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Clonal haematopoiesis, which is highly prevalent in older individuals, arises from somatic mutations that endow a proliferative advantage to haematopoietic cells. Clonal haematopoiesis increases the risk of myocardial infarction and stroke independently of traditional risk factors1. Among the common genetic variants that give rise to clonal haematopoiesis, the JAK2V617F (JAK2VF) mutation, which increases JAK–STAT signalling, occurs at a younger age and imparts the strongest risk of premature coronary heart disease1,2. Here we show increased proliferation of macrophages and prominent formation of necrotic cores in atherosclerotic lesions in mice that express Jak2VF selectively in macrophages, and in chimeric mice that model clonal haematopoiesis. Deletion of the essential inflammasome components caspase 1 and 11, or of the pyroptosis executioner gasdermin D, reversed these adverse changes. Jak2VF lesions showed increased expression of AIM2, oxidative DNA damage and DNA replication stress, and Aim2 deficiency reduced atherosclerosis. Single-cell RNA sequencing analysis of Jak2VF lesions revealed a landscape that was enriched for inflammatory myeloid cells, which were suppressed by deletion of Gsdmd. Inhibition of the inflammasome product interleukin-1β reduced macrophage proliferation and necrotic formation while increasing the thickness of fibrous caps, indicating that it stabilized plaques. Our findings suggest that increased proliferation and glycolytic metabolism in Jak2VF macrophages lead to DNA replication stress and activation of the AIM2 inflammasome, thereby aggravating atherosclerosis. Precise application of therapies that target interleukin-1β or specific inflammasomes according to clonal haematopoiesis status could substantially reduce cardiovascular risk. Accelerated atherosclerosis in a mouse model of clonal haematopoiesis is prevented by genetic interruption of AIM2 inflammasome activation or by inhibition of interleukin-1β.

Background: The LDLR (low-density lipoprotein receptor) in the liver is the major determinant of LDL-cholesterol levels in human plasma. The discovery of genes that regulate the activity of LDLR helps to identify pathomechanisms of hypercholesterolemia and novel therapeutic targets against atherosclerotic cardiovascular disease. Methods: We performed a genome-wide RNA interference screen for genes limiting the uptake of fluorescent LDL into Huh-7 hepatocarcinoma cells. Top hit genes were validated by in vitro experiments as well as analyses of data sets on gene expression and variants in human populations. Results: The knockdown of 54 genes significantly inhibited LDL uptake. Fifteen of them encode for components or interactors of the U2-spliceosome. Knocking down any one of 11 out of 15 genes resulted in the selective retention of intron 3 of LDLR . The translated LDLR fragment lacks 88% of the full length LDLR and is detectable neither in nontransfected cells nor in human plasma. The hepatic expression of the intron 3 retention transcript is increased in nonalcoholic fatty liver disease as well as after bariatric surgery. Its expression in blood cells correlates with LDL-cholesterol and age. Single nucleotide polymorphisms and 3 rare variants of one spliceosome gene, RBM25 , are associated with LDL-cholesterol in the population and familial hypercholesterolemia, respectively. Compared with overexpression of wild-type RBM25 , overexpression of the 3 rare RBM25 mutants in Huh-7 cells led to lower LDL uptake. Conclusions: We identified a novel mechanism of posttranscriptional regulation of LDLR activity in humans and associations of genetic variants of RBM25 with LDL-cholesterol levels.

6 pags., 4 figs., 1 tab.-- Open Access funded by Creative Commons Atribution Licence 4.0, Inclusive one- and multi-nucleon removal cross sections have been measured for several Sn, Sb and Te isotopes just beyond the N=82 neutron shell closure. The beams were produced in the projectile fission of a U beam at the Radioactive Isotope Beam Factory at RIKEN. The experimental cross sections are compared to predictions from the most recent version of the Liege intranuclear cascade model. Although the overall agreement is good, severe discrepancies are observed for the cases of one- and two-neutron removal from Sn and Sb projectiles and one-proton knockout from all measured N=84 isotones. These discrepancies, as well as the relevance of quasi-elastic reaction channels to the one-neutron removal cross sections, are discussed. In addition, the measured inclusive one-proton knockout cross section for the semi-magic Sn projectile is compared to eikonal direct reaction theory calculations to assess if the suppression factors to these calculated cross sections, deduced from data on reactions of lighter projectile nuclei, are also applicable to heavy nuclei., We thank the staff of the RIKEN Nishina Center accelerator complex for providing high-intensity beams to the experiment. This work was supported by the Spanish Ministerio de Economía y Competitividad under contracts FPA2014-57196-C5-4-P and FPA2017-84756-C4-2-P. J.A.T. acknowledges the support of the Science and Technology Facilities Council (UK) grant ST/L005314/1 and R.O. that of JSPS KAKENHI Grant No. 26887048. G.M.T. grate-fully acknowledges funding of this research from the Research Council of Norway, Project Grant No. 222287.

