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Objective To examine the association of placental and fetal DNA copy number variants (CNVs) with fetal structural malformations (FSMs) in stillborn fetuses. Design A secondary analysis of stillbirth cases in the Stillbirth Collaborative Research Network (SCRN) study. Setting Multicenter, 59 hospitals in 5 geographic regions in the USA. Population 384 stillbirth cases of the SCRN study (2006-2008). Methods FSMs were grouped by anatomic system and specific malformation type (e.g., central nervous system, thoracic, cardiac, gastrointestinal, skeletal, umbilical cord and craniofacial defects). Single-nucleotide polymorphism array detected CNVs of at least 500kb. CNVs were classified into two groups: normal, defined as no CNVs>500kb or benign CNVs, and abnormal, defined as pathogenic or variants of unknown clinical significance. Main outcome measures The proportions of abnormal CNVs and normal CNVs were compared between stillbirth cases with and without FSMs using the Wald Chi-squared test. Results The proportion of stillbirth cases with any FSMs was higher among those with abnormal CNVs compared with those with normal CNVs (46.7% vs. 19.6%; p-value

Multiple regression equations (MREs) provide an empirical direct method of transforming coordinates between geodetic datums. Since they offer a means of modelling distortions, they are capable of a more accurate fit to datum-shift datasets than more basic direct methods. MRE models of datum shifts traditionally consist of polynomials based on relative latitude and longitude. However, the limited availability of low-power terms often leads to high-power terms being included, and these are a potential cause of instability. This paper introduces three variations based on simple partitions and 2 or 4 smoothly conjoined polynomials. The new types are North/South, East/West and Four-Quadrant. They increase the availability of low-order terms, enabling distortions to be modelled with fewer side effects. Case studies in Great Britain, Slovenia and Western Australia provide examples of partitioned MREs that are more accurate than conventional MREs with the same number of terms.

Objective To examine the association of DNA copy number variants (CNVs) with pathologic placental lesions (PPLs) in stillborn fetuses. Design A secondary analysis of stillbirth cases in the Stillbirth Collaborative Research Network case-control study. Setting Multicenter, 59 hospitals in 5 geographic regions in the USA. Population 387 stillbirth cases (2006-2008). Methods Using standard definitions, PPLs were categorized by type including maternal and fetal vascular, inflammatory and immune/idiopathic lesions. Using single-nucleotide polymorphism array, CNVs of at least 500 kb were detected. CNVs were classified into two groups: normal, defined as no CNVs>500 kb or benign CNVs, and abnormal, defined as pathogenic or variants of unknown clinical significance. Main outcome measures The proportions of abnormal CNVs and normal CNVs were compared between stillbirth cases with and without PPLs using the Wald Chi-squared test. Results Of 387 stillborn fetuses, 327 (84.5%) had maternal vascular PPLs and 60 (15.6%) had abnormal CNVs. Maternal vascular PPLs were more common in stillborn fetuses with abnormal CNVs compared with those with normal CNVs (81.7% vs. 64.2%; p=0.008). The proportions of fetal vascular, maternal/fetal inflammatory, and immune/idiopathic PPLs were similar among stillborn fetuses with abnormal CNVs compared to those with normal CNVs. Pathogenic CNVs in stillborn fetuses with maternal vascular PPLs spanned several genes with known relevant mechanisms. Conclusions Abnormal placental/fetal CNVs were associated with maternal vascular PPLs in stillborn fetuses. Findings may provide insight on the mechanisms of specific genetic abnormalities associated with placental dysfunction and stillbirth.

Background The caudal fin of actinopterygians transitioned from a heterocercal dorsoventrally asymmetrical fin to a homocercal externally symmetrical fin in teleosts through poorly understood evolutionary developmental mechanisms. We studied the caudal skeleton of major living actinopterygian lineages, including polypteriformes, acipenseriformes, Holostei (gars and bowfin), and teleosts, compared with reports of extinct neopterygians and basal teleosteans. We focused on the hypural diastema complex, which includes (1) a gap between hypurals 2 and 3, that (2) separates two plates of connective tissue at (3) the branching of caudal vasculature; these features had been considered as a shared, derived trait of teleosts, a synapomorphy. Results These studies revealed that gars and teleosts share all three features of the hypural diastema complex. Absence of a complex with these features from bowfin, fossil Holostei, and stem Teleostei argues in favor of repetitive, independent emergence in several neopterygian and basal Teleostei lineages, or less likely, many independent losses. We further observed that, in gars and teleosts, the earliest developing lepidotrichia align with the horizontal adult body axis, thus participating in external symmetry. Conclusions These results suggest that the hypural diastema complex in teleosts and gars represents a homoplasy among neopterygians and that it emerged repeatedly by parallel evolution due to shared inherited underlying genetic and developmental programs (latent homology). Because the hypural diastema complex exists in gars with heterocercal tails, this complex is independent of homocercality. Developmental Dynamics 247:832-853, 2018. © 2018 Wiley Periodicals, Inc.

