Experimental Determination of α Widths of

The efficiency of the weak s process in low-metallicity rotating massive stars depends strongly on the rates of the competing ^{17}O(α,n)^{20}Ne and ^{17}O(α,γ)^{21}Ne reactions that determine the potency of the ^{16}O neutron poison. Their reaction rates are poorly known in the astrophysical energy range of interest for core helium burning in massive stars because of the lack of spectroscopic information (partial widths, spin parities) for the relevant states in the compound nucleus ^{21}Ne. In this Letter, we report on the first experimental determination of the α-particle spectroscopic factors and partial widths of these states using the ^{17}O(^{7}Li,t)^{21}Ne α-transfer reaction. With these the ^{17}O(α,n)^{20}Ne and ^{17}O(α,γ)^{21}Ne reaction rates were evaluated with uncertainties reduced by a factor more than 3 with respect to previous evaluations and the present ^{17}O(α,n)^{20}Ne reaction rate is more than 20 times larger. The present (α,n)/(α,γ) rate ratio favors neutron recycling and suggests an enhancement of the weak s process in the Zr-Nd region by more than 1.5 dex in metal-poor rotating massive stars.

Publisher Correction: An increase in the 12C + 12C fusion rate from resonances at astrophysical energies.

In equation (1) of this Letter, the closing bracket was missing; in Extended Data Fig. 1 and the accompanying legend, 'Φ(pd)' should have been 'Φ2(pd)', and in the Methods the text "Odd J assignments are uncertain by ±1." has been added. These errors have all been corrected online.

An increase in the 12C + 12C fusion rate from resonances at astrophysical energies.

Carbon burning powers scenarios that influence the fate of stars, such as the late evolutionary stages of massive stars 1 (exceeding eight solar masses) and superbursts from accreting neutron stars2,3. It proceeds through the 12C + 12C fusion reactions that produce an alpha particle and neon-20 or a proton and sodium-23-that is, 12C(12C, α)20Ne and 12C(12C, p)23Na-at temperatures greater than 0.4 × 109 kelvin, corresponding to astrophysical energies exceeding a megaelectronvolt, at which such nuclear reactions are more likely to occur in stars. The cross-sections 4 for those carbon fusion reactions (probabilities that are required to calculate the rate of the reactions) have hitherto not been measured at the Gamow peaks 4 below 2 megaelectronvolts because of exponential suppression arising from the Coulomb barrier. The reference rate 5 at temperatures below 1.2 × 109 kelvin relies on extrapolations that ignore the effects of possible low-lying resonances. Here we report the measurement of the 12C(12C, α0,1)20Ne and 12C(12C, p0,1)23Na reaction rates (where the subscripts 0 and 1 stand for the ground and first excited states of 20Ne and 23Na, respectively) at centre-of-mass energies from 2.7 to 0.8 megaelectronvolts using the Trojan Horse method6,7 and the deuteron in 14N. The cross-sections deduced exhibit several resonances that are responsible for very large increases of the reaction rate at relevant temperatures. In particular, around 5 × 108 kelvin, the reaction rate is boosted to more than 25 times larger than the reference value 5 . This finding may have implications such as lowering the temperatures and densities 8 required for the ignition of carbon burning in massive stars and decreasing the superburst ignition depth in accreting neutron stars to reconcile observations with theoretical models 3 .

Demonstrating the reliability of in vivo metabolomics based chemical grouping: towards best practice.

