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Cu nanoparticles (NPs) have been shown to be excellent electrocatalysts, particularly for CO2 reduction – a critical reaction for sequestering anthropogenic, atmospheric carbon. Herein, the micro interface between two immiscible electrolyte solutions (ITIES) is exploited for the simultaneous electropolymerization of 2,2′:5′,2′′-terthiophene (TT) and reduction of Cu2+ to Cu nanoparticles (NPs) generating a flexible electrocatalytic composite electrode material. TT acts as an electron donor in 1,2-dichloroethane (DCE) through heterogeneous electron transfer across the water|DCE (w|DCE) interface to CuSO4 dissolved in water. The nanocomposite formation process was probed using cyclic voltammetry as well as electrochemical impedance spectroscopy (EIS). CV and EIS data show that the film forms quickly; however, the interfacial reaction is not spontaneous and does not proceed without an applied potential. At high [TT] the heterogeneous electron transfer wave was recorded voltammetrically but not at low [TT]. However, probing the edge of the polarizable potential window was found to be sufficient to initiate electrogeneration/electropolymerization. SEM and TEM were used to image and analyze the final Cu NP/poly-TT composites and it was discovered that there is a concomitant decrease in NP size with increasing [TT]. Preliminary electrocatalysis results at a nanocomposite modified large glassy carbon electrode saw a > 2 × increase in CO2 reduction currents versus an unmodified electrode. These data suggest that this strategy is a promising means of generating electrocatalytic materials for carbon capture. However, films electrosynthesized at a micro and ~ 1 mm ITIES demonstrated poor reusability.

BackgroundThe cancer genome is commonly altered with thousands of structural rearrangements including insertions, deletions, translocation, inversions, duplications, and copy number variations. Thus, structural variant (SV) characterization plays a paramount role in cancer target identification, oncology diagnostics, and personalized medicine. As part of the SEQC2 Consortium effort, the present study established and evaluated a consensus SV call set using a breast cancer reference cell line and matched normal control derived from the same donor, which were used in our companion benchmarking studies as reference samples.ResultsWe systematically investigated somatic SVs in the reference cancer cell line by comparing to a matched normal cell line using multiple NGS platforms including Illumina short-read, 10X Genomics linked reads, PacBio long reads, Oxford Nanopore long reads, and high-throughput chromosome conformation capture (Hi-C). We established a consensus SV call set of a total of 1788 SVs including 717 deletions, 230 duplications, 551 insertions, 133 inversions, 146 translocations, and 11 breakends for the reference cancer cell line. To independently evaluate and cross-validate the accuracy of our consensus SV call set, we used orthogonal methods including PCR-based validation, Affymetrix arrays, Bionano optical mapping, and identification of fusion genes detected from RNA-seq. We evaluated the strengths and weaknesses of each NGS technology for SV determination, and our findings provide an actionable guide to improve cancer genome SV detection sensitivity and accuracy.ConclusionsA high-confidence consensus SV call set was established for the reference cancer cell line. A large subset of the variants identified was validated by multiple orthogonal methods.

Clinical applications of precision oncology require accurate tests that can distinguish true cancer-specific mutations from errors introduced at each step of next-generation sequencing (NGS). To date, no bulk sequencing study has addressed the effects of cross-site reproducibility, nor the biological, technical and computational factors that influence variant identification. Here we report a systematic interrogation of somatic mutations in paired tumor–normal cell lines to identify factors affecting detection reproducibility and accuracy at six different centers. Using whole-genome sequencing (WGS) and whole-exome sequencing (WES), we evaluated the reproducibility of different sample types with varying input amount and tumor purity, and multiple library construction protocols, followed by processing with nine bioinformatics pipelines. We found that read coverage and callers affected both WGS and WES reproducibility, but WES performance was influenced by insert fragment size, genomic copy content and the global imbalance score (GIV; G > T/C > A). Finally, taking into account library preparation protocol, tumor content, read coverage and bioinformatics processes concomitantly, we recommend actionable practices to improve the reproducibility and accuracy of NGS experiments for cancer mutation detection.

