing different sequences, and by extension different epitope variants, can increase the detectable breadth of the HIV-1-specific CTL response. Interpreting the true extent of cross-reactivity may be hampered by the use of 15-mer peptides at a single concentration and a lack of knowledge of the sequence that primed any given CTL response. Therefore, reagent choice and knowledge of the exact sequences that prime CTL responses will be important factors in experimentally defining cross-reactive CTL responses and their role in HIV-1 disease pathogenesis and validating vaccines aimed at generating broadly cross-reactive CTL responses.

This study examines the relationship between cognitive functioning and depressive symptoms across 3 years in a prospective study of 273 community-dwelling, Hispanic older adults in Miami. The analyses extend the literature by testing for a bidirectional or reciprocal relationship between depressive symptoms and cognitive functioning over time and by examining the relationship between these variables among Hispanics, an understudied population at risk of developing depressive symptoms and cognitive impairments. Structural equation modeling with a cross-lagged panel design showed that depressive symptoms were unrelated to subsequent cognitive functioning. However, cognitive functioning was related to subsequent depressive symptoms at every time point, such that poorer cognitive functioning was related to higher depressive symptoms. Findings suggest that cognitive declines may predict depressive symptoms in community-dwelling Hispanic older adults. [ABSTRACT FROM AUTHOR]

Primordial neutral atomic gas, mostly composed of hydrogen, is the raw material for star formation in galaxies. However, there are few direct constraints on the amount of neutral atomic hydrogen (H i) in galaxies at early cosmic times. We analyzed James Webb Space Telescope (JWST) near-infrared spectroscopy of distant galaxies, at redshifts ≳8. From a sample of 12 galaxies, we identified three that show strong damped Lyman-α absorption due to H i in their local surroundings. The galaxies are located at spectroscopic redshifts of 8.8, 10.2, and 11.4, corresponding to 400 to 600 million years after the Big Bang. They have H i column densities ≳10 22 cm -2 , which is an order of magnitude higher than expected for a fully neutral intergalactic medium, and constitute a gas-rich population of young star-forming galaxies.

Retinal ganglion cell (RGC) death in glaucoma and other optic neuropathies results in irreversible vision loss due to the mammalian central nervous system's limited regenerative capacity. RGC repopulation is a promising therapeutic approach to reverse vision loss from optic neuropathies if the newly introduced neurons can reestablish functional retinal and thalamic circuits. In theory, RGCs might be repopulated through the transplantation of stem cell-derived neurons or via the induction of endogenous transdifferentiation. The RGC Repopulation, Stem Cell Transplantation, and Optic Nerve Regeneration (RReSTORe) Consortium was established to address the challenges associated with the therapeutic repair of the visual pathway in optic neuropathy. In 2022, the RReSTORe Consortium initiated ongoing international collaborative discussions to advance the RGC repopulation field and has identified five critical areas of focus: (1) RGC development and differentiation, (2) Transplantation methods and models, (3) RGC survival, maturation, and host interactions, (4) Inner retinal wiring, and (5) Eye-to-brain connectivity. Here, we discuss the most pertinent questions and challenges that exist on the path to clinical translation and suggest experimental directions to propel this work going forward. Using these five subtopic discussion groups (SDGs) as a framework, we suggest multidisciplinary approaches to restore the diseased visual pathway by leveraging groundbreaking insights from developmental neuroscience, stem cell biology, molecular biology, optical imaging, animal models of optic neuropathy, immunology & immunotolerance, neuropathology & neuroprotection, materials science & biomedical engineering, and regenerative neuroscience. While significant hurdles remain, the RReSTORe Consortium's efforts provide a comprehensive roadmap for advancing the RGC repopulation field and hold potential for transformative progress in restoring vision in patients suffering from optic neuropathies., (© 2023. Editorial Group and BioMed Central Ltd., part of Springer Nature.)

