Fitting Multiplet Simulations to L-Edge XAS Spectra of Transition-Metal Complexes Using an Adaptive Grid Algorithm.

A new methodology based on an adaptive grid algorithm followed by an analysis of the ground state from the fit parameters is presented to analyze and interpret experimental XAS L2,3-edge data. The fitting method is tested first in a series of multiplet calculations for d0-d7 systems and for which the solution is known. In most cases, the algorithm is able to find the solution, except for a mixed-spin Co2+ Oh complex, where it instead revealed a correlation between the crystal field and the electron repulsion parameters near spin-crossover transition points. Furthermore, the results for the fitting of previously published experimental data sets on CaO, CaF2, MnO, LiMnO2, and Mn2O3 are presented and their solution discussed. The presented methodology has allowed the evaluation of the Jahn-Teller distortion in LiMnO2, which is consistent with the observed implications in the development of batteries, which use this material. Moreover, a follow-up analysis of the ground state in Mn2O3 has demonstrated an unusual ground state for the highly distorted site which would be impossible to optimize in a perfect octahedral environment. Ultimately, the presented methodology can be used in the analysis of X-ray absorption spectroscopy data measured at the L2,3-edge for a large number of materials and molecular complexes of first-row transition metals and can be expanded to the analysis of other X-ray spectroscopic data in future studies.

How soon should urgent EEG be performed following a first epileptic seizure?

PURPOSE: Patients with a first unprovoked epileptic seizure are often seen in emergency services. Electroencephalography (EEG) is indicated for diagnosing epilepsy, but the optimal time to perform this test has not been defined. This study aimed to determine the time interval following a seizure within which EEG has the greatest diagnostic yield. METHODS: We conducted a retrospective study of all adult patients with a first unprovoked seizure who had undergone emergency EEG (July 2014-December 2019). Data collection included demographics, seizure type, time interval to EEG study, EEG pattern identified, and the prescription after emergency assessment. An optimal cut-off point for time to EEG was obtained, and an adjusted regression model was performed to establish associations with the presence of epileptiform abnormalities. RESULTS: A total of 170 patients were included (mean age: 50.7 years, 40.6% women). Epileptiform discharges were identified in 34.1% of recordings, nonepileptiform abnormalities in 46.5%, and normal findings in 19.4%. A lower latency from seizure to EEG was associated with a higher probability of finding epileptiform discharges (median: 12.7 in the epileptiform EEGs vs. 20 h in the nonepileptiform EEGs, p < 0.001). The time interval associated with the highest probability of detecting an epileptiform EEG pattern was within the first 16 h after seizure onset: 52.1% of recordings performed before the 16-h cut-off showed these abnormal patterns compared with 20.2% performed after (p < 0.001). These findings were not related to the presence of an epileptogenic lesion in neuroimaging or to other clinical variables. The finding of epileptiform abnormalities was followed by a greater prescription of antiseizure drugs (96.4% vs. 66% in nonepileptiform patterns, p < 0.001). CONCLUSION: The diagnostic yield of EEG following a first unprovoked epileptic seizure is highest when this test is performed within the first 16 h after onset of the event.

Galactose-α-1,3-galactose (alpha-gal) allergy: first pediatric case in a series of patients in Spain.

INTRODUCTION AND OBJECTIVES: Allergy to galactose-α-1,3-galactose (alpha-gal) is a peculiar form of food allergy generally manifesting as an anaphylactic reaction hours after mammalian meat consumption, due to the presence of specific IgE against this oligosaccharide. In addition, immediate anaphylaxis may develop after exposure to other sources of alpha-gal, such as monoclonal antibody cetuximab, vaccines, plasma expanders or anti-snake venoms. Sensitization to alpha-gal has also been implicated in the rapid degeneration of biological valve implants, and recognized as a cause of occupational disease in cattle raisers. The implication of tick bites in this type of sensitization has been accepted by all the research groups dedicated to this disease. PATIENTS AND METHOD: The present study describes the clinical and sensitization characteristics of 39 patients diagnosed with alpha-gal allergy in the hospitals of our province (Lugo, Monforte de Lemos and Burela, Spain). RESULTS: Most patients were middle-age males. Of note, is the fact that the series includes the first pediatric patient reported in Spain to date. The predominant clinical manifestations were urticaria or delayed anaphylaxis after consumption of mammalian meat. Seventy-four percent of the patients reported having suffered a previous tick bite, and the clinical presentation of anaphylaxis was significantly more prevalent in those with a persistent local reaction following the bite than in those with no such reaction (p = 0.032). CONCLUSIONS: A review is also made of the disorder which, due to its variable clinical expression, is referred to as alpha-gal syndrome. The study concludes that a diagnosis of alpha-gal allergy should be considered in patients with urticaria-anaphylaxis of uncertain origin or manifesting after the administration of vaccines or products of bovine/porcine origin.

