1) The DIAN-TU trial aims to assess the safety and efficacy of two monoclonal antibody treatments, solanezumab and gantenerumab, in reducing amyloid plaques in individuals at risk for familial Alzheimer's disease.
2) Eligible participants must be between 15 years before and 10 years after their predicted symptom onset age. They can be asymptomatic or mildly affected.
3) The trial involves annual clinical assessments, cognitive testing, MRI, PET scans, blood tests, and lumbar punctures over two years. Participants will receive monthly intravenous infusions or subcutaneous injections of either the study drug or placebo.
Ethical and Legal Issues Related to Medical Genetics Rayhan Shahrear
Define ethics and bioethics.
State the major ethical issues related to medical genetics.
Outline the uniqueness of medical genetics.
Outline the relevant ethical principles in medicine.
Discuss some ethical dilemmas that arise in the genetic clinic.
Explain the ethical dilemmas and public interest.
Dr. Najnin Akhter
Phase-A, Year-2, Block-6
Guided by Prof. K M Shamim
Perinatal and long-term outcomes in fetuses diagnosed with isolated unilateral ventriculomegaly: systemic review and meta-analysis
C. Scala, A. Familiari, A. Pinas, A.T. Papageorghiou, A. Bhide, B. Thilaganathan, A. Khalil
Volume 49, Issue 4, Date: April (pages 450–459)
Slides prepared by Dr Yael Raz (UOG Editor-for-Trainees)
Link to free-access article: http://onlinelibrary.wiley.com/doi/10.1002/uog.15943/full
Neurodevelopmental outcome in isolated mild fetal ventriculomegaly: systematic review and meta-analysis
G. Pagani, B. Thilaganathan and F. Prefumo
Volume 44, Issue 3, Date: September 2014, Pages 254-260
http://onlinelibrary.wiley.com/doi/10.1002/uog.13364/abstract
Increased nuchal translucency thickness and risk of neurodevelopmental disorders
S. G. Hellmuth, L. H. Pedersen, C. B. Miltoft, O. B. Petersen, S. Kjærgaard, C. Ekelund, A. Tabor
Volume 49, Issue 5; Date: May (pages 592–598)
Slides prepared by Dr Maddalena Morlando (UOG Editors-for-Trainees)
Link to free-access article: http://onlinelibrary.wiley.com/doi/10.1002/uog.15961/full
Genetic testing (evaluation)
This is a type of clinical test that identifies changes in chromosomes, genes, or proteins. Genetic testing can provide information about a person's genes and chromosomes.
The results of a genetic test can confirm or rule out a suspected genetic condition or help determine a person’s chance of developing or passing on a genetic disorder.
At present, more than 1,000 types of genetic tests are currently in use, and more are being developed.
Methods used for genetic testing:
Molecular genetic tests (or gene tests): It tests single genes or short lengths of DNA to identify variations or mutations that lead to a genetic disorder.
Chromosomal genetic tests: It analyze whole chromosomes or long lengths of DNA to see if there are large genetic changes.
Biochemical genetic tests: It tests the amount or activity level of protein abnormalities to indicate changes in the DNA that result in a genetic disorder.
Genetic testing is voluntary. Because testing has benefits as well as limitations and risks, the decision about whether to be tested is a personal and complex one. A geneticist or genetic counselor can help by providing information about the pros and cons of the test and discussing the social and emotional aspects of testing.
Cervical length screening for prevention of preterm birth in singleton pregnancy with threatened preterm labor: systematic review and meta-analysis of randomized controlled trials using individual patient-level data
V. Berghella, M. Palacio, A. Ness, Z. Alfirevic, K. H. Nicolaides and G. Saccone
Volume 49, Issue 3, Date: March (pages 322–329)
Slides prepared by Dr Shireen Meher (UOG Editors-for-Trainees)
Link to free-access article: http://onlinelibrary.wiley.com/doi/10.1002/uog.17388/full
Multicenter screening for pre-eclampsia by maternal factors and biomarkers at 11–13 weeks' gestation: comparison with NICE guidelines and ACOG recommendations
N. O'Gorman, D. Wright, L. C. Poon, D. L. Rolnik, A. Syngelaki, M. de Alvarado, I. F. Carbone, V. Dutemeyer, M. Fiolna, A. Frick, N. Karagiotis, S. Mastrodima, C. de Paco Matallana, G. Papaioannou, A. Pazos, W. Plasencia, K. H. Nicolaides
Volume 49, Issue 6, Pages 756–760
Slides prepared by Dr Fiona Brownfoot (UOG Editor-for-Trainees)
Read the free-access article: http://onlinelibrary.wiley.com/doi/10.1002/uog.17455/full
GENETIC TESTING: Introduction, definition, methods: molecular, chromosomal and biochemical, indications, types: preimplantation, forensic, newborn, carrier, prenatal, ethical, social and legal issues, interpretation of tests, risks and limitations, role of nurse
Ethical and Legal Issues Related to Medical Genetics Rayhan Shahrear
Define ethics and bioethics.
