Integrated results from the COPERNICUS and GALILEO studies.

OBJECTIVES: To report on the efficacy and safety of intravitreal aflibercept in patients with macular edema secondary to central retinal vein occlusion (CRVO) in an integrated analysis of COPERNICUS and GALILEO. PATIENTS AND METHODS: Patients were randomized to receive intravitreal aflibercept 2 mg every 4 weeks or sham injections until week 24. From week 24 to week 52, all intravitreal aflibercept-treated patients in both studies and sham-treated patients in COPERNICUS were eligible to receive intravitreal aflibercept based on prespecified criteria. In GALILEO, sham-treated patients continued to receive sham treatment through week 52. RESULTS: At week 24, mean gain in best-corrected visual acuity and mean reduction in central retinal thickness were greater for intravitreal aflibercept-treated patients compared with sham, consistent with individual trial results. At week 52, after 6 months of intravitreal aflibercept as-needed treatment in COPERNICUS, patients originally randomized to sham group experienced visual and anatomic improvements but did not improve to the extent of those initially treated with intravitreal aflibercept, while the sham group in GALILEO did not improve over week 24 mean best-corrected visual acuity scores. Ocular serious adverse events occurred in CONCLUSION: This analysis of integrated data from COPERNICUS and GALILEO confirmed that intravitreal aflibercept is an effective treatment for macular edema following CRVO

Ibrutinib Unmasks Critical Role of Bruton Tyrosine Kinase in Primary CNS Lymphoma.

Bruton tyrosine kinase (BTK) links the B-cell antigen receptor (BCR) and Toll-like receptors with NF-κB. The role of BTK in primary central nervous system (CNS) lymphoma (PCNSL) is unknown. We performed a phase I clinical trial with ibrutinib, the first-in-class BTK inhibitor, for patients with relapsed or refractory CNS lymphoma. Clinical responses to ibrutinib occurred in 10 of 13 (77%) patients with PCNSL, including five complete responses. The only PCNSL with complete ibrutinib resistance harbored a mutation within the coiled-coil domain of CARD11, a known ibrutinib resistance mechanism. Incomplete tumor responses were associated with mutations in the B-cell antigen receptor-associated protein CD79B

Emergent sustainability in open property regimes

Current theoretical models of the commons assert that common-pool resources can only be managed sustainably with clearly defined boundaries around both communities and the resources that they use. In these theoretical models, open access inevitably leads to a tragedy of the commons. However, in many open-access systems, use of common-pool resources seems to be sustainable over the long term (i.e., current resource use does not threaten use of common-pool resources for future generations). Here, we outline the conditions that support sustainable resource use in open property regimes. We use the conceptual framework of complex adaptive systems to explain how processes within and couplings between human and natural systems can lead to the emergence of efficient, equitable, and sustainable resource use. We illustrate these dynamics in eight case studies of different social–ecological systems, including mobile pastoralism, marine and freshwater fisheries, swidden agriculture, and desert foraging. Our theoretical framework identifies eight conditions that are critical for the emergence of sustainable use of common-pool resources in open property regimes. In addition, we explain how changes in boundary conditions may push open property regimes to either common property regimes or a tragedy of the commons. Our theoretical model of emergent sustainability helps us to understand the diversity and dynamics of property regimes across a wide range of social–ecological systems and explains the enigma of open access without a tragedy. We recommend that policy interventions in such self-organizing systems should focus on managing the conditions that are critical for the emergence and persistence of sustainability

The influence of context and process when implementing e-health

Peer reviewedPublisher PD

Effects of gestational age at birth on cognitive performance : a function of cognitive workload demands

Objective: Cognitive deficits have been inconsistently described for late or moderately preterm children but are consistently found in very preterm children. This study investigates the association between cognitive workload demands of tasks and cognitive performance in relation to gestational age at birth. Methods: Data were collected as part of a prospective geographically defined whole-population study of neonatal at-risk children in Southern Bavaria. At 8;5 years, n = 1326 children (gestation range: 23–41 weeks) were assessed with the K-ABC and a Mathematics Test. Results: Cognitive scores of preterm children decreased as cognitive workload demands of tasks increased. The relationship between gestation and task workload was curvilinear and more pronounced the higher the cognitive workload: GA2 (quadratic term) on low cognitive workload: R2 = .02, p<0.001; moderate cognitive workload: R2 = .09, p<0.001; and high cognitive workload tasks: R2 = .14, p<0.001. Specifically, disproportionally lower scores were found for very (<32 weeks gestation) and moderately (32–33 weeks gestation) preterm children the higher the cognitive workload of the tasks. Early biological factors such as gestation and neonatal complications explained more of the variance in high (12.5%) compared with moderate (8.1%) and low cognitive workload tasks (1.7%). Conclusions: The cognitive workload model may help to explain variations of findings on the relationship of gestational age with cognitive performance in the literature. The findings have implications for routine cognitive follow-up, educational intervention, and basic research into neuro-plasticity and brain reorganization after preterm birth

Extragalactic magnetism with SOFIA (SALSA Legacy Program) -- V: First results on the magnetic field orientation of galaxies