The gracilis myocutaneous flap is a versatile reconstructive option. Despite wide applicability, concerns are often raised regarding the unreliable vascular perfusion of the distal third of the flap’s skin paddle. This study presents our experience utilizing the pedicled gracilis myocutaneous flap for various oncologic defects to highlight the versatility, safety, and utility of this flap. A retrospective analysis was performed for patients who underwent reconstruction utilizing a gracilis myocutaneous flap over the course of 20 years (January 1998–June 2018). Postoperative outcomes were reviewed to determine the incidence of infection, dehiscence, seroma, or hematoma for both donor and recipient sites. Incidence of flap skin or muscle loss was also recorded. A total of 37 patients met our inclusion criteria, and data from 41 vertically oriented gracilis myocutaneous flaps was analyzed. A majority of our patients had a previously irradiated wound bed (73%). The overall donor site complication rate was 19.5%. The recipient site complication rate was 41.5% and included partial flap loss (14.6%). Partial flap loss included distal flap skin necrosis incidence (9.7%). When taking into account the size of the primary defect prompting reconstruction and prior recipient bed irradiation history, our cohort shows reasonable complication rates. Distal tip skin necrosis rate was also low, which suggests that the distal third’s vascular supply should not be a limiting factor. Level of evidence Level IV, therapeutic study.

Optimizing esthetics in delayed breast reconstruction is a challenge, as there is a lack of breast volume and native breast skin. Abdominal flaps are commonly used for patients desiring autologous reconstruction, but the result is an unnatural appearing breast as non-breast skin is used to recreate the breast mound. To improve esthetics for these patients, we propose a two-staged approach utilizing prepectoral tissue expander placement. A retrospective analysis of all patients undergoing delayed breast reconstruction with prepectoral tissue expander placement at our single tertiary-care institution was performed. We collected demographics, complication rates, and surgical information from both the first and second stage surgeries for all patients. Charts were further reviewed to determine whether patients pursued revisions. Five patients (eight breasts) met inclusion criteria. Following tissue expander placement, there was one incidence of seroma (n = 1), and no other complication occurred. Complications after autologous reconstruction included donor-site hematoma (n = 1), recipient-site dehiscence (n = 1), and recipient-site fat necrosis (n = 1). No flap losses or other complications occurred for our series of patients. Delayed, two-staged autologous breast reconstruction requires an additional short, surgical procedure that results in a lifelong improved breast esthetic and better lower-pole ptosis. Complication rates remain low, which makes this a viable and safe option to improve outcomes for patients seeking delayed autologous reconstruction. Our study utilizes prepectoral expander placement, which we believe will further enhance the quality of patient care. Level of evidence: Level V, therapeutic study.

Wound complication following gastrointestinal surgery substantially impacts the quality and costs of surgical care. The impact of wound complication on subsequent long-term healthcare utilization has not been fully studied. We assessed the impact of surgical wound complication on inpatient and outpatient healthcare utilization in the 2 years after gastrointestinal (GI) surgery. An observational retrospective cohort study was conducted on Veterans Affairs health system patients who underwent an inpatient GI surgical procedure, were assessed by the Veterans Affairs Surgical Quality Improvement Program (VASQIP), and were discharged alive from Veterans Affairs (VA) hospitals between October 1, 2007 and September 30, 2014. Population-based A total of 64,351 patients underwent a GI surgical procedure in the VA system between 2007 and 2014. The cohort was 93.5% male, with a median age of 63.0 years (interquartile range (IQR) 57.0–70.0). A total of 7880 patients (12.2%) had at least one reported wound complication, 5460 of which had their postoperative wound complication classified by a VASQIP nurse. VASQIP-assessed or ICD-9-coded wound complication in the 30 days after surgery Inpatient visits, total inpatient days, outpatient visits, and emergency department visits, and operative interventions up to 2 years after discharge from index admission Patients with a postoperative wound complication had greater inpatient healthcare utilization compared with no-wound complication for up to 2 years after surgery: inpatient admissions (mean number 3.5 vs. 2.8; P