Background: Bipolar disorder is associated with circadian disruption and a high risk of suicidal behavior. In a previous exploratory study of patients with bipolar I disorder, we found that a history of suicide attempts was associated with differences between winter and summer levels of solar insolation. The purpose of this study was to confirm this finding using international data from 42% more collection sites and 25% more countries. Methods: Data analyzed were from 71 prior and new collection sites in 40 countries at a wide range of latitudes. The analysis included 4876 patients with bipolar I disorder, 45% more data than previously analyzed. Of the patients, 1496 (30.7%) had a history of suicide attempt. Solar insolation data, the amount of the sun’s electromagnetic energy striking the surface of the earth, was obtained for each onset location (479 locations in 64 countries). Results: This analysis confirmed the results of the exploratory study with the same best model and slightly better statistical significance. There was a significant inverse association between a history of suicide attempts and the ratio of mean winter insolation to mean summer insolation (mean winter insolation/mean summer insolation). This ratio is largest near the equator which has little change in solar insolation over the year, and smallest near the poles where the winter insolation is very small compared to the summer insolation. Other variables in the model associated with an increased risk of suicide attempts were a history of alcohol or substance abuse, female gender, and younger birth cohort. The winter/summer insolation ratio was also replaced with the ratio of minimum mean monthly insolation to the maximum mean monthly insolation to accommodate insolation patterns in the tropics, and nearly identical results were found. All estimated coefficients were significant at p < 0.01. Conclusion: A large change in solar insolation, both between winter and summer and between the minimum and maximum monthly values, may increase the risk of suicide attempts in bipolar I disorder. With frequent circadian rhythm dysfunction and suicidal behavior in bipolar disorder, greater understanding of the optimal roles of daylight and electric lighting in circadian entrainment is needed. © 2021, The Author(s).

Reduced transition probabilities have been measured for the neutron-rich Ni73,74,75 nuclei with relativistic Coulomb excitation performed at the RIKEN Nishina Center. For the even-even Ni isotope the determined B(E2;0+→2+) value is compatible within errors with the result of a previous intermediate energy Coulomb excitation experiment, although being somewhat larger. For the odd Ni isotopes B(E2) values have been determined for the first time. In the middle νg9/2 shell nucleus Ni73 three peak candidates have been observed and tentatively assigned to the (5/2+), (13/2+), and (11/2+) excitations. Two peak candidates have been observed in Ni75 and tentatively assigned to the (13/2+) and (11/2+) levels. The measured B(E2) values are in line with the large B(E2) reported in Ni70 and at variance with the small strength measured in Ni72. Excitation energies compare well with the result of large-scale shell-model calculations, while B(E2) values are larger than predicted. This could indicate an increasing contribution of proton excitations across the Z=28 shell closure when approaching Ni78.

Nukleer radyasyonlarin enerji olcumlerinde spektrometrenin karakteristiklerinin belirlenmesi son derece onemlidir. Gelen gama isinlarinin enerjisine bagli olarak, detektorden elde edilen pulslar, puls yuksekligi analizi (Puls Height Analysis-PHA) metoduyla cok kanalli analizorde (Multi Channel Analyzer-MCA) gama spektrumlari olarak gozlenir. MCA’de kanal basina dusen gama enerjilerini belirlemek icin dedektorun enerji kalibrasyonunun ve enerjileri birbirine yakin pikleri ayirt edebilme yetenegi olan enerji cozunurlugunun bilinmesi gereklidir. Bu calismada, gama isinlari icin yuksek verime sahip olan NaI(Tl) detektorunun enerji kalibrasyonu ve enerji cozunurlugu 137 Cs, 60 Co, 22 Na, 133 Ba standart gama isini kaynaklarinin puls yuksekligi spektrumlari olculerek elde edilmistir.

The level structures of 70 Co and 70 Ni, populated from the β decay of 70 Fe, have been investigated using β -delayed γ -ray spectroscopy following in-flight fission of a 238 U beam. The experimental results are compared to Monte-Carlo Shell-Model calculations including the pf+g9/2+d5/2 orbitals. The strong population of a (1+) state at 274 keV in 70 Co is at variance with the expected excitation energy of ∼1 MeV from near spherical single-particle estimates. This observation indicates a dominance of prolate-deformed intruder configurations in the low-lying levels, which coexist with the normal near spherical states. It is shown that the β decay of the neutron-rich A=70 isobars from the new island of inversion to the Z=28 closed-shell regime progresses in accordance with a newly reported type of shell evolution, the so-called Type II, which involves many particle-hole excitations across energy gaps. Elsevier

The reduced transition probability B(E2;01+→21+) to the first excited 2+ state of the neutron-rich nucleus Te136, with two protons and two neutrons outside the doubly magic Sn132 core, was measured via Coulomb excitation at relativistic energies at the RIKEN Radioactive Isotope Beam Factory. A value of B(E2)=0.191(26) e2b2 was extracted from the measured inelastic scattering cross section on an Au target taking into account the contributions from both Coulomb and nuclear excitations. In addition, an upper limit for the transition strength to a 2+ state of mixed-symmetry character in the excitation energy range of 1.5-2.2 MeV was determined and compared to the predictions of various theoretical calculations. Because of the high statistics gathered in the present experiment the error of the deduced B(E2) value is dominated by the systematic uncertainties involved in the analysis of Coulomb excitation experiments at beam energies around 150 MeV/u. Therefore, the latter are for the first time assessed in detail in the present work.

