CONTEXT Maternal depressive symptoms during pregnancy have been reported in some, but not all, studies to be associated with an increased risk of preterm birth (PTB), low birth weight (LBW), and ...intrauterine growth restriction (IUGR). OBJECTIVE To estimate the risk of PTB, LBW, and IUGR associated with antenatal depression. DATA SOURCES AND STUDY SELECTION We searched for English-language and non–English-language articles via the MEDLINE, PsycINFO, CINAHL, Social Work Abstracts, Social Services Abstracts, and Dissertation Abstracts International databases (January 1980 through December 2009). We aimed to include prospective studies reporting data on antenatal depression and at least 1 adverse birth outcome: PTB (<37 weeks' gestation), LBW (<2500 g), or IUGR (<10th percentile for gestational age). Of 862 reviewed studies, 29 US-published and non–US-published studies met the selection criteria. DATA EXTRACTION Information was extracted on study characteristics, antenatal depression measurement, and other biopsychosocial risk factors and was reviewed twice to minimize error. DATA SYNTHESIS Pooled relative risks (RRs) for the effect of antenatal depression on each birth outcome were calculated using random-effects methods. In studies of PTB, LBW, and IUGR that used a categorical depression measure, pooled effect sizes were significantly larger (pooled RR 95% confidence interval = 1.39 1.19-1.61, 1.49 1.25-1.77, and 1.45 1.05-2.02, respectively) compared with studies that used a continuous depression measure (1.03 1.00-1.06, 1.04 0.99-1.09, and 1.02 1.00-1.04, respectively). The estimates of risk for categorically defined antenatal depression and PTB and LBW remained significant when the trim-and-fill procedure was used to correct for publication bias. The risk of LBW associated with antenatal depression was significantly larger in developing countries (RR = 2.05; 95% confidence interval, 1.43-2.93) compared with the United States (RR = 1.10; 95% confidence interval, 1.01-1.21) or European social democracies (RR = 1.16; 95% confidence interval, 0.92-1.47). Categorically defined antenatal depression tended to be associated with an increased risk of PTB among women of lower socioeconomic status in the United States. CONCLUSIONS Women with depression during pregnancy are at increased risk for PTB and LBW, although the magnitude of the effect varies as a function of depression measurement, country location, and US socioeconomic status. An important implication of these findings is that antenatal depression should be identified through universal screening and treated.Arch Gen Psychiatry. 2010;67(10):1012-1024-->
Background
Glioblastomas with a specific mutation in the isocitrate dehydrogenase 1 (IDH1) gene have a better prognosis than gliomas with wild-type IDH1.
Methods
Here we compare the IDH1 mutational ...status in 172 contrast-enhancing glioma patients with the invasion profile generated by a patient-specific mathematical model we developed based on MR imaging.
Results
We show that IDH1-mutated contrast-enhancing gliomas were relatively more invasive than wild-type IDH1 for all 172 contrast-enhancing gliomas as well as the subset of 158 histologically confirmed glioblastomas. The appearance of this relatively increased, model-predicted invasive profile appears to be determined more by a lower model-predicted net proliferation rate rather than an increased model-predicted dispersal rate of the glioma cells. Receiver operator curve analysis of the model-predicted MRI-based invasion profile revealed an area under the curve of 0.91, indicative of a predictive relationship. The robustness of this relationship was tested by cross-validation analysis of the invasion profile as a predictive metric for IDH1 status.
Conclusions
The strong correlation between IDH1 mutation status and the MRI-based invasion profile suggests that use of our tumor growth model may lead to noninvasive clinical detection of IDH1 mutation status and thus lead to better treatment planning, particularly prior to surgical resection, for contrast-enhancing gliomas.
A comprehensive analysis of the genomics of undifferentiated sarcomas (UDS) is lacking. We analyzed copy-number alterations and fusion status in patients with UDS prospectively treated on Children's ...Oncology Group protocol ARST0332.
Copy-number alterations were assessed by OncoScan FFPE Express on 32 UDS. Whole-exome and transcriptome libraries from eight tumors with sufficient archived material were sequenced on HiSeq (2 × 100 bp). Targeted RNA-sequencing using Archer chemistry was performed on two additional cases.