Background The caudal fin of actinopterygians experienced substantial morphological changes during evolution. In basal actinopterygians, the caudal fin skeleton supports an asymmetrical heterocercal caudal fin, while most teleosts have a symmetrical homocercal caudal fin. The transition from the ancestral heterocercal form to the derived homocercal caudal fin remains poorly understood. Few developmental studies provide an understanding of derived and ancestral characters among basal actinopterygians. To fill this gap, we examined the development of the caudal fin of spotted gar Lepisosteus oculatus, one of only eight living species of Holostei, the sister group to the teleosts. Results Our observations of animals from fertilization to more than a year old provide the most detailed description of the development of caudal fin skeletal elements in any Holostean species. We observed two different types of distal caudal radials replacing two transient plates of connective tissue, identifying two hypaxial ensembles separated by a space between hypurals 2 and 3. These features have not been described in any gar species, but can be observed in other gar species, and thus represent anatomical structures common to lepisosteiformes. Conclusions The present work highlights the power and importance of ontogenic studies and provides bases for future evolutionary and morphological investigations on actinopterygians fins. Developmental Dynamics 247:724-740, 2018. © 2018 Wiley Periodicals, Inc.

Using a family-based approach with whole exome sequencing (WES) and custom bioinformatics tools we identified a novel mutation (M527L) in the Nuclear Factor of Activated T-Cells 1 gene (NFATc1). This nonsynonymous heterozygous substitution segregates in an autosomal dominant pattern within a family with a young onset Atrial Fibrillation (AF) phenotype. Patient specific inducible pluripotent stem cell derived-cardiomyocytes (iPSC-CM) from a patient carrying this variant showed abbreviated repolarization resulting in a shorter action potential duration compared to iPSC-CM from a healthy sibling control. Unlike familial monogenic AF where the mutation occurs in an ion channel gene, NFATc1 is a transcription factor that influences expression of multiple genes. Using single-cell RNA sequencing on 30 day post-differentiation iPSC-CM, we identified four subpopulations by K-mean clustering (k=4) of single cell transcriptomes and subsequent marker expression. We then performed gene-annotation enrichment analysis of differentially expressed genes specifically in the mutant (MT) and wild-type (WT) cardiomyocyte (CM) populations, detecting several key functional and pathological cardiac pathways affected in response to the NFATc1 mutation. These included Wnt, NF-kappaB and MAPK signaling, Ca homeostasis and gene categories that have been associated with atrial fibrillation. These results suggest that NFATc1 mutation may play an important role in the pathophysiology of familial atrial fibrillation by its broad impact on gene expression and subsequent pathway regulation.

BACKGROUND/PURPOSE To present a novel case of paracentral acute middle maculopathy in association with birdshot chorioretinopathy. METHODS Case report. RESULTS A patient presented with decreased vision and findings of uveitis, vasculitis and a paracentral scotoma. Multimodal imaging was consistent with paracentral acute middle maculopathy in the setting of a multifocal chorioretinopathy and a laboratory workup was consistent with birdshot chorioretinopathy. CONCLUSION Paracentral acute middle maculopathy is a newly described entity that may be associated with birdshot chorioretinopathy, and clinicians should be aware of it when patients present with new paracentral scotoma and signs of intraocular inflammation.

Purpose The aim of the study is to demonstrate whether resident performance on the United States Medical Licensing Exam (USMLE) Step 1 and the Ophthalmology Knowledge Assessment Program (OKAP) correlates to American Board of Ophthalmology Written Qualifying Examination (ABO-WQE). Design This is a retrospective cohort study. Participants Forty-one residents who completed their postgraduate training between 1999 and 2011 from our institution were included in the study. Methods Percentiles on the USMLE Step 1, OKAP, and ABO-WQE first attempt were recorded and analyzed for possible correlations among scores across examinations using Pearson rank correlation, chi-square analysis, Fisher exact test, and Student t-test. Results The percentile score on the USMLE Step 1 was the only standardized test that had a statistically significant association with the percentile score on the ABO-WQE (Pearson rank coefficient = 0.45, p = 0.01). Not achieving a score of 20th percentile on the OKAP examination among second-year residents had the highest statistical association with failing the ABO-WQE on first attempt (p = 0.001) with an odds ratio of 20.4, and the relative risk of failing the ABO-WQE was 11.3; however, the relative risk of passing if the cutoff was achieved was only 1.8, and a positive predictive value for failing the ABO-WQE on first attempt of 0.47. Conclusions Percentile scores on the OKAP are not indicative of percentile scores on the ABO-WQE. While OKAP examinations in the second and third year appear to separate out residents at risk of failing the ABO-WQE, there is a large disparity between the risk of passing and failing which is likely due to the inadequate prognostic value of the test. It is likely OKAP examinations may be a useful tool to identify residents who are at low risk for failing the ABO-WQE on first attempt, but much less useful for identifying residents who are at high risk for failing the ABO-WQE.