We present the analysis of the magnetic field ($B$-field) structure of galaxies measured with far-infrared (FIR) and radio (3 and 6 cm) polarimetric observations. We use the first data release of the Survey on extragALactic magnetiSm with SOFIA (SALSA) of 14 nearby ($<20$ Mpc) galaxies with resolved (5 arcsec-18 arcsec; $90$ pc--$1$ kpc) imaging polarimetric observations using HAWC+/SOFIA from $53$ to $214$ \um. We compute the magnetic pitch angle ($\Psi_{B}$) profiles as a function of the galactrocentric radius. We introduce a new magnetic alignment parameter ($\zeta$) to estimate the disordered-to-ordered $B$-field ratio in spiral $B$-fields. We find FIR and radio wavelengths to not generally trace the same $B$-field morphology in galaxies. The $\Psi_{B}$ profiles tend to be more ordered with galactocentric radius in radio ($\zeta_{\rm{6cm}} = 0.93\pm0.03$) than in FIR ($\zeta_{\rm{154\mu m}} = 0.84\pm0.14$). For spiral galaxies, FIR $B$-fields are $2-75$\% more turbulent than the radio $B$-fields. For starburst galaxies, we find that FIR polarization is a better tracer of the $B$-fields along the galactic outflows than radio polarization. Our results suggest that the $B$-fields associated with dense, dusty, turbulent star-forming regions, those traced at FIR, are less ordered than warmer, less-dense regions, those traced at radio, of the interstellar medium. The FIR $B$-fields seem to be more sensitive to the activity of the star-forming regions and the morphology of the molecular clouds within a vertical height of few hundred pc in the disk of spiral galaxies than the radio $B$-fields.Comment: 26 pages, 13 figure

Novel Human Parechovirus 3 Diversity, Recombination, and Clinical Impact Across 7 Years: An Australian Story

BACKGROUND A novel human parechovirus 3 Australian recombinant (HPeV3-AR) strain emerged in 2013 and coincided with biennial outbreaks of sepsis-like illnesses in infants. We evaluated the molecular evolution of the HPeV3-AR strain and its association with severe HPeV infections. METHODS HPeV3-positive samples collected from hospitalized infants aged 5-252 days in 2 Australian states (2013-2020) and from a community-based birth cohort (2010-2014) were sequenced. Coding regions were used to conduct phylogenetic and evolutionary analyses. A recombinant-specific polymerase chain reaction was designed and utilized to screen all clinical and community HPeV3-positive samples. RESULTS Complete coding regions of 54 cases were obtained, which showed the HPeV3-AR strain progressively evolving, particularly in the 3' end of the nonstructural genes. The HPeV3-AR strain was not detected in the community birth cohort until the initial outbreak in late 2013. High-throughput screening showed that most (>75%) hospitalized HPeV3 cases involved the AR strain in the first 3 clinical outbreaks, with declining prevalence in the 2019-2020 season. The AR strain was not statistically associated with increased clinical severity among hospitalized infants. CONCLUSIONS HPeV3-AR was the dominant strain during the study period. Increased hospital admissions may have been from a temporary fitness advantage and/or increased virulence

Extragalactic Magnetism with SOFIA (SALSA Legacy Program). VII. A tomographic view of far infrared and radio polarimetric observations through MHD simulations of galaxies

The structure of magnetic fields in galaxies remains poorly constrained, despite the importance of magnetism in the evolution of galaxies. Radio synchrotron and far-infrared dust polarization (FIR) polarimetric observations are the best methods to measure galactic scale properties of magnetic fields in galaxies beyond the Milky Way. We use synthetic polarimetric observations of a simulated galaxy to identify and quantify the regions, scales, and interstellar medium (ISM) phases probed at FIR and radio wavelengths. Our studied suite of magnetohydrodynamical cosmological zoom-in simulations features high-resolutions (10 pc full-cell size) and multiple magnetization models. Our synthetic observations have a striking resemblance to those of observed galaxies. We find that the total and polarized radio emission extends to approximately double the altitude above the galactic disk (half-intensity disk thickness of $h_\text{I radio} \sim h_\text{PI radio} = 0.23 \pm 0.03$ kpc) relative to the FIR total and polarized emission that are concentrated in the disk midplane ($h_\text{I FIR} \sim h_\text{PI FIR} = 0.11 \pm 0.01$ kpc). Radio emission traces magnetic fields at scales of $\gtrsim 300$ pc, whereas FIR emission probes magnetic fields at the smallest scales of our simulations. These scales are comparable to our spatial resolution and well below the spatial resolution ($<300$ pc) of existing FIR polarimetric measurements. Finally, we confirm that synchrotron emission traces a combination of the warm neutral and cold neutral gas phases, whereas FIR emission follows the densest gas in the cold neutral phase in the simulation. These results are independent of the ISM magnetic field strength. The complementarity we measure between radio and FIR wavelengths motivates future multiwavelength polarimetric observations to advance our knowledge of extragalactic magnetism.Comment: Submitted to ApJ. 32 pages, 15 figure