Risk factors for Clostridium difficile infection in intestinal transplant recipients during the first year post-transplant.

BACKGROUND: Clostridium difficile is the most common cause of healthcare-associated infectious diarrhea. Risk factors for C. difficile infections (CDI) in intestinal transplant recipients (ITR) are not well-defined. The aim of our study was to assess specific risk factors for CDI in ITR. METHODS: This is a 1:3 case-control study that included 29 ITR who developed CDI (cases) and 87 ITR without CDI (controls) observed during the first year post-transplantation. Wilcoxon rank sum and Fisher's exact tests were used to compare variables. Univariate and multivariable conditional logistic regressions analysis were performed to identify risk factors for CDI. RESULTS: The multivariable conditional logistic regression analysis showed that proton pump inhibitors (PPI) administration (odds ratio [OR] = 0.06; 95% confidence interval [CI]: 0.007-0.52; P = .01) was the only factor associated with lower rates of CDI. Outcomes for cases vs controls: rejection episodes 24.14% vs 20.69% (P = .7), graft loss 0% vs 2.3% (P = .99), and survival rate 1 year post-transplantation 79.3% (59.6-90.1%) vs 87.2% (78.1-92.7%) (P = .38). CONCLUSIONS: Proton pump inhibitor administration might be protective for CDI in ITR. Risks factors for CDI might be different in ITR compared to other populations; anatomical differences and medications administered in the post-transplantation period may affect intestinal microbiota.

Prognosis of status epilepticus in elderly patients.

PURPOSE: To evaluate the clinical features and prognosis of status epilepticus (SE) in patients above 70 years old. METHODS: Retrospective analysis of all patients ≥70 years old with SE registered prospectively during 4 years. Follow-up after discharge was performed. RESULTS: Ninety patients were evaluated. Acute symptomatic etiology was the most prevalent. The mean number of antiepileptic drugs (AEDs) used was 2.7 ± 1.2, and 21% of the patients required sedation. A poor outcome was considered when death (31.1%) or developing of new neurological impairment at discharge (32.2%) occurred. After multivariate analysis, four variables predicted a poor outcome: acute symptomatic etiology (OR: 6.320; 95% CI: 1.976-20.217; P = .002), focal motor SE type (OR: 9.089; 95% CI: 2.482-33.283; P = .001), level of consciousness (OR: 4.596; 95% CI: 1.903-11.098; P = .001), and SE duration >12 hours (OR: 3.763; 95% CI: 1.130-12.530; P = .031). Independent predictive factors of mortality were SE duration >12 hours (OR: 4.306; 95% CI: 1.044-17.757; P = .043), modified Status Epilepticus Severity Score (mSTESS) (OR: 2.216; 95% CI: 1.313-3.740; P = .003), and development of complications (OR: 3.334; 95% CI: 1.004-11.070, P = .049). Considering long-term mortality, age (HR 1.036; 95% CI 1.001-1.071; P = .044), a potentially fatal underlying cause (HR 2.609; 95% CI 1.497- 4.548; P = .001), and mSTESS score >4 (HR 1.485; 95% CI 1.158-1.903; P = .002) remained as predictive factors. There was no association between sedation and the number of AEDs used with outcome at discharge or long-term mortality (P > .05). CONCLUSIONS: SE above 70 years old has a high morbimortality. Prognosis is not related to treatment aggressiveness.

Seroprevalence and risk factors associated with Brucella seropositivity in dairy and mixed cattle herds from Ecuador.

