Our aim was to examine the impact of gestational diabetes (GDM), from before the GDM-diagnosis is made, on fetal growth trajectories, and to compare it in Europeans and South Asians; two ethnic groups with dissimilar fetal growth patterns.We studied European (n = 349) and South Asian (n = 184) pregnant women, from the population-based STORK-Groruddalen cohort in Oslo, Norway. Mothers were enrolled in early pregnancy, screened for GDM in gestational week 28 ±2, and classified as “non-GDM”, “mild GDM” or “moderate/severe GDM”. We measured fetal head circumference, abdominal circumference and femur length by ultrasound, and estimated fetal weight in gestational week 24, 32 and 37, and performed corresponding measurements at birth.In non-GDM pregnancies, South Asian fetuses (n = 156) had a slower growth from gestational week 24, compared with Europeans (n = 310). More than two thirds of the European mothers later diagnosed with GDM were overweight or obese in early pregnancy, while this was not observed in South Asians. Fetuses of GDM mothers tended to be smaller than fetuses of non-GDM mothers in week 24, but thereafter grew faster until birth. This pattern was especially pronounced in fetuses of South Asian mothers with moderate/severe GDM. In week 24 these fetuses had a -0.95 SD  lower estimated fetal weight than their non-GDM counterparts. In contrast, at birth they were 0.45 SD  larger.Offspring of GDM mothers were smaller in mid pregnancy, but subsequently grew faster until birth, compared with offspring of non-GDM mothers. This pattern was most prominent in South Asian mothers with moderate to severe GDM. However, the most remarkable characteristic of these fetuses was not a large size at birth, but the small size in mid pregnancy, before the GDM diagnosis was set. The association between birth weight and later risk of type 2 diabetes is U-shaped. One arm comprise men and women born small, due to maternal undernutrition or other factors. The other arm comprises of individuals born large, due to maternal adiposity and diabetes .South Asians have a higher prevalence of type 2 diabetes compared with Europeans, and are diagnosed at a younger age and with a lower BMI . South AThe usual description of a baby born to a mother with gestational diabetes (GDM) includes macrosomia and large for gestational age phenotypes in late pregnancy and at birth. Some studies indicate a stronger association between maternal hyperglycemia and offspring birth weight in ethnic South Asians than in Europeans –8. HowevThe population-based multi-ethnic STORK-Groruddalen cohort provided a unique opportunity to explore these relationships. We compared maternal characteristics in early pregnancy, and fetal size and growth rate during the second half of pregnancy, in ethnic South Asian and European pregnancies with and without GDM in Oslo, Norway.Pregnant women attending the Child Health Clinics for antenatal care in three municipalities in Groruddalen, Oslo, from May 2008 to May 2010 were given oral and written information about the Stork Groruddalen project and invited to participate. The women who chose to participate gave informed written consent at inclusion, on behalf of themselves and their offspring . The stuThe study design has been presented in detail elsewhere . Prior tThe participating woman and fetus were defined as ethnic European or South Asian if the participating woman or her mother were born in Europe or South Asia respectively. Europeans also included three women of European origin born in North-America . As few Glycated haemoglobin (HbA1c) and fasting glucose were measured at enrollment. HbA1c was measured with HPLC . A standard 75 g oral glucose tolerance test (OGTT) was performed in gestational week 28±2. Women were diagnosed with gestational diabetes according to the 1999 WHO-criteria (fasting plasma glucose ≥7.0 mmol/l or 2-hour glucose ≥7.8 mmol/l). Glucose was measured on site (within 5 minutes after vein puncture) in venous EDTA blood according to a standardized protocol, using a patient-near method  calibrated for plasma . Accordi2) was calculated using self-reported pre-pregnant weight, to the nearest kg, and measured height [Maternal height was measured twice to the nearest 0.1 cm with a fixed stadiometer at inclusion, and the mean was used . Pre-pred height . Weight 2 x femur length) + (0.03312 x HC3) [At each ultrasound visit, scheduled at 24, 32 and 37 weeks of gestation, participants were randomly allocated to one of four study-ultrasonographers. One Voluson Pro  machine, with a AB2-7 scan head, was used. Methods have been described in detail elsewhere . Using s2 x HC3) , as usedBirth weight was routinely measured on calibrated electronic scales immediately after birth. Within 72 hours after birth, study-specific anthropometric measurements were performed by trained study personnel, according to study protocol, unless contraindicated for medical reasons , 14. CroZ-scores for fetal measurements  were calculated using formulas derived from an ethnic Norwegian reference population , 16. NatStatistical analyses were performed using SPSS version 22.0 for Windows . The significance level was set to p<0.05. Differences between pregnancies complicated by mild or moderate/severe GDM, compared with non-GDM pregnancies were explored using Chi Square test for categorical and t-tests for continuous variables.Differences in fetal growth from week 24 until birth were examined using linear mixed effects modelling, assessed separately for the outcomes weight, HC, AC and length. Z-scores through four different time points  were entered. For the analysis of length we used z-scores for femur length at three time points in pregnancy and CH-length from birth. For the analyses of weight we used z-scores of EFW from three time points during pregnancy and birth weight. All models were run with a random intercept and a random slope. We first explored the impact of ethnicity on fetal growth in non-GDM pregnancies. Ethnicity was first entered as a fixed variable together with gestational age (weeks) and the interaction term between these two variables (to assess the impact of ethnicity on growth velocity). A priori, we added the covariates offspring gender and maternal parity to the adjusted models. As lower maternal height is often perceived to explain a substantial part of ethnic differences in fetal growth, maternal height was also included in the last supplementary model. A second degree term for gestational age was also included as a fixed variable in all models, due to a small, but systematic variation in the distribution of the fetal z-scores across the four time points. Interaction terms between other covariates and gestational age were tested for and included if significant. We then performed similar analyses replacing ethnicity with GDM as explanatory variable, first treated as non-GDM or GDM, thereafter stratified into non-GDM, mild GDM and moderate/severe GDM. We then added the covariates maternal ethnicity, parity and offspring gender to the adjusted models, and maternal height in a final supplementary model. Lastly, we performed the analyses in Europeans and South Asians separately. Estimated mean SD-scores from the adjusted mixed models from each of the four time points were extracted.The present study was restricted to women of European (n = 379) and South Asian (n = 200) ethnic origin. After excluding twins and those with missing newborn data, OGTT or ultrasound, the final study sample consisted of 349 European and 184 South Asian (63% Pakistani and 37% Sri Lankan/Indian) women , South Asian women were shorter, younger and less educated than European women. Their mean BMI was slightly lower , but theIn total 39 (11%) European and 28 (15%) South Asian women were diagnosed with GDM in week 28 according to the WHO 1999 guidelines . RelativEuropean women later diagnosed with GDM were more likely to be overweight or obese when entering pregnancy than their non-GDM counterparts, in particular women diagnosed with moderate/severe GDM. However, they showed less weight gain throughout pregnancy than non-GDM women . A diffeIn week 24, fetuses of South Asian non-GDM mothers had longer femurs, but smaller ACs than their European counterparts . From thFetuses of mothers who were later diagnosed with GDM were smaller on all fetal measures in week 24 , p = 0.01), compared with fetuses of non-GDM mothers. From this time until birth they showed faster growth . HoweverSouth Asian fetuses exposed to mild GDM had a similar size and growth rate during the second half of pregnancy as South Asian non-GDM fetuses . In contEuropean fetuses exposed to GDM also tended to be smaller in week 24 and show faster growth than their non-GDM counterparts .In this study we observed that fetuses of mothers later diagnosed with GDM tended to be smaller in week 24, compared with fetuses of non-GDM mothers. From this time until birth they showed a faster growth. This pattern was most pronounced in South Asian fetuses of mothers diagnosed with moderate/severe GDM, who were the smallest for all body measures in mid pregnancy.This study is unique, as we were able to combine longitudinal maternal and offspring data from early pregnancy to birth, including GDM-data from universal screening, in a well-characterized population-based cohort, in two different ethnic groups. The smaller fetal size in mid-pregnancy in GDM, compared with non-GDM pregnancies, was unexpected. However, an early fetal growth delay has been reported both in Type 1 and Type 2 diabetes , 19. TheThe slower growth in early pregnancy in Type 1 and Type 2 diabetes has been associated with indicators of poor glucose control in early pregnancy and with lower levels of some biomarkers indicating impaired early placentation . Few womOur results could also indicate that there may be different types of GDM. One being GDM in an obese women, with pre-existing insulin resistance and a sufficient capacity to produce insulin in a non-pregnant situation, but decreased capacity to compensate for the added insulin resistance caused by pregnancy. The other being GDM in a “thin-fat” woman, predominantly due to a reduced capacity to produce insulin but also diminished insulin sensitivity due reduced muscle mass .It has also been speculated that maternal hyperglycemia during the second half of pregnancy may in part be triggered by the fetus through the placenta, to promote intrauterine “catch-up” after early growth failure . If suchThe key challenge is that optimal fetal growth remains to be defined. Customized fetal growth charts aim to predict the growth potential, i.e. “optimal growth” for each baby, by adjusting for characteristics which influence birth weight, such as maternal height, parity and ethnic origin, and by excluding pathological factors such as smoking and diabetes. However, ethnic differences in fetal growth are observed, and only partly explained by key maternal factors, such as parity, socioeconomic position and height , 27. FacThe study has some limitations. Most women diagnosed with GDM were treated non-pharmacologically, indicating that there were few cases of severe GDM. However, treatment could still have influenced the fetal growth patterns. Furthermore, the limited number of GDM-cases, further categorized into two groups, primarily based on elevated 2-hour-values, restricts our power to adjust for many covariates, and to explore interactions. However, as women in the two GDM-categories were given different follow-up after being diagnosed, the alternative of not taking this into account could cause bias. Almost all South Asian women with moderate/severe GDM were normal weight before entering pregnancy but had similar weight gain as non-GDM women. Most Europeans, however, were obese and had substantially less weight gain than their non-GDM counterparts. Adjusting for these factors could therefore potentially also cause bias. Our findings illustrate the complexity involved in the relationship between maternal factors and fetal growth, should be interpreted with caution.To conclude, we observed differences in fetal size and body proportions from before diagnosis and treatment of glucose intolerance. The most prominent growth deviations was observed in fetuses of South Asian mothers diagnosed with moderate/severe GDM. Their babies were small in size in mid-pregnancy but but subsequently grew faster until birth compared with babies of non-GDM mothers. The mechanisms underlying these differences are likely to be at least partly present before the pregnancy. Our results highlights the need for large-scale comparative studies of serial fetal growth from early pregnancy. This could have implications for the timing of diagnosis and the treatment of pregnancy-related hyperglycemia in different ethnic groups.S1 Fig(PDF)Click here for additional data file.S2 Fig(PDF)Click here for additional data file.S1 Table(DOC)Click here for additional data file.S2 Table(DOCX)Click here for additional data file.