While grouping/read-across is widely used to fill data gaps, chemical registration dossiers are often rejected due to weak category justifications based on structural similarity only. Metabolomics provides a route to robust chemical categories via evidence of shared molecular effects across source and target substances. To gain international acceptance, this approach must demonstrate high reliability, and best-practice guidance is required. The MetAbolomics ring Trial for CHemical groupING (MATCHING), comprising six industrial, government and academic ring-trial partners, evaluated inter-laboratory reproducibility and worked towards best-practice. An independent team selected eight substances (WY-14643, 4-chloro-3-nitroaniline, 17α-methyl-testosterone, trenbolone, aniline, dichlorprop-p, 2-chloroaniline, fenofibrate); ring-trial partners were blinded to their identities and modes-of-action. Plasma samples were derived from 28-day rat tests (two doses per substance), aliquoted, and distributed to partners. Each partner applied their preferred liquid chromatography-mass spectrometry (LC-MS) metabolomics workflows to acquire, process, quality assess, statistically analyze and report their grouping results to the European Chemicals Agency, to ensure the blinding conditions of the ring trial. Five of six partners, whose metabolomics datasets passed quality control, correctly identified the grouping of eight test substances into three categories, for both male and female rats. Strikingly, this was achieved even though a range of metabolomics approaches were used. Through assessing intrastudy quality-control samples, the sixth partner observed high technical variation and was unable to group the substances. By comparing workflows, we conclude that some heterogeneity in metabolomics methods is not detrimental to consistent grouping, and that assessing data quality prior to grouping is essential. We recommend development of international guidance for quality-control acceptance criteria. This study demonstrates the reliability of metabolomics for chemical grouping and works towards best-practice.

The kinetics of the ice-water interface from ab initio machine learning simulations.

Molecular simulations employing empirical force fields have provided valuable knowledge about the ice growth process in the past decade. The development of novel computational techniques allows us to study this process, which requires long simulations of relatively large systems, with ab initio accuracy. In this work, we use a neural-network potential for water trained on the revised Perdew-Burke-Ernzerhof functional to describe the kinetics of the ice-water interface. We study both ice melting and growth processes. Our results for the ice growth rate are in reasonable agreement with previous experiments and simulations. We find that the kinetics of ice melting presents a different behavior (monotonic) than that of ice growth (non-monotonic). In particular, a maximum ice growth rate of 6.5 Å/ns is found at 14 K of supercooling. The effect of the surface structure is explored by investigating the basal and primary and secondary prismatic facets. We use the Wilson-Frenkel relation to explain these results in terms of the mobility of molecules and the thermodynamic driving force. Moreover, we study the effect of pressure by complementing the standard isobar with simulations at a negative pressure (-1000 bar) and at a high pressure (2000 bar). We find that prismatic facets grow faster than the basal one and that pressure does not play an important role when the speed of the interface is considered as a function of the difference between the melting temperature and the actual one, i.e., to the degree of either supercooling or overheating.

Decreased inferior vena cava diameter as an early marker in postpartum hemorrhage.

OBJECTIVES: To examine the association between inferior vena cava (IVC) diameter and postpartum blood loss and assess whether IVC diameter is a useful marker in the evaluation of intravascular volume status in women with postpartum hemorrhage (PPH). METHODS: This was a prospective case-control study conducted in a university medical teaching center in Afula, Israel, between November 2018 and March 2020. The study cohort consisted of women with a singleton pregnancy who delivered vaginally at term. The PPH group included women diagnosed with PPH based on visually estimated blood loss of 1000 mL or more at the time of enrolment. Hemodynamically unstable women or women with major bleeding at the time of diagnosis were not included. The control group consisted of women with an uneventful fourth stage of labor. IVC diameter was measured using transabdominal ultrasonography during inspiration (IVCi diameter) and expiration (IVCe diameter), and the collapsibility index was calculated ((IVCe - IVCi)/IVCe × 100). The primary outcome was the percentage difference in IVC diameter and collapsibility index between the PPH group and controls. The performance of the IVC collapsibility index in the prediction of the need for blood transfusion in women with PPH was assessed. In order to demonstrate a difference of 20% with a power of 80% and alpha of 0.05, 108 women, at a ratio of 1:2 in the study and control groups, respectively, were needed. RESULTS: Overall, 36 and 72 women were included in the final analysis in the PPH and control groups, respectively. IVCi and IVCe diameters were significantly smaller in the PPH group (0.93 ± 0.30 cm and 1.26 ± 0.32 cm, respectively) than in controls (1.42 ± 0.31 cm and 1.75 ± 0.28 cm, respectively) (P = 0.001 for both). The percentage reductions in IVCi and IVCe diameters in the PPH group compared with controls were 35.0% and 28.0%, respectively. IVC collapsibility index was increased significantly, by 42.9% (26.04 ± 8.67% vs 18.15 ± 5.07%; P = 0.001) in the PPH group compared with controls. IVC collapsibility index was a significant predictor of the need for blood transfusion and correctly predicted 81% of cases. Logistic regression analysis demonstrated that IVC collapsibility index was also a significant predictor of a drop in hemoglobin level of ≥ 2 g/dL (P = 0.001). CONCLUSIONS: IVC diameter changes in response to postpartum blood loss. Measurement of IVC diameter using transabdominal ultrasonography is an objective and useful non-invasive method for the early evaluation of intravascular volume status in women with PPH and for the prediction of cases that might require blood transfusion. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Survival probability during one-year follow-up after index hospitalization for heart failure: an Italian retrospective study.

