Applying the Pennsylvania Environmental Rights Amendment Meaningfully to Climate Disruption

The Pennsylvania Constitution contains a unique Environmental Rights Amendment (ERA), which recognizes an individual right to “clean air, pure water, and to the preservation of the natural, scenic, historic and esthetic values of the environment.” The ERA also includes a public trust element that makes “Pennsylvania’s public natural resources . . . the common property of all the people, including generations yet to come.” It makes the Commonwealth the “trustee of these resources,” requiring it to “conserve and maintain them for the benefit of all the people.” Recent decisions by the Pennsylvania Supreme Court (the Court) in Robinson Township v. Commonwealth and Pennsylvania Environmental Defense Foundation v. Commonwealth provide significant support for Pennsylvania regulations to address the threat of climate disruption posed by greenhouse gas (GHG) emissions to achieve net zero carbon emissions by the middle of this century. In light of the threats that climate disruption poses to Pennsylvania’s public natural resources, the text of the ERA, and the principles articulated in those recent cases, we argue that a stable climate (a climate that has not been disrupted by anthropogenic emissions of GHGs) should be considered protected by the rights recognized by the ERA, and the public trust duties it creates. We argue that these rights and duties require Pennsylvania to employ regulatory measures to reduce GHG emissions to the level warranted by the social cost of carbon and to achieve carbon neutrality (net zero emissions) by mid-century. Further, we argue that there are judicially recognizable standards to compel the Commonwealth to exercise its existing authority to limit GHG emissions. In light of existing legislative authority, the obligations imposed by the United Nations Framework Convention on Climate Change, the Paris Agreement, and the federal Clean Air Act, we make the case that this regulatory program should take the form of an economy-wide cap-and-trade program providing for the auction of allowances with a reserve price based on the social cost of carbon and additional measures to prevent leakage and a cap reaching carbon neutrality by mid-century

CEDNIK: Phenotypic and molecular characterization of an additional patient and review of the literature

Synaptosomal-associated protein 29 (SNAP29) is a t-SNARE protein that is implicated in intracellular vesicle fusion. Mutations in the SNAP29 gene have been associated with cerebral dysgenesis, neuropathy, ichthyosis, and keratoderma syndrome (CEDNIK). In patients with 22q11.2 deletion syndrome, mutations in SNAP29 on the nondeleted chromosome are linked to similar ichthyotic and neurological phenotypes. Here, the authors report a patient with cerebral dysgenesis, neuropathy, ichthyosis, and keratoderma syndrome who presented with global developmental delay, polymicrogyria, dysgenesis of the corpus callosum, optic nerve dysplasia, gaze apraxia, and dysmorphic features. He has developed ichthyosis and palmoplantar keratoderma as he has grown. Exome sequencing identified a homozygous nonsense mutation in SNAP29 gene designated as c.85C>T (p.Arg29X). The authors compare the findings in the proband with previously reported cases. The previously unreported mutation in this patient and his phenotype add to the characterization of cerebral dysgenesis, neuropathy, ichthyosis, and keratoderma syndrome and the accumulating scientific evidence that implicates synaptic protein dysfunction in various neuroectodermal conditions

Enlarged perivascular spaces in infancy and autism diagnosis, cerebrospinal fluid volume, and later sleep problems