The low-lying structures of the midshell νg9/2 Ni isotopes 72Ni and 74Ni have been investigated at the RIBF facility in RIKEN within the EURICA collaboration. Previously unobserved low-lying states were accessed for the first time following β decay of the mother nuclei 72Co and 74Co. As a result, we provide a complete picture in terms of the seniority scheme up to the first (8+) levels for both nuclei. The experimental results are compared to shell-model calculations in order to define to what extent the seniority quantum number is preserved in the first neutron g9/2 shell. We find that the disappearance of the seniority isomerism in the (81+) states can be explained by a lowering of the seniority-four (6+) levels as predicted years ago. For 74Ni, the internal de-excitation pattern of the newly observed (62+) state supports a restoration of the normal seniority ordering up to spin J=4. This property, unexplained by the shell-model calculations, is in agreement with a dominance of the single-particle spherical regime near 78Ni. The low-lying structures of the midshell νg9/2 Ni isotopes 72Ni and 74Ni have been investigated at the RIBF facility in RIKEN within the EURICA collaboration. Previously unobserved low-lying states were accessed for the first time following β decay of the mother nuclei 72Co and 74Co. As a result, we provide a complete picture in terms of the seniority scheme up to the first (8+) levels for both nuclei. The experimental results are compared to shell-model calculations in order to define to what extent the seniority quantum number is preserved in the first neutron g9/2 shell. We find that the disappearance of the seniority isomerism in the (81+) states can be explained by a lowering of the seniority-four (6+) levels as predicted years ago. For 74Ni, the internal de-excitation pattern of the newly observed (62+) state supports a restoration of the normal seniority ordering up to spin J=4. This property, unexplained by the shell-model calculations, is in agreement with a dominance of the single-particle spherical regime near 78Ni. ispartof: Physics Letters B vol:781 pages:706-712 status: published

The level structure of the neutron-rich ^{77}Cu nucleus is investigated through β-delayed γ-ray spectroscopy at the Radioactive Isotope Beam Factory of the RIKEN Nishina Center. Ions of ^{77}Ni are produced by in-flight fission, separated and identified in the BigRIPS fragment separator, and implanted in the WAS3ABi silicon detector array, surrounded by Ge cluster detectors of the EURICA array. A large number of excited states in ^{77}Cu are identified for the first time by correlating γ rays with the β decay of ^{77}Ni, and a level scheme is constructed by utilizing their coincidence relationships. The good agreement between large-scale Monte Carlo shell model calculations and experimental results allows for the evaluation of the single-particle structure near ^{78}Ni and suggests a single-particle nature for both the 5/2_{1}^{-} and 3/2_{1}^{-} states in ^{77}Cu, leading to doubly magic ^{78}Ni.

Excited states in the nucleus 133Sn, with one neutron outside the doubly-magic 132Sn core, were populated following one-neutron knockout from a 134Sn beam on a carbon target at relativistic energies at the Radioactive Isotope Beam Factory at RIKEN. Besides the rays emitted in the decay of the known neutron single-particle states in 133Sn additional strength in the energy range 3.5-5.5 MeV was observed for the fi rst time. Since the neutron-separation energy of 133Sn is low, Sn=2.402(4) MeV, this observation provides direct evidence for the radiative decay of neutron- unbound states in this nucleus. The ability of electromagnetic decay to compete successfully with neutron emission at energies as high as 3 MeV above threshold is attributed to a mismatch between the wave functions of the initial and final states in the latter case. These fi ndings suggest that in the region south-east of 132Sn nuclear structure effects may play a signifi cant role in the neutron vs. competition in the decay of unbound states. As a consequence, the common neglect of such effects in the evaluation of the neutron-emission probabilities in calculations of global b -decay properties for astrophysical simulations may have to be reconsidered.

Purpose To assess the relationships between mucosal thickness, T1-weighted, T2-weighted signals and restricted diffusion on magnetic resonance imaging (MRI) with the degree of symptoms in patients with incidentally detected inflammatory sinonasal disease. Materials and methods Conventional and diffusion-weighted MRI of 100 patients with incidental sinonasal mucosal thickening were prospectively evaluated. There were 53 men and 47 women, with a mean age of 44.6 years ± 15.17 (SD) (range: 18–81 years). Correlations between quantitative values (T1-signal, T2-signal and apparent diffusion coefficient [ADC]) and three different quality of life questionnaires (chronic sinusitis survey, sinonasal outcomes test-22 and nasal obstruction and septoplasty effectiveness scale [NOSE]) were searched using the Spearman correlation test. Results The mean SNOT-22 score was 35.81 ± 20.36 (SD) (range: 0–83), CSS score was 4.64 ± 3.42 (SD) (range: 0–14), and NOSE score was 5.91 ± 4.84 (range: 0–18). All patients (100%) had maxillary sinus involvement. Ethmoidal sinus involvement was present in 57% of patients, frontal sinus involvement in 33% and sphenoidal sinus involvement in 27%. Morphologically, 40 patients (40%) had septal deviation, 41 (41%) had maxillary sinus retention cyst and 78 (78%) had hypertrophy of the conchae. No correlations were found between morphological abnormalities, quantitative values and patient scores in none of the questionnaires. Conclusion Incidental morphological abnormalities or restricted diffusion of the paranasal sinuses on MRI do not correlate with the degree of symptoms in patients with incidentally detected inflammatory sinonasal disease.