An extensive cross-sectional study to determine the seroprevalence of and associated risk factors for Brucella infection was performed in dairy and mixed (dairy-beef) cattle herds in Ecuador. A total of 2666 serum samples from 386 farms were analyzed using Rose Bengal test and a blocking ELISA test. In addition, a questionnaire with 57 variables related to management, feeding, facilities, biosecurity, and animal health was filled in every cattle farm. A Generalized Estimating Equations model was used to determine the factors associated with Brucella seropositivity. The true prevalence of Brucella seropositivity in dairy and mixed cattle from Ecuador reached 17.0% (CI95% 15.6-18.4%). The herd prevalence was 45.1% (174/386) (CI95% 40.1-50.1%), and the within-herd prevalence ranged from 10 to 100% (mean 38.9%; Q1 14.3%, Q2 26.8%, Q3 52.5%). Seven factors were included in the GEE model for Brucella seropositivity: the nominal variables sex (OR 2.03; CI95% 1.32-3.13), herd type (dairy) (OR 1.79; CI95% 1.11-2.87), closed facilities in the farm (OR 1.80; CI95% 1.19-2.74), and ad libitum feeding (OR: 0.32; CI95%: 0.19-0.54), and the quantitative variables age (OR 1.005; CI95% 1.001-1.009), average slope in the farm (%) (OR 1.013; CI95% 1.002-1.024), and annual abortion rate (OR 1.016; CI95% 1.002-1.031). This study remarks the high spread of Brucella infection in cattle farms from Ecuador. In addition, it reports the risk factors associated to this infection in the predominant extensive system existent in this country.

A Biradical Balancing Act: Redox Amphoterism in a Diindenoanthracene Derivative Results from Quinoidal Acceptor and Aromatic Donor Motifs.

The reduced and oxidized states of an open-shell diindeno[b,i]anthracene (DIAn) derivative have been investigated by experimental and theoretical techniques. As a result of moderate biradical character and the ability of cyclopenta-fused scaffolds to stabilize both positive and negative charges, DIAn exhibits rich redox chemistry with four observable and isolable charged states. Structural and electronic properties of the DIAn system are brought to light by UV-vis-NIR and Raman spectroelectrochemical measurements. Aromatization of the diindeno-fused anthracene core upon successive single-electron injections is revealed through single-crystal X-ray diffraction of radical anion and dianion salts. We present a rare case where the pseudoaromatic/quinoidal ground state of a neutral biradical polycyclic hydrocarbon leads to a stable cascade of five redox states. Our detailed investigation of the transformation of molecular structure along all four redox events provides a clearer understanding of the nature of charge carriers in ambipolar organic field-effect transistors.

The effect of frequency-dependent selection on resistance and tolerance to herbivory.

Negative frequency-dependent selection (FDS), where rare genotypes are favoured by selection, is commonly invoked as a mechanism explaining the maintenance of genetic variation in plant defences. However, empirical tests of FDS in plant-herbivore interactions are lacking. We evaluated whether the oviposition preference of the specialist herbivore Lema daturaphila is a mechanism through which this herbivore can exert FDS on its host plant Datura stramonium. The frequency of contrasting resistance-tolerance strategies was manipulated within experimental plots, and the plants were exposed to a similar initial density of their natural herbivore. Herbivore oviposition preference and final density, as well as plant damage and seed production, were estimated. Overall, we found that the high-resistant-low-tolerant genotypes produced four times more seeds when common than when rare, whereas the high-tolerant-low-resistant genotypes achieved twice its fitness when rare than when common. This pattern was the result of differential oviposition preferences. In addition, when the high-resistant-low-tolerant genotypes were common, there was a three-fold decreased in herbivore final density which led to a decrease in damage level by 10%. Thus, in our experiment positive FDS seems to favour resistance over tolerance. We discuss how this result would change if the extent of herbivore local adaptation and damage modify the pattern of positive FDS acting on resistance and the optimal allocation to tolerance.

A new clinical score for the prognosis of status epilepticus in adults.