Informal economic activity has been increasing in Brazil in the midst of neoliberal reforms, skyrocketing unemployment, and business strategies designed to cut labor costs. Today half of the Brazilian economically active population works informally, as do 40 percent of private-sector employees, now the largest group of informal workers. In both Salvador and Brazil there are more informal salaried workers than there are informal self-employed entrepreneurs, contrary to what most theories of informality would predict. The state is not adequately enforcing its labor legislation, and employers increasingly contract their employees informally. Outsourcing (subcontracting to smaller firms) also contributes to informality, since micro-enterprises are less likely to formalize their employees’ status. Theories of informality need to recognize that there is no such thing as a separate “informal sector” of the economy and that informality increasingly extends to employees of formal firms.

In addition to desirable physical properties including a density of 7.4 g/cm3 , an effective atomic number of 66, and no hygroscopicity, Lu2SiO5:Ce has well-known scintillation properties of ~30 900 photons/MeV, an emission peak near 420 nm, and a decay time of ~43 ns. These scintillation properties are achieved with Ce doping concentrations roughly in the range of 0.05 to 0.5 atomic percent relative to Lu. These properties make Lu2SiO5:Ce a widely used scintillator in positron emission tomography, in particular. We have found that both the light output and decay time may be improved by a combination of optimized crystal growth atmosphere and co-doping with divalent cations such as Ca. Scintillation light output of ~38 800 photons/MeV has been achieved as well as scintillation decay time as short as 31 ns with no long components. The relationship between growth conditions, dopant concentration, decay time, and light output is well defined, thus allowing one to reliably "tune" the crystal to the desired combination of light output and decay time. Possible explanations of the underlying mechanism are being explored and include compensation of oxygen vacancies, alteration of the relative occupancies of the cerium lattice sites, and suppression of trapping centers. In addition to higher count-rate capability and better coincidence timing, the improved decay time is expected to be particularly advantageous for time-of-flight positron emission tomography. Also, phoswich detectors comprising "standard" LSO (~43 ns decay time) and "fast" LSO (~31 ns decay time) become an attractive alternative to typical phoswich designs that often suffer from problems of mismatched light outputs and indices of refraction or the absorption of one scintillator's light by the other.

Lutetium oxyorthosilicate (LSO) is a well-known scintillator that is widely used for gamma-ray detection in positron emission tomography (PET) as well as in other applications. LSO is typically doped with 0.05–0.5% Ce while controlling other impurities at low levels, but recent research has begun to explore the manner in which various co-dopants may influence scintillation properties. We have found that some co-dopants, particularly Ca, have a desirable impact on scintillation, leading to improvements in both light yield and decay time that are related to co-dopant concentration. However, it has been observed that in concentrations high enough to optimize scintillation properties some of these co-dopants can have a pronounced negative effect on the growth stability in Czochralski growth systems. We have observed acentric growth shortly after reaching full diameter despite no obvious change in thermal gradients or convective flow. Visual observations of the liquid meniscus suggest that Ca co-doping significantly reduces surface tension; one possible explanation is that the resulting enhanced Marangoni flow is responsible for the unstable growth behavior. Fortunately, we have found that an additional co-dopant can be used to restore adequate surface tension and thus stabilize growth with no negative impact on the scintillation properties of the crystal. To date, the most effective co-dopant for this purpose is Zn, when introduced in concentrations greater than that of Ce and Ca.

Transverse (lateral) sinus thrombosis is a well-known complication of acute otitis media and mastoiditis in the pediatric and adult population. Thrombosis involving the transverse sinus can ultimately cause elevation of intracranial pressure (ICP) as a result of decreased cerebrospinal fluid absorption. If treatment to lower ICP is not undertaken, it can lead to ophthalmological complications including irreversible vision loss. The following case report describes an 11-year-old girl who was diagnosed with AOM by her pediatrician and subsequently presented to the emergency department complaining of nausea, vomiting, headache, and diplopia.