Hydrogen and solid carbon were produced through methane decomposition in a plasma reactor with a parallel set of screw type helix and rod-like electrodes. The novel configuration led to the 3-dimensional movement of plasma zone in the axial and angular directions as well as arc elongation. The effect of arc elongation and movement at various angular velocities of high voltage electrode was investigated on the reactor performance in terms of methane conversion, hydrogen yield, and energy yield. In addition, the influence of fluid flow direction was considered. Methane conversion of 47% and hydrogen production rate of 132.7 ml/min with the energy yield of 36.8 g/kWh were achieved at stable operating conditions. The deposition rate of carbon was 35 mg/min which had a graphite-like structure. A reaction pathway is proposed according to reaction path analysis in order to interpret the underlying plasma chemical process.

Spirocerca lupi (family: Spirocercidae; order: Spirurida) are parasitic nematodes found in the esophagus of cats and dogs, as well as in other carnivore animals throughout the tropical, subtropical, and temperate countries of Asia and the Americas. These animals become infested by eating an intermediate host or a transport host. In adult felines, this parasite often resides in the mucosa of the esophagus, where it forms granulomatous nodules. In this work, a wild immature female Pallas’s cat (Otocolobus manul) that was younger than 1 year old was killed by a herding dog (heeler) in Mashhad, Iran. After necropsy, parasite samples were gathered from the stomach and after clarification by lactophenol, the nematodes were recognized as Spirocerca lupi. Microscopic diagnoses in the stomach include granulomatous nodules, mucosal gland destruction, necrosis, and inflammatory cell infiltration. This report characterizes the first documented case of spirocercosis in a Pallas’s cat in the world.

To have met inclusion criteria, the patient must have undergone delayed breast reconstruction without having had any prior breast reconstruction The transverse rectus abdominis Muscle (TRAM) flap was used in 2 breasts, and the muscle-sparing TRAM flap was used in 6 breasts (Table 1) Dear Sir, We thank Mantelakis et al [[1]] for their interest in our article "Delayed, two-staged autologous breast reconstruction: an approach to improving delayed reconstructive outcomes" [[2]] [Extracted from the article] Copyright of European Journal of Plastic Surgery is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission However, users may print, download, or email articles for individual use This abstract may be abridged No warranty is given about the accuracy of the copy Users should refer to the original published version of the material for the full abstract (Copyright applies to all Abstracts )

Uncontrolled expansion of combustion wave in spark ignited internal combustion engine causes knock effect which seriously degrades efficiency and lifetime of the engine. Thus, accurate knock detection and control are essential for obtaining a desired performance from the engine. Usually, knock sensor is used to detect this phenomenon but it has limited accuracy especially at engine high-speed rotations because of natural vibration and external noises. In this study an effective method based on Non-Local Mean (NLM) algorithm has been proposed to improve the knock detection accuracy. This method is evaluated based on four different indicators and four engine cylinders. The results show 52.9 % improvement in knock detection. Also feasibility of real time execution of this method based on embedded hardware has been studied.

Apoptosis of infected host macrophages by Leishmania spp. is mainly addressed as one of the survival mechanisms of the parasite. However, there is no eligible data about whether tumor suppressor p53 could induce the apoptosis of host lymphocytes-treated Leishmania major via the mitochondrial intrinsic pathway. In this study, the amastigotes of L. major obtained from ten cutaneous leishmaniases (CL) patients were separately isolated and cultured in N.N.N and RPMI 1640 media. L. major was definitely confirmed by targeting Cyt b gene following sequencing. Subsequently, 2–3 × 106 lymphocytes obtained from ten healthy individuals were isolated and co-cultured with 1–2 × 106 L. major promastigotes. Following 6 h of exposure time, the enzymatic activity of caspase-3 was determined by fluorometric assay in each L. major-treated lymphocytes and cell control (only lymphocyte). The mRNA expressions of Bax, Bcl-2, p53, and caspase-3 genes were assessed by quantitative real-time-PCR analysis following 6 to 9 h of exposure times. The Bcl-2 mRNA expression in L. major-treated lymphocytes was 100-fold down-regulated relative to cell control. The mRNA expressions of p53 and caspase-3 were over-expressed 1.8- and 3.2-fold up-regulated relative to control lymphocytes, respectively. The Bax/Bcl-2 ratio and caspase-3 activity were higher than the control group (Pv