BACKGROUND AND PURPOSE: The severity of status epilepticus (SE) has an important impact in clinical outcomes. The Status Epilepticus Severity Score (STESS) is a score for predicting mortality in SE at admission. The baseline modified Rankin Scale (mRS) might be a prognostic factor for assessing the short-tem outcomes of SE. Therefore, our aim was to evaluate the effectiveness of mRS and whether its addition to the STESS improves the prediction of mortality. METHODS: Consecutive patients with SE and aged >16 years were recruited during 3 years. Receiver operating characteristic curves and a logistic regression model were developed to estimate the scores of the new score, designated as modified STESS (mSTESS), and it was subsequently compared with the STESS. RESULTS: In all, 136 patients were included. Mean age was 62.01 ± 17.62 (19-95) years, and 54% were male. The capacity of the STESS to predict mortality was 74.3% (95% confidence interval 63.8%-81.8%), whilst the capacity of the mRS to predict mortality was 65.2% (95% confidence interval 54.2%-76.2%). The logistic regression model and receiver operating characteristic curves enabled the classification of mRS as follows: 0, mRS = 0; 1, mRS = 1-3; and 2, mRS > 3. These values, when added to the other items of the STESS, resulted in the mSTESS with scores between 0 and 8 points. The capacity of the mSTESS to predict mortality was 80.1%. An mSTESS > 4 established an overall accuracy of 81.8% for predicting mortality, which was considerably higher than the overall accuracy of STESS ≥ 3 (59.6%). CONCLUSIONS: The baseline mRS was associated with high mortality risk. It is proposed to use mSTESS to improve the prediction of mortality risk in SE.

Multifaceted Regioregular Oligo(thieno[3,4-b]thiophene)s Enabled by Tunable Quinoidization and Reduced Energy Band Gap.

Thiophene-based materials have occupied a crucial position in the development of organic electronics. However, the energy band gaps of oligo- and polythiophenes are difficult to modulate without resorting to push-pull electronic effects. We describe herein a new series of monodisperse oligo(thieno[3,4-b]thiophene) derivatives with well-defined regioregular structures synthesized efficiently by direct C-H arylation. These compounds show a unique palette of colors and amphoteric redox properties with widely tunable energy band gaps. The capacity to stabilize both cations and anions results in both anodic and cathodic electrochromism. Under excitation, these compounds can produce photoionized states able to interconvert into neutral triplet or form these through singlet exciton fission or intersystem crossing. These features arise from a progressive increase in quinoidization on a fully planar platform making the largest effective conjugation length among hetero-oligomers. Oligo(thieno[3,4-b]thiophene)s might represent the more distinctive family of oligothiophenes of this decade.

Chromosome constitution of human embryos generated after in vitro maturation including 3-isobutyl-1-methylxanthine in the oocyte collection medium.

STUDY QUESTION: Do cleavage-stage embryos obtained from oocytes matured in vitro after pre-incubation with a phosphodiesterase inhibitor (IBMX) carry more chromosomal abnormalities than those generated from oocytes matured in vivo? SUMMARY ANSWER: The rate and type of chromosomal abnormalities in normally developing cleavage-stage embryos generated with an in vitro maturation (IVM) system including pre-incubation with IBMX are not different from those observed in supernumerary embryos obtained from oocytes matured in vivo. WHAT IS KNOWN ALREADY: Very limited information is available about the chromosomal constitution of IVM embryos. Previous studies were carried out using FISH on single biopsied blastomeres or arrested whole embryos and only provided fragmentary information on chromosomal abnormalities in IVM embryos. There is no systematic study of chromosomal abnormalities in all blastomeres of human Day 3 embryos with good morphology. STUDY DESIGN, SIZE, DURATION: Between July 2012 and December 2012, 16 young (age <35 years old) egg donors underwent 18 IVM cycles for the generation of research embryos. Eighteen embryos developed to Day 3 and were analysed using array comparative genomic hybridization (aCGH). PARTICIPANTS/MATERIALS, SETTING, METHODS: Immature oocytes were retrieved from 2 to 10 mm follicles after mild ovarian stimulation with gonadotrophins but without hCG ovulation trigger. At collection, oocytes were pre-incubated with 3-isobutyl-1-methylxanthine (IBMX), a phosphodiesterase inhibitor and matured in vitro. After IVM culture, mature oocytes were microinjected with sperm from a single donor. Embryos were cultured to Day 3 after ICSI and all blastomeres of 18 good-morphology embryos were collected individually for aCGH. MAIN RESULTS AND THE ROLE OF CHANCE: Oocyte maturation rate in vitro was 50.2% (120/239). The mean fertilization rate was 68.3% (82/120) and 30.5% (25/82) of fertilized oocytes developed into a morphologically good quality embryo on Day 3 after ICSI. Of these, 18 embryos that developed well up to Day 3 were analysed using aCGH. Eighty of the 123 blastomeres analysed showed at least one chromosomal abnormality. Three out of eighteen embryos had completely normal cells. A single embryo carried a meiotic abnormality, 11 embryos were mosaic and three were chaotic. Although the aneuploidy data of this study are too limited to allow statistical analysis, these data are comparable to our own published data on the chromosome constitution of whole day 3 and day 4 embryos after conventional ART. LIMITATIONS, REASONS FOR CAUTION: Array CGH technology determines relative quantification of chromosomal domains but does not allow for the visualization of chromosomal rearrangements, assessment of ploidy or detection of uniparental isodisomy. Conclusions drawn on segmental abnormalities should be treated with caution. Although the limited number of embryos analysed here precludes firm conclusions, they provide valuable data on possible causes of the reduced potential of IVM embryos. WIDER IMPLICATIONS OF THE FINDINGS: This is the first study to describe the complete chromosome complement of all single blastomeres of good-morphology day 3 embryos obtained with IVM (including the presence of IBMX in a pre-incubation medium). The results demonstrate that a high proportion of good-morphology embryos are aneuploid and that there is no obvious increase in aneuploidies as a result of IVM which seems to suggest that the reduced efficiency of IVM technology compared with standard IVF may be accounted for by factors other than aneuploidy, such as cytoplasmic defects or reduced endometrial receptivity. STUDY FUNDING/COMPETING INTERESTS: This study was funded by the TBM (Applied Biomedical Research with Societal Finality) programme of the IWT (Agency for Innovation through Science and Technology - Flanders, 110680) and by a Methusalem grant of the Vrije Universiteit Brussel. C.S. is a post-doctoral fellow of the Fund for Scientific Research Flanders (FWO - Vlaanderen). K.J. is a PhD student funded by the FWO. The University of Adelaide owns a patent family associated with IVM technologies that is licensed to Cook Medical. R.B.G. and J.G.T. are inventors. The remaining authors have no conflict of interest to declare.