The level structure of the neutron-rich ^{77}Cu nucleus is investigated through β-delayed γ-ray spectroscopy at the Radioactive Isotope Beam Factory of the RIKEN Nishina Center. Ions of ^{77}Ni are produced by in-flight fission, separated and identified in the BigRIPS fragment separator, and implanted in the WAS3ABi silicon detector array, surrounded by Ge cluster detectors of the EURICA array. A large number of excited states in ^{77}Cu are identified for the first time by correlating γ rays with the β decay of ^{77}Ni, and a level scheme is constructed by utilizing their coincidence relationships. The good agreement between large-scale Monte Carlo shell model calculations and experimental results allows for the evaluation of the single-particle structure near ^{78}Ni and suggests a single-particle nature for both the 5/2_{1}^{-} and 3/2_{1}^{-} states in ^{77}Cu, leading to doubly magic ^{78}Ni.

International audience; Excited states in the nucleus Sn133, with one neutron outside the double magic Sn132 core, were populated following one-neutron knockout from a Sn134 beam on a carbon target at relativistic energies at the Radioactive Isotope Beam Factory at RIKEN. Besides the γ rays emitted in the decay of the known neutron single-particle states in Sn133 additional γ strength in the energy range 3.5–5.5 MeV was observed for the first time. Since the neutron-separation energy of Sn133 is low, Sn=2.402(4) MeV, this observation provides direct evidence for the radiative decay of neutron-unbound states in this nucleus. The ability of electromagnetic decay to compete successfully with neutron emission at energies as high as 3 MeV above threshold is attributed to a mismatch between the wave functions of the initial and final states in the latter case. These findings suggest that in the region southeast of Sn132 nuclear structure effects may play a significant role in the neutron versus γ competition in the decay of unbound states. As a consequence, the common neglect of such effects in the evaluation of the neutron-emission probabilities in calculations of global β-decay properties for astrophysical simulations may have to be reconsidered.

SUMMARY One of the most dynamic adult human tissues is the endometrium. Through coordinated, cyclical proliferation, differentiation, leukocyte recruitment, apoptosis, and desquamation, the uterine lining is expanded and shed monthly, unless pregnancy is established. Errors in these steps potentially cause endometrial dysfunction, abnormal uterine bleeding, failed embryonic implantation, infertility, or endometrial carcinoma. Our prior studies showed that gap junctions comprised of Gap junction alpha-1 (GJA1) protein, also known as connexin 43 (CX43), subunits are critical to endometrial stromal cell differentiation. The current studies were undertaken to explore the mechanism of endometrial dysfunction when gap junction intercellular communication (GJIC) is disrupted. Gap junction blockade by two distinct GJIC inhibitors, 18α-glycyrrhetinic acid (AGA) and octanol (OcOH), suppressed proliferation and induced apoptosis in endometrial stromal cells, as manifested by reduced biomarkers of cell viability, increased TUNEL staining, caspase-3 activation, sub-G1 chromosomal DNA complement, as well as shortened telomere length. Unexpectedly, we also observed that the chemical inhibitors blocked CX43 gene expression. Moreover, when endometrial stromal cells were induced to undergo hormonal decidualization, following a 7-day exposure to 10 nM 17β-estradiol + 100 nM progesterone + 0.5 mM dibutyryl cAMP, characteristic epithelioid changes in cell shape and secretion of prolactin were blunted in the presence of AGA or OcOH, recapitulating effects of RNA interference of CX43. Our findings indicate that endometrial stromal cell proliferation and maintenance of decidualized endometrial function are GJIC-dependent, and that disruption of gap junctions induces endometrial stromal cell apoptosis. These observations may have important implications for several common clinical endometrial pathologies. Mol. Reprod. Dev. 81: 666–675, 2014. © 2014 Wiley Periodicals, Inc.

With growing environmental awareness, natural fibers have recently received significant interest as reinforcement in polymer composites. Among natural fibers, silk can potentially be a natural alternative to glass fibers, as it possesses comparable specific mechanical properties. In order to investigate the processability and properties of silk reinforced composites, vacuum assisted resin transfer molding (VARTM) was used to manufacture composite laminates reinforced with woven silk preforms. Specific mechanical properties of silk/epoxy laminates were found to be anisotropic and comparable to those of glass/epoxy. Silk composites even exhibited a 23% improvement of specific flexural strength along the principal weave direction over the glass/epoxy laminate. Applying 300 kPa external pressure after resin infusion was found to improve the silk/epoxy interface, leading to a discernible increase in breaking energy and interlaminar shear strength. Moreover, the effect of fabric moisture on the laminate properties was investigated. Unlike glass mats, silk fabric was found to be prone to moisture absorption from the environment. Moisture presence in silk fabric prior to laminate fabrication yielded slower fill times and reduced mechanical properties. On average, 10% fabric moisture induced a 25% and 20% reduction in specific flexural strength and modulus, respectively.