Purpose: The Retinal Ganglion Cell (RGC) Repopulation, Stem Cell Transplantation, and Optic Nerve Regeneration (RReSTORe) consortium was founded in 2021 to help address the numerous scientific and clinical obstacles that impede development of vision-restorative treatments for patients with optic neuropathies. The goals of the RReSTORe consortium are: (1) to define and prioritize the most critical challenges and questions related to RGC regeneration; (2) to brainstorm innovative tools and experimental approaches to meet these challenges; and (3) to foster opportunities for collaborative scientific research among diverse investigators., Design and Participants: The RReSTORe consortium currently includes > 220 members spanning all career stages worldwide and is directed by an organizing committee comprised of 15 leading scientists and physician-scientists of diverse backgrounds., Methods: Herein, we describe the structure and organization of the RReSTORe consortium, its activities to date, and the perceived impact that the consortium has had on the field based on a survey of participants., Results: In addition to helping propel the field of regenerative medicine as applied to optic neuropathies, the RReSTORe consortium serves as a framework for developing large collaborative groups aimed at tackling audacious goals that may be expanded beyond ophthalmology and vision science., Conclusions: The development of innovative interventions capable of restoring vision for patients suffering from optic neuropathy would be transformative for the ophthalmology field, and may set the stage for functional restoration in other central nervous system disorders. By coordinating large-scale, international collaborations among scientists with diverse and complementary expertise, we are confident that the RReSTORe consortium will help to accelerate the field toward clinical translation., Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (© 2023 by the American Academy of Ophthalmology.)

Semaphorins and Plexins form ligand/receptor pairs that are crucial for a wide range of developmental processes from cell proliferation to axon guidance. The ability of semaphorins to act both as signaling receptors and ligands yields a multitude of responses. Here, we describe a novel role for Semaphorin-6D (Sema6D) and Plexin-A1 in the positioning and targeting of retinogeniculate axons. In Plexin-A1 or Sema6D mutant mice of either sex, the optic tract courses through, rather than along, the border of the dorsal lateral geniculate nucleus (dLGN), and some retinal axons ectopically arborize adjacent and lateral to the optic tract rather than defasciculating and entering the target region. We find that Sema6D and Plexin-A1 act together in a dose-dependent manner, as the number of the ectopic retinal projections is altered in proportion to the level of Sema6D or Plexin-A1 expression. Moreover, using retinal in utero electroporation of Sema6D or Plexin-A1 shRNA, we show that Sema6D and Plexin-A1 are both required in retinal ganglion cells for axon positioning and targeting. Strikingly, nonelectroporated retinal ganglion cell axons also mistarget in the tract region, indicating that Sema6D and Plexin-A1 can act non-cell-autonomously, potentially through axon-axon interactions. These data provide novel evidence for a dose-dependent and non-cell-autonomous role for Sema6D and Plexin-A1 in retinal axon organization in the optic tract and dLGN. SIGNIFICANCE STATEMENT Before innervating their central brain targets, retinal ganglion cell axons fasciculate in the optic tract and then branch and arborize in their target areas. Upon deletion of the guidance molecules Plexin-A1 or Semaphorin-6D, the optic tract becomes disorganized near and extends within the dorsal lateral geniculate nucleus. In addition, some retinal axons form ectopic aggregates within the defasciculated tract. Sema6D and Plexin-A1 act together as a receptor-ligand pair in a dose-dependent manner, and non-cell-autonomously, to produce this developmental aberration. Such a phenotype highlights an underappreciated role for axon guidance molecules in tract cohesion and appropriate defasciculation near, and arborization within, targets., (Copyright © 2023 the authors.)

The current study investigated the effectiveness of three distinct educational technologies-two game-based applications (From Here to There and DragonBox 12+) and two modes of online problem sets in ASSISTments (an Immediate Feedback condition and an Active Control condition with no immediate feedback) on Grade 7 students' algebraic knowledge. More than 3,600 Grade 7 students across nine in-person and one virtual schools within the same district were randomly assigned to one of the four conditions. Students received nine 30-minute intervention sessions from September 2020 to March 2021. Hierarchical linear modeling analyses of the final analytic sample (N = 1,850) showed significantly higher posttest scores for students who used From Here to There and DragonBox 12+ compared to the Active Control condition. No significant difference was found for the Immediate Feedback condition. The findings have implications for understanding how game-based applications can affect algebraic understanding, even within pandemic pressures on learning., (© The Author(s) 2023.)