Prognosis of status epilepticus (SE): Relationship between SE duration and subsequent development of epilepsy.

UNLABELLED: In animal models, SE duration is related to epileptogenesis. Data in humans are scarce, mainly in NCSE; therefore, we aimed to study the prognosis of SE de novo and which factors may influence subsequent development of epilepsy. METHODS: We evaluated patients with SE without previous epilepsy at our hospital (February 2011-February 2014), including demographics, etiology, number of AEDs, duration of SE, mortality, and occurrence of seizures during follow-up. RESULTS: Eighty-nine patients were evaluated. Median age was 69 (19-95) years old. Among them, 33.7% were convulsive. Regarding etiology, 59 were considered acute symptomatic (41 lesions, 18 toxic-metabolic), 17 remote or progressive symptomatic, and 13 cryptogenic. The median recovery time was 24h (30 min-360 h). In-hospital mortality was 29% (n = 26). After a median follow-up of 10 months, 58.7% of survivors (n = 37) showed seizures. Subsequently, we analyzed which factors might be related to the development of epilepsy, and we found that epilepsy development was more frequent with longer SE duration (37 vs. 23 h, p = 0.004); furthermore, patients with a toxic-metabolic etiology developed epilepsy less frequently (33% vs. 67%; p = 0.022). Epilepsy was also correlated (tendency) with focal SE (p = 0.073), a lesion in neuroimaging (p = 0.091), and the use of 2 or more AEDs (p = 0.098). Regarding SE duration, a cutoff of above 24h was clearly related to chronic seizures (p = 0.014); however, combining etiology and duration, the association of longer SE and epilepsy was significant in acute lesional SE (p = 0.034), but not in epilepsy with cryptogenic or remote/progressive etiology. After a logistic regression, only a duration longer than 24h (OR = 3.800 (1.277-11.312), p = 0.016) was found to be an independent predictor of the development of epilepsy. CONCLUSION: In patients with SE, the longer duration is associated with an increased risk of subsequent epilepsy at follow-up, mainly in symptomatic SE due to an acute lesion. It is unclear if it might be the result of a more severe injury causing both prolonged seizures and subsequent epilepsy, and therefore whether more aggressive treatment in this group might avoid this possibility. Most of the patients with cryptogenic or remote/progressive SE developed epilepsy regardless of SE duration. This article is part of a Special Issue entitled "Status Epilepticus".