The expression and activities of RNA binding proteins are frequently dysregulated in human cancer. Their roles, however, appears to be complex, with reports indicating both pro-tumorigenic and tumor suppressive functions. Here we show, using two classical mouse cancer models, that the role of KH-type RNA binding protein, Sam68, in tumor development can be influenced by the status of the p53 tumor suppressor. We demonstrate that in mice expressing wild type p53, Sam68-deficiency resulted in a higher incidence and malignancy of carcinogen-induced tumors, suggesting a tumor suppressive role for Sam68. In marked contrast, Sam68-haploinsufficiency significantly delayed the onset of tumors in mice lacking p53 and prolonged their survival, indicating that Sam68 accelerates the development of p53-deficient tumors. These findings provide considerable insight into a previously unknown relationship between Sam68 and the p53 tumor suppressor in tumorigenesis. Src-associated in mitosis of 68 kDa (Sam68), also known as KHDRBS1, is a KH-type RNA binding protein of the signal transduction and activation of RNA metabolism (STAR) family . The expbona fide tumor suppressor like p53 [To further investigate the physiological roles of Sam68, a mouse model was generated by homologous recombination . These wlike p53 , 25. Howlike p53 .As a prototypic member of the STAR proteins, Sam68 has signaling properties and functions downstream of Src family kinases to promote cell survival , 27. In in vivo. It has been proposed that the loss of Sam68 leads to NIH3T3 cell transformation; however, this was not rescued by Sam68, suggesting that additional events were responsible for transformation in this report [Sam68 has also been shown to harbor tumor suppressive functions, but this activity is not well understood, nor is there any evidence of this tumor suppressive role s report . Consists report . Moreoves report , 33.TP53 occurs in approximately 50% of all cancers [The development of mouse cancer models has greatly advanced our understanding of the mechanisms underlying tumor initiation, progression, metastasis, and acquired chemoresistance –36. Spec cancers , 39. Ind cancers , 41. Rec cancers , suggestIn this study, we report the role of Sam68 in tumorigenesis using both p53-proficient and p53-deficient mouse models of cancer. We show that in p53 wild type mice, Sam68-deficiency enhanced AOM-induced colon tumorigenesis, whereas in p53-deficient mice, Sam68-haploinsufficiency delayed the onset of spontaneous tumors. Hence, we demonstrate for the first time that p53 status can influence the role of Sam68 during tumorigenesis.+/+; Sam68+/+ and p53+/+; Sam68−/− mice, backcrossed 7 generations in the FVB background, were treated with AOM for 8 weeks and examined each week for 13 weeks. Three of the p53+/+; Sam68−/− mice were sacrificed early due to acute clinical features. In the remaining p53+/+; Sam68−/− mice, as well as the p53+/+; Sam68+/+ mice, aberrant growths were restricted to the colon with no macroscopically visible metastasis. The p53+/+; Sam68−/− mice had a statistically significant increase in colon weight (0.69 g ± 0.03 versus 0.43 g ± 0.03) because of the higher tumor burden  and carcinomas (8.67 ± 0.33 versus 6.5 ± 0.5) compared to p53+/+;Sam68+/+ mice  with p53−/− mice, but the breeding was complicated by the fact that Sam68 homozygous females have impaired fertility and males are infertile [−/− females were obtained, therefore the breeding was performed with p53−/−; Sam68+/− males and p53+/−;Sam68+/− females. Few p53−/−;Sam68−/− mice were obtained for unknown reasons but they did survive into adulthood. Thus, we compared tumor latency between p53−/−;Sam68+/+ and p53−/−;Sam68+/− mice. We observed that Sam68-haploinsufficiency significantly delayed tumor onset in p53-deficient mice from 140 days  to 195 days  developed tumors in the 300 days of the experiment  mice displayed higher tumor burden with increased malignancy than wild type controls , demonstrating that Sam68 has tumor suppressor-like activities in vivo. We also generated p53-null mice expressing Sam68  or haploinsufficient dose of Sam68 . In this p53−/− C57BL/6 background, we observed that Sam68 haploinsufficiency caused significant delays in the onset of spontaneous tumors compared to Sam68 wild type mice. These findings show that in the absence of p53, Sam68 can exhibit pro-tumorigenic properties. Collectively, our results demonstrate that p53 seems to act as a switch to influence whether Sam68 slows or accelerates tumor development. Taken together, these findings provide insight into a previously unknown relation between Sam68 and the p53 tumor suppressor in tumorigenesis.In the present study, we examined the physiological role of Sam68 in tumor development using two different mouse cancer models. For Sam68-proficient and deficient mice in a p53 wild type FVB background, we implemented the azoxymethane (AOM)-inducible colon carcinogenesis model. We observed that Sam68-deficient  splicing [−/− mice are not predisposed to spontaneous tumor development [−/− and p21−/−;Puma−/−;Noxa−/− mice [p21 gene, that no known mutations of Sam68 have been found in human tumors [RNA binding proteins are becoming increasingly appreciated as fundamental players in human cancers , 46. Liksplicing –33. Moresplicing . Interessplicing , which pelopment , similar−/− mice , 49. Thin tumors . Furthern tumors , 52.−/− mice showed that decreased Sam68 expression significantly delayed the onset of spontaneous tumors, indicating a pro-tumorigenic role for Sam68 in this mouse model. Fu et al. recently reported that Sam68 lessens colon tumor development in Apcmin716/+ mice via regulation of the PARP1-NF-κB-anti-apoptotic gene axis [Given the interplay between Sam68 and p53, it is almost expected that Sam68 would lose its tumor suppressive function when p53 is depleted. Indeed, studies in p53−/−;Sam68+/− mice. Of note, mammary tumor cells derived from the MMTV-PyMT mice are p53 wild type and are sensitive to p53 gene therapy, but the antitumor mechanisms remain elusive [Although it is uncertain how p53 loss or inactivation can contribute to the pro-tumorigenic function of Sam68, a large body of literature has elucidated molecular mechanisms by which Sam68 can support tumor growth. As a STAR family protein, Sam68 can link signal transduction with RNA processing to modulate cancer-relevant splicing events that enhance cell survival and proliferation –3. For i elusive . Further elusive , a nucle elusive . Sam68 a elusive . Additio elusive . In furt elusive , 16.Sam68 overexpression, phosphorylation, and its cytoplasmic localization have been associated with a significant risk factor for poor prognosis , 59. It Although further studies are required to understand the mechanism underlying p53's ability to switch the functional outcome of Sam68, we have illustrated the importance of defining the molecular contexts in which targeting RNA binding proteins may be beneficial for anticancer therapy. Much remains to be defined on how RNA binding proteins and their regulatory networks contribute to tumor initiation and progression.+/+;Sam68+/+ and p53+/+; Sam68−/− mice in FVB background (cohorts of 15 in each group) were injected intraperitoneally once a week for 8 weeks with 10 mg/kg of body weight azoxymethane (AOM) (Sigma-Aldrich) dissolved in saline. Animals were systematically examined twice per week for the appearance of clinical symptoms. Animals showing signs of discomfort such as weight loss, rectal bleed, and prolapse were sacrificed. End points were defined as 13 weeks after the first injection. After sacrificing the mice, entire colons were removed, rinsed with PBS, opened longitudinally and fixed flat on strips of 4% paraformaldehyde-soaked Whatman filter paper. Colons were assessed in a blinded fashion under a stereo-dissecting microscope as previously described [2 graph paper, and the total surface area was determined based on the total number of squares overlaying the tumor, as described [All animal procedures followed the Canadian Council on Animal Care guidelines and were approved by the McGill Animal Care Committee. Age-matched (10 to 12 weeks) p53escribed . Tumors escribed .−/− mice  were obtained from JAX laboratories. Both Sam68−/− and p53−/− mice were maintained on a C57BL/6 background and crossbred. Animals showing signs of discomfort such as weight loss were sacrificed.The p53Sam68 (forward 1) 5′- GAT ATG ATG GAT GAT ATC TTG TCA G-3′; (forward 2) 5′- CTA AAG CGC ATG CTC CAG A-3′; (reverse) 5′- AAA TCC TAA CCC TCC TCA GTC A-3′; p53 (forward) 5′- ACA GCG TGG TGG TAC CTT AT-3′; (reverse 1) 5′-TAT ACT CAG AGC CGG CCT-3′; (reverse 2) 5′-CTA TCA GGA CAT AGC GTT GG-3′. PCR products were analyzed on 1.5% agarose gel stained with ethidium-bromide.Total genomic DNA was extracted from mouse earpiece using AccuStart II Mouse Genotyping Kit (Quanta) following the manufacturer's protocol. Genomic PCR was performed with the following primers: +/+; Sam68+/+ and p53+/+; Sam68−/− mice colons at the IRIC . Quantitative assessment was done as previously described [Hematoxylin and eosin (H&E) or immunohistochemistry staining were performed on p53escribed .t test with the GraphPad software. A p-value of < 0.05 was considered to be statistically significant.Statistical analysis was performed using Student's


Chiral anomaly materials  are new states of quantum matter. Anomalous Hall effect can occur in CAM, the anomalous Hall effect is closely related to the topological magneto-electric effect, i.e., when an electric field is applied to CAM, not only the electric field is induced, but also the magnetic field, vice versa. According to those properties, we design an electric cloak with quantized CAM and conductor, and a magnetic cloak with quantized CAM and superconductor. Simulation and calculation results show that the electric cloak can cloak applied electric field and induce magnetic field, and the magnetic cloak can cloak applied magnetic field and induce electric field. When applied electric field is generated by a point charge, the monopole can be obtained. Inspired by those theoretical works, varieties of electromagnetic wave cloak11, acoustic wave cloak14, matter wave cloak15, mass diffusion cloak16, heat diffusion cloak20, magnetic cloak23, electric cloak26 have been theoretically designed and experimentally demonstrated. Generally speaking, it is difficult to construct a perfect invisible electromagnetic wave cloak by natural material, for it requires inhomogeneous and anisotropic material, yet a perfect dc electric cloak can be fabricated from natural material. Utilizing resistor network, Yang et al. designed anisotropic electric conductance and experimentally demonstrated dc electric cloak24, their work shows that the dc electric cloak can guide electric current around the cloaked region smoothly. Utilizing ferromagnetic and superconductor, Gömöry et al. experimentally realized a magnetic cloak22, which did not require anisotropic metamaterial owing to zero permeability of superconductor. With the similar method, we designed a bi-layer steady current cloak by the use of insulator and conductor25, the bi-layer steady current cloak did not require anisotropic metamaterial owing to zero conductivity of insulator either. According to the similarity of the electric conduction equation and heat diffusion equation, the bi-layer heat cloak is designed20, the bi-layer heat cloak can shield heat diffusion flux, however, the heat shielding is temporal heat diffusion protection rather than a permanent heat diffusion protection, in the steady state, the cloaked region eventually achieves a constant temperature.In the past few years, electromagnetic invisibility cloaks have drawn enormous attention. Many achievements of invisibility cloak have been motivated thanks to the pioneering theoretical work33 and topological band theory35. Under an applied electric field, a quantized Hall current is induced on the surface of the topological insulator, which in turn generates a magnetic polarization and vice versa, namely, electric field induces magnetic field, and magnetic field induces