Background: Heart failure affects about 64 million people worldwide, and despite the economic resources employed to improve its prognosis, mortality is still alarming. The aim of this study was to investigate the impact of patients' characteristics on survival probability during one-year follow-up after an index hospitalization for heart failure. Study design: A three-year retrospective study was conducted on the records of the Hospitals belonging the Local Health Unit of L'Aquila, a Healthcare Facility located in the centre of Italy. Methods: Patients admitted to hospital with a heart failure event as main diagnosis were selected and followed up for one year after their discharge to obtain data for survival analysis. Results: During the observational period for 1,929 patients hospitalized with a Heart failure index event, 1,655 (85.8%) of them were discharged alive and followed up for one year after the discharge. Fourteen percent of patients (n = 232) died for reasons related to Heart failure during the follow-up period. Fifty percent of them (n = 116), died within three months from the index hospitalization discharge. Age ≥75 years (HR 3.192, 95% CI 1.964-5.188), discharging to home (HR 0.399, 95% CI 0.297-0.536), length of stay ≥8 days during the index hospitalization (HR 1.533, 95% CI 1.163-2.019), and high education level (HR 0.517, 95% CI 0.273-0.977), were found to be associated with the survival probability. Conclusion: Study results indicate that older patients, especially those with a low educational level, those with longer index hospitalization, and those not sent directly to home, deserve more care and attention after discharge.

Advancement of Photospheric Radius Expansion and Clocked Type-I X-Ray Burst Models with the New

We report the first (in)elastic scattering measurement of ^{25}Al+p with the capability to select and measure in a broad energy range the proton resonances in ^{26}Si contributing to the ^{22}Mg(α,p) reaction at type I x-ray burst energies. We measured spin-parities of four resonances above the α threshold of ^{26}Si that are found to strongly impact the ^{22}Mg(α,p) rate. The new rate advances a state-of-the-art model to remarkably reproduce light curves of the GS 1826-24 clocked burster with mean deviation <9% and permits us to discover a strong correlation between the He abundance in the accreting envelope of the photospheric radius expansion burster and the dominance of ^{22}Mg(α,p) branch.

Effects of extreme potassium stress on blood pressure and renal tubular sodium transport.

We characterized mouse blood pressure and ion transport in the setting of commonly used rodent diets that drive K+ intake to the extremes of deficiency and excess. Male 129S2/Sv mice were fed either K+-deficient, control, high-K+ basic, or high-KCl diets for 10 days. Mice maintained on a K+-deficient diet exhibited no change in blood pressure, whereas K+-loaded mice developed an ~10-mmHg blood pressure increase. Following challenge with NaCl, K+-deficient mice developed a salt-sensitive 8 mmHg increase in blood pressure, whereas blood pressure was unchanged in mice fed high-K+ diets. Notably, 10 days of K+ depletion induced diabetes insipidus and upregulation of phosphorylated NaCl cotransporter, proximal Na+ transporters, and pendrin, likely contributing to the K+-deficient NaCl sensitivity. While the anionic content with high-K+ diets had distinct effects on transporter expression along the nephron, both K+ basic and KCl diets had a similar increase in blood pressure. The blood pressure elevation on high-K+ diets correlated with increased Na+-K+-2Cl- cotransporter and γ-epithelial Na+ channel expression and increased urinary response to furosemide and amiloride. We conclude that the dietary K+ maneuvers used here did not recapitulate the inverse effects of K+ on blood pressure observed in human epidemiological studies. This may be due to the extreme degree of K+ stress, the low-Na+-to-K+ ratio, the duration of treatment, and the development of other coinciding events, such as diabetes insipidus. These factors must be taken into consideration when studying the physiological effects of dietary K+ loading and depletion.