IMPORTANCE: Perivascular spaces (PVS) and cerebrospinal fluid (CSF) are essential components of the glymphatic system, regulating brain homeostasis and clearing neural waste throughout the lifespan. Enlarged PVS have been implicated in neurological disorders and sleep problems in adults, and excessive CSF volume has been reported in infants who develop autism. Enlarged PVS have not been sufficiently studied longitudinally in infancy or in relation to autism outcomes or CSF volume. OBJECTIVE: To examine whether enlarged PVS are more prevalent in infants who develop autism compared with controls and whether they are associated with trajectories of extra-axial CSF volume (EA-CSF) and sleep problems in later childhood. DESIGN, SETTING, AND PARTICIPANTS: This prospective, longitudinal cohort study used data from the Infant Brain Imaging Study. Magnetic resonance images were acquired at ages 6, 12, and 24 months (2007-2017), with sleep questionnaires performed between ages 7 and 12 years (starting in 2018). Data were collected at 4 sites in North Carolina, Missouri, Pennsylvania, and Washington. Data were analyzed from March 2021 through August 2022. EXPOSURE: PVS (ie, fluid-filled channels that surround blood vessels in the brain) that are enlarged (ie, visible on magnetic resonance imaging). MAIN OUTCOMES AND MEASURES: Outcomes of interest were enlarged PVS and EA-CSF volume from 6 to 24 months, autism diagnosis at 24 months, sleep problems between ages 7 and 12 years. RESULTS: A total of 311 infants (197 [63.3%] male) were included: 47 infants at high familial likelihood for autism (ie, having an older sibling with autism) who were diagnosed with autism at age 24 months, 180 high likelihood infants not diagnosed with autism, and 84 low likelihood control infants not diagnosed with autism. Sleep measures at school-age were available for 109 participants. Of infants who developed autism, 21 (44.7%) had enlarged PVS at 24 months compared with 48 infants (26.7%) in the high likelihood but no autism diagnosis group (P = .02) and 22 infants in the control group (26.2%) (P = .03). Across all groups, enlarged PVS at 24 months was associated with greater EA-CSF volume from ages 6 to 24 months (β = 4.64; 95% CI, 0.58-8.72; P = .002) and more frequent night wakings at school-age (F = 7.76; η2 = 0.08; P = .006). CONCLUSIONS AND RELEVANCE: These findings suggest that enlarged PVS emerged between ages 12 and 24 months in infants who developed autism. These results add to a growing body of evidence that, along with excessive CSF volume and sleep dysfunction, the glymphatic system could be dysregulated in infants who develop autism

Case report: A novel EIF2B3 pathogenic variant in central nervous system hypomyelination/vanishing white matter

Leukodystrophies are a group of heterogeneous disorders affecting brain myelin. Among those, childhood ataxia with central nervous system hypomyelination/vanishing white matter (CACH/VWM) is one of the more common inherited leukodystrophies. Pathogenic variants in one of the genes encoding five subunits of EIF2B are associated with CACH/VWM. Herein, we presented a case of CACH/VWM who developed ataxia following a minor head injury. Brain magnetic resonance imaging showed extensive white matter signal abnormality. Diagnosis of CACH/VWM was confirmed by the presence of compound heterozygous variants i

Longitudinal prediction of infant MR images with multi-contrast perceptual adversarial learning

The infant brain undergoes a remarkable period of neural development that is crucial for the development of cognitive and behavioral capacities (Hasegawa et al., 2018). Longitudinal magnetic resonance imaging (MRI) is able to characterize the developmental trajectories and is critical in neuroimaging studies of early brain development. However, missing data at different time points is an unavoidable occurrence in longitudinal studies owing to participant attrition and scan failure. Compared to dropping incomplete data, data imputation is considered a better solution to address such missing data in order to preserve all available samples. In this paper, we adapt generative adversarial networks (GAN) to a new application: longitudinal image prediction of structural MRI in the first year of life. In contrast to existing medical image-to-image translation applications of GANs, where inputs and outputs share a very close anatomical structure, our task is more challenging as brain size, shape and tissue contrast vary significantly between the input data and the predicted data. Several improvements over existing GAN approaches are proposed to address these challenges in our task. To enhance the realism, crispness, and accuracy of the predicted images, we incorporate both a traditional voxel-wise reconstruction loss as well as a perceptual loss term into the adversarial learning scheme. As the differing contrast changes in T1w and T2w MR images in the first year of life, we incorporate multi-contrast images leading to our proposed 3D multi-contrast perceptual adversarial network (MPGAN). Extensive evaluations are performed to assess the qualityand fidelity of the predicted images, including qualitative and quantitative assessments of the image appearance, as well as quantitative assessment on two segmentation tasks. Our experimental results show that our MPGAN is an effective solution for longitudinal MR image data imputation in the infant brain. We further apply our predicted/imputed images to two practical tasks, a regression task and a classification task, in order to highlight the enhanced task-related performance following image imputation. The results show that the model performance in both tasks is improved by including the additional imputed data, demonstrating the usability of the predicted images generated from our approach

Chief Joseph Kokanee Enhancement Project; Strobe Light Deterrent Efficacy Test and Fish Behavior Determination at Grand Coulee Dam Third Powerplant Forebay, 2005-2006 Annual Report.