In brain grey matter, excitatory synaptic transmission activates glutamate uptake into astrocytes, inducing sodium signals which propagate into neighboring astrocytes through gap junctions. These sodium signals have been suggested to serve an important role in neuro-metabolic coupling. So far, it is unknown if astrocytes in white matter-that is in brain regions devoid of synapses-are also able to undergo such intra- and intercellular sodium signalling. In the present study, we have addressed this question by performing quantitative sodium imaging in acute tissue slices of mouse corpus callosum. Focal application of glutamate induced sodium transients in SR101-positive astrocytes. These were largely unaltered in the presence of ionotropic glutamate receptors blockers, but strongly dampened upon pharmacological inhibition of glutamate uptake. Sodium signals induced in individual astrocytes readily spread into neighboring SR101-positive cells with peak amplitudes decaying monoexponentially with distance from the stimulated cell. In addition, spread of sodium was largely unaltered during pharmacological inhibition of purinergic and glutamate receptors, indicating gap junction-mediated, passive diffusion of sodium between astrocytes. Using cell-type-specific, transgenic reporter mice, we found that sodium signals also propagated, albeit less effectively, from astrocytes to neighboring oligodendrocytes and NG2 cells. Again, panglial spread was unaltered with purinergic and glutamate receptors blocked. Taken together, our results demonstrate that activation of sodium-dependent glutamate transporters induces sodium signals in white matter astrocytes, which spread within the astrocyte syncytium. In addition, we found a panglial passage of sodium signals from astrocytes to NG2 cells and oligodendrocytes, indicating functional coupling between these macroglial cells in white matter.

Besides astrocytes and oligodendrocytes, NG2 proteoglycan-expressing cells (NG2 glia) represent a third subtype of macroglia in the brain. Originally described as oligodendrocyte precursor cells, they feature several characteristics not expected from mere progenitor cells, including synaptic connections with neurons. There is accumulating evidence that the properties of NG2 glia differ between different brain regions and developmental stages. To further analyze this proposed heterogeneity, we studied electrophysiological properties, transcript and protein expression, distribution and proliferative capacity of NG2 glia during postnatal development, focusing on the hippocampus and corpus callosum. All NG2 glia displayed a 'complex' current pattern consisting of voltage- and time-dependent in- and outward currents. In juvenile mice, Kir current densities and rectification index were highly variable and on average significantly lower than in adult animals. Single cell RT-PCR analyses of electrophysiologically characterized cells demonstrated that different glial genes were expressed at variable extent, independent of developmental stage and genetic background. In the hippocampus proper and the corpus callosum, the density of NG2 glia was highest at postnatal days (P)10-12, decreased by ~50 % at P25-35 and then remained stable in adults (P80-90). Interestingly, co-expression of NG2 and S100β, a marker for mature astrocytes, increased from 7 % at P10-12 to 27 % at P25-35 in the hippocampus proper, and then dropped again in the stratum radiatum at P80-90. In the dentate gyrus and corpus callosum, co-expression of NG2 and S100β was very low (3 %) and constant throughout development. Age-related differences were also observed with Ki-67, a proliferation marker. In NG2 glia of the CA1 region, its expression decreased from 16 % at P10-12 to 9 % (P25-35) and then 3 % (P80-90). Triple-stainings revealed that Ki-67 was also expressed in 2-3 % of NG2/S100β-positive cells in the juvenile and mature stratum radiatum, indicating that the latter, in contrast to S100β-positive astrocytes, still host proliferative potential. Taken together, we found significant differences in transcript and protein expression, electrophysiological properties and proliferative capacity of NG2 glia in the mouse forebrain, suggesting the co-existence of several subpopulations of NG2 glia. Our data thus support the idea of a substantial regional and developmental heterogeneity in this subtype of macroglia.