electric field28. Axion insulator is also a new state of quantum matter38, when an applied electric field is applied on an axion insulator, the electric field can also induce magnetic field, vice versa.Topological insulator is a new state of quantum matter, the concept of the topological insulator can be defined with topological field theory39: Dirac, Weyl and Majorana fermions. Dirac fermions have been observed for decades in high-energy physics, Weyl and Majorana fermions have not been observed in high-energy physics, but, Dirac42, Weyl47 and Majorana52 fermions have been discovered in condensate matter. Weyl semimetal47 is a new state of quantum matter, the chiral anomaly of Weyl semimetal60 leads to the result that an applied electric field induces magnetic polarization and an applied magnetic field induces electric polarization. Chiral anomaly38 would emerge in all topological insulator and axion insulator, some of Weyl semimetal can generate chiral anomaly60 too, the chiral anomaly55 is closely related to the topological magneto-electric response, utilizing the property of topological magneto-electric response, we designed an electric cloak with CAM and conductor bi-layer shell, and a magnetic cloak with CAM and superconductor bi-layer shell. The simulation and calculation results show that the CAM and conductor bi-layer electric cloak can cloak electric field and induce magnetic field; and the CAM and superconductor bi-layer magnetic cloak can cloak magnetic field and induce electric field.Three type fermions play a fundamental role in our understanding of natureS0 = (8/π)∫d3xdt(εE2 − B2/μ), together with a topological θ term 60, here ε and μ are material-dependent permittivity and permeability, respectively, α = e2/c is the fine-structure constant, e is the electron charge, c is the speed of light, and θ is the dimensionless parameter describing the insulator, which refers to the axion field in high-energy physics60. θ is also called topological magneto-electric polarizability33. When time reversal symmetry as well as spatial symmetry like inversion are broken, the topological magneto-electric polarizability θ is not quantized38 and is very small, for example, the magneto-electric polarizability of Cr2O3 and BiFeO3 is about 10−3 and 10−4, respectively38. How to improve magneto-electric polarizability? The key point is to quantize the magneto-electric polarizability. When time reversal invariant, the magneto-electric polarizability θ is quantized, i.e., θ = (2n + 1)π , in this work, we take θ = π53, i.e., the topological magneto-electric effect was quantized.The electromagnetic response of three dimensional insulator is described by the Maxwell action 31, (SI unit) 32ε0 = 8.85 × 10−12F/m and μ0 = 4π × 10−7 H/m are the permittivity and permeability of the free space, respectively.Because the electric field induces magnetic polarization and the magnetic field induces electric polarization, the constitute relations of CAM can be written asz = 0) show the bi-layer cylindrical magnetic cloak, the outer layer is CAM, and the inner layer is superconductor, the permittivity and permeability of the CAM are ε2 and μ2, respectively, the permittivity and permeability of the superconductor are ε3 and μ3, respectively, the outer radius and inner radius of the CAM are a and b, respectively, the outer radius and inner radius of the superconductor are b and c, respectively. The permittivity and permeability of the surroundings are ε1 and μ1, respectively, the permittivity and permeability of the cloaked region are ε4 and μ4, respectively. When a uniform magnetic field r, θ, z) in the four regions can be written as22A, B, C, D, E and F are unknown coefficients. The relation between the magnetic field and the magnetic scalar potential is φm is the magnetic scalar potential, A0, A1, B1, C1, D1, E1 and F1 are unknown coefficients. Because of no physics electric field in region I, so A0 = 0. The relation between the electric field and the electric potential is A = 0, the magnetic field is still H0 in region I, when F = 0, the magnetic field vanishes in region IV, namely, the device is a magnetic cloak. When A1, B1, C1, D1, E1 and F1 are non-zero, the electric field is induced by the applied magnetic field. That is to say, we can cloak the magnetic field and induce electric field. The calculation results show that it is impossible to obtain a cloak when the inner layer and the outer layer are both the CAM, however, when the outer layer is CAM, the inner layer is superconductor, the bi-layer cylinder can cloak applied magnetic field and induce electric field.Figure θ3 = 0, the permeability of the superconductor μ3 = 0, we take the permittivity of the superconductor ε3 = 1. The outer layer is CAM, the quantized magneto-electric polarizability of the CAM is θ2 = π, the permittivity of the CAM ε2 = 2, the fine-structure constant α = 1/137, the other parameters are ε1 = 1, ε4 = 1, μ1 = 1, μ4 = 1, setting A = 0, F = 0, we can obtain the conditions of the cloak, the relations between the size parameters and material parameters areX = 4(αθ2/π)2a2b2, Z = (a2 − b2)[a2(ε2 + 1)2 − b2(ε2 − 1)2]. Figure a/b and the permeability μ2, for example, if a/b = 5, μ2 = 1.083, then A = 0, F = 0; if a/b = 1.25, μ2 = 4.556, then A = 0, F = 0.Supposed that the inner layer is a superconductor, namely, the magneto-electric polarizability a = 0.025 m, b = 0.020 m, c = 0.010 m, H0 = 10000 A/m, μ2 = 4.556, other parameters are the same in the Fig. r > 0.025 m, the magnetic field H1 = H0 = 10000 A/m; the induced electric field E1 varies with size parameters a and b, and has nothing to do with the size parameter c; the induced electric field E1 varies with material parameter ε, less influenced by material parameter μ. When 0.020 m < r < 0.025 m, the magnetic field H2 and the induced electric field E2 both vary with size parameters a and b, and have nothing to do with the size parameter c; the magnetic field H2 varies with material parameter μ, less influenced by material parameter ε; the induced electric field E2 varies with material parameters ε, less influenced by material parameter μ. When 0.010 m < r < 0.020 m, the magnetic field H3 varies with size parameters a, b, c and material parameters μ, less influenced by material parameter ε; the induced electric field E3 = 13166 V/m is uniform. Noting that the magnetic flux density is zero in this region, this is because the superconductor (μ3 = 0) repulse magnetic flux density. When r < 0.010 m, the magnetic field H4 = 0, the induced electric field E4 = 13166 V/m is uniform, namely, the CAM and superconductor bi-layer cylinder cloaked applied magnetic field and induced electric field. The induced electric field E3 = E4 = 13166 V/m is uniform in the superconductor (0.010 m < r < 0.02 m), this is because we chose the permittivity of the superconductor ε3 = 1, when ε3 ≠ 1, the induced electric field E3 is not uniform in the superconductor. When θ2 = 0, θ3 = 0, μ3 = 0, the CAM and superconductor bi-layer magnetic cloak is simplified as a conventional magnetic cloak23, utilizing ferromagnetic and superconductor bi-layer material, Gömöry et al. experimentally demonstrated the magnetic cloak22. The cloak is also influenced by magneto-electric polarizability, if the magneto-electric polarizability is quantized, then θ = π; if the magneto-electric polarizability is not quantized, then θ is very small38, in this case, the electric field induced by magnetic field can be ignored, and the magnetic field induced by electric field can be ignored too.Figure z = 0) show the bi-layer cylindrical electric cloak, the outer layer is CAM, and the inner layer is conductor. When a uniform electric field r, θ, z) in the four regions can be written as22A, B, C, D, E and F are unknown coefficients. The relation between the electric field and the electric potential is A0, A1, B1, C1, D1, E1 and, F1 are unknown coefficients. The relation between the magnetic field and the magnetic scalar potential is A0 = 0. When A = 0, the electric field is still E0 in region I; when F = 0, the electric field vanishes in region IV, namely, the device is an electric cloak. When A1, B1, C1, D1, E1, and F1 are non-zero, the magnetic fields are induced by the applied electric field. That is to say, we can cloak the electric field and induce magnetic field. The calculation results show that it is impossible to obtain a cloak when the inner layer and the outer layer are both the CAM, however, when the outer layer is CAM, the inner layer is conductor, the bi-layer cylinder can cloak electric field and induce magnetic field. Supposed that the inner layer is a conductor, namely, the magneto-electric polarizability of the conductor is θ3 = 0, the permittivity of conductor is ε3 → ∞, setting A = 0, F = 0, we can obtain the conditions of the electric cloak.Figure 0 = 10000 V/m, the permittivity of the surrounding and the conductor is ε1 = 9.11 and ε3 → ∞, respectively, the magneto-electric polarizability of the conductor is θ3 = 0, the other parameters are the same in the Fig. r > 0.025 m, the electric field E1 = E0 = 10000 V/m; the induced magnetic field H1 varies with size parameters a and b, and has nothing to do with the size parameter c; the induced magnetic field H1 varies with material parameter μ, less influenced by material parameter ε. When 0.020 m < r < 0.025 m, the electric field E2 and the induced magnetic field H2 both vary with size parameters a and b, and have nothing to do with the size parameter c; the electric field E2 varies with material parameters ε, less influenced by material parameter μ; the induced magnetic field H2 varies with material parameters μ, less influenced by material parameter ε. When 0.010 m < r < 0.020 m, the electric field E3 = 0, this is because the electric field is zero in conductor, yet the induced magnetic field H3 = 0.0968 A/m. When r < 0.010 m, the electric field E4 = 0, the induced magnetic field H4 = 0.0968 A/m is uniform. Namely, the CAM and conductor bi-layer can cloak applied electric field and induce magnetic field, the induced magnetic field is very weak. Noting that H3 = H4 = 0.0968 A/m, this is because we chose μ3 = μ4 = 1, if μ3 ≠ μ4, then H3 ≠ H4. If θ2 = 0, θ3 = 0, our cloak is simplified as a conventional electric cloak, utilizing dielectric and conductor, Lan et al. designed bi-layer electrostatic cloak, and experimentally demonstrated bi-layer electrostatic cloak61. When ε3 = 0 , the CAM and dual superconductor bi-layer electric cloak can be designed. Noting that ε1 = 9.11 is very large, we can decrease ε1 by adjusting size parameters a and b.Figure z = 0) show the bi-layer spherical cloak, the outer layer is CAM, and the inner layer is conductor, Q is a point electric charge. The electric potential in the four regions is (See Supplementary Information) An, Bn, Cn, Dn, En and Fn are unknown coefficients, it should be pointed out that φe2, φe3 and φe4 are the electric potential superposition of the point electric charge and spherical cloak. The relation between the electric field and electric potential is A01, A01 = 0. We can obtain the magnetic field in the four regions (See Supplementary Information). When An = 0, only the electric field of the point electric charge is in region I; when Fn = 0, the electric field vanishes in region IV, namely, the device is an electric cloak. When An = 0, Fn = 0, solving the boundary conditions, we can obtain 63, the interesting thing take places, namely, many monopoles are induced in the four regions. For example, neglecting infinitesimal of the higher order (See Supplementary Information), we obtain coefficient Figure θ. Expanding Eq. , or cloak magnetic field and induce electric field, yet most of topological insulators (for example Bi2Se3) involve p-electron orbit38, whose Coulomb interaction is weak and cannot support magnetism, the control ability to magnetic field is weak. The axion insulator38 as a magneto-electric material can also cloak electric field and induce magnetic field (or monopole), or cloak magnetic field and induce electric field. The axion insulator can be obtained by the Coulomb correlation and exotic electronic properties, for example, when Coulomb correlation U < 0.4 eV, compound CaOs2O4 is a metal; when 0.4 eV < U < 0.9 eV, compound CaOs2O4 is an axion insulator; when 0.9 eV < U < 1.4 eV, compound CaOs2O4 is a Weyl semimetal metal; when U > 1.4 eV, compound CaOs2O4 is a Mott insulator38.Utilizing quantized Faraday and Kerr rotation effect of topological insulator, Wu Utilizing CAM and superconductor (conductor), we designed bi-layer cloak. According to the electromagnetic field theory, we obtain the magnetic scalar potential and electric potential. We demonstrated that the CAM and superconductor bi-layer can cloak applied magnetic field and induce electric field, and the CAM and conductor bi-layer can cloak applied electric field and induce magnetic field. Those cloaks can be experimentally demonstrated and be applied to electric and magnetic field switch, namely, magnetic field controls electric field or electric field controls magnetic field. By measuring electric field and magnetic field, we can measure the fine-structure constant or topological magneto-electric polarizability.66, the anomalous Hall effect is closely related to the topological magneto-electric effect, i.e., when an electric field is applied to CAM, both the electric and magnetic field are induced. Utilizing those properties, the constitute relations of the CAM are obtained r, θ, z), the solution of the Laplace equation is r, θ, φ), the solution of the Laplace equation is In the conventional material, the electric field induces electric polarization; the magnetic field induces magnetic polarization. In the chiral anomaly materials, e.g., axion insulator, topological insulator and some of Weyl semimetal, the anomalous Hall effect emergeSupplementary Information for “Quantized chiral anomaly materials cloak”