In albinism, aberrations in the ipsi-/contralateral retinal ganglion cell (RGC) ratio compromise the functional integrity of the binocular circuit. Here, we focus on the mouse ciliary margin zone (CMZ), a neurogenic niche at the embryonic peripheral retina, to investigate developmental processes regulating RGC neurogenesis and identity acquisition. We found that the mouse ventral CMZ generates predominantly ipsilaterally projecting RGCs, but this output is altered in the albino visual system because of CyclinD2 downregulation and disturbed timing of the cell cycle. Consequently, albino as well as CyclinD2-deficient pigmented mice exhibit diminished ipsilateral retinogeniculate projection and poor depth perception. In albino mice, pharmacological stimulation of calcium channels, known to upregulate CyclinD2 in other cell types, augmented CyclinD2-dependent neurogenesis of ipsilateral RGCs and improved stereopsis. Together, these results implicate CMZ neurogenesis and its regulators as critical for the formation and function of the mammalian binocular circuit., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

The study compares receipt and timeliness of newborn hearing screening and follow-up diagnostic services between the pre-pandemic birth cohort and the pandemic birth cohort in four participating states. Findings from this study will help inform state Early Hearing Detection and Intervention (EHDI) programs in the future should a major public health event occur again., Competing Interests: Disclosures: The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the Centers for Disease Control and Prevention. The authors declare no conflicts of interest.

This perspective aims to highlight aspects of the Early Hearing Detection and Intervention (EHDI) newborn hearing screening and follow-up processes that were impacted by the COVID-19 pandemic and considers factors that likely impacted follow-up after failing newborn hearing screening among infants born in the United States during 2020. Efforts to minimize the potential impact of missed or delayed identification of hearing loss in infants and young children will also be discussed to help guide future program improvement activities.

Background: A primary goal of early intervention is to assist children in achieving age-appropriate language skills. The amount of intervention a child receives is ideally based on his or her individual needs, yet it is unclear if language ability impacts amount of intervention and/or if an increased frequency of intervention sessions results in better outcomes. The purpose of this study was to determine the relationship between the frequency of early intervention sessions and vocabulary outcomes in young children with hearing loss., Methods: This was a longitudinal study of 210 children 9 to 36 months of age with bilateral hearing loss living in 12 different states. Expressive vocabulary skills were evaluated using the MacArthur-Bates Communicative Development Inventories., Results: A higher number of intervention sessions reported at the first assessment predicted better vocabulary scores at the second assessment, and more sessions reported at the second assessment predicted better scores at the third assessment. For each increase in the number of sessions reported, there was a corresponding, positive increase in vocabulary quotient. In contrast, children's vocabulary ability at an earlier time point did not predict intervention session frequency at a later point in time., Conclusions: A significant prospective effect was apparent with more therapy sessions resulting in improved vocabulary scores 9 months later. These findings underscore the importance of early intervention. Pediatricians and other health care professionals can help apply these findings by counseling parents regarding the value of frequent and consistent participation in early intervention.

Objectives: To investigate trends in population-level school-aged reading scores among students with hearing loss in an urban Colorado school district after implementation of universal newborn hearing screening (UNHS) and Early Hearing Detection and Intervention., Methods: The final sample included 1422 assessments conducted during the 2000-2001 through 2013-2014 school years for 321 children with hearing loss in grades 3 through 10. Longitudinal hierarchical linear modeling analyses were used to examine reading proficiency (controlling for birth year, grade in school, free and reduced lunch status, additional disability services, and English not spoken in the home). The Colorado Student Assessment Program was administered to students in third through 10th grades throughout the state. The test years chosen included children born before and after implementation of UNHS., Results: After implementation of UNHS, significant longitudinal reading proficiency improvements were observed by birth year and grade overall and for all subgroups. However, gains in reading proficiency were substantially less for children eligible for free and reduced lunch and those with moderate-severe to profound hearing loss. With each succeeding birth cohort and grade, increased numbers of children participated in testing because of improved language skills, with higher proportions identified as proficient or advanced readers., Conclusions: Notable improvements in reading proficiency after Early Hearing Detection and Intervention implementation were demonstrated, as all groups of children with hearing loss became more likely to achieve proficient and advanced reading levels. On the other hand, some disparities increased, with greater improvements in reading proficiency for children in economically advantaged families., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2021 by the American Academy of Pediatrics.)