Phylogenomic Analyses of Members of the Widespread Marine Heterotrophic Genus Pseudovibrio Suggest Distinct Evolutionary Trajectories and a Novel Genus, Polycladidibacter gen. nov.

Bacteria belonging to the Pseudovibrio genus are widespread, metabolically versatile, and able to thrive as both free-living and host-associated organisms. Although more than 50 genomes are available, a comprehensive comparative genomics study to resolve taxonomic inconsistencies is currently missing. We analyzed all available genomes and used 552 core genes to perform a robust phylogenomic reconstruction. This in-depth analysis revealed the divergence of two monophyletic basal lineages of strains isolated from polyclad flatworm hosts, namely, Pseudovibrio hongkongensis and Pseudovibrio stylochi These strains have reduced genomes and lack sulfur-related metabolisms and major biosynthetic gene clusters, and their environmental distribution appears to be tightly associated with invertebrate hosts. We showed experimentally that the divergent strains are unable to utilize various sulfur compounds that, in contrast, can be utilized by the type strain Pseudovibrio denitrificans Our analyses suggest that the lineage leading to these two strains has been subject to relaxed purifying selection resulting in great gene loss. Overall genome relatedness indices (OGRI) indicate substantial differences between the divergent strains and the rest of the genus. While 16S rRNA gene analyses do not support the establishment of a different genus for the divergent strains, their substantial genomic, phylogenomic, and physiological differences strongly suggest a divergent evolutionary trajectory and the need for their reclassification. Therefore, we propose the novel genus Polycladidibacter gen. nov.IMPORTANCE The genus Pseudovibrio is commonly associated with marine invertebrates, which are essential for ocean health and marine nutrient cycling. Traditionally, the phylogeny of the genus has been based on 16S rRNA gene analysis. The use of the 16S rRNA gene or any other single marker gene for robust phylogenetic placement has recently been questioned. We used a large set of marker genes from all available Pseudovibrio genomes for in-depth phylogenomic analyses. We identified divergent monophyletic basal lineages within the Pseudovibrio genus, including two strains isolated from polyclad flatworms. These strains showed reduced sulfur metabolism and biosynthesis capacities. The phylogenomic analyses revealed distinct evolutionary trajectories and ecological adaptations that differentiate the divergent strains from the other Pseudovibrio members and suggest that they fall into a novel genus. Our data show the importance of widening the use of phylogenomics for better understanding bacterial physiology, phylogeny, and evolution.

Functional Changes of Mentalizing Network in SCA2 Patients: Novel Insights into Understanding the Social Cerebellum.

In recent years, increasing evidence of the cerebellar role in social cognition has emerged. The cerebellum has been shown to modulate cortical activity of social brain regions serving as a regulator of function-specific mentalizing and mirroring processes. In particular, a mentalizing area in the posterior cerebellum, specifically Crus II, is preferentially recruited for more complex and abstract forms of social processing, together with mentalizing cerebral areas including the dorsal medial prefrontal cortex (dmPFC), the temporo-parietal junction (TPJ), and the precuneus. In the present study, the network-based statistics approach was used to assess functional connectivity (FC) differences within this mentalizing cerebello-cerebral network associated with a specific cerebellar damage. To this aim, patients affected by spinocerebellar ataxia type 2 (SCA2), a neurodegenerative disease specifically affecting regions of the cerebellar cortex, and age-matched healthy subjects have been enrolled. The dmPFC, left and right TPJ, the precuneus, and the cerebellar Crus II were used as regions of interest to construct the mentalizing network to be analyzed and evaluate pairwise functional relations between them. When compared with controls, SCA2 patients showed altered internodal connectivity between dmPFC, left (L-) and right (R-) TPJ, and right posterior cerebellar Crus II.The present results indicate that FC changes affect a function-specific mentalizing network in patients affected by cerebellar damage. In particular, they allow to better clarify functional alteration mechanisms driven by the cerebellar damage associated with SCA2 suggesting that selective cortico-cerebellar functional disconnections may underlie patients' social impairment in domain-specific complex and abstract forms of social functioning.

Listening to the neurological teams for multiple sclerosis: the SMART project.