The first child’s birth is for most mothers a profound experience carrying the potential to change life orientations and values. However, little is known of how becoming a mother influences the existential dimensions of life within the parental relationship for example how motherhood may change how we view our partner and what we find important. The aim of this study was to explore how becoming a mother might change the parental relationship seen from the mother’s perspective with a specific focus on dimensions related to existential meaning-making.n = 127) and mothers who gave birth at full term (n = 372). Item 1 focused on thoughts and conversations with her partner about the life change. Item 2 referred to the potential feeling of stronger ties to the partner. Item 3 related to the feeling of being connected to ‘something bigger than one self’ together with the partner. Item 4 focused on potential conflicts due to having a child, and item 5 referred to the experience of dreams. Possible answers ranged from ‘To a high degree’ to ‘Not at all’.In 2011, 499 Danish first time mothers answered a questionnaire, from which five core items related to changes in the partner relationship from the perspective of the mother, informed this study. The cohort consisted of mothers who gave birth before the 32nd week of gestation (Most respondents found birth of the first child to have forged stronger ties to their partner and have led to both thoughts and conversations about how life together as a couple changed. At the same time, some experienced more conflicts with their partner than before giving birth, however, the majority did actually not. More than half felt their relationship linked to ‘something bigger than themselves’ or had had dreams on being a family.Findings suggest motherhood transition to be a significant transformer of partnership relation influencing also existential meaning-making. Having the potential to be of importance for the health and vitality of the mother, partner and child, it seems essential to scientifically and clinically address concerns related to existential meaning-making in partner relationship. Parenthood is a powerful life-event that often changes life orientations and sometimes increases conflicts among couples –3. The cMotherhood actualizes considerations related to existential meaning-making. We previously explored existential meaning-making among new first time mothers, who gave birth either at full term or preterm. Surprisingly we found no differences between mothers related to time of birth, when exploring either secular existential concerns or even prayer and meditation practices: Overall, we found mothers in a secular culture like the Danish to experience intensified considerations of death, vulnerability of life, and responsibility regardless of the child was born preterm or at full term . We thenThe aim of this study was to explore how becoming a mother changed the parental relationship seen from the mother’s perspective, with a specific focus on dimensions related to existential meaning-making.This study drew on data collected in 2011 from a national questionnaire survey among Danish first time mothers who gave birth in 2010. Initially, the cohort was sampled from the Danish Medical Birth Registry to investigate differences between full term mothers (> 37 completed weeks of gestation: FT mothers) and mothers giving birth preterm (< 32 completed weeks of gestation: PT mothers). The sampling ratio was 3:1 in favour of FT mothers and PT mothers were therefore over-represented compared to the background population. Both groups included mothers who experienced perinatal loss in the pregnancy for which they were included (stillbirth after 22nd week of gestation or death within 7 days postpartum).secular, religious, and spiritual ways of making meaning, since existential meaning-making in Northern Europe is considered linked to mainly secular viewpoints, contrary to for example America [N = 517). We excluded women who reported being without a partner at the time of birth (N = 18). The final study population consisted of 499 women. The Regional Research Ethics Committee of Southern Denmark approved the study, and all recommendations from Danish Data Protection Agency were followed.The overall aim of the questionnaire was to measure dimensions of existential meaning-making related to motherhood transition. We used the theoretical framework developed by la Cour and Hvidt to distinguish between  America . We refe America . The quesecular orientations in existential meaning-making ’. We linked data on each woman in the cohort to the Danish Medical Birth Registry by use of the unique individual person identification number assigned to all Danish individuals . The DanWe tabulated the characteristics of the cohort in regard to socioeconomic and obstetric factors. The distribution of answers for each item was graphically displayed and we present proportions of mothers agreeing (by answering ‘to a high degree’ or ‘to some degree’) to each item. Due to the initial selection of the study sample, we used logistic regression models to estimate odds ratios for the association between gestational age (preterm or full term) and agreement with statement in each item. Women giving birth at full term served as reference. Women reporting ‘don’t know’ or did not answer the specific item were excluded in the comparative analyses. In the multivariate analyses, we adjusted for caesarian section and perinatal loss. Results are presented as point estimates with 95% confidence intervals (95% CI). Analyses were performed using STATA 14.0 .The average age was 29 years and all categories of educational status were represented although few had no education. The median gestational age was 39 weeks (interquartile range 32-41), and 127 (25.5%) gave birth preterm. More than one in four (28%) gave birth by caesarian section, and 32 women (6%) experienced perinatal loss , and the respondents did also know More than 89% of the mothers Table  found thIn the two items prompting most ‘I don’t know’- answers (item 3 and 5), 59% found that having a child linked them and their partner to something greater than themselves, and 62% of the mothers found themselves having had dreams facilitating reflections on self and family.For all items, we found no difference in agreeing to the item statement between mothers giving birth preterm compared to mothers giving birth full term. However, there were small differences in answers tending to more mothers giving birth preterm agreeing to items 1 and 2, whereas item 3-5 were more equally answered among FT and PT mothers Table .Danish first-time mothers, asked between 6 and 18 months after birth, experienced stronger ties to their partner, which led to both thoughts and conversations about how life together changed. At the same time, a minority (43%) experienced more conflicts than before giving birth. There were no differences in distribution of answers between mothers having given birth full term and preterm. Thus, according to these findings experiencing conflicts in a parental relationship does not necessarily contrast forging stronger ties, which may be an important message to new parents. In general, our results echo other findings pointing to parenthood as both challenge and joy in a relationship , 13. NelThe two items pointing to something subconscious or transcending oneself appeared more difficult to grasp, as more respondents did not know what to answer. These two items were concerned with the feeling of being connected to ‘something bigger than ourselves’ or to have ‘had dreams leading to reflections on self and family’. However, having a child made 59% of the mothers link their relationship to ‘something bigger’ than themselves. As discussed in a previous study, exploring existential meaning-making among first-time mothers, ‘something bigger’ can be interpreted in several ways , 16.More than 62% of the mothers had dreams ‘leading to reflections on self and family’. The heightened level of dreams among pregnant and new mothers are often linked to normal emotional concerns or mood, interpreted as normal but sleep disturbing . HoweverPreviously factors such as couple communications skills, child temperament, and sleep patterns have been found to change in relation to the specific event of couples’ transition to parenthood , 19. HowTwo underlying basic assumptions grounded the study: firstly, that pregnancy, birthing and the postpartum period both individually and as a complete experience can facilitate considerations of existential meaning, and therefore change partner relationship. Connected to this, we also assumed answers were different between FT and PT mothers, since research among mothers having given birth preterm underline this as a very stressful period , 21. In In other arenas of health care services, for example in the field of palliation, care of existential or spiritual concerns in life is sought embedded, in line with recommendations from WHO and national authorities , 24. OurAmong the strengths in this study is the use of a transparent theoretical framework guiding the development of the survey, thereby enabling cultural sensitive exploration of existential meaning-making in relation to motherhood transition , 26. No We are well aware, that our findings rely on 5 items exploring partnership relation on a five point Likert scale, which lacks nuances and complexity. However it indicates directions of how partnership relations may evolve when becoming a mother. Furthermore findings relates to the period between 6 and 18 months postpartum. The wide timespan may affect responses leading to different perceptions of partner relationship between mothers who gave birth 6 months previously and those who gave birth 18 months previously. Research suggests relationship satisfaction to decline over a 3-year period from second trimester to 30 months postpartum  and our Through the lens of a first-time mother in a secular society, having a child forged stronger ties to her partner and increased thoughts and conversations of the life change with the partner. Less than half experienced more conflicts with their partner 6-18 months postpartum. More than half felt their relationship linked to ‘something bigger than ourselves’ and had dreams facilitating reflections on family and selves. Although this cross-sectional survey does not leave room for interpretational complexity, findings suggest motherhood transition to be a potential transformer of partnership relation with regard to existential meaning-making. Future research should provide in-depth exploration in this field with the use of qualitative methods. Moreover, in the light of these findings, we suggest research to focus also on existential meaning-making through the lens of fatherhood transition, since becoming a father may also potentially also transform partnership relation. Having the potential to be of importance for the health and vitality of the mother, partner, and child, it seem essential to scientifically and clinically address concerns related to existential meaning-making in partner relationship.