Purpose: To characterize the impact of slowed processing speed on the efficiency of broader cognitive function in temporal lobe epilepsy (TLE)., Methods: Participants included 100 patients with TLE and 89 healthy controls (mean ages 36.8 and 33.6, respectively) administered a neuropsychological battery consisting of 15 cognitive metrics. Confirmatory factor analysis using structural equation modeling (SEM) latent variable modeling demonstrated a cognitive structure representing the domains of verbal intelligence, immediate memory, delayed memory, executive function, working memory, and processing speed. Furthermore, the latent variable measurement model determined the direct and indirect relationships of verbal intelligence and processing speed with immediate memory, delayed memory, executive function, and working memory., Results: Following SEM of hypothesized structural models, the results demonstrated that, among controls, intelligence had a direct and unmediated (by processing speed) relationship with all identified cognitive domains. In contrast, among participants with TLE, processing speed mediated the relationship between verbal intelligence and performance across all cognitive domains., Conclusion: Slowing of cognitive/psychomotor processing speed appears to play a critical mediating role in the broader cognitive status of participants with TLE and may serve as a target through which to attempt to exert a broad positive impact on neuropsychological status., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: Metastatic breast cancer is the second leading cause of cancer-related death in women. The 5-year survival rate for metastatic breast cancer has remained near 26.9 % for over a decade. The recruitment of hematopoietic stem cells with high expression of the vascular endothelial growth factor receptor 1 (VEGFR-1) has been implicated in early stages of metastasis formation. We propose the use of an 18 F-labeled single-chain version of VEGF121, re-engineered to be selective for VEGFR-1 (scVR1), as a positron emission tomography (PET) imaging agent to non-invasively image early-stage metastases., Procedures: scVR1 was 18 F-labeled via a biorthogonal click reaction between site-specifically trans-cyclooctene functionalized scVR1 and an Al 18 F labeled tetrazine-NODA (1,4,7-triazacyclononane-1,4-diiacetic acid). The [ 18 F]AlF-NODA-scVR1 was purified using a PD10 column and subsequently analyzed on HPLC to determine radiochemical purity. Animal experiments were performed in 6-8-week-old female BALB/c mice bearing orthotopic primary 4T1 breast tumors or 4T1 metastatic lesions. The [ 18 F]AlF-NODA-scVR1 tracer was administered via tail vein injection; PET imaging and ex vivo analysis was performed 2 h post-injection., Results: The [ 18 F]AlF-NODA-scVR1 was prepared with a 98.2 ± 1.5 % radiochemical purity and an apparent molar activity of 7.5 ± 1.2 GBq/μmol. The specific binding of scVR1 to VEGFR-1 was confirmed via bead-based assay. The ex vivo biodistribution showed tumor uptake of 3.5 ± 0.5 % ID/g and was readily observable in PET images. Metastasis formation was detected with [ 18 F]AlF-NODA-scVR1 tracer showing colocalization with bioluminescent imaging as well as ex vivo autoradiography and immunofluorescent staining of VEGFR-1., Conclusions: The diagnostic capabilities of the [ 18 F]AlF-NODA-scVR1 PET tracer was confirmed in both orthotopic and metastatic murine cancer models. These results support the potential use of [ 18 F]AlF-NODA-scVR1 as a PET tracer that could image metastases, providing clinicians with an additional tool to assess a patient's need for adjuvant therapies.