1-(2,4-Dimethylphenyl)-5-amino-1H-tetrazole (DAT) nanoparticles was synthesized and its inhibiting action on the corrosion of stainless steel 316L (SS316L) in sulfuric acid was investigated by means of potentiodynamic polarization and electrochemical impedance spectroscopy (EIS). A good correlation was observed between the potentiodynamic studies and EIS with electrochemical noise (EN) measurements. Hence, it seemed that the EN method could be applied as a complementary quantitative technique to study the corrosion behavior of inhibitors. The effect of inhibitors concentration on interpretation of noise resistance and spectral noise impedance was evaluated. Furthermore, Quantum chemical calculations were employed to provide further insight into the mechanism of inhibition by DAT. It was shown that the adsorption of inhibitors on the SS surface took place through both physical and chemical adsorption. The best fit to the experimental data was obtained using Langmuir adsorption isotherm.

A recently designed rotating ground electrode plasma reactor has been used to produce synthesis gas by partial oxidation of methane at room temperature and atmospheric pressure without a catalyst. Experiments were performed to investigate the effects of feed flow rate, feed composition, and the presence of nitrogen in the feed. It was shown that increasing the O2-to-CH4 molar ratio reduces conversion of the reagents at low feed flow rates but promotes conversion at high feed flow rates. Increasing the O2-to-CH4 molar ratio also results in further methane partial oxidation reactions at high feed flow rates. Use of air instead of pure oxygen increases the conversion of methane and oxygen but reduces selectivity for the main products (H2 and CO). This reactor can be used to produce a wide variety of H2-to-CO molar ratios for different applications under stable conditions.

Since nanofluids increase the thermal conductivity of a fluid mixture compared with the base fluid, it is important to investigate any damaging effects caused by the presence of the solid particles. Thus, this paper explores the nanofluid synergistic effects produced by the addition of 1 g dm−3 Al2O3 nanoparticles to sea water and compares the performance with the base fluid without nanoparticles. Studies are conducted on carbon steel, using a hydrodynamically smooth-rotating cylinder electrode in turbulent flow at 298 K. The pure corrosion rate and erosion rate of carbon steel in the fluids free of nanoparticles are, respectively, higher (up to 82 %) and lower (ca. 11 %) than in the nanofluids. The synergistic effect of erosion and corrosion in a nanofluid is much higher (up to 237 %) than in the base fluid. These results indicate that the presence of nanoparticles in a flowing fluid could lead to considerable rates of material loss.

A novel type of plasma reactor having a rotating electrode is proposed for CO2 reforming of methane without catalyst at room temperature and atmospheric pressure. Results indicated that employing rotating ground electrode leads to a stable discharge for any period of time. Effects of feed composition, feed flow rate, applied power and electrodes separation on the carbon dioxide and methane conversions as well as the products selectivity were investigated. Increasing CO2/CH4 molar ratio in the feed favors the reagents conversion and consequently promotes the formation of hydrogen and carbon monoxide. If the target product is hydrogen, it is proposed to operate the reactor at CO2/CH4 = 1 molar ratio and if the target product is carbon monoxide then CO2/CH4 = 3 molar ratio is the preferred option for feed composition. This reactor system has advantages of stable operation and high conversion ability. Also, the obtained syngas with flexible molar ratio of H2 to CO is suitable for vast industrial applications.