Pulsed electric field treatment is now widely used in diverse biological and medical applications: gene delivery, electrochemotherapy, and cancer therapy. This minimally invasive technique has several advantages over traditional ablation techniques, such as nonthermal elimination and blood vessel spare effect. Different electrodes are subsequently developed for a specific treatment purpose. Here, we provide a systematic review of electrode modality development in pulsed electric field treatment. For electrodes invented for experiment in vitro, sheet electrode and electrode cuvette, electrodes with high-speed fluorescence imaging system, electrodes with patch-clamp, and electrodes with confocal laser scanning microscopy are introduced. For electrodes invented for experiment in vivo, monopolar electrodes, five-needle array electrodes, single-needle bipolar electrode, parallel plate electrodes, and suction electrode are introduced. The pulsed electric field provides a promising treatment for cancer. In recent years, pulsed electric field treatment has been gaining extensive attention in virtue of its biological and medical applications, such as gene delivery –5, electConventional appliance consists of three parts: pulse generator, electrodes, and connection links between them. The pulse generator produces square wave pulses at regular intervals. Amplitude, pulse width, period, and phase delay are the primary parameters to determine the shape of the output waveform. Electric field strength, depending on the amplitude of the pulse and the distance between the electrodes, is often crucial for completed treatment effect . When elWe incorporate papers that are representative of existing technology and indicative of future directions, based on the massive amount of literature about electrode assemblies used in pulsed electric field treatment. As current medical applications of pulsed electric fields are mainly concentrated on cell and tissue treatment, this review is divided into two sections: section A, electrodes invented for in vitro (cell response to the treatment), and section B, electrodes invented for in vivo (tissue response to the treatment).A cell is often described as a conductive body (the cytoplasm) surrounded by a dielectric layer (the surface membrane). When a cell is applied to an electric field in a conductive medium, electric charges accumulate at the cell membrane and consequently form a voltage across the membrane. Frey et al.  designed6 [Another nonignorable conclusion drawn from this electrode model is intracellular effect of nanosecond pulsed electric fields—almost all the voltage was applied across the interior of the cell. This phenomenon has been confirmed by several studies –34. Amon3+ [2+ [2+ [2+ is mostly related to biological functions. Increased intracellular Ca2+ may be involved in triggering mitochondrial apoptosis pathway via cytochrome c [When plasma membrane voltage exceeds a critical value about 500 mV), transmembrane pores form, which is known as electroporation . It is f00 mV, tr3+ , Cu2+ [43+ [2+ , and Ca2 [2+ [2+ , among wchrome c –48.2+ comes from intracellular Ca2+ pools or extracellular solutions. Vernier et al. [2+ release from the endoplasmic reticulum in Jurkat cells, and White et al. [2+ release from the endoplasmic reticulum using adrenal chromaffin cells. They fabricated microelectrode chambers on a glass microscope slide with gold electrodes , placed partly overlapped. This design ensures a homogeneous electric field and maximally eliminates “fringing effects” due to the sharp edges of the microchamber electrodes. When a large number of cells need to be treated, the electroporation cuvette (1 mm electrode) may be the first choice. It could contain nearly 106 cells in a 200 μl suspension and provide a homogeneous electric field, but “fringing effects” seems hard to avoid.Sheet electrodes are characterized by two parallel pieces of gold foil , making it feasible to record Ca2+ influx in milliseconds. The results showed that an increased Ca2+ concentration was visible after 3.5 ms. In addition, it provides evidence that intracellular Ca2+ concentration increases in the absence of extracellular calcium; alluding intracellular calcium pools play a major role in intracellular Ca2+ concentration increase when exposed to nanosecond pulsed electric field. These results benefit mostly from the utilization of high-speed fluorescence imaging system and visualize the Ca2+ in milliseconds. Taking advantage of this appliance, other micromolecules can be detected in the very early stage such as Tl3+ and Cu2+.As stated above, Craviso et al. put forward that intracellular Car et al.  set up acroscopy , are tooRm) was still detected, accompanied by the loss of the membrane potential. The early studies estimated that pulsed electric fields cause cell membrane permeabilization opening big pores in cell membrane, but currently, patch clamp technology revealed that ultrashort intensive pulsed electrictric field opens small plasma membrane pores [INa and ICa [Another important question is how long the nanopores last. Patch-clamp was employed to explore nanopores on cell membrane and provide new insights . Cells wne pores , 49, 53. and ICa , 55.As mentioned in Section 2.1, nanosecond pulsed electric field can penetrate into the cell interior, disturbing mitochondrial membrane potential. However, experiments visualizing the internal membrane to monitor the real-time response to the nanosecond pulsed electric field are rare. Confocal laser scanning microscopy is often deemed to be competent to view subcellular structures. Berghöfer et al. then designed confocal microscopy to the nanosecond pulsed electric field system . TobaccoBeside resection or transplantation surgery, the focal ablation techniques such as cryosurgery, microwave (MW), laser interstitial thermal therapy (LITT), high-intensity focused ultrasound (HIFU), and radiofrequency ablation (RFA) remain to be fundamental means for cancer treatment. Cryosurgery freezes the tissue as low as −40°C to cause tissue necrosis. MW, LITT, HIFU, and RFA often heat the tissue to be more than 60°C, producing cell death and coagulative necrosis . HoweverThe prevailing electrodes used for the treatment of solid cancer consist of two needles, one is charged and the other is grounded (as shown in μm diameter) extending 2 mm from a Teflon base. The center needle forms the anode; the other four surrounding needles spaced 4 mm from the center electrode form the cathode. To avoid flashover between needles and accompanying skin damage, skin was coated with vegetable oil. Melanomas shrinks to about 10% of original size after the first treatment and complete remission is observed after the second treatment. The effect of 5-needle array was also confirmed in another study [To enlarge the treatment area, five-needle array was applied . The neeer study  in whichAlthough the larger electrode with multiple needles could cause enlarged electric field coverage, problems such as placement complexity and more physical damage from electrode penetration come up consequently. So, a single needle bipolar electrode was used . The eleAs techniques improve, noninvasive surgery and instruments are in great need. The noninvasive parallel plate electrodes were designed by Nuccitelli et al. . The parSimilar to parallel plate electrodes, Nuccitelli et al. designed suction electrodes  for noniWhen applied to clinical application, pulsed electric field was initially used to destroy substantial volumes of tissue , 65–68, Here, we provide a brief review of the electrode reported in the pulsed electric field treatments in vitro and in vivo. The specific applications, the advantages, and the disadvantages are also discussed. It was reported  that a f


Anecdotal evidence suggests that US practice patterns for ART differ by geographical region. The purpose of this study was to determine whether use of ICSI differs by region and to evaluate whether these rates are correlated with differences in live birth rates.Public data for 2012 were obtained from the Centers for Disease Control and Prevention. Clinics with ≥100 fresh, non-donor cycles were grouped by 10 nationally recognized Department of Health & Human Services regions and 11 metropolitan Megaregions and were compared for use of ICSI, frequency of male factor infertility, and live birth rate in women <35 years.P < 0.0001). Live birth rates per cycle in women <35 years differed  but did not correlate with rates of ICSI  per cycle. For Megaregions, rates of ICSI per cycle differed  as did live birth rates per cycle for women <35  but there was only minimal correlation between them . Highest rates of ICSI occurred in Front Range (93.5%) and Gulf Coast (83.1%) Megaregions. Lowest rates occurred in the Northeast (63.4%) and Florida (64.8%) Megaregions. Male factor infertility rates did not differ across regions.There were 274 clinics in the Health & Human Services regions and 247 in the Megaregions. ICSI utilization rates in Health & Human Services groups ranged between 52.5–78.2% (ICSI utilization and live birth rates per cycle for each clinic group were significantly different across geographical regions of the U.S. However, higher ICSI utilization rate was not associated with higher rates of male factor infertility nor were they strongly correlated with higher live birth rates per cycle. Studies are needed to understand factors that may influence ICSI overutilization in the U.S. The field of assisted reproductive technologies (ART) continues to grow exponentially after the first successful pregnancy via in-vitro fertilization (IVF) in 1978 which resulted in the live birth of a healthy baby . With thAlong with increases in other aspects of ART, the use of ICSI, which was originally developed for severe male factor infertility, has increased substantially over the years and is now often used for indications other than male factor infertility –13. StudAnecdotal evidence suggests that US practice patterns for use of ICSI in ART differ by geographic region. The goal of this study was to determine whether use of ICSI differs by region and in particular, whether there are differences in usage in urban areas, and to evaluate whether rates of ICSI utilization are correlated with differences in the frequency of male factor infertility, clinical pregnancy, and live birth rates between different regions of the US.This retrospective database analysis was conducted using the National Assisted Reproductive Technology Surveillance System (NASS) from the Centers for Disease Control and Prevention (CDC). Publically available data for 2012 from the NASS were downloaded from the Centers for Disease Control and Prevention (CDC) website . NASS daHHS is represented nationally through 10 regional offices that directly serve multiple states by providing guidance regarding current challenges and actively conduct public health research initiatives. The breakdown is used to address strategic planning for specific national problems over a 4-year period . HHS regClinics with ≥100 fresh, non-donor cycles were included and grouped by region according to the 10 nationally recognized HHS regions and 11 Megaregions. Utilization of ICSI by clinics within each HHS region and Megaregion was correlated with ICSI utilization and with live birth rate per cycle in women <35 