Five-year overall survival for patients with UDS was 83% (95% CI, 69%-97%) with risk-adapted therapy (surgery, chemotherapy, and radiotherapy). Both focal and arm-level copy-number alterations were common including gain of 1q (8/32, 25%) and loss of 1p (7/32, 22%), both of which occurred more often in clinically defined high-risk tumors. Tumors with both loss of 1p and gain of 1q carried an especially poor prognosis with a 5-year event-free survival of 20%. GISTIC analysis identified recurrent amplification of FGF1 on 5q31.3 (
= 0.03) and loss of
and
on 9p21.3 (
= 0.07). Known oncogenic fusions were identified in eight of 10 cases analyzed by next-generation sequencing.
Pediatric UDS generally has a good outcome with risk-adapted therapy. A high-risk subset of patients whose tumors have copy-number loss of 1p and gain of 1q was identified with only 20% survival. Oncogenic fusions are common in UDS, and next-generation sequencing should be considered for children with UDS to refine the diagnosis and identify potentially targetable drivers.
.
Salivary gland-type tumors have been rarely described in the thyroid gland. Mammary Analog Secretory Carcinoma (MASC) is a recently defined type of salivary gland carcinoma characterized by a ...t(12;15)(p13;q25) resulting in an
ETV6
-
NTRK3
fusion gene. We report 3 cases of MASC involving the thyroid gland without clinical evidence of a salivary gland or breast primary; the clinico-pathologic characteristics are reviewed. Assessment for rearrangement of the
ETV6
(12p13) locus was conducted by fluorescence in situ hybridization (FISH) on representative FFPE sections using an
ETV6
break apart probe (Abbott Molecular, Des Plaines, IL, USA). The patients were two females (52 and 55 years-old) and 1 male (74 years-old). The tumors were poorly circumscribed solid white tan nodules involving the thyroid. Histologically, they were invasive and showed solid, microcystic, cribriform, and tubular growth patterns composed of variably bland polygonal eosinophilic cells with vesicular nuclear chromatin and conspicuous nucleoli. All three cases showed metastasis to lymph nodes; one case showed lateral neck involvement. The tumor cells were positive for S100 and mammaglobin. GATA-3 and PAX-8 were positive in 2 cases, one of which only focally so. All three cases were negative for TTF-1 and thyroglobulin. Rearrangement of the
ETV6
locus was confirmed in all cases and a diagnosis of MASC rendered for each case. A site of origin distinct from the thyroid gland was not identified, with a median follow up of 24 months. MASC may rarely involve the thyroid gland. The origin of these lesions is unknown; while an origin from ectopic salivary gland-type cells is entertained, a metastatic origin from an occult primary cannot be definitively excluded at this time. Given the histologic (follicular-like microcystic pattern with colloid-like secretions and papillary pattern), immunophenotypic (PAX-8), and even molecular overlap, MASC can be mistaken for papillary thyroid carcinoma and should be considered in the differential diagnosis of a thyroid mass.
Malignant peripheral nerve sheath tumors (MPNST) are highly aggressive sarcomas with variable patient survival and few known prognostically relevant genomic biomarkers. To identify ...survival-associated genomic biomarkers, we performed high-resolution array-based comparative genomic hybridization (aCGH) on a large set of MPNSTs.
Candidate gene alterations identified by aCGH in 38 MPNSTs were validated at the DNA, RNA, and protein levels on these same tumors and an independent set of 87 MPNST specimens.
aCGH revealed highly complex copy number alterations, including both previously reported and completely novel loci. Four regions of copy number gain were associated with poor patient survival. Candidate genes in these regions include SOX5 (12p12.1), NOL1 and MLF2 (12p13.31), FOXM1 and FKBP1 (12p13.33), and CDK4 and TSPAN31 (12q14.1). Alterations of these candidate genes and several others of interest (ERBB2, MYC and TP53) were confirmed by at least 1 complementary methodology, including DNA and mRNA quantitative real-time PCR, mRNA expression profiling, and tissue microarray-based fluorescence in situ hybridization and immunohistochemistry. Multivariate analysis showed that CDK4 gain/amplification and increased FOXM1 protein expression were the most significant independent predictors for poor survival in MPNST patients (P < 0.05).
Our study provides new and independently confirmed candidate genes that could serve as genomic biomarkers for overall survival in MPNST patients.
Inflammatory myofibroblastic tumor (IMT) is a rare, but distinctive mesenchymal neoplasm composed of fascicles of bland myofibroblasts admixed with a prominent inflammatory component. Genetic studies ...of IMTs have demonstrated chromosomal abnormalities of 2p23 and rearrangement of the anaplastic lymphoma kinase (
ALK) gene locus. In a subset of IMTs, the ALK C-terminal kinase domain is fused with a tropomyosin N-terminal coiled-coil domain. In the current study, fusion of
ALK with the clathrin heavy chain (
CTLC) gene localized to 17q23 was detected in two cases of IMT. One of these cases exhibited a 2;17 translocation in addition to other karyotypic anomalies 46,XX,t(2;17)(p23;q23),add(16)(q24).