A 38-year-old woman developed bilateral carotid cavernous fistulae (CCF) following a motor vehicle collision. Her initial ophthalmologic findings included periorbital edema, palsies of the left oculomotor and abducens nerves, and residual dilated pupils. She subsequently developed significant optic disc edema and retinal vascular dilation bilaterally. Patients with similar injuries typically require neurosurgical or vascular intervention. In this case, the patient’s signs resolved spontaneously by 21 months after onset, leaving no residual ocular deficits.

The authors discuss the challenges of treating adult survivors of physical, emotional, and sexual abuse, and specifically how the relationship with God can psychologically promote healing or maintain an abusive cycle. With this population, it is critical that clinicians understand the dynamic bonding process between abuser and survivor and how this “bonded” relationship is typically transferred to God. The authors detail a theory of psychospiritual bonding between abuser and survivor and survivor and God and provide implications for treatment.

In this paper properties of LuAP (LuAlO/sub 3/:Ce), and LuYAP (Lu/sub 0.7/Y/sub 0.3/AlO/sub 3/:Ce) crystals are studied. The previously reported self-absorption has been confirmed, and a possible mechanism is discussed. The thermal stability of the material was evaluated, and both LuAP and LuYAP have been found to readily decompose when heated to a sufficiently high temperature. XRD studies were done to determine that a solid-solid phase transformation occurs under those conditions. In addition, thermoluminescence studies reveal the presence of additional traps in the LuYAP crystal, apparently the result of the yttrium addition to the crystal lattice.

This work presents the results from experiments performed on Lu/sub 2/SiO/sub 5/:Ce (LSO:Ce). It looks for potential correlations of light yield non-proportionality and other scintillation properties including intrinsic energy resolution with thermoluminescence properties. Samples were chosen from various crystal batches that were known to have significantly different properties. Single crystal LSO:Ce samples were coupled to an XP2020Q photomultiplier and to large area avalanche photodiodes and measured as a function of gamma-ray energy between 14.7 and 1770 keV at room temperature and also near liquid nitrogen temperature. In order to explain the experimental results obtained from spectrometric methods, the properties of the samples were further studied using thermoluminescence techniques within the temperature range from 250 to 600 K. The relationships between data obtained from these two types of experiments are reported.

The following is the abstract of the article discussed in the subsequent letter: We determined the effect of fat adaptation on metabolism and performance during 5 h of cycling in seven competitive athletes who consumed a standard carbohydrate (CHO) diet for 1 day and then either a high-CHO diet (11

Diversity exists in both the structure and function of the endothelial cells (EC) that comprise the microvasculature of different organs. Studies of EC have been aided by our ability to first isolate and subsequently establish cultures from microvascularized tissue. After the isolation of microvessel endothelial cells (MEC) derived from rat cerebrum, we observed morphologic differences in colonies of cells that grew in primary cultures. The morphologies ranged from a cobblestone phenotype considered typical of EC in culture to elongated and stellate cell appearances. Serially passaged cell lines were established based on two parameters: initially by growth and, seconds, on differences in primary colony morphology using selective weeding techniques. Each culture was examined for the presence of EC-characteristic markers which include Factor-VIII-related antigen, angiotensin-I-converting enzyme activity, collagen type IV synthesis, and PGI2 production. Variable expression of each of these characteristics among the established EC lines was observed. Growth curves established for each of the EC cultures demonstrated differences in both population doubling rates and cell densities at confluence. The endocytic capacity of each EC line was also evaluated. Our ability to isolate and establish a number of morphologically distinct EC cultures indicates that diversity exists within the EC that comprise the cerebral microvasculature. Diversity in the established cell lines suggests either the EC that line the brain microvasculature exist as a mosaic or that morphologically distinct cultures may originate from different microanatomical origins (arteriolar, true capillary, or venular) or may have resulted from cells at different points in their in vitro life spans at the time of isolation.

