Topic modeling to characterize the natural history of ANCA-Associated vasculitis from clinical notes: A proof of concept study

Abstract Aim The aim of the study is to assess the effectiveness of low dose CT scan (LDCT) to pick up nodules and carcinomas in smokers in India. Methods A retrospective study of 350 smokers scanned with LDCT was performed in a private practice center in Mumbai, India. Their demographic profile, smoking history in pack-years, lung nodules, and associated findings/superimposed complications were recorded and analyzed. The nodules were assigned the appropriate Lung-RADS category and results of the patients undergoing biopsy were recorded. Results Of the 350 smokers, 15 (4%) were women . The mean age was 61 years (32–90 years) with a mean smoking history of 22 pack-years (1–160 pack-years). Lung nodules were found in 335 (93%) smokers, with Lung-RADS category 1 nodules seen in 117 (36%), category 2 in 133 (41%), category 3 in 29 (9%), and category 4 in 46 (14%) of positive scans. Seven of the category 4 patients who underwent biopsy showed carcinoma, with a mean smoking history of 30 pack years. Superimposed interstitial lung disease, airways diseases, and infections were also seen in the scans and recorded. Discussion It has been proven in the Western world that screening for lung cancer with LDCT saves lives with early pick-up of malignant nodules. This pilot study from India, shows that even in a tuberculosis endemic country, LDCT picks up malignant lung nodules early and saves lives. Conclusion Smokers with a more than 20 pack years history have a higher incidence of lung nodules, which may represent carcinoma, in a tuberculosis endemic country like India, as has been proven in other countries in the Western world. Larger studies and trials may be performed to elaborate further on this proof-of-concept study.

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First-in-human AAV Gene Therapy for Tay-Sachs Disease

10.21203/rs.3.rs-195847/v1 ◽

2021 ◽

Author(s):

Miguel Sena-Esteves ◽

Terence Flotte ◽

Oguz Cataltepe ◽

Ajit Puri ◽

Ana Rita Batista ◽

...

Keyword(s):

Gene Therapy ◽

Natural History ◽

Post Injection ◽

Proof Of Concept ◽

Safety And Efficacy ◽

Tay Sachs Disease ◽

Younger Patient ◽

Hexosaminidase A ◽

History Of ◽

Preclinical Work

Abstract Tay-Sachs Disease (TSD) is an inherited neurological disorder caused by deficiency of hexosaminidase A (HexA). Preclinical work demonstrated safety and efficacy of CNS gene therapy using AAVrh8-HEXA/HEXB. Here we describe an expanded access trial in two patients with infantile TSD (IND 18225). Case TSD-001 demonstrated neurodevelopmental regression by 8 months of age and severe seizures by 1 year was treated at 30 months. An equimolar mix of AAVrh8-HEXA and AAVrh8-HEXB (now AXO-AAV-GM2) was administered intrathecally (IT), with 75% of the dose (1x1014vg) delivered to the cisterna magna and 25% at the thoraco-lumbar junction. The second patient (TSD-002) was treated at 7 months of age with 4.2x1013 vg by a combination of bilateral thalamic (0.18 mL; 1.5x1012vg per thalamus), and IT infusion (3.9x1013vg). Both patients underwent immunosuppression with sirolimus, corticosteroids, and rituximab. Injection procedures were well tolerated and have shown no vector-related adverse events to date. CSF HexA activity nearly doubled from baseline and remained stable. In TSD-002 (now 16 months of age), MRI showed stabilization of disease by 3 months post-injection and appeared to temporarily deviate from the natural history of infantile TSD but declined again 6 months post-treatment. TSD-001 (now 4.5 years of age remains seizure-free on the same anti-convulsant therapy as pre-therapy, but TSD-002 developed seizures between 13 and 17 months posttreatment (by 2 years of age). Administration of AXO-AAV-GM2 by IT and thalamic injections was safe, HexA activity increased in CSF and ongoing myelination was apparent in the younger patient treated at an early symptomatic stage. This study provides early safety and proof-of-concept in humans for treatment of TSD patients by AAV gene therapy.

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How is the moral stance related to the intentional stance and group thinking?

Behavioral and Brain Sciences ◽

10.1017/s0140525x19002413 ◽

2020 ◽

Vol 43 ◽

Author(s):

Hannes Rakoczy

Keyword(s):

Natural History ◽

Social Cognitive ◽

Intentional Stance ◽

Cognitive Capacities ◽

Shared Intentionality ◽

History Of ◽

Group Thinking ◽

Moral Stance

Abstract The natural history of our moral stance told here in this commentary reveals the close nexus of morality and basic social-cognitive capacities. Big mysteries about morality thus transform into smaller and more manageable ones. Here, I raise questions regarding the conceptual, ontogenetic, and evolutionary relations of the moral stance to the intentional and group stances and to shared intentionality.

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