Background The human genome contains variants ranging in size from small single nucleotide polymorphisms (SNPs) to large structural variants (SVs). High-quality benchmark small variant calls for the pilot National Institute of Standards and Technology (NIST) Reference Material (NA12878) have been developed by the Genome in a Bottle Consortium, but no similar high-quality benchmark SV calls exist for this genome. Since SV callers output highly discordant results, we developed methods to combine multiple forms of evidence from multiple sequencing technologies to classify candidate SVs into likely true or false positives. Our method (svclassify) calculates annotations from one or more aligned bam files from many high-throughput sequencing technologies, and then builds a one-class model using these annotations to classify candidate SVs as likely true or false positives. Results We first used pedigree analysis to develop a set of high-confidence breakpoint-resolved large deletions. We then used svclassify to cluster and classify these deletions as well as a set of high-confidence deletions from the 1000 Genomes Project and a set of breakpoint-resolved complex insertions from Spiral Genetics. We find that likely SVs cluster separately from likely non-SVs based on our annotations, and that the SVs cluster into different types of deletions. We then developed a supervised one-class classification method that uses a training set of random non-SV regions to determine whether candidate SVs have abnormal annotations different from most of the genome. To test this classification method, we use our pedigree-based breakpoint-resolved SVs, SVs validated by the 1000 Genomes Project, and assembly-based breakpoint-resolved insertions, along with semi-automated visualization using svviz. Conclusions We find that candidate SVs with high scores from multiple technologies have high concordance with PCR validation and an orthogonal consensus method MetaSV (99.7 % concordant), and candidate SVs with low scores are questionable. We distribute a set of 2676 high-confidence deletions and 68 high-confidence insertions with high svclassify scores from these call sets for benchmarking SV callers. We expect these methods to be particularly useful for establishing high-confidence SV calls for benchmark samples that have been characterized by multiple technologies. Electronic supplementary material The online version of this article (doi:10.1186/s12864-016-2366-2) contains supplementary material, which is available to authorized users.

A continuous production of hydrogen and carbon black from methane without CO2 emission in atmospheric pressure has been investigated by non thermal decomposition of methane using a system of direct current (DC)-spark discharge plasma, which has great advantages over other systems, like thermal plasma or catalytic conversion of methane in H2 production. A plasma reactor with specific design of electrodes was employed to examine the reactor performance regarding operating conditions such as feed flow rate, input power and electrodes distance. The experimental results showed that designed reactor increases not only the concentration of the produced hydrogen in continues condition but also guarantees stable plasma. As the methane supply rate increased, the hydrogen concentration decreased but on the other hand the hydrogen volume flow rate increased. In general, under the specified operating condition (power = 21 W and methane flow rate = 150 ml/min), the plasma converter produced a hydrogen concentration of 45 % at hydrogen volume flow rate of 75 ml/min.

The aim of this study was to investigate the effects of transplanted Wharton's jelly mesenchymal stem cells (WJMSCs) of caprine umbilical cord on cutaneous wound healing process in goat. After collection of caprine pregnant uterus of mixed breed goats from abattoir, the Wharton's jelly (WJ) of umbilical cord was harvested. The tissues were minced in ventilated flasks and explant culture method was used for separating mesenchymal stem cells (MSCs). The isolated cells were immunostained for Actin protein, histochemically assayed for the presence of alkaline phosphatase activity, and analyzed for detection of matrix receptors (CD44) and hematopoetic lineage markers (CD34), using flow cytometery. After The isolated cells, 3×10(6) MSCs were stained with BrdU and prepared for transplantation to each wound. Four 3-cm linear full thickness skin incisions were made on both sides of thoracic vertebrate of four Raeini goats (two wounds on each side). The left wounds were implanted with MSCs in 0.6 ml of Phosphate buffer saline (PBS), and the right wounds considered as control group that received 0.6 ml of PBS. The samples were taken from the wounds 7 and 12 days after the wounding, and healing process was compared histologically between the two groups. Anti-BrdU staining showed that the transplanted cells were still alive in the wound bed during the study. The histopathological study revealed that re-epithelialization was complete at days 7 in treated wounds with WJMSCs, whereas in control wound the wounds still showed incomplete epithelialization 12 days after wounding. Also, microscopic evaluation showed less inflammation, thinner granulation tissue formation with minimum scar in the treated wounds in comparison with control wounds. In conclusion, this study demonstrates the beneficial effect of caprine WJMSCs in cutaneous wound healing in goat.