years. Usage was compared using ANOVA. Frequency of male factor infertility at each clinic was also evaluated. Regional clinic ICSI rates per cycle were compared with clinic implantation, pregnancy and live birth rates per cycle in women <35 using correlation coefficients. A sensitivity analysis was performed to evaluate whether low numbers of clinics in some of the Megaregions unduly influenced results.There were 274 clinics with ≥100 fresh, non-donor cycles within the 10 HHS regions (Table P < 0.0001) (Table P < 0.03) as well as pregnancy  and live birth rates per cycle  in women <35 years of age also differed. Male factor infertility diagnosis rates per cycle were not significantly different across HHS regions. Correlation coefficients between ICSI and pregnancy , or live birth (R2 = 0.2096:P-0.18) were low. The correlation coefficient for ICSI and implantation rate was higher . Figure The mean rate of ICSI per cycle in each clinic group in HHS regions ranged from 52.5 to 78.2% of all clinic cycles P < 0.000 (Table PP < 0.0001) as did, implantation rate , pregnancy rates per cycle (range 42.7–65.5 P < 0.001), and live birth rates per cycle  for women <35 . Figure P = 0.01). Highest rates of ICSI occurred in the Front Range (93.5%) and Gulf Coast (83.1%) Megaregions. Lowest rates occurred in the Northeast (63.4%) and Florida (64.8%) Megaregions. There was no significant difference in male factor infertility rates per cycle across Megaregions.In Megaregions, the mean rate of ICSI differed  despite a lack of difference in frequency of the diagnosis of male factor infertility between HHS regions or Megaregions. Additionally, there were significant differences in live birth rates for women under 35 years old (P < 0.001), by HHS region and by Megaregion. Nationally, ICSI rates have increased steadily over the past 11 years from 55% in 2003 to 69% in 2014 [This study demonstrates a significant difference in ICSI utilization among both HHS regions and Megaregions ( in 2014 . These rUse of the HHS regions allowed us to group the clinics such that all regions of the country were represented. By contrast, the Megaregions were used to enable us to evaluate the clinical outcomes in large metropolitan areas. Using both of these regional designations, there were differences in ICSI usage as well as differences in pregnancy and birth outcomes. Although additional designations were available based on insurance coverage, given the complexity of changing state by state and plan by plan coverage we could not determine the proportion of covered cycles in each location. Although Megaregion data included fewer clinics, these were concentrated in metropolitan areas where competition as well as regional interaction may be more concentrated and consistent. This may explain why the differences in Megaregions were more pronounced than those in HHS regions.Furthermore, although use of ICSI has increased steadily in recent years –13, studThis study has several strengths and limitations. The strength is in the fact that all regions of the country are represented and that over 95% of clinics report to NASS. Limitations include the retrospective nature of the study which does not permit consideration of several variables including patient-specific demographics as well as comorbidities and socioeconomic status. Use of published data from NASS limited our ability to evaluate pregnancy and birth outcomes for all cycles regardless of age since the NASS data publishes clinic specific values by age category. We chose age < 35 as best representing the overall clinical and laboratory success of the clinics studied. Further, the presence of differing insurance coverage within each region and the proportion of private versus hospital-affiliated clinics within a region could not be considered and may be confounding factors. Future research may determine the impact of these variables on ICSI utilization rates and the correlation with live birth rates.In summary, these data suggest that ICSI is most likely over-utilized in regions with the greatest utilization in the US. It is speculated that regions with the greatest utilization are regions using ICSI for non-male factor reasons. Furthermore, we speculate that the usage of ICSI does not result in an improvement of outcomes as it is likely employed in cases that do not involve male factor infertility. These data further support the concept that ICSI does not improve outcomes when it is used for non-male factor infertility and supports the contention that it is being over applied. Overutilization of ICSI is associated with increased risk and cost to patients undergoing ART. Further study is needed to identify the reasons which contribute to overutilization of ICSI. Possible explanations may relate to insurance coverage availability, laboratory efficiencies, and/or perceived competition among clinics in specific regions of the country. Another relevant consideration for further examination is the specific criteria used to define male factor infertility and the indication for ICSI used by clinics in different regions of the country.


Independent replication is vital for study findings drawn from Electronic Health Records (EHR). This replication study evaluates the relationship between seasonal effects at birth and lifetime cardiovascular condition risk. We performed a Season-wide Association Study on 1,169,599 patients from Mount Sinai Hospital (MSH) to compute phenome-wide associations between birth month and CVD. We then evaluated if seasonal patterns found at MSH matched those reported at Columbia University Medical Center. Coronary arteriosclerosis, essential hypertension, angina, and pre-infarction syndrome passed phenome-wide significance and their seasonal patterns matched those previously reported. Atrial fibrillation, cardiomyopathy, and chronic myocardial ischemia had consistent patterns but were not phenome-wide significant. We confirm that CVD risk peaks for those born in the late winter/early spring among the evaluated patient populations. The replication findings bolster evidence for a seasonal birth month effect in CVD. Further study is required to identify the environmental and developmental mechanisms. External replication and validation are essential to medical research145Recently, two of the co-authors (Boland and Tatonetti) developed a method called SeaWAS: Season-Wide Association Study that reveals relationships between birth month  and lifetime disease riskTo perform a proper replication study, we sought to follow the original SeaWAS study as closely as possibleWe extracted all individuals born between 1926 and 2000 inclusive  who were treated at MSH (between 1979–2015), demographics given in We are especially interested in cardiovascular condition – birth month associations because they represent the novel findings from the original SeaWAS studyhttps://github.com/maryreginaboland/SeaWAS) to fit the database schema of MSH. We first performed a phenome-wide exploration of all birth month – disease associations for conditions with at least 1000 patients (1433 conditions). We employed the Benjamini-Hochberg method to correct for multiple hypotheses and control for the false discovery rate (FDR)We modified the SeaWAS algorithm obtained from the public domain . We assess statistical significance by comparing the actual correlation between the two institutions to an empirically derived null distribution. We generated empirical null distributions for each condition by randomizing the birth month–disease risk curve from MSH. We then computed the Pearson correlation for the random curve and CUMC’s birth month-disease risk curve. We repeated this procedure 1000 times producing 1000 random correlation results. We determined the empirically derived p-value as the proportion of random correlations greater than the actual correlation between true MSH data and true CUMC data divided by 1000. If this value is zero then the p-value is reported as “p < 0.001.”et al. 2004To place our findings in the context of biological mechanisms deemed important in birth month associations, we obtained peak flu season data obtained from the Centers for Disease Prevention and Control (CDC) data on flu activity from 1982–83 through 2013–14We used SeaWAS to mine birth month associations at MSH for all 1433 conditions with at least 1000 individuals born between 1926 and 2000, inclusive. We applied multiplicity correction using FDR to adjust the p-values. We limited our analysis to only the circulatory system conditions (as defined by the ICD-9 codes) that were found in both datasets, allowing us to compare the patterns of birth month-disease risk between the two institutions. SeaWAS-CUMC analysis found 9 circulatory system conditions were associated with birth month at an FDR threshold of 0.05 computed phenome-wide (1433 conditions) . Four ofWe performed pattern analysis of the birth month – disease risk curves for the circulatory system conditions between MSH and CUMC (set of 108 conditions). This was done to ascertain whether or not the birth month – disease relationship was the same between the two institutions. We found that seven of nine CUMC findings had significantly similar patterns at MSH . More dehttp://www.cdc.gov/flu/about/season/flu-season.htm) containing the number of times each month was the peak month for a given flu season. This data was aggregated from 1982–83 through 2013–14We overlaid data on seasonal variation in vitamin D levels and flu diagnosis levels to identify trends that could imply a biological rationale for observed cardiovascular – birth month association patterns. Replication of novel research findings is critical to biomedical research1457Coronary arteriosclerosis, essential hypertension, angina and pre-infarction syndrome were all significantly associated with birth month at the phenome-wide level at both MSH (after adjusting for 1433 tests) and CUMC (after adjusting for 1688 tests). Their seasonal patterns were also significantly correlated , Fig. 2 Three conditions, atrial fibrillation, cardiomyopathy, and chronic myocardial ischemia, were significantly correlated between CUMC and MSH but were not significantly associated with birth month at the phenome-wide level at MSH. These conditions could be associated with birth month through their common comorbidities, namely essential hypertension, angina, coronary arteriosclerosis and pre-infarction syndromeThere are several additional reasons why results from CUMC and MSH may differ. Firstly, many of these circulatory system conditions are comorbid with one another Several mechanisms have been proposed previously that could explain the relationship between cardiovascular conditions and birth month24et al.et al.A limitation of our approach includes the exclusive use of diagnosis codes collected during the clinical encounter and recorded in EHRs. Therefore, we know that these patients were diagnosed with a cardiovascular condition, but they may not necessarily have had cardiovascular disease. We used only diagnosis codes in order to properly validate the original results presented in Boland The condition most correlated between MSH and CUMC was coronary arteriosclerosis , which iIn this replication study, we study the cardiovascular condition – birth month relationship at another institution (MSH) with the same climate and urban setting as CUMC (both located in NYC). We found that seven of nine cardiovascular conditions associated with birth month at CUMC were also significantly correlated with the patterns revealed at MSH. These findings support the relationship between risk for cardiovascular conditions and birth month. We describe two leading putative mechanisms behind this relationship: maternal infection and low vitamin D levels. We also discuss the possibility of a combined mechanism  underlying the disease – birth month observations. Further study is required to identify the particular environmental and developmental mechanisms driving the observed associations.How to cite this article: Li, L. et al. Replicating Cardiovascular Condition-Birth Month Associations. Sci. Rep.6, 33166; doi: 10.1038/srep33166 (2016).


