Unpacking the modeling process for energy policy making.

This article explores how the modeling of energy systems may lead to an undue closure of alternatives by generating an excess of certainty around some of the possible policy options. We retrospectively exemplify the problem with the case of the International Institute for Applied Systems Analysis (IIASA) global modeling in the 1980s. We discuss different methodologies for quality assessment that may help mitigate this issue, which include Numeral Unit Spread Assessment Pedigree (NUSAP), diagnostic diagrams, and sensitivity auditing (SAUD). We illustrate the potential of these reflexive modeling practices in energy policy-making with three additional cases: (i) the case of the energy system modeling environment (ESME) for the creation of UK energy policy; (ii) the negative emission technologies (NETs) uptake in integrated assessment models (IAMs); and (iii) the ecological footprint indicator. We encourage modelers to adopt these approaches to achieve more robust, defensible, and inclusive modeling activities in the field of energy research.

Long-Term Follow-Up of a Family with Retinal Dystrophy Caused by RPE65 Mutation.

We present here the case histories of two siblings, a boy and a girl, with Leber's congenital amaurosis (LCA). The diagnosis was based on non-recordable full-field electroretinogram (ffERG). The long-term ophthalmologic follow-up included kinetic perimetry (Goldmann), visual evoked potentials with flash stimulation, optical coherence tomography (OCT: B-scan images at the area of fovea), and multifocal ERG. The boy (sibling 1, born in 1986) was sent for electrophysiological examination at the age of four because he had nystagmus from birth. The diagnosis would be LCA based on non-recordable ffERG. Four years later, his visual acuity decreased rapidly due to vitreous opacification, caused by the autoimmune reaction of the retinal pigment epithelial cells. This was treated successfully with steroid injections, administered parabulbarly. Retinal autoimmune panel was not performed. Genetic testing became available only in 2019, and it revealed a RPE65 gene mutation: (NM_000329.2) c.{442G>A};{442G>A} (p.{Glu148Lys}; {Glu148Lys}). His sister (sibling 2, born in 1993) showed similar symptoms, caused by the same genetic mutation. Even though their parents were free of symptoms, it appeared that they were heterozygous carriers of the same mutation. Research of the family tree revealed a consanguineous marriage four generations before. Both siblings received successful gene therapy relatively late in their age: sibling 1 was 35 and sibling 2 was 28 years old, meaning that they were at an advanced stage of the disease. Nevertheless, follow-up examinations showed measurable improvements in their retinal function. The study shows that electrophysiological examinations, including flash-evoked responses, are useful in the objective evaluation of the progression in the central photoreceptor loss during the follow-up of LCA. The results also show that gene therapy can have beneficial effects even at an advanced stage of the disease.

[Gene therapy treatment based on an ophthalmic indication in hereditary retinal dystrophy caused by RPE65 biallelic gene mutation.] / Szemészeti javallat alapján végzett génterápiás kezelés RPE65 biallelikus génmutáció okozta öröklodo ideghártya-dystrophiában.

INTRODUCTION: Leber's congenital amaurosis is a genetically determined disease belonging to the group of hereditary retinal dystrophies that leads to significant visual impairment in childhood. The disease initially causes a concentric narrowing of the visual field and, with time, loss of central vision. The RPE65 gene mutation-related retinal dystrophy is the first ophthalmic disease for which gene therapy is available using voretigene neparvovec (Luxturna®, Novartis Pharmaceuticals AG, Basel, Switzerland). OBJECTIVE: To present the treatment outcomes of Hungarian patients who were the first to receive voretigene neparvovec gene therapy for the RPE65 biallelic gene mutation. METHOD: Two patients with RPE65 biallelic gene mutations confirmed by genetic testing received voretigene neparvovec gene therapy in one eye each. Before treatment and during the follow-up period, we assessed the best corrected visual acuity, the central retinal thickness, the degree of visual field defects and performed electrophysiological studies. RESULTS: Both the best corrected visual acuity (+3 letters in the older sibling and +10 letters in the younger sibling) and the degree of visual field narrowing improved in both patients. The change in visual function resulted in a significant improvement in the quality of life of our patients. CONCLUSION: Postoperative outcomes of our patients correlate with the results of clinical trials. Orv Hetil. 2022; 163(48): 1923-1931.