State the major ethical issues related to medical genetics.
Outline the uniqueness of medical genetics.
Outline the relevant ethical principles in medicine.
Discuss some ethical dilemmas that arise in the genetic clinic.
Explain the ethical dilemmas and public interest.
Dr. Najnin Akhter
Phase-A, Year-2, Block-6
Guided by Prof. K M Shamim
Perinatal and long-term outcomes in fetuses diagnosed with isolated unilateral ventriculomegaly: systemic review and meta-analysis
C. Scala, A. Familiari, A. Pinas, A.T. Papageorghiou, A. Bhide, B. Thilaganathan, A. Khalil
Volume 49, Issue 4, Date: April (pages 450–459)
Slides prepared by Dr Yael Raz (UOG Editor-for-Trainees)
Link to free-access article: http://onlinelibrary.wiley.com/doi/10.1002/uog.15943/full
Neurodevelopmental outcome in isolated mild fetal ventriculomegaly: systematic review and meta-analysis
G. Pagani, B. Thilaganathan and F. Prefumo
Volume 44, Issue 3, Date: September 2014, Pages 254-260
http://onlinelibrary.wiley.com/doi/10.1002/uog.13364/abstract
Increased nuchal translucency thickness and risk of neurodevelopmental disorders
S. G. Hellmuth, L. H. Pedersen, C. B. Miltoft, O. B. Petersen, S. Kjærgaard, C. Ekelund, A. Tabor
Volume 49, Issue 5; Date: May (pages 592–598)
Slides prepared by Dr Maddalena Morlando (UOG Editors-for-Trainees)
Link to free-access article: http://onlinelibrary.wiley.com/doi/10.1002/uog.15961/full
Genetic testing (evaluation)
This is a type of clinical test that identifies changes in chromosomes, genes, or proteins. Genetic testing can provide information about a person's genes and chromosomes.
The results of a genetic test can confirm or rule out a suspected genetic condition or help determine a person’s chance of developing or passing on a genetic disorder.
At present, more than 1,000 types of genetic tests are currently in use, and more are being developed.
Methods used for genetic testing:
Molecular genetic tests (or gene tests): It tests single genes or short lengths of DNA to identify variations or mutations that lead to a genetic disorder.
Chromosomal genetic tests: It analyze whole chromosomes or long lengths of DNA to see if there are large genetic changes.
Biochemical genetic tests: It tests the amount or activity level of protein abnormalities to indicate changes in the DNA that result in a genetic disorder.
Genetic testing is voluntary. Because testing has benefits as well as limitations and risks, the decision about whether to be tested is a personal and complex one. A geneticist or genetic counselor can help by providing information about the pros and cons of the test and discussing the social and emotional aspects of testing.
Cervical length screening for prevention of preterm birth in singleton pregnancy with threatened preterm labor: systematic review and meta-analysis of randomized controlled trials using individual patient-level data
V. Berghella, M. Palacio, A. Ness, Z. Alfirevic, K. H. Nicolaides and G. Saccone
Volume 49, Issue 3, Date: March (pages 322–329)
Slides prepared by Dr Shireen Meher (UOG Editors-for-Trainees)
Link to free-access article: http://onlinelibrary.wiley.com/doi/10.1002/uog.17388/full
Multicenter screening for pre-eclampsia by maternal factors and biomarkers at 11–13 weeks' gestation: comparison with NICE guidelines and ACOG recommendations
N. O'Gorman, D. Wright, L. C. Poon, D. L. Rolnik, A. Syngelaki, M. de Alvarado, I. F. Carbone, V. Dutemeyer, M. Fiolna, A. Frick, N. Karagiotis, S. Mastrodima, C. de Paco Matallana, G. Papaioannou, A. Pazos, W. Plasencia, K. H. Nicolaides
Volume 49, Issue 6, Pages 756–760
Slides prepared by Dr Fiona Brownfoot (UOG Editor-for-Trainees)
Read the free-access article: http://onlinelibrary.wiley.com/doi/10.1002/uog.17455/full
GENETIC TESTING: Introduction, definition, methods: molecular, chromosomal and biochemical, indications, types: preimplantation, forensic, newborn, carrier, prenatal, ethical, social and legal issues, interpretation of tests, risks and limitations, role of nurse
The leaflet aims at providing general objective information on genetic tests, including their nature and the potential implications of their results. It presents the different types of tests available, their applications in the medical field and the extent and limit of the significance of the information resulting from these tests.