The level structures of the N = 50 83As, 82Ge, and 81Ga isotones have been investigated by means of multi-nucleon transfer reactions. A first experiment was performed with the CLARA–PRISMA setup to identify these nuclei. A second experiment was carried out with the GASP array in order to deduce the γ-ray coincidence information. The results obtained on the high-spin states of such nuclei are used to test the stability of the N = 50 shell closure in the region of 78Ni ( Z = 28 ). The comparison of the experimental level schemes with the shell-model calculations yields an N = 50 energy gap value of 4.7(3) MeV at Z = 28 . This value, in a good agreement with the prediction of the finite-range liquid-drop model as well as with the recent large-scale shell model calculations, does not support a weakening of the N = 50 shell gap down to Z = 28 .

A. I. Morales et al.; 14 págs.; 9 figs.; 3 tabs., Low-lying excited states in Ni72 have been investigated in an in-flight fission experiment at the RIBF facility of the RIKEN Nishina Center. The combination of the state-of-the-art BigRIPS and EURICA setups has allowed for a very accurate study of the β decay from Co72 to Ni72, and has provided first experimental information on the decay sequence Fe72→Co72→Ni72 and on the delayed neutron-emission branch Co73→Ni72. Accordingly, we report nearly 60 previously unobserved γ transitions which deexcite 21 new levels in Ni72. Evidence for the location of the so-sought-after (42+),(62+), and (81+) seniority states is provided. As well, the existence of a low-spin β-decaying isomer in odd-odd neutron-rich Co isotopes is confirmed for mass A=72. The new experimental information is compared to simple shell-model calculations including only neutron excitations across the fpg shells. It is shown that, in general, the calculations reproduce well the observed states. ©2016 American Physical Society, The excellent work of the RIKEN accelerator staff for providing a stable and high-intensity 238U beam is acknowledged. Part of he WAS3ABi was supported by the Rare Isotope Science Project, which is funded by the Ministry of Science, ICT and Future Planning (MSIP) and National Research Foundation (NRF) of Korea. This work is cofinanced by the European Union and the European Social Fund. Support from italian Programmi di Ricerca Scientifica di Rilevante Interesse Nazionale (PRIN) Grant No. 2001024324_01302, the NuPNET-ERANET within the NuPNET GANAS project under Grant Agreement No. 202914, and the European Union within the 7th Framework Program FP7/2007-2013 under Grant Agreement No. 262010 ENSAR-INDESYS is acknowledged. This work was also financed by the Spanish Ministerio de Ciencia e Innovación under ContractsNo. FPA2009-13377-C02 and No. FPA2011-29854-C04, the Hungarian Research Fund OTKA Contract No. K100835 and No. K106035, the European Commission through the Marie Curie Actions Contract No. PIEFGA-2001-30096, and by the Japanese JSPS KAKENHI Grants No. 24740188 and No. 25247045

Exposures to sex steroids during fetal development are thought to contribute to the unique urogenital anatomy and social dominance of the female spotted hyena: overt phenotypes not shared by other hyenids (i.e. striped hyena, brown hyena, and aardwolf). Because both androgens and estrogens influence development of genitalia and behavior, and because plasma SHBG regulates their access to tissues, we compared the Shbg gene sequences, structures, and steroid-binding properties in the four extant hyenids. We found the hyenid Shbg genes (>95% identical) and mature protein sequences (98% identical) are highly conserved. As in other mammals, the hyenid SHBG all bind 5α-dihydrotestosterone with high affinity (Kd = 0.62–1.47 nm), but they also bind estrone and dehydroepiandrosterone with similarly high affinity, and this unusual property was attributed to specific amino acids within their SHBG steroid-binding sites. Phylogenetic comparisons also indicated that the spotted hyena SHBG precursor uniquely lacks two leucine residues and has a L15W substitution within its secretion signal polypeptide, the reduced size and hydrophobicity of which markedly decreases the production of SHBG and may therefore explain why serum SHBG concentrations in male and female spotted hyenas are approximately five times lower than in other hyenids. This is important because low plasma SHBG concentrations in spotted hyenas will increase exposure to biologically active androgens and estrogen as well as to their precursors (dehydroepiandrosterone and estrone), which may contribute to the masculinized external genitalia of female spotted hyenas and to female social dominance over males.

