Treatment algorithm for infants diagnosed with spinal muscular atrophy through newborn screening

Spinal muscular atrophy (SMA) is an autosomal recessive disease characterized by the degeneration of alpha motor neurons in the spinal cord, leading to muscular atrophy. SMA is caused by deletions or mutations in the survival motor neuron 1 gene (SMN1). In humans, a nearly identical copy gene, SMN2, is present. Because SMN2 has been shown to decrease disease severity in a dose-dependent manner, SMN2 copy number is predictive of disease severity. To develop a treatment algorithm for SMA-positive infants identified through newborn screening based upon SMN2 copy number. A working group comprised of 15 SMA experts participated in a modified Delphi process, moderated by a neutral third-party expert, to develop treatment guidelines. The overarching recommendation is that all infants with two or three copies of SMN2 should receive immediate treatment (n = 13). For those infants in which immediate treatment is not recommended, guidelines were developed that outline the timing and appropriate screens and tests to be used to determine the timing of treatment initiation. The identification SMA affected infants via newborn screening presents an unprecedented opportunity for achievement of maximal therapeutic benefit through the administration of treatment pre-symptomatically. The recommendations provided here are intended to help formulate treatment guidelines for infants who test positive during the newborn screening process

PROPERTIES OF ACATALASIC CELLS GROWING IN VITRO

Acatalasia, a disease due to homozygosity for a Mendelian gene, is characterized by the absence of the enzyme catalase from the tissues of the human body. Red cells from heterozygotes have enzyme activities about one-half normal. In this paper, the development of cell lines from skin biopsies on an affected homozygote, a heterozygote, and eight control patients is described. The cell type is the euploid "fibroblast." It was found that acatalasic cells lacked the enzyme, even after growing for many months in a medium rich in catalase. The control lines all had mean catalase activities double or more that of the heterozygous line. Selection experiments, in which the growth of cells exposed for 20 minutes to varying concentrations of hydrogen peroxide was measured, did not provide a system for preferentially eliminating acatalasic cells. Certain other experiments bearing on the enzymatic defect in this disease were performed

Patterns of woodboring beetle activity following fires and bark beetle outbreaks in montane forests of California, USA

Increasingly frequent and severe drought in the western United States has contributed to more frequent and severe wildfires, longer fire seasons, and more frequent bark beetle outbreaks that kill large numbers of trees. Climate change is expected to perpetuate these trends, especially in montane ecosystems, calling for improved strategies for managing Western forests and conserving the wildlife that they support. Woodboring beetles (e.g., Buprestidae and Cerambycidae) colonize dead and weakened trees and speed succession of habitats altered by fire or bark beetles, while serving as prey for some early-seral habitat specialists, including several woodpecker species. To understand how these ecologically important beetles respond to different sources of tree mortality, we sampled woodborers in 16 sites affected by wildfire or bark beetle outbreak in the previous one to eight years. Study sites were located in the Sierra Nevada, Modoc Plateau, Warner Mountains, and southern Cascades of California, USA. We used generalized linear mixed models to evaluate hypotheses concerning the response of woodboring beetles to disturbance type, severity, and timing; forest stand composition and structure; and tree characteristics.</p

Extreme magnification of an individual star at redshift 1.5 by a galaxy-cluster lens

Galaxy-cluster gravitational lenses can magnify background galaxies by a total factor of up to ~50. Here we report an image of an individual star at redshift z = 1.49 (dubbed MACS J1149 Lensed Star 1) magnified by more than ×2,000. A separate image, detected briefly 0.26″ from Lensed Star 1, is probably a counterimage of the first star demagnified for multiple years by an object of ≳3 solar masses in the cluster. For reasonable assumptions about the lensing system, microlensing fluctuations in the stars’ light curves can yield evidence about the mass function of intracluster stars and compact objects, including binary fractions and specific stellar evolution and supernova models. Dark-matter subhaloes or massive compact objects may help to account for the two images’ long-term brightness ratio

Including ELSI research questions in newborn screening pilot studies

Background The evidence review processes for adding new conditions to state newborn screening (NBS) panels rely on data from pilot studies aimed at assessing the potential benefits and harms of screening. However, the consideration of ethical, legal, and social implications (ELSI) of screening within this research has been limited. This paper outlines important ELSI issues related to newborn screening policy and practices as a resource to help researchers integrate ELSI into NBS pilot studies. Approach Members of the Bioethics and Legal Workgroup for the Newborn Screening Translational Research Network facilitated a series of professional and public discussions aimed at engaging NBS stakeholders to identify important existing and emerging ELSI challenges accompanying NBS. Results Integrating ELSI questions into pilot studies will help NBS programs to better understand the potential impact of screening for a new condition on newborns and families, and make crucial policy decisions aimed at maximized benefits and mitigating the potential negative medical or social implications of screening