The fronto-striato-thalamic circuitry is a key network associated with several symptoms observed in patients with schizophrenia (SZPs). In this study, we use diffusion tensor imaging (DTI) to investigate the integrity of white matter (WM) pathways involved in this network in SZPs relative to healthy controls (HCs). We also evaluate the differential impact of chronic exposure to clozapine as well as other atypical and typical antipsychotics on fasciculi integrity in this network in schizophrenia.63 HCs and 41 SZPs were included in this study. Of the SZPs, 16 were treated with clozapine (SZPsC), 17 with atypical antipsychotics (SZPsA), and 8 with typical antipsychotics (SZPsT). We reconstructed three tracts belonging to the fronto-striato-thalamic network in the left hemisphere using tractography: one fronto-subcortical tract (FSC), one prefronto-subcortical tract (PFSC), and one prefronto-frontal tract (PFF). Diffusion parameters were individually extracted in each tract.SZPs exhibited lower integrity in both the FSC and PFSC relative to HCs, and SZPsT patients showed altered integrity compared to SZPsC patients. There were no WM integrity differences in the PFF between SZP groups or between SZPs and HCs.These results suggest that SZPs exhibit structural connectivity abnormalites in the prefronto-fronto-subcortical network that are specifically and differentially impacted by the type of antipsychotic treatment. Additional studies are needed to separate the contributions of clozapine-mediated neuroprotection, neurotoxicity related to typical antipsychotics, and the illness itself to the observed differences.


At the Division of Neonatology, Department of Paediatrics, Medical University Graz, a unique regimen of necrotizing enterocolitis (NEC) prophylaxis in preterm infants showing a < 1500 g birth weight  is used. The regimen includes oral antibiotic and antifungal therapy and probiotic preparations as well as a standardised feeding regimen. The incidence of NEC in preterm infants treated by this regimen has been shown to be lower, reflecting 0.7% when treatment was initiated on the first day of life, compared to international incidence rates (5.1%). However, the impact of the prophylaxis regimen on the intestinal microbiome is yet unknown.We here report the protocol of an observational multicentre STROBE compliant pilot study in VLBW preterm infants. Research will compare three groups as defined by different NEC prophylaxis regimens. Each centre will provide 20 infants. Stool samples will be collected every 2 days throughout the first 2 weeks of life. Samples will be stored at − 80 °C until 16S-rRNA sequencing. 16S-rRNA genes will be amplified using suitable primers  and prepared for MiSeq Sequencing. Analyses will be performed using public analysis-pipelines, such as Mothur and Qiime, thus allowing an analysis of high-throughput community sequencing data. Abundance and composition changes in intestinal microbiota will be compared between the groups throughout the first 2 weeks of life.Different surroundings at the three participating study centres, including contacts to care takers and parents, as well as feeding or medication all might influence intestinal microbiota composition and abundance. In the planned sequel study, this should be kept in mind and a more standardised process ought to be established. However, the results obtained from the presented pilot study will display the burden of bias and help to establish a more strict protocol for the future.DRKS00009290).Trial has been registered with the German Registry for Clinical Trials (registry ID The online version of this article (10.1186/s40814-017-0195-y) contains supplementary material, which is available to authorized users. The genesis of the microbiome starts by vertical transmission of maternal microbiota, either during birth or even before delivery. Recent studies suggest the presence of a microbiome within the placenta and foetal meconium , 2. The The intestinal microbiome interacts in a symbiotic relationship with its host. It contributes to nutrient utilisation by increasing digestive capacity and the ability to harvest nutrients from food. It supports vitamin biosynthesis and the production of other metabolites , 19, 20.Enterococcus, Enterobacter, and Lactobacillus spp., as well as numbers of Staphylococcus spp. dominate while numbers of anaerobes like Bifidobacterium, Bacteroides and Atopobium spp. were found to be decreased [Bifidobacterium spp. by day 7 of life while preterm infants were not [The intestinal microbiome of the preterm infant shows reduced microbial diversity with a concurrent increase in colonisation with pathogenic organisms , 8. It iecreased –24. Healwere not . Pretermwere not , 27, 28.NEC resembles the most common life-threatening emergency of the gastrointestinal tract in the neonatal period. The prevalence of NEC accounts for 7–11% in VLBW infants , 30, witProteobacteria spp. while the Bacterioidetes spp. decrease [Among risk factors, prematurity and accompanying intestinal colonisation represent the only consistently identified criteria . Therefodecrease . Differedecrease . The timdecrease . Thus, iAt the Division of Neonatology, Department of Paediatrics, Medical University of Graz, a unique regimen as prophylaxis of necrotizing enterocolitis (NEC) is used in preterm infants of < 1500 g birth weight . The regDifferences in therapeutic and preventive approach to VLBW infants as defined by use of different preparations of probiotics, antibiotics, antifungal agents and feeding strategies might influence diversity and composition of gut microbiota. Thus, intestinal microbial diversity and abundance, as well as development of the intestinal microbiome within the first weeks of life in preterm infants should differ depending on the applied regimen. Differences regarding intestinal microbiota may be found that might additionally have long-term, up to now unknown, impacts on infant health and development. These differences may lead to the development of tailored probiotic formulas to improve NEC protection for the future.Proteobacteria spp. and higher rates of germs used as probiotics and further aided by the consumption of human milk, such as Bifidobacteria spp.Abundance and composition of intestinal microbiota might be found to differ between infants treated by the Graz NEC prophylaxis regimen and infants not receiving the prophylaxis regimen. Infants receiving the Graz NEC prophylaxis regimen might further show lower rates of The primary outcomes are intestinal microbiota composition and abundance, which will be summarised separately for each group in order to inform sample size estimation for a future definitive randomised trial. Secondary outcomes include hypothetical predominance or lack of specific species in infants having received the Graz NEC prophylaxis regimen.We propose a prospective controlled triple-centre cohort pilot study including preterm infants with a birth weight of < 1500 g treated at three NICUs with different regimens of NEC prophylaxis and feeding strategies. Data from the proposed project will be used to support planning and statistical power calculations for a larger sequel study.To compare our infants with two other groups, we now co-operate with the Division of Neonatology, Department of Paediatrics, General Hospital of Klagenfurt, and the Division of Neonatology, Department of Paediatrics, General Hospital of Leoben, where different prophylactic approaches are performed. Regimens are shown in Table n = 20), the Department of Paediatrics, General Hospital of Klagenfurt (n = 20) and the Department of Paediatrics, General Hospital of Leoben (n = 20) will be collected every 2 days within the first weeks of life. Figure Stool samples of 60 VLBW preterm infants, treated at the NICUs at the Department of Paediatrics, Medical University Graz (Very low birth weight preterm infants (i.e. < 1500 g birth weight).Inclusion criteria comprise birth weight < 1500 g, treatment at the NICU, Department of Paediatrics, Medical University Graz; NICU, Department of Paediatrics, General Hospital of Leoben; NICU, Department of Paediatrics, General Hospital of Klagenfurt between October 2015, and March 2017.Exclusion criteria comprise infants nonviable at birth, death within the first 2 weeks of life, infants suffering from genetic diseases, genetic syndromes or congenital anomalies, and meconium ileus.Follow up: no follow up planned.Infants will be recruited at all three centres to compare microbiota-analysis data between these groups. Prior to inclusion, infants’ parents are informed about the intention and purpose of the study, procedure of stool sampling, advantages, and disadvantages for their infant, and that the infant does not get harmed or treated differently for the purpose of the study. Parental information is provided by a written consent form, as well as by an attending paediatrician. Parents must give written informed consent before inclusion of the infant. Overall, seven stool samples, stored in two containers, of spontaneously produced faeces should be collected throughout 2 weeks, starting on the day of the infants’ first defecation, i.e. meconium loss. No additional interventions to stimulate defecation, deviating from standard care, are performed for study purposes. Collection of stool samples will be performed using sterile microspatula  and sterile stool sample containers . Up to 1 ml of faeces is taken. All samples taken will be allocated a running number. In order to record sample numbers and progress of sample collection, a standardised protocol-sheet is used. Storage of the samples taken will be performed using a deep-freezing storage device at − 80 °C as soon as possible. Within the freezer sample, containers are kept inside cardboard boxes  to protect them from any damage. Delivery of samples from Klagenfurt and Leoben will be performed by a professional delivery service using dry ice cooling and a temperature control protocol. After collection is completed, microbiome analysis will be performed.We plan to include 20 infants of < 1500 g birth weight (VLBW) from each of the three participating study centres. This, in turn, means a number of 60 infants included in our study. Starting on the day of the infants’ first spontaneous stool, collection of seven samples, acquired every 2 days throughout the first weeks of life, is performed in every infant. Finally, all 420 samples will be analysed using 16S-rRNA-analysis techniques.To provide high quality throughout all steps of the study protocol, all procedures as described above have been defined as standard operating procedures (SOP) for every centre.Maternal and pregnancy associated data: mothers’ age, number of prior pregnancies, number of infants born, multiple pregnancy, existence of mother-child-passport , pregnancy associated complications, application of steroids to induce lung maturation, tocolysis.Perinatal