6 pags.; 4 figs.; This is an open access article under the CC BY license. Funded by SCOAP, © 2015 The Authors. The β decays Mn68→Fe68, Mn69→Fe69 and Mn70→Fe70 have been measured at the RIBF facility at RIKEN using the EURICA γ spectrometer combined with an active stopper consisting of a stack of Si detectors. The nuclei were produced as fission fragments from a beam of 238U at a bombarding energy of 345 MeV/nucleon impinging on a Be target and selected using the BigRIPS separator. Half-lives and β-delayed neutron emission probabilities have been extracted for these decays, together with first experimental information on excited states populated in 69,70Fe. The data indicate a continuously increasing deformation for Fe isotopes up to A=70. This is interpreted, as for Cr isotopes, in terms of the interplay between the quadrupole correlations of the ν1d5/2 and ν0g9/2 orbitals and the monopole component of the π0f7/2-ν0f5/2 interaction., The project is co-financed by the European Union and the European Social Fund. This work was supported by NuPNET-ERANET within the NuPNET GANAS project, under grant agreement No. 202914 and from the European Union, within the 7th Framework Program FP7/2007-2013, under grant agreement No. 262010 ENSAR-INDESYS. This work was also supported by Programmi di Ricerca Scientifica di Rilevante Interesse Nazionale (PRIN) number 2001024324_01302. We here acknowledge support from the Spanish Ministerio de Ciencia e Innovación under Contracts No. FPA2009-13377-C02 and No. FPA2011-29854-C04, the Hungarian Research Fund OTKA contract numbers K100835 and NN104543, the European Commission through the Marie Curie Actions Contract No. PIEFGA-2001-30096 and by Japanese JSPS KAKENHI Grants No. 24740188 and No. 25247045.

Study Objective To evaluate the use of a technique consisting of culdocentesis followed by saline solution–enhanced pelvic ultrasonography in cases suspect for ectopic pregnancy in which an accurate diagnosis could not be made using routine transvaginal ultrasound. Design Retrospective clinical study (Canadian Task Force classification III). Setting Academic medical center. Patients Twenty patients with an initial diagnosis of pregnancy of unknown location. Interventions In 20 patients with symptoms of early pregnancy and serum quantitative human chorionic gonadotropin concentration, ectopic pregnancy could not be confirmed or ruled out. Transvaginal ultrasound-guided culdocentesis was performed, and 300 to 400 mL of normal saline solution was injected into the posterior cul-de-sac and pelvis. Transvaginal ultrasound was repeated with particular attention to the floating fallopian tubes Measurements and Main Results Using this technique, a tubal pregnancy was visualized in 15 of 20 patients, and ectopic pregnancy was ruled out in 5 patients. In all patients, appropriate management was provided according to the final diagnosis, and consisted of either methotrexate, laparoscopic salpingostomy or salpingectomy, or expectant management in patients with abnormal intrauterine pregnancies. Conclusion Ultrasound-guided culdocentesis followed by saline solution–enhanced pelvic ultrasound can be considered as a diagnostic tool in patients with suspected ectopic pregnancy in whom other methods fail to demonstrate this diagnosis.

To compare the effectiveness of hysterectomy and endometrial ablation in women with dysfunctional uterine bleeding.The Surgical Treatments Outcomes Project for Dysfunctional Uterine Bleeding was a multicenter, randomized controlled trial. Eligible women were premenopausal with dysfunctional uterine bleeding and aged 18 years or older. Primary outcomes were problems that led the woman to seek care solved, bleeding, pain, and fatigue at 12 months. Additional outcomes included quality of life, adverse events, reoperation, and others at 24 months and up to 5 years.We randomly assigned 237 women between January 1998 and June 2001. Follow-up ended in June 2003. We completed 24 months of follow-up on 114 of 123 women assigned to endometrial ablation and 111 of 114 assigned to hysterectomy. Approximately 85% of women were aged younger than 45 years; 76.4% classified themselves as white, 18.6% as African American, less than 1% as Asian, 4.6% as American Indian, and 8.4% as Hispanic (classification within more than one category possible). Both endometrial ablation and hysterectomy were effective at 24 months in solving the problem that led women to seek care (84.9% compared with 94.4%), and in relieving bleeding, pain, fatigue, and other symptoms, although hysterectomy was more effective for bleeding. By 48 months, 32 of the 110 women initially receiving endometrial ablation required reoperation. Adverse events were more frequent with hysterectomy.Both endometrial ablation and hysterectomy are effective treatments in women with dysfunctional uterine bleeding. Hysterectomy (as the index surgery) was associated with more adverse events and a substantial number of patients receiving endometrial ablation had reoperation.ClinicalTrials.gov, www.clinicaltrials.gov, NCT00114088I.