More information - www.coe.int/bioethics
Topics Include; Emerging Therapies and The Clinical Trial Process presented by Dennis Dlugos, MD, MSCE, Involvement Opportunities for LGS Families presented by John Currier, MBA and Christina SanInocencio, MS, Cannabis for LGS: Overview, Experiences and Clinical Practice presented by Heather Barnes Jackson and Jeremy Toler, MD
Deep Behavioral Phenotyping in Systems Neuroscience for Functional Atlasing a...Ana Luísa Pinho
Functional Magnetic Resonance Imaging (fMRI) provides means to characterize brain activations in response to behavior. However, cognitive neuroscience has been limited to group-level effects referring to the performance of specific tasks. To obtain the functional profile of elementary cognitive mechanisms, the combination of brain responses to many tasks is required. Yet, to date, both structural atlases and parcellation-based activations do not fully account for cognitive function and still present several limitations. Further, they do not adapt overall to individual characteristics. In this talk, I will give an account of deep-behavioral phenotyping strategies, namely data-driven methods in large task-fMRI datasets, to optimize functional brain-data collection and improve inference of effects-of-interest related to mental processes. Key to this approach is the employment of fast multi-functional paradigms rich on features that can be well parametrized and, consequently, facilitate the creation of psycho-physiological constructs to be modelled with imaging data. Particular emphasis will be given to music stimuli when studying high-order cognitive mechanisms, due to their ecological nature and quality to enable complex behavior compounded by discrete entities. I will also discuss how deep-behavioral phenotyping and individualized models applied to neuroimaging data can better account for the subject-specific organization of domain-general cognitive systems in the human brain. Finally, the accumulation of functional brain signatures brings the possibility to clarify relationships among tasks and create a univocal link between brain systems and mental functions through: (1) the development of ontologies proposing an organization of cognitive processes; and (2) brain-network taxonomies describing functional specialization. To this end, tools to improve commensurability in cognitive science are necessary, such as public repositories, ontology-based platforms and automated meta-analysis tools. I will thus discuss some brain-atlasing resources currently under development, and their applicability in cognitive as well as clinical neuroscience.
Richard's aventures in two entangled wonderlandsRichard Gill
Since the loophole-free Bell experiments of 2020 and the Nobel prizes in physics of 2022, critics of Bell's work have retreated to the fortress of super-determinism. Now, super-determinism is a derogatory word - it just means "determinism". Palmer, Hance and Hossenfelder argue that quantum mechanics and determinism are not incompatible, using a sophisticated mathematical construction based on a subtle thinning of allowed states and measurements in quantum mechanics, such that what is left appears to make Bell's argument fail, without altering the empirical predictions of quantum mechanics. I think however that it is a smoke screen, and the slogan "lost in math" comes to my mind. I will discuss some other recent disproofs of Bell's theorem using the language of causality based on causal graphs. Causal thinking is also central to law and justice. I will mention surprising connections to my work on serial killer nurse cases, in particular the Dutch case of Lucia de Berk and the current UK case of Lucy Letby.
Observation of Io’s Resurfacing via Plume Deposition Using Ground-based Adapt...Sérgio Sacani
Since volcanic activity was first discovered on Io from Voyager images in 1979, changes
on Io’s surface have been monitored from both spacecraft and ground-based telescopes.