The construction of Grand Coulee and Chief Joseph dams on the Columbia River resulted in the complete extirpation of the anadromous fishery upstream of these structures. Today, this area is totally dependent upon resident fish resources to support local fisheries. The resident fishing is enhanced by an extensive stocking program for target species in the existing fishery, including kokanee (Oncorhynchus nerka kennerlyi) and rainbow trout (O. mykiss). The kokanee fishery in Lake Roosevelt has not been meeting the return goals set by fisheries managers despite the stocking program. Investigations of physical and biological factors that could affect the kokanee population found predation and entrainment had a significant impact on the fish population. In 1999 and 2000, walleye (Sander vitreum) consumed between 15% and 9%, respectively, of the hatchery kokanee within 41 days of their release, while results from a study in the late 1990s estimated that entrainment at Grand Coulee Dam could account for up to 30% of the total mortality of the stocked fish. To address the entrainment loss, the Bonneville Power Administration commissioned a study to determine if fish would avoid areas illuminated by strobe lights in the forebay of the third powerplant. This work was conducted by Pacific Northwest National Laboratory (PNNL) in conjunction with the Confederated Tribes of the Colville Reservation (Colville Confederated Tribes). From 2002 through 2004, six strobe lights were suspended in the center of the opening to the third powerplant forebay during summer months. Results from those studies indicated that fish appeared to be attracted to the illuminated area but only at night and when flow conditions within the third powerplant forebay were minimal. However, small but consistent results from these studies indicated that under high flow conditions, fish might be avoiding the lights. The 2005 study was designed to examine whether, under high flow conditions near the penstock openings, fish would avoid the lighted regions. Four omnidirectional strobe lights were deployed on the one trash rack directly in front of one turbine penstock. Seven splitbeam transducers were deployed to monitor fish approaching three penstock openings either from in front of the trash racks or moving down the dam behind the trash racks. Four key results emerged from the 2005 study. The results provide insight into the current level of entrainment and how fish respond to strobe lights under high flow conditions. First, very few fish were detected inside the trash racks. Of the more than 3,200 targets identified by the data processing, less than 100 were detected inside the trash racks. Only 23 fish were found inside the trash racks behind the strobe lights. Of those 21 fish, 13 were detected when the lights were on. Most of the fish detected behind the trash racks were above the turbine penstock but were headed downward. No fish were detected at night when minimal flows occurred between midnight and 4:00 a.m. Second, significantly more fish (P < 0.001) were detected in front of the trash racks when the lights were on at night. On a count-per-hour basis, the difference between lights off and lights on was apparent in the early morning hours at depths between 25 m and 50 m from the transducers. The lights were approximately 34 m below the splitbeam transducers, and fish detected at night with lights on were found at a median depth of approximately 35 m, compared to a median depth of from 20.6 to 23.5 m when the lights were off. The differences in depth between lights on and off at night were also significant (P < 0.001). Additionally, the increase in fish occurred only in front of the trash rack where the strobe lights were mounted; there was no increase in the number of detections by the transducers aimed away from the lights. Third, fish clearly manifested a behavioral response to the strobe lights during the day. When the lights were on, fish detected by three of the four transducers generally were swimming north, parallel to the face of the dam. However, the distribution of swimming directions for fish detected by the transducer immediately to the north of the lights was bimodal, with some fish swimming south toward the lighted region. This behavior was similar to that seen at night when the lights were on. Fourth, kokanee, rainbow trout, and walleye were detected near the strobe lights. Data were obtained from three sources: fish size from the hydroacoustic sensors and fish species from gill netting and video recording. Fish ranging in length from 30 to 600 mm (averaging 125 mm) were detected by the splitbeam transducers. There was little difference in target strength for fish detected above 25 m depth with respect to time of day or light treatment. Below 25 m and closer to the strobe lights, larger fish were present when the lights were on during the night, and smaller fish were present during the day

