Guidelines on the diagnosis, clinical assessments, treatment and management for CLN2 disease patients.

BACKGROUND: CLN2 disease (Neuronal Ceroid Lipofuscinosis Type 2) is an ultra-rare, neurodegenerative lysosomal storage disease, caused by an enzyme deficiency of tripeptidyl peptidase 1 (TPP1). Lack of disease awareness and the non-specificity of presenting symptoms often leads to delayed diagnosis. These guidelines provide robust evidence-based, expert-agreed recommendations on the risks/benefits of disease-modifying treatments and the medical interventions used to manage this condition. METHODS: An expert mapping tool process was developed ranking multidisciplinary professionals, with knowledge of CLN2 disease, diagnostic or management experience of CLN2 disease, or family support professionals. Individuals were sequentially approached to identify two chairs, ensuring that the process was transparent and unbiased. A systematic literature review of published evidence using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidance was independently and simultaneously conducted to develop key statements based upon the strength of the publications. Clinical care statements formed the basis of an international modified Delphi consensus determination process using the virtual meeting (Within3) online platform which requested experts to agree or disagree with any changes. Statements reaching the consensus mark became the guiding statements within this manuscript, which were subsequently assessed against the Appraisal of Guidelines for Research and Evaluation (AGREEII) criteria. RESULTS: Twenty-one international experts from 7 different specialities, including a patient advocate, were identified. Fifty-three guideline statements were developed covering 13 domains: General Description and Statements, Diagnostics, Clinical Recommendations and Management, Assessments, Interventions and Treatment, Additional Care Considerations, Social Care Considerations, Pain Management, Epilepsy / Seizures, Nutritional Care Interventions, Respiratory Health, Sleep and Rest, and End of Life Care. Consensus was reached after a single round of voting, with one exception which was revised, and agreed by 100% of the SC and achieved 80% consensus in the second voting round. The overall AGREE II assessment score obtained for the development of the guidelines was 5.7 (where 1 represents the lowest quality, and 7 represents the highest quality). CONCLUSION: This program provides robust evidence- and consensus-driven guidelines that can be used by all healthcare professionals involved in the management of patients with CLN2 disease and other neurodegenerative disorders. This addresses the clinical need to complement other information available

The McDonald Accelerating Stars Survey (MASS):Discovery of a Long-Period Substellar Companion Orbiting the Old Solar Analog HD 47127

Brown dwarfs with well-determined ages, luminosities, and masses provide rare but valuable tests of low-temperature atmospheric and evolutionary models. We present the discovery and dynamical mass measurement of a substellar companion to HD 47127, an old ($\approx$7-10 Gyr) G5 main sequence star with a mass similar to the Sun. Radial velocities of the host star with the Harlan J. Smith Telescope uncovered a low-amplitude acceleration of 1.93 $\pm$ 0.08 m s$^{-1}$ yr$^{-1}$ based on 20 years of monitoring. We subsequently recovered a faint ($\Delta H$=13.14 $\pm$ 0.15 mag) co-moving companion at 1.95$''$ (52 AU) with follow-up Keck/NIRC2 adaptive optics imaging. The radial acceleration of HD 47127 together with its tangential acceleration from Hipparcos and Gaia EDR3 astrometry provide a direct measurement of the three-dimensional acceleration vector of the host star, enabling a dynamical mass constraint for HD 47127 B (67.5-177 $M_\mathrm{Jup}$ at 95% confidence) despite the small fractional orbital coverage of the observations. The absolute $H$-band magnitude of HD 47127 B is fainter than the benchmark T dwarfs HD 19467 B and Gl 229 B but brighter than Gl 758 B and HD 4113 C, suggesting a late-T spectral type. Altogether the mass limits for HD 47127 B from its dynamical mass and the substellar boundary imply a range of 67-78 $M_\mathrm{Jup}$ assuming it is single, although a preference for high masses of $\approx$100 $M_\mathrm{Jup}$ from dynamical constraints hints at the possibility that HD 47127 B could itself be a binary pair of brown dwarfs or that another massive companion resides closer in. Regardless, HD 47127 B will be an excellent target for more refined orbital and atmospheric characterization in the future.Comment: Accepted to ApJ Letter

Guidelines on the diagnosis, clinical assessments, treatment and management for CLN2 disease patients

Background: CLN2 disease (Neuronal Ceroid Lipofuscinosis Type 2) is an ultra-rare, neurodegenerative lysosomal storage disease, caused by an enzyme deficiency of tripeptidyl peptidase 1 (TPP1). Lack of disease awareness and the non-specificity of presenting symptoms often leads to delayed diagnosis. These guidelines provide robust evidence-based, expert-agreed recommendations on the risks/benefits of disease-modifying treatments and the medical interventions used to manage this condition. Methods: An expert mapping tool process was developed ranking multidisciplinary professionals, with knowledge of CLN2 disease, diagnostic or management experience of CLN2 disease, or family support professionals. Individuals were sequentially approached to identify two chairs, ensuring that the process was transparent and unbiased. A systematic literature review of published evidence using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidance was independently and simultaneously conducted to develop key statements based upon the strength of the publications. Clinical care statements formed the basis of an international modified Delphi consensus determination process using the virtual meeting (Within3) online platform which requested experts to agree or disagree with any changes. Statements reaching the consensus mark became the guiding statements within this manuscript, which were subsequently assessed against the Appraisal of Guidelines for Research and Evaluation (AGREEII) criteria. Results: Twenty-one international experts from 7 different specialities, including a patient advocate, were identified. Fifty-three guideline statements were developed covering 13 domains: General Description and Statements, Diagnostics, Clinical Recommendations and Management, Assessments, Interventions and Treatment, Additional Care Considerations, Social Care Considerations, Pain Management, Epilepsy / Seizures, Nutritional Care Interventions, Respiratory Health, Sleep and Rest, and End of Life Care. Consensus was reached after a single round of voting, with one exception which was revised, and agreed by 100% of the SC and achieved 80% consensus in the second voting round. The overall AGREE II assessment score obtained for the development of the guidelines was 5.7 (where 1 represents the lowest quality, and 7 represents the highest quality). Conclusion: This program provides robust evidence- and consensus-driven guidelines that can be used by all healthcare professionals involved in the management of patients with CLN2 disease and other neurodegenerative disorders. This addresses the clinical need to complement other information available

Conduct disorder and antisocial personality disorders: challenges for treatment in adolescence and young adulthood

Aggressive behaviour is a typical phenomenon in childhood and adolescence. Aggression is one of the frequent reasons for parents to seek child and adolescent psychiatric and psychotherapeutic treatment. Disorders with increased aggressive behaviour, such as conduct or oppositional defiant disorder, carry an increased risk for long-lasting negative impact on well-being, especially when comorbid with substance abuse or affective symptoms. Barriers for treatment are frequently a lack of insight into consequences and non-compliance with intervention shown by adolescents. In addition, interdisciplinary intervention needs to combine psychiatric and psychotherapeutic interventions as well as complex interventions supported by the youth welfare system, and in particular including families. Further research is needed for the implementation of evidence-based treatments in routine care as well in special populations, such as girls with conduct disorders or youth with substance abuse