Lead-free solders were never an industry choice until government legislation, their wide spread use is still in its infancy due to long term reliability issues. A specific SAC (Tin-Silver-Copper) family of solder alloys has emerged as the favourite to offer technical advantages as well as meeting those legislative requirements. This paper investigates accelerated life behaviour of lead-free solder joints and printed circuit boards using thermal and electrical stress cycling. The aim is to understand the degradation of these materials in a practical operating environment. Whilst corrosion and debris deposits have been found, no significant evidence has been obtained for tin whiskering. EDX analysis has shown the presence of high concentrations of elements considered to arise from the packaging material. Thermal cycling tests have presented an aggressive environment to the samples and the effect on them has been supported by microscopic and macroscopic observations of debris and corrosion. The electrical behaviour, i.e., the joint resistance, has not however, significantly degraded.

Congenital diaphragmatic hernia (CDH) is a common, life threatening birth defect. Although there is strong evidence implicating genetic factors in its pathogenesis, few causative genes have been identified, and in isolated CDH, only one de novo, nonsense mutation has been reported in FOG2 in a female with posterior diaphragmatic eventration. We report here that the homozygous null mouse for the Pdgfralpha gene has posterolateral diaphragmatic defects and thus is a model for human CDH. We hypothesized that mutations in this gene could cause human CDH. We sequenced PDGFRalpha and FOG2 in 96 patients with CDH, of which 53 had isolated CDH (55.2%), 36 had CDH and additional anomalies (37.5%), and 7 had CDH and known chromosome aberrations (7.3%). For FOG2, we identified novel sequence alterations predicting p.M703L and p.T843A in two patients with isolated CDH that were absent in 526 and 564 control chromosomes respectively. These altered amino acids were highly conserved. However, due to the lack of available parental DNA samples we were not able to determine if the sequence alterations were de novo. For PDGFRalpha, we found a single variant predicting p.L967V in a patient with CDH and multiple anomalies that was absent in 768 control chromosomes. This patient also had one cell with trisomy 15 on skin fibroblast culture, a finding of uncertain significance. Although our study identified sequence variants in FOG2 and PDGFRalpha, we have not definitively established the variants as mutations and we found no evidence that CDH commonly results from mutations in these genes.

Congenital diaphragmatic hernia (CDH) is a common birth defect with a high mortality and morbidity. There have been few studies that have assessed copy number changes in CDH. We present array comparative genomic hybridization data for 29 CDH patients to identify and map chromosome aberrations in this disease. Three patients with 15q26.1-15q26.2 deletions had heterogeneous breakpoints that overlapped with the critical 4 Mb region previously delineated for CDH, confirming 15q26.1-15q26.2 as a critical region for CDH. The three other most compelling CDH-critical regions for genomic deletions based on these data and a literature review are located at chromosomes 8p23.1, 4p16.3-4pter, and 1q41-1q42.1. Based on these recurrent deletions at 15q26.1-15q26.2, we hypothesized that loss-of-function mutations in a gene or genes from this region could cause CDH and sequenced six candidate genes from this region in more than 100 patients with CDH. For three of these genes (CHD2, ARRDC4, and RGMA), we identified missense changes and that were not identified in normal controls; however, none of these alterations appeared unambiguously causal with CDH. These data suggest that CDH caused by chromosome deletions at 15q26.2 may arise because of a contiguous gene deletion syndrome or may have a multifactorial etiology. In addition, there is evidence for substantial genetic heterogeneity in CDH and diaphragmatic hernias can be non-penetrant in patients who have deletions involving CDH-critical regions.