data: complications during birth, birth-mode, APGAR-score, umbilical cord pH.Neonatal data: sex, birth weight, small-for-gestational age , duration of hospitalisation, duration of NICU stay, duration of oxygen supplementation, appearance of neonatal morbidities , application of caffeine and surfactant, as well as inotropes and cardiovascular supportive therapy.Data on specific medication: dosage, active pharmaceutical ingredient and time of application of antibiotics, antifungal agents and probiotics, as well as parenteral or enteral nutrition.The following data will be collected throughout hospitalisation, and noted in an excel sheet. For backup purposes, an additional hard copy containing the data will be deposited at each centre:Data will be collected in order to prove correlations to specific intestinal microbiota patterns. SKK, CME, GG, and BR will have access to the final trial dataset.bacteria, fungi, and archaea) and prepared for MiSeq Sequencing [archea. Analysis will be performed using public analysis-pipelines, like Mothur (mothur.org) and Qiime (qiime.org) [Microbial DNA will be extracted from stool samples using a combination of mechanical and enzyme-based lysis . From exquencing , which wime.org) , represeIn the frame of the Microbiome Initiative Graz , the necessary expertise in order to analyse and interpret the data is available. All tools, pipelines, and expert knowledge of the Microbiome Initiative will be made available.Statistical analysis will focus on confidence interval estimation. Since the study has not been powered any hypothesis testing will be considered entirely exploratory. Full analysis will be performed in close co-operation with the core facility for bio-informatics and biostatistics, ZMF, Medical University Graz.The project is scheduled to last 24 months. At the Division of Neonatology, Department of Paediatrics, Medical University of Graz, we treat about 100 infants of < 1500 g birth weight per year. At the Division of Neonatology, Department of Paediatrics, General Hospital of Klagenfurt, between 40 and 60 infants < 1500 g birth weight are treated per year, and at the Division of Neonatology, Department of Paediatrics, General Hospital of Leoben around 30 infants < 1500 g birth weight are treated annually. Therefore, the active recruitment and treatment period regarding the study is planned to take place throughout the first 18 months. Stool microbiota analysis will take place throughout the following 2 months, and the final 4 months will be used for the statistical and biostatistical analyses of data, and for the presentation of data .Different surroundings at the three participating study centres, including contacts to caretakers and parents, as well as feeding or medication all might influence intestinal microbiota composition and abundance. In the planned sequel study, this should be kept in mind and a more standardised process  ought to be established. However, the results obtained from the presented pilot study will display the burden of bias and help to establish a more strict protocol for the future.Additional file 1:SPIRIT 2013 checklist. (DOC 120 kb)Additional file 2:SPIRIT flow-chart. (DOC 53 kb)


Various guidelines for the protection of human beings against possible adverse effects resulting from exposure to electromagnetic fields (EMFs) have been published with a view towards continual improvement; therefore, decreasing exposure is an important research area. The aim of this study was to investigate the possibility of decreasing electric field exposure with arc flash rated personal protective equipment (PPE), which in this case was a set of coveralls, and to compare the measurement results to calculations using the helmet-mask measuring system. We collected the data under a 400-kV power line. The test person stood on isolated aluminum paper, and the current between the ground and the aluminum paper was measured. When the test subject wore the arc flash PPE, the current to the ground was only 9.5% of the current measured when wearing normal clothes, which represents a clear decrease in exposure. When electricians work under high voltage power lines or in electrical substations, they are exposed to an alternating, very low frequency electric field. The alternating electric field induces a surface electric charge and a current in the worker’s body, which leads to a current flowing between the worker and the ground through any contact point, e.g., the feet or hands that touch railings. Typically, the workers are not grounded with a conductor and do not wear equipment that would specifically protect them from exposure to the electric field. Occupational and public electric field exposures have been studied earlier in Finland ,5,6,7,8.Various legislation and guidelines of occupational electromagnetic field exposure have been published: (1) directive 2013/35/EU on the minimum health and safety requirements regarding the exposure of workers to the risks arising from physical agents (electromagnetic fields) ; (2) theDirective 2013/35/EU includes minimum requirements for the protection of workers from risks to their health and safety arising from exposure to electromagnetic fields at their work sites. The action levels  of the directive regarding electric fields (50 Hz) are as follows: low AL 10 kV/m (rms) and high AL 20 kV/m (rms) .Indirect effects of electromagnetic fields may result from physical contact between a person and an object of a dissimilar electric potential. This causes a flow of electric charge (contact current). In the frequency range up to approximately 100 kHz, the flow of electric current from an object in the field to the body of an individual may result in the stimulation of muscles, peripheral nerves, or both. With increasing levels of current, this may be manifested as perception, pain from electric shock, burn, or both, inability to release the object, difficulty in breathing, and, at very high currents, cardiac ventricular fibrillation . ThreshoA study published in 1996 examined statistical data collected from French electric utility workers. It showed that being exposed to a very low frequency electric field may increase the risk of brain tumors, and an association with colon cancer was also found. Links to other kinds of cancers were not found . A meta-In a previous study conducted at Tampere University of Technology, the maximum total contact currents of workers were measured using a helmet–mask measuring system at 400-kV substations and under 400-kV power lines . TampereIn another study at Tampere University of Technology on the possibility of decreasing the 50-Hz electric field exposure with different jackets was studied under a 400-kV power line using a wooden frame from which the jackets could be suspended . The eleThe aim of this study was to investigate the possibility of decreasing the 50-Hz electric field exposure with arc flash personal protective equipment (PPE) under 400-kV power lines and to compare the measurement results to those of the helmet-mask measuring system. Furthermore, the aim was to compare the new results to earlier measurement results of coveralls under 400-kV power lines.First, we measured the electric field at the experiment site . We perfSecondly, the test subject stood on aluminum paper using the helmet-mask measuring system and wearing regular safety boots . The meaThirdly, the test subject stood on aluminum paper, which was isolated from the ground with a plastic bag, while wearing different suits . The curThe arc flash PPE was manufactured in Italy by Carraro S.R.L. , and it The measurements were performed on two separate days because the arc flash PPE was not available for use during the first scheduled measurement day. A total of 7 measurements were taken, one for each set of clothing. On the first measurement day, the electric field strength was 4.5 kV/m (height 1.7 m); on the second day, it was 4.6 kV/m (height 1.7 m). On both days, the air temperature was between 5 °C and 11 °C, and the relative air humidity ranged from 66% to 74%.When the test subject used the helmet-mask measuring system, the current measured by the system was 52.2 μA, and the current between the ground and the aluminum paper was 50.0 μA. When the test subject wore a regular helmet, normal clothes, and no socks, the current between the ground and the aluminum paper was 64 μA. When she used the PPE (with grounding), the current between the ground and the aluminum paper was 6.1 μA. This was a 90.5% reduction in the measured current.In the comparison between the measurement method  and the helmet-mask measuring system, the currents were quite similar . In an earlier study , the meaThe use of arc flash PPE was very successful in reducing the induced current between the aluminum paper and the ground. The induced current was reduced to 10% of the value measured while wearing normal clothes. In the earlier experiment , the proThe contact currents measured were significantly lower than the ICNIRP reference level of 1 mA, which is due to the relatively low strength of the electric field under the power line. Significantly higher electric field strengths can be found in electrical substations, where the contact currents would be correspondingly higher than in this study. More measurements at electrical substations should be taken in the future.The usefulness of the PPE is hindered by the fact that it has to be grounded by a conductor wire. This limits worker mobility and range to the length of the conductor. To limit the exposure to a minimum, the worker should also use the shrouded hood of the PPE, which limits visibility and restricts breathing. The PPE can also significantly increase the heat load of the worker during hot days.The earlier study  found thThe achieved results may not take into account either short-term measurement variability or variability in electric field strength at different times of the year. The measurements in the present paper should be seen as a pilot study; more time points and repeated measurements per condition should be added to future studies so that the experiments can be conducted under more realistic (higher) exposure conditions experienced by electricians.Based on our measurements, we can conclude that the arc flash PPE is one possible way to effectively decrease workers’ exposure to electric fields. Since the highest measured contact currents were significantly lower than the ICNIRP reference level of 1 mA, workers should be safe from occupational exposure at ground level under 400-kV power lines even without a PPE. However, the PPE can be somewhat difficult to use because workers need to ground the coveralls and preferably use the facial shroud, which restricts breathing. It can also be useful in workplaces where spark discharges can be of nuisance, as the PPE can conduct the discharge currents to the ground without the test subject even noticing them.