An Unusually Small Singlet-Triplet Gap in a Quinoidal 1,6-Methano[10]annulene Resulting from Baird's 4n π-Electron Triplet Stabilization.

Within the continuum of π-extended quinoidal electronic structures exist molecules that by design can support open-shell diradical structures. The prevailing molecular design criteria for such structures involve proaromatic nature that evolves aromaticity in open-shell diradical resonance structures. A new diradical species built upon a quinoidal methano[10]annulene unit is synthesized and spectroscopically evaluated. The requisite intersystem crossing in the open-shell structure is accompanied by structural reorganization from a contorted Möbius aromatic-like shape in S0 to a more planar shape in the Hückel aromatic-like T1. This stability was attributed to Baird's Rule which dictates the aromaticity of 4n π-electron triplet excited states.

Synthesis of novel fatty acid 3,4-dihydropyrimidin-2-(1H)-one and antitumoral activity against breast and gastric cancer cells.

Monastrol is the best-known small compound from the dihydropyrimidinones/thiones (DHPMs) heterocycle family, a cell-permeable molecule recognized as an inhibitor of mitotic kinesin Eg5, that is over-expressed in tumor cells and is a very promising target for the development of new drugs for cancer. The lipophilic properties of the DHPMs have been demonstrated to be of pivotal importance in the design of new molecules. This work describes the synthesis and antitumoral activity of novel C5-substituted fatty-DHPMs against breast and gastric cancer cell lines. The compounds were synthesized via Biginelli multicomponent reaction from oleyl ß-ketoester in good yields (40-72%) using a simple approach catalyzed by nontoxic and free-metal sulfamic acid. Among the compounds tested, the compound 10c, derived from 3-hydroxybenzaldehyde and urea, exhibited 77% cellular viability to normal cells (C2C12) and was selected to be evaluated against tumoral breast (MCF-7) and gastric (AGS) cell lines. The results obtained afforded an IC50 of breast cancer cells of 2.3 µM, qualifying the molecule as the most potent, and making it a promising compound for future experiments in vivo.

Human antral follicles <6 mm: a comparison between in vivo maturation and in vitro maturation in non-hCG primed cycles using cumulus cell gene expression.

Within the context of an oocyte in vitro maturation (IVM) program for reproductive treatment, oocyte cumulus complexes (COCs) derived from follicles <6 mm in patients with PCOS were matured in vitro. Key transcripts related to meiotic maturation (FSHR, LHCGR, EGFR, PGR) and oocyte competence (AREG, ADAMTS, HAS2, PTGS2) were quantified in cumulus cells (CCs) before and after maturation. Control CC samples were collected from PCOS and normo-ovulatory patients who had undergone conventional gonadotrophin stimulation for IVF/ICSI. Additional control samples from a non-stimulated condition were obtained ex vivo from patients undergoing ovariectomy for fertility preservation. Expression data from CCs from follicles with a diameter of <6 mm before (IVM-CCs) and after in vitro maturation (IVM-CCs) were obtained after pooling CCs into four groups in relation to the percentage of matured (MII) oocytes obtained after 40 h of IVM (0; 40-60; 61-80; 100% MII) and values were compared with in vivo matured controls (IVO-CCs). Genes encoding key receptors mediating meiotic resumption are expressed in human antral follicles of <6 mm before and after IVM. The expression levels of FSHR, EGFR and PGR in CCs were significantly down-regulated in the IVO-CCs groups and in the 100% MII IVM group compared with the BM groups; all the receptors studied in the 100% MII IVM group reached an expression profile similar to that of IVO-CCs. However, after maturation in a conventional IVF/ICSI cycle, IVO-CCs from large follicles contained significantly increased levels of ADAMTS1, AREG, HAS2 and PTGS2 compared with IVM-CCs and IVM-CCs; the expression patterns for these genes in all IVM-CCs were unchanged compared with IVM-CCs. In conclusion, genes encoding receptors involved in oocyte meiotic resumption appeared to be expressed in CCs of small human antral follicles. Expression levels of genes-encoding factors reflecting oocyte competence were significantly altered in IVM-CCs compared with in vivo matured oocytes from large follicles. Observed differences might be explained by the different stimulation protocols, doses of gonadotrophin or by the intrinsic differences between in vivo and in vitro maturation.