Imaging features of neonatal systemic juvenile xanthogranuloma: A case report and review of the literature

Juvenile xanthogranuloma (JXG) is the most common non-Langerhans cell histiocytic disorder in children. This report describes the case of a 28-day-old boy that presented with multiple subcutaneous nodular lesions on the trunk and extremities, and multiple red nodular lesions on the scrotum. Magnetic resonance imaging (MRI) of the brain showed a well-demarcated extra-axial dura-based mass that appeared isointense or slightly hyperintense on T1-weighted images, hypointense on T2-weighted images and had intense enhancement on gadolinium-enhanced T1-weighted images. Computed tomography (CT) or MRI scans of the chest and abdomen revealed multiple scattered nodular or patchy lesions of varying sizes in the lungs, liver and left kidney. Histological analysis of a subcutaneous mass suggested JXG. The patient was diagnosed with neonatal systemic JXG with involvement of the central nervous system, lungs, liver, kidneys, subcutaneous soft tissue and skin. CT and MRI after 3 months of treatment with methylprednisolone sodium succinate demonstrated that the lesions were obviously diminished. This report discusses the imaging findings in this current case of multi-organ JXG and reviews the imaging literature on this condition to improve awareness of the lesions in order to help radiologists establish an accurate differential diagnosis when confronted with similar cases

De novo development of gliomas in a child with neurofibromatosis type 1, fragile X and previously normal brain magnetic resonance imaging

AbstractFifteen to 20% of children with neurofibromatosis type 1 develop low-grade glial neoplasms. However, since neuroimaging is not routinely obtained until a child is clinically symptomatic, little is known about presymptomatic radiographic characteristics of gliomas in this at-risk population. Herein, we describe a child with neurofibromatosis type 1 who initially had normal brain imaging before the development of multifocal gliomas. Comparison of these serial images demonstrated that brain tumors can arise de novo in children with this cancer predisposition syndrome, further underscoring the limited prognostic value of normal baseline magnetic resonance imaging

Trial of erythropoietin for hypoxic-ischemic encephalopathy in newborns

BACKGROUND: Neonatal hypoxic-ischemic encephalopathy is an important cause of death as well as long-term disability in survivors. Erythropoietin has been hypothesized to have neuroprotective effects in infants with hypoxic-ischemic encephalopathy, but its effects on neurodevelopmental outcomes when given in conjunction with therapeutic hypothermia are unknown. METHODS: In a multicenter, double-blind, randomized, placebo-controlled trial, we assigned 501 infants born at 36 weeks or more of gestation with moderate or severe hypoxic-ischemic encephalopathy to receive erythropoietin or placebo, in conjunction with standard therapeutic hypothermia. Erythropoietin (1000 U per kilogram of body weight) or saline placebo was administered intravenously within 26 hours after birth, as well as at 2, 3, 4, and 7 days of age. The primary outcome was death or neurodevelopmental impairment at 22 to 36 months of age. Neurodevelopmental impairment was defined as cerebral palsy, a Gross Motor Function Classification System level of at least 1 (on a scale of 0 [normal] to 5 [most impaired]), or a cognitive score of less than 90 (which corresponds to 0.67 SD below the mean, with higher scores indicating better performance) on the Bayley Scales of Infant and Toddler Development, third edition. RESULTS: Of 500 infants in the modified intention-to-treat analysis, 257 received erythropoietin and 243 received placebo. The incidence of death or neurodevelopmental impairment was 52.5% in the erythropoietin group and 49.5% in the placebo group (relative risk, 1.03; 95% confidence interval [CI], 0.86 to 1.24; P = 0.74). The mean number of serious adverse events per child was higher in the erythropoietin group than in the placebo group (0.86 vs. 0.67; relative risk, 1.26; 95% CI, 1.01 to 1.57). CONCLUSIONS: The administration of erythropoietin to newborns undergoing therapeutic hypothermia for hypoxic-ischemic encephalopathy did not result in a lower risk of death or neurodevelopmental impairment than placebo and was associated with a higher rate of serious adverse events. (Funded by the National Institute of Neurological Disorders and Stroke; ClinicalTrials.gov number, NCT02811263.)