From 1974 to 1983 we treated 16 children between 1 and 16 years old for soft tissue sarcoma arising in the pelvis, bladder or prostate. An incisional biopsy was obtained in every patient. Each child then was treated with a combination chemotherapy program, incorporating vincristine, actinomycin D and cyclophosphamide with or without doxorubicin, cis-platinum and etoposide. Of the 16 patients 13 (81 per cent) also received radiation therapy. In 8 children with urinary obstruction or hematuria sarcomas arose in the bladder or bladder-prostate region, including 7 who had localized tumors and 1 who had lung metastases at diagnosis. The median tumor diameter in these patients was 5 cm. Of these 8 patients 3 eventually required total cystectomy and prostatectomy to eradicate persistent local tumor, and 6 are alive and remain free of recurrent sarcoma for 1 to 9 years after initiation of therapy. The 8 other children had a pelvic mass at diagnosis, which arose adjacent to but outside of the bladder or prostate, and 2 had lung metastases at diagnosis. The median tumor diameter in these patients was 15 cm. Only 3 of these 8 children are alive and remain free of sarcoma for 1 to 8 years after initiation of therapy. In only 1 of these children was complete tumor excision ever possible despite the use of local radiation therapy and aggressive chemotherapy. Sarcomas arising in the bladder-prostate region are found when relatively small, perhaps because they soon produce overt signs, and they appear to have a better prognosis than those arising in the retroperitoneum-pelvis outside the bladder. Better treatment strategies are needed for the latter group of tumors that often are locally uncontrollable.

In this paper we present scintillation, optical, and thermoluminescence properties of recently discovered scintillation material, LPS (Lu2Si2O7:Ce) and composition with yttrium LYPS ((Lu,Y)2Si2O7 :Ce). The latter was first grown at Siemens Medical Solutions Molecular Imaging, and had an yttrium concentration of 50%. Both have the thorveitite structure, with monoclinic symmetry, space group C2/m. XRD measurements confirmed the expected crystal structure in which there is a single crystallographic site for lutetium or yttrium ions, with six oxygen neighbors. The trivalent cerium activator ions are assumed to occupy the cation lattice site. The excited 5d state of Ce3+ is split into 2 observable levels with luminescence emission occurring only from the lowest 5d level to the 4f ground state with a Stokes shift of ~2250 cm-1. In this paper, we report on the scintillation properties of LPS and LYPS crystals. The difference in scintillation properties observed between samples is discussed. It was based on thermoluminescence data obtained in the temperature range from 30 to 600 K. These data show that the analyzed samples have surprisingly different sets of traps. Crystal growth and cutting issues of LPS and LYPS are also briefly discussed

In recent years the scintillation properties of several cerium-doped rare earth oxyorthosilicate scintillators, Ln/sub 2/SiO/sub 5/:Ce where Ln = Y, La - Lu, have been reported and, in some cases, extensively studied. In addition, binary and ternary compounds such as (Lu,Y)/sub 2/SiO/sub 5/:Ce, (Lu,Gd)/sub 2/SiO/sub 5/ and (Lu,Y,Gd)/sub 2/SiO/sub 5/:Ce have been reported. All of these crystals have either monoclinic P or C structures with characteristic SiO/sub 4/ tetrahedra and trivalent cations occupying two unique crystallographic positions. The trivalent cerium activator ions are assumed to occupy the cation lattice sites and possibly interstitial positions as well. The excited 5d state of Ce/sup 3+/ is split into 3 observable levels with luminescence emission occurring only from the lowest 5d level to the 4f ground state (/spl sim/3 eV) with a Stokes shift of /spl sim/ 0.5 eV. The band gap is about 6 eV, and the index of refraction is close to 1.8, with some variation according to crystallographic axes. Despite these similarities, important differences remain among the crystals including scintillation efficiency, decay time, rise time, and afterglow. In this paper, we report thermoluminescence measurements between 10K and 350K that allow the determination of trapping levels that may influence scintillation properties. The thermoluminescence data shows that the various scintillators compositions have surprisingly dissimilar sets of traps that may at least partially explain some of the differences in their scintillation properties.

Seven children aged 2-16 years with sarcomas arising in the retroperitoneum or pelvis (not in bladder or prostate) were treated at the CCRC from 1974-1983. 6 presented with abdominal distention and a palpable mass; the other had back pain and weight loss. 5 had localized tumors, and 2 had lung metastases. Median primary tumor diameter was 15 cm. All pts underwent exploratory laparotomy and biopsy; none had complete excision. All pts received local radiotherapy (med, 4000 rad) and intravenous vincristine, actinomycin D, and cyclophosphamide; 5 also received Adriamycin. Four pts responded completely and 2 of them survive free of recurrence at 1.5 and 7.5 yrs. The other 5 pts died of tumor 2-62 months (med, 18 mos) from diagnosis after local (3 pts) or distant (2 pts) recurrence. By contrast, all 5 pts with bladder-prostate sarcoma treated at the CCRC from 1974-1983 are free of recurrence at 1.3-8.7 yrs (med, 4.3 yrs). These 5 pts presented with acute urinary obstruction and had smaller tumors, without metastases. We conclude that retroperitoneal-pelvic sarcoma is a particularly lethal form of childhood cancer, because it is advanced at diagnosis; local control is difficult due to large tumor size.