Here, we present the highest spatial resolution images of Io ever obtained from a groundbased telescope. These images, acquired by the SHARK-VIS instrument on the Large
Binocular Telescope, show evidence of a major resurfacing event on Io’s trailing hemisphere. When compared to the most recent spacecraft images, the SHARK-VIS images
show that a plume deposit from a powerful eruption at Pillan Patera has covered part
of the long-lived Pele plume deposit. Although this type of resurfacing event may be common on Io, few have been detected due to the rarity of spacecraft visits and the previously low spatial resolution available from Earth-based telescopes. The SHARK-VIS instrument ushers in a new era of high resolution imaging of Io’s surface using adaptive
optics at visible wavelengths.
Salas, V. (2024) "John of St. Thomas (Poinsot) on the Science of Sacred Theol...Studia Poinsotiana
I Introduction
II Subalternation and Theology
III Theology and Dogmatic Declarations
IV The Mixed Principles of Theology
V Virtual Revelation: The Unity of Theology
VI Theology as a Natural Science
VII Theology’s Certitude
VIII Conclusion
Notes
Bibliography
All the contents are fully attributable to the author, Doctor Victor Salas. Should you wish to get this text republished, get in touch with the author or the editorial committee of the Studia Poinsotiana. Insofar as possible, we will be happy to broker your contact.
Earliest Galaxies in the JADES Origins Field: Luminosity Function and Cosmic ...Sérgio Sacani
We characterize the earliest galaxy population in the JADES Origins Field (JOF), the deepest
imaging field observed with JWST. We make use of the ancillary Hubble optical images (5 filters
spanning 0.4−0.9µm) and novel JWST images with 14 filters spanning 0.8−5µm, including 7 mediumband filters, and reaching total exposure times of up to 46 hours per filter. We combine all our data
at > 2.3µm to construct an ultradeep image, reaching as deep as ≈ 31.4 AB mag in the stack and
30.3-31.0 AB mag (5σ, r = 0.1” circular aperture) in individual filters. We measure photometric
redshifts and use robust selection criteria to identify a sample of eight galaxy candidates at redshifts
z = 11.5 − 15. These objects show compact half-light radii of R1/2 ∼ 50 − 200pc, stellar masses of
M⋆ ∼ 107−108M⊙, and star-formation rates of SFR ∼ 0.1−1 M⊙ yr−1
. Our search finds no candidates
at 15 < z < 20, placing upper limits at these redshifts. We develop a forward modeling approach to
infer the properties of the evolving luminosity function without binning in redshift or luminosity that
marginalizes over the photometric redshift uncertainty of our candidate galaxies and incorporates the
impact of non-detections. We find a z = 12 luminosity function in good agreement with prior results,
and that the luminosity function normalization and UV luminosity density decline by a factor of ∼ 2.5
from z = 12 to z = 14. We discuss the possible implications of our results in the context of theoretical
models for evolution of the dark matter halo mass function.
Professional air quality monitoring systems provide immediate, on-site data for analysis, compliance, and decision-making.
Monitor common gases, weather parameters, particulates.
Toxic effects of heavy metals : Lead and Arsenicsanjana502982
Heavy metals are naturally occuring metallic chemical elements that have relatively high density, and are toxic at even low concentrations. All toxic metals are termed as heavy metals irrespective of their atomic mass and density, eg. arsenic, lead, mercury, cadmium, thallium, chromium, etc.
2. Overview
• What has the DIAN –L study taught us?
• DIAN – TU – the treatment trial
– The rationale
– Who is eligible
– What is involved
3. Dominantly Inherited Alzheimer Network
• International observational trial (US, UK, Australia) started 2011
• Patients with a family history of dominantly inherited Alzheimer’s
disease
• Both at risk and affected participants (>280; 33 DRC)
• Biomarker study (Blood, CSF)
• Imaging
• Clinical assessment
• Only UK site - Dementia Research Centre, NHNN, Queen Square
4. •Courtesy of Tammie Benzinger and Tyler Blazey
Amyloid deposition may begin at least 15 years prior to
dementia onset in mutation carriers
5. Motivation for prevention studies
Completing/Completed
Phase III trials
Newer
Phase II/III trials
Prevention
studies
http://adni.loni.ucla.edu/about/biomarkers/
6. •Current therapeutic trials may be too late: proposed therapeutics
for Alzheimer’s disease currently target slowing or halting the
underlying disease (disease modifying), but are not likely to
reverse the extensive neuronal death present at the onset of
symptoms.