A prediction model to select PCOS patients suitable for IVM treatment based on anti-Mullerian hormone and antral follicle count.

STUDY QUESTION: Which baseline patient characteristics can help assisted reproductive technology practitioners to identify patients who are suitable for in-vitro maturation (IVM) treatment? SUMMARY ANSWER: In patients with polycystic ovary syndrome (PCOS) who undergo oocyte IVM in a non-hCG-triggered system, circulating anti-Müllerian hormone (AMH), antral follicle count (AFC) and total testosterone are independently related to the number of immature oocytes and hold promise as outcome predictors to guide the patient selection process for IVM. WHAT IS ALREADY KNOWN: Patient selection criteria for IVM treatment have been described in normo-ovulatory patients, although patients with PCOS constitute the major target population for IVM. With this study, we assessed the independent predictive value of clinical and endocrine parameters that are related to oocyte yield in patients with PCOS undergoing IVM. STUDY DESIGN, SIZE, DURATION: Cohort study involving 124 consecutive patients with PCOS undergoing IVM whose data were prospectively collected. Enrolment took place between January 2010 and January 2012. Only data relating to the first IVM cycle of each patient were included. PARTICIPANTS/MATERIALS, SETTING, METHOD: Patients with PCOS underwent oocyte retrieval for IVM after minimal gonadotrophin stimulation and no hCG trigger. Correlation coefficients were calculated to investigate which parameters are related to immature oocyte yield (patient's age, BMI, baseline hormonal profile and AMH, AFC). The independence of predictive parameters was tested using multivariate linear regression analysis. Finally, multivariate receiver operating characteristic (ROC) analyses for cumulus oocyte complexes (COC) yield were performed to assess the efficiency of the prediction model to select suitable candidates for IVM. MAIN RESULTS AND THE ROLE OF CHANCE: Using multivariate regression analysis, circulating baseline AMH, AFC and baseline total testosterone serum concentration were incorporated into a model to predict the number of COC retrieved in an IVM cycle, with unstandardized coefficients [95% confidence interval (CI)] of 0.03 (0.02-0.03) (P < 0.001), 0.012 (0.008-0.017) (P < 0.001) and 0.37 (0.18-0.57) (P < 0.001), respectively. Logistic regression analysis shows that a prediction model based on AMH and AFC, with unstandardized coefficients (95% CI) of 0.148 (0.03-0.25) (P < 0.001) and 0.034 (-0.003-0.07) (P = 0.025), respectively, is a useful patient selection tool to predict the probability to yield at least eight COCs for IVM in patients with PCOS. In this population, patients with at least eight COC available for IVM have a statistically higher number of embryos of good morphological quality (2.9 ± 2.3; 0.9 ± 0.9; P < 0.001) and cumulative ongoing pregnancy rate [30.4% (24 out of 79); 11% (5 out of 45); P = 0.01] when compared with patients with less than eight COC. ROC curve analysis showed that this prediction model has an area under the curve of 0.7864 (95% CI = 0.6997-0.8732) for the prediction of oocyte yield in IVM. LIMITATIONS, REASONS FOR CAUTION: The proposed model has been constructed based on a genuine IVM system, i.e. no hCG trigger was given and none of the oocytes matured in vivo. However, other variables, such as needle type, aspiration technique and whether or not hCG-triggering is used, should be considered as confounding factors. The results of this study have to be confirmed using a second independent validation sample. WIDER IMPLICATIONS OF THE FINDINGS: The proposed model could be applied to patients with PCOS after confirmation through a further validation study. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by a research grant by the Institute for the Promotion of Innovation by Science and Technology in Flanders, Project number IWT 070719.

Structural and electrical characterization of ultra-thin SrTiO3 tunnel barriers grown over YBa2Cu3O7 electrodes for the development of high Tc Josephson junctions.

The transport properties of ultra-thin SrTiO(3) (STO) layers grown over YBa(2)Cu(3)O(7) electrodes were studied by conductive atomic force microscopy at the nano-scale. A very good control of the barrier thickness was achieved during the deposition process. A phenomenological approach was used to obtain critical parameters regarding the structural and electrical properties of the system. The STO layers present an energy barrier of 0.9 eV and an attenuation length of 0.23 nm, indicating very good insulating properties for the development of high-quality Josephson junctions.