Emergency department (ED) visits for children seeking mental health care have increased. Few studies have examined national patterns and characteristics of EDs that these children present to. In data ...from the National Pediatric Readiness Project, it is reported that less than half of EDs are prepared to treat children. Our objective is to describe the trends in pediatric mental health visits to US EDs, with a focus on low-volume, nonmetropolitan EDs, which have been shown to be less prepared to provide pediatric emergency care.
Using 2007 to 2016 Nationwide Emergency Department Sample databases, we assessed the number of ED visits made by children (5-17 years) with a mental health disorder using descriptive statistics. ED characteristics included pediatric volume, children's ED classification, and location.
Pediatric ED visits have been stable; however, visits for deliberate self-harm increased 329%, and visits for all mental health disorders rose 60%. Visits for children with a substance use disorder rose 159%, whereas alcohol-related disorders fell 39%. These increased visits occurred among EDs of all pediatric volumes, regardless of children's ED classification. Visits to low-pediatric-volume and nonmetropolitan areas rose 53% and 41%, respectively.
Although the total number of pediatric ED visits has remained stable, visits among children with mental health disorders have risen, particularly among youth presenting for deliberate self-harm and substance abuse. The majority of these visits occur at nonchildren's EDs in both metropolitan and nonurban settings, which have been shown to be less prepared to provide higher-level pediatric emergency care.
AbstractMeasuring static or dynamic displacement is often an integral component of evaluating bridge conditions. This article introduces a wireless, low-cost, and high-accuracy smart radar sensor ...network to measure bridge displacement. This sensor technology consists of two major systems, a continuous-wave radar sensor and a wireless smart sensor network platform. The continuous-wave radar sensor, paired with an active transponder, has demonstrated submillimeter accuracy for structural displacement measurements. The hardware and software designs of the sensor network are presented in this article. The WiSeMote wireless sensor platform is adopted to establish a sensor network synchronized to the microsecond level. Critical performance metrics of the sensor network are quantified, including power consumption and wireless transmission range. The sensor network’s static and dynamic measurement accuracy have also been verified in a series of pedestrian bridge experiments. In addition, the ability of the sensor network to detect the vehicle speed is validated.
Mixed neuronal‐glial tumors are rare and challenging to subclassify. One recently recognized variant, papillary glioneuronal tumor (PGNT), is characterized by prominent pseudopapillary structures and ...glioneuronal elements. We identified a novel translocation, t(9;17)(q31;q24), as the sole karyotypic anomaly in two PGNTs. A fluorescence in situ hybridization (FISH)‐based positional cloning strategy revealed SLC44A1, a member of the choline transporter‐like protein family, and PRKCA, a protein kinase C family member of serine/threonine‐specific protein kinases, as the 9q31 and 17q24 breakpoint candidate genes, respectively. Reverse transcription‐polymerase chain reaction (RT‐PCR) analysis using a forward primer from SLC44A1 exon 5 and a reverse primer from PRKCA exon 10 confirmed the presence of a SLC44A1‐PRKCA fusion product in both tumors. Sequencing of each chimeric transcript uncovered an identical fusion cDNA junction occurring between SLC44A1 exon 15 and PRKCA exon 9. A dual‐color breakpoint‐spanning probe set custom‐designed for interphase cell recognition of the translocation event identified the fusion in a third PGNT. These results suggest that the t(9;17)(q31;q24) with the resultant novel fusion oncogene SLC44A1‐PRKCA is the defining molecular feature of PGNT that may be responsible for its pathogenesis. The FISH and RT‐PCR assays developed in this study can serve as valuable diagnostic adjuncts for this rare disease entity.
Summary Several soft tissue tumors are characterized by fibrous stroma with a conspicuous vascular component including cellular angiofibroma, nasopharyngeal angiofibroma, and solitary fibrous tumor. ...Recently, a distinctive fibroblastic tumor composed of bland spindle cells and a complex vascular network has been characterized morphologically and shown to harbor a recurrent t(5;8) translocation with AHRR-NCOA2 gene fusion. We report our recent experience with 2 examples of this benign tumor, the diagnosis for one of which was supported by fluorescence in situ hybridization for NCOA2 rearrangement. Identification of this tumor is important to prevent misdiagnosis as a low-grade sarcoma.
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