42 research outputs found
Subcortical brain volume, regional cortical thickness, and cortical surface area across disorders: findings from the ENIGMA ADHD, ASD, and OCD Working Groups
Objective Attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and obsessive-compulsive disorder (OCD) are common neurodevelopmental disorders that frequently co-occur. We aimed to directly compare all three disorders. The ENIGMA consortium is ideally positioned to investigate structural brain alterations across these disorders.
Methods Structural T1-weighted whole-brain MRI of controls (n=5,827) and patients with ADHD (n=2,271), ASD (n=1,777), and OCD (n=2,323) from 151 cohorts worldwide were analyzed using standardized processing protocols. We examined subcortical volume, cortical thickness and surface area differences within a mega-analytical framework, pooling measures extracted from each cohort. Analyses were performed separately for children, adolescents, and adults using linear mixed-effects models adjusting for age, sex and site (and ICV for subcortical and surface area measures).
Results We found no shared alterations among all three disorders, while shared alterations between any two disorders did not survive multiple comparisons correction. Children with ADHD compared to those with OCD had smaller hippocampal volumes, possibly influenced by IQ. Children and adolescents with ADHD also had smaller ICV than controls and those with OCD or ASD. Adults with ASD showed thicker frontal cortices compared to adult controls and other clinical groups. No OCD-specific alterations across different age-groups and surface area alterations among all disorders in childhood and adulthood were observed.
Conclusion Our findings suggest robust but subtle alterations across different age-groups among ADHD, ASD, and OCD. ADHD-specific ICV and hippocampal alterations in children and adolescents, and ASD-specific cortical thickness alterations in the frontal cortex in adults support previous work emphasizing neurodevelopmental alterations in these disorders
THE RATE OF BINARY BLACK HOLE MERGERS INFERRED FROM ADVANCED LIGO OBSERVATIONS SURROUNDING GW150914
A transient gravitational-wave signal, GW150914, was identi
fi
ed in the twin Advanced LIGO detectors on 2015
September 2015 at 09:50:45 UTC. To asse
ss the implications of this discovery,
the detectors remained in operation with
unchanged con
fi
gurations over a period of 39 days around the time of t
he signal. At the detection statistic threshold
corresponding to that observed for GW150914, our search of the 16 days of simultaneous two-detector observational
data is estimated to have a false-alarm rate
(
FAR
)
of
<
́
--
4.9 10 yr
61
, yielding a
p
-value for GW150914 of
<
́
-
210
7
. Parameter estimation follo
w-up on this trigger identi
fi
es its source as a binary black hole
(
BBH
)
merger
with component masses
(
)(
)
=
-
+
-
+
mm
M
,36,29
12
4
5
4
4
at redshift
=
-
+
z
0.09
0.04
0.03
(
median and 90% credible range
)
.
Here, we report on the constraints these observations place on the rate of BBH coalescences. Considering only
GW150914, assuming that all BBHs in the universe have the same masses and spins as this event, imposing a search
FAR threshold of 1 per 100 years, and assuming that the BBH merger rate is constant in the comoving frame, we infer a
90% credible range of merger rates between
–
--
2
53 Gpc yr
31
(
comoving frame
)
. Incorporating all search triggers that
pass a much lower threshold while accounting for the uncerta
inty in the astrophysical origin of each trigger, we estimate
a higher rate, ranging from
–
--
13 600 Gpc yr
31
depending on assumptions about the BBH mass distribution. All
together, our various rate estimat
es fall in the conservative range
–
--
2
600 Gpc yr
31
Specificity analysis of two new mouse monoclonal antibodies reactive with prostate cancer
Expression of c-kit and kit-ligand in benign and malignant prostatic tissues
The tyrosine kinase receptor c-kit and its
ligand [kit ligand (KL) or stem cell factor (SCF)] exert a
broad range of biological activities during organogenesis
and normal cell development. Recent studies have
revealed that altered c-kit levels occur in a variety of
malignancies and cancer cell lines. KL has also been
shown to stimulate the growth of malignant cells, as well
as to promote chemotaxis. We had previously reported
expression of KL in stroma cells of normal human
prostate.
The present study was undertaken in order to
analyze the patterns of expression of c-kit and KL in a
well characterized set of prostatic tissues, including
normal prostate (n=4), benign prostatic hyperplasia
(BPH) (n=53) and adenocarcinoma (n=46) samples. The
distribution of c-kit and KL proteins was studied by
immunohistochemical analyses, while transcript levels
were determined by in situ hybridization with specific
RNA probes on a subset of the benign and malignant
tissues referred above. In addition, reverse-transcriptase
polymerase chain reaction (RT-PCR) was performed to
determine levels of c-kit and KL expression in cultures
of epithelial and stroma cells, as well as in the prostate
cancer cell lines LNCaP, DUI45 and PC3.
c-kit protein in normal prostate was exclusively
detected in mast cells by immunohistochemistry and in
situ hybridization. However, c-kit transcripts, but not ckit
protein, were detected in low levels and with an
heterogeneous pattern in basal epithelial cells of ducts
and acini. c-kit in BPH was detected in epithelial cells in
9 of 53 (17%) specimens. c-kit protein expression in
malignant epithelial cells was identified in 1 of 46 (2%)
tumors. However, c-kit transcripts were detected in low
levels by in situ hybridization in most of the tumors
analyzed.
KL protein and transcripts in normal prostate were
detected in high levels in stroma cells. However,
epithelial cells were unreactive for anti-KL antibody, but
Offprint requests to: Dr. Carlos Cordon-Cardo, MD, PhD, Department of
Pathology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue
New York, NY 10021, USA. Fax: 212-794-3186. e-mail: cordonc@
mskcc.org
showed low levels of KL transcripts mainly in cells of
the basal layer. Basal epithelial cells in hyperplastic
glands showed KL expression in 13 of 53 (24%)
specimens. KL protein in tumor cells was noted in 18 of
46 (39%) cases.
c-kit transcripts were not found in normal prostate
and in the 3 cancer cell lines analyzed by RT-PCR,
however, it was present in cultured epithelial cells of
BPH, and in cultures of stroma cells from both normal
and BPH. The majority of cultured cell lines of epithelial
and stromal origin displayed considerable levels of KL.
In addition all prostate cell lines studied showed
significant levels of KL transcripts.
In summary, CO-expression of c-kit and KL in a
subset of BPH cases may suggest an autocrine mode of
signaling. Data from this study reveals that altered
patterns of c-kit and KL expression are associated with
BPH and adenocarcinoma of prostate. It appears that KL
induces mast cells proliferation and maturation and
enhances their release of protease. This could explain the
accumulation of mast cells at tumor sites. a phenomenon
that was not observed in normal prostate or BPH
samples
Advanced ultrasonic tissue-typing and imaging based on radio-frequency spectrum analysis and neural-network classification for guidance of therapy and biopsy procedures
Hormone therapy in the management of prostate cancer: evidence-based approaches
Hormonal therapy has been the standard for advanced prostate cancer for over 60
years. Recently, the utility of androgen ablation through various means has been
demonstrated for earlier stages of disease. In particular, the strongest
evidence to date involves the use of hormonal therapy in combination with
radiation therapy. In this article we review the basic concepts in hormonal
ablation for prostate cancer and review the evidence-based studies that support
the use of hormonal therapy in early stage prostate cancer