The complete valence shell photoelectron spectrum of tetrafluoromethane has been recorded using synchrotron radiation and the observed structure has been interpreted using ionisation energies and relative spectral intensities computed using the third-order algebraic-diagrammatic-construction (ADC(3)) scheme for the one-particle Green’s function and the outer valence Green’s function (OVGF) method. The ADC(3) calculations were performed using both the original variant based on the Dyson equation and the recently proposed non-Dyson scheme. The theoretical predictions for the single-hole ionic states due to outer valence shell ionisation agree satisfactorily with the experimental results. Ionisation from the inner valence 2t2 and 3a1 orbitals is strongly influenced by reorganisation effects and the intensity is spread amongst numerous satellites. Highly resolved spectra have been measured for the C ∼ 2 T 2 and the D ∼ 2 A 1 states, and the vibrational structure has been associated primarily with excitation of the ν 1 + ( a 1 ) mode. However, the analyses also provide evidence for excitation of the Jahn-Teller active ν 2 + ( e ) mode in the C ∼ 2 T 2 state, and the ν 3 + ( t 2 ) mode in the D ∼ 2 A 1 state. Excitation of this latter mode can be explained in terms of vibronic coupling between the C ∼ 2 T 2 and the D ∼ 2 A 1 states. Photoelectron angular distributions and branching ratios have been determined and demonstrate that shape resonances affect the outer valence shell photoionisation dynamics. The experimental results are compared with previous theoretical predictions but a consistent interpretation has not been obtained. The major difficulty concerns the uncertainty in the locations of valence shell transitions into the 5a1 and the 5t2 virtual orbitals.

BACKGROUND: Tubal ectopic pregnancy can be surgically treated by salpingectomy, in which the affected Fallopian tube is removed, or salpingotomy, in which the tube is preserved. Despite potentially increased risks of persistent trophoblast and repeat ectopic pregnancy, salpingotomy is often preferred over salpingectomy because the preservation of both tubes is assumed to offer favourable fertility prospects, although little evidence exists to support this assumption. We aimed to assess whether salpingotomy would improve rates of ongoing pregnancy by natural conception compared with salpingectomy.METHODS: In this open-label, multicentre, international, randomised controlled trial, women aged 18 years and older with a laparoscopically confirmed tubal pregnancy and a healthy contralateral tube were randomly assigned via a central internet-based randomisation program to receive salpingotomy or salpingectomy. The primary outcome was ongoing pregnancy by natural conception. Differences in cumulative ongoing pregnancy rates were expressed as a fecundity rate ratio with 95% CI, calculated by Cox proportional-hazards analysis with a time horizon of 36 months. Secondary outcomes were persistent trophoblast and repeat ectopic pregnancy (expressed as relative risks [RRs] with 95% CIs) and ongoing pregnancy after ovulation induction, intrauterine insemination, or IVF. The researchers who collected data for fertility outcomes were masked to the assigned intervention, but patients and the investigators who analysed the data were not. All endpoints were analysed by intention to treat. We also did a (non-prespecified) meta-analysis that included the findings from the present trial. This trial is registered, number ISRCTN37002267.FINDINGS: 446 women were randomly assigned between Sept 24, 2004, and Nov 29, 2011, with 215 allocated to salpingotomy and 231 to salpingectomy. Follow-up was discontinued on Feb 1, 2013. The cumulative ongoing pregnancy rate was 60·7% after salpingotomy and 56·2% after salpingectomy (fecundity rate ratio 1·06, 95% CI 0·81-1·38; log-rank p=0·678). Persistent trophoblast occurred more frequently in the salpingotomy group than in the salpingectomy group (14 [7%] vs 1 [INTERPRETATION: In women with a tubal pregnancy and a healthy contralateral tube, salpingotomy does not significantly improve fertility prospects compared with salpingectomy.FUNDING: Netherlands Organisation for Health Research and Development (ZonMW), Region Västra Götaland Health & Medical Care Committee.

Specific alterations in the pulsatility of luteinizing hormone (LH) are linked to obesity-related subfertility in ovulatory women. Vervet monkeys (Chlorocebus aethiops sabaeus) are an Old World nonhuman primate that develops obesity and has a menstrual cycle similar to humans. We evaluated follicular-phase LH pulses in 12 adult normal-weight female vervets. Serum was collected every 10 min for 4 h by using a tether device in conscious, freely moving monkeys on menstrual cycle days 2 through 5. Serum estradiol was collected daily during the follicular phase to identify the luteal–follicular transition. For comparison, we used data from 12 ovulatory normal-weight women who had undergone frequent blood sampling of early-follicular LH. LH pulse frequency was similar, with 2.8 ± 0.7 LH pulses during 4 h in vervets compared with 2.3 ± 0.7 LH pulses during 4 h in women. The LH pulse mass (percentage change in the pulse peak over the preceding nadir) was 123.2% ± 27.4% in vervets and 60.9% ± 14.9% in humans. The first day of low serum estradiol after the follicular-phase peak was denoted as the day of the luteal–follicular transition. Luteectomy was performed on luteal days 7 through 9, and corpora lutea were confirmed by histology. We demonstrate that follicular LH patterns in vervets are similar to those in humans and that the luteal phase is easily identified by monitoring daily serum estradiol. These findings demonstrate that vervet monkeys are a suitable animal model for evaluating LH pulse dynamics longitudinally in studies of diet-induced obesity.

The goal of regenerative medicine is to repair, replace, or regenerate diseased tissues/organs in order to restore normal function. In this paper we will first discuss the general principle of regenerative medicine and the various techniques and approaches that have been used to replace or regenerate cells in diseased tissues and organs. Then, we will review different regenerative medicine approaches that have been used to treat specific diseased tissues and organs of the reproductive system in both animal and human experiments. It is clear from this article that regenerative medicine holds significant promise, and we hope that the review will serve as a platform for further development of regenerative medicine technologies for the treatment of inadequacies of the reproductive system.