•There is certain risk (~100% with known mutation in PS1, PS2 or
APP) of the disease which enables prevention studies and
increases the power of treating minimally symptomatic patients.
•Disease modifying therapeutics are largely developed with animal
models based on human disease causing mutations. Thus, AD
caused by known autosomal dominant mutations is most likely to
respond to these proposed disease modifying treatments.
•Results from treatment trials in autosomal dominant AD will bridge
cellular and mouse therapeutic research with sporadic AD
therapeutic research.
Rationale for treatment trials in individuals at risk for
Autosomal Dominant Alzheimer’s disease
7. Treatment approach
• Immunotherapy approach
- Using drugs that stimulate the immune
system in order to remove abnormal
proteins that have been deposited
- Many current studies use monoclonal
antibodies - bind to proteins and stimulate
the immune system in order to remove
amyloid
8. DIAN TU trial
• Aim: To assess the safety, tolerability and biomarker
efficacy of gantenerumab and solanezumab in
subjects who are known to have an Alzheimer's
disease causing mutation.
9. What’s the treatment?
• Two different treatment options
• Both monoclonal antibodies that bind to amyloid (abnormal
protein) in the brain and remove it
– Solanezumab (given by infusion)
– Gantenerumab (given by subcutaneous injection)
• Monthly treatment
• Participants randomly assigned to either treatment option
• May get placebo (dummy) drug (3:1 chance of getting active
drug in mutation positive participants)
• Two year duration
10. Who’s eligible?
• Age 18 years and above
• Be ‘at risk’ for Familial AD (have a first degree relative with
a known disease-causing mutation)
• Be -15 years to +10 years from predicted age of onset of
symptoms
• Can be asymptomatic or mildly affected
• Does NOT need to know mutation status and does NOT
need to learn status to participate
11. DIAN TU trial – what will it entail?
• Annual visit
– Clinical assessments
– Cognitive testing
– MRI scan
– PET scanning (at UCLH and Cambridge)
– Blood tests
– Lumbar puncture
– Collateral source questionnaires
12. DIAN TU trial – what will it entail?
• Monthly visits to the DRC
• Depending on the drug arm, participants will receive either a monthly
subcutaneous injection or intravenous infusion
13. FAQs
• Can participants taking medications for memory
impairment (e.g. donepezil) remain on their
medications during trial participation?
Yes, but we ask that the dose stays the same. You would
discuss this with the study nurse.
14. FAQs
• Who decides whether participants get the active drug
or placebo?
A computer system randomly assigns participants to active
drug or placebo. The assignment to drug or placebo is
“blinded” which means neither the participant nor any member
of the study team will know whether the individual is receiving
the study medication or placebo. All mutation negative
participants will be assigned to placebo for safety purposes.
15. FAQs
• Will the study personnel know participants’ genetic
status?
No. Genetic status of participants will not be known by study
personnel. Participants will remain blinded to their genetic
status unless they have previously found this out. If participants
wish to know their gene status, they will be referred for genetic
counselling. Participants who know that they are gene negative
are not eligible.
16. FAQs
• If you have side effects from a drug, does mean that
you are mutation positive?
No. Even people on placebo may have side-effects. A side effect
is likely to be mild and may not be different from everyday type
discomforts such as headache, fatigue and nausea. All side
effects that you experience will be documented.
17. DIAN Expanded Registry
•Provides an overview of Autosomal Dominant Alzheimer’s
disease
(ADAD), links to other web resources (alzforum.org).
•Operational as of Feb 2012
•Posts of past webinars
•Register an interest in participation in DIAN-TU
18. Contact details
• Dr Chris Lane (Clinical Research Fellow) –
c.lane@ucl.ac.uk
• Jane Douglas (Clinical Trials nurse) –
jane.douglas@ucl.ac.uk or 02034483560
So we know they will develop at some point and we know when that is likely to be because of their parent. Age they are likely to get is the same as their parents.
In summary, our findings indicate that the Alzheimer&apos;s disease process begins more than 20 years before the clinical onset of dementia. Treatment and prevention trials can incorporate these pathophysiological changes to gauge the likelihood of future clinical success. Secondary prevention trials that are designed to prevent or delay cognitive and clinical impairment may ultimately test the amyloid hypothesis, just as the cholesterol hypothesis of heart disease was tested three decades ago.33