Symptomatic cesarean scar defect is one of the commonly reported long-term complications of cesarean section.We present two cases of symptomatic cesarean scar defect treated conservatively by robotic-assisted laparoscopy at our institution. Both patients presented with hematocele, pelvic discomfort and secondary infertility. Transvaginal ultrasound revealed hematocele measuring 3.7 x 1.9 x 3.8 cm and 3.0 x 2.0 x 1.6 cm in the lower uterine segments, respectively. After surgery normal menses resumed in both patients, and their childbearing potential was preserved. The patients conceived 3 and 11 months after surgery, respectively.Recognition of cesarean scar defect is important in the explanation of certain menstrual disorders since surgical intervention can result in improvement of symptoms and prevent the related secondary obstetric and gynecologic complications. Robotic-assisted laparoscopic approach is a good minimally invasive alternative for the repair of cesarean scar defect.

Severe postovum retrieval complications such as tuboovarian abscess are rare. We present an early pelvic infection case following egg retrieval.A 31-year-old woman with unexplained infertility developed early pelvic infection subsequent to transvaginal oocyte retrieval (TVOR). Broad spectrum antibiotics were administered. Upon persistence of fever and ultrasonographic appearance of probable abscess, transvaginal ultrasound-guided drainage was performed on post-TVOR day 9 as well as posterior colpotomy and T-drain replacement into the cul de sac. Signs and symptoms of pelvic infection improved following drain replacement. Her beta-hCG was found to be positive in the following days. Drain was removed after 3 weeks. Her pregnancy follow-up was uncomplicated. She delivered a healthy baby vaginally at 38 gestational weeks.Early diagnosis with prompt administration of antibiotics and drainage may prevent poor pregnancy outcome in ovarian abscess patients subsequent to transvaginal oocyte retrieval.

Objective To describe a technique for frozen-banked ovarian tissue transplantation using robotic-assisted laparoscopy. Design Case study. Setting Academic tertiary care center. Patient(s) A 38-year-old patient in remission for non-Hodgkin lymphoma, whose ovarian tissue had been frozen for 3 years. Intervention(s) Robotic-assisted laparoscopic transplantation of thawed ovarian cortical tissue to the remaining ovary and peritoneum. Main Outcome Measure(s) Resumption of spontaneous menses, follicular development, and ovulation as demonstrated by ultrasound, and serum E 2 and P levels. Result(s) The patient experienced cyclic spontaneous menstruation 6 months after the transplantation. Ovulation was confirmed by ultrasound and serum E 2 and P levels at month 11 after surgery. Conclusion(s) Robotic-assisted laparoscopic surgery may be a good, minimally invasive alternative for the ovarian tissue transplantation procedure to restore ovarian function.

To report our experience of conservative treatment in four patients with cervical ectopic pregnancy.Case series.Academic medical center.Four women diagnosed with cervical ectopic pregnancy managed conservatively.Systemic methotrexate alone or combined with subsequent uterine artery embolization (UAE).Conservative management with decreased rate of serious complications.No hysterectomies were needed. One patient required subsequent intervention, UAE.Conservative treatment of cervical pregnancy might be successful with careful follow up and subsequent conservative interventions.

Concentrations of androgens (androstenedione, testosterone, 5 alpha-dihydrotestosterone), oestrogen and progesterone were measured in relation to pregnancy in the spotted hyaena (Crocuta crocuta). The gestation period was estimated to be about 110 days. There was a marked progressive rise in all the steroids starting in the first third of gestation. Chromatographic separation of plasma showed that much of the oestrogen is not oestradiol (only 12% of total measured) and that a significant fraction of the 'testosterone' may be dihydrotestosterone. In the final third of pregnancy, concentrations of androgen (especially testosterone plus dihydrotestosterone) in the female circulation reached the maximal values of adult males; the percentage of dihydrotestosterone relative to total testosterone plus dihydrotestosterone was higher in females (44 +/- 3.9%, n = 20) than in males (29.5 +/- 3.5%, n = 17). Plasma androstenedione was also significantly higher in females, but the increment was less than for oestrogen, testosterone and progesterone, and the temporal pattern was less clear. Samples from the maternal uterine and ovarian circulation showed that androstenedione is largely of ovarian origin and metabolized by the placenta, while testosterone, progesterone and oestrogen are primarily of placental or uterine origin. Fetal samples were taken from two mixed-sex sets of twins and one male singleton. Gradients across the placenta measured in the fetal circulation confirmed that the placenta metabolizes androstenedione and is a source of testosterone for the female fetus; there were no consistent differences in androgens between male and female fetuses. It is suggested that the conspicuous masculinization of the female spotted hyaena, especially evident in the external genitalia at birth, is a result, at least in part, of high placental production of testosterone or dihydrotestosterone derived from the metabolism of high maternal androstenedione.