OBJECTIVE: Aim of the research was to define the quality of life of Italian neurologists and nurses' professional caring for multiple sclerosis, to understand their living the clinical practice and identify possible signals of compassion fatigue. MATERIAL AND METHODS: One hundred five neurologists and nurses from 30 Italian multiple sclerosis centres were involved in an online quali-quantitative survey on the organization of care, combined with the Satisfaction and Compassion Fatigue Test and a collection of narratives. Descriptive statistics of the quantitative data were integrated with the results obtained by the narrative medicine methods of analysis. RESULTS: Most of the practitioners were neurologists, 46 average years old, 69% women, 43% part time dedicated to multiple sclerosis. An increased number of patients in the last 3 years were referred in 29 centres. Differences were found between neurologists and nurses. Physicians showed higher risks of burnout, reporting intensive working paces, lack of medical personnel, and anxiety caused by the precarious employment conditions. Nurses appeared more satisfied, although the reference to the lack of spaces, and the cross professional roles risk of compassion fatigue. Both positive and negative relationships of care were depicted as influencing the professional quality of life. CONCLUSION: The interviewed neurological teams need to limit the risk of compassion fatigue, which appeared from the first years of the career. The prevalence of the risk among neurologists suggests more awareness among scientific societies and health care managers on the risk for this category, as first step to prevent it.

Neuroactive steroids and diabetic complications in the nervous system.

Important complications of diabetes mellitus in the nervous system are represented by diabetic peripheral neuropathy and diabetic encephalopathy. In this context, an important link is represented by neuroactive steroids (i.e., steroids coming from peripheral glands and affecting nervous functionality as well as directly synthesized in the nervous system). Indeed, diabetes does not only affect the reproductive axis and consequently the levels of sex steroid hormones, but also those of neuroactive steroids. Indeed, as will be here summarized, the levels of these neuromodulators present in the central and peripheral nervous system are affected by the pathology in a sex-dimorphic way. In addition, some of these neuroactive steroids, such as the metabolites of progesterone or testosterone, as well as pharmacological tools able to increase their levels have been demonstrated, in experimental models, to be promising protective agents against diabetic peripheral neuropathy and diabetic encephalopathy.

The safety of quinolones and fluoroquinolones in pregnancy: a meta-analysis.

BACKGROUND: Quinolones were contraindicated during pregnancy because of concerns regarding fetal malformations and carcinogenesis in animals. The literature is conflicting regarding their safety in humans. OBJECTIVES: To conduct a meta-analysis evaluating the risk for fetal malformations and pregnancy complications following exposure to quinolones during pregnancy. SEARCH STRATEGY: We searched Embase, PubMed, Medline, the Cochrane database, clinicaltrials.gov, and Dart Databases. We added articles found through the references of included articles. SELECTION CRITERIA: Relevant English citations using the terms quinolone/s, fluoroquinolone/s, and pregnancy in humans. Exclusion criteria were case reports, reviews, and articles without data regarding the study outcomes. DATA COLLECTION AND ANALYSIS: Two authors performed the database search, assessment of eligibility, and abstraction of data from included studies. Disagreement was settled by consensus among all authors. The pooled odds ratios (with 95% CIs) were estimated. The Cochrane's Q-test of heterogeneity and I² were used for the measurement of heterogeneity. A total of 256 papers were retrieved, 13 of which met the inclusion criteria and were then analysed. MAIN RESULTS: No association was found between quinolones and fetal malformations (pooled odds ratio, OR 1.08; 95% CI 0.96-1.21), preterm delivery (pooled OR 0.97; 95% CI 0.75-1.24), stillbirth (pooled OR 1.11; 95% CI 0.34-3.6), or miscarriage (pooled OR 1.78; 95% CI 0.93-3.38). CONCLUSIONS: Quinolones are not associated with unfavourable pregnancy outcomes; however, larger studies are needed before safety is established. Until then, it is suggested that quinolones should not be used as a first-line therapy during the first trimester. TWEETABLE ABSTRACT: Quinolones were associated with favourable pregnancy outcomes; caution should be taken in the first trimester.

Expression of FK506-binding protein 51 (FKBP51) in Mycosis fungoides.

BACKGROUND: Mycosis fungoides (MF) is the major subtype of cutaneous T-cell lymphomas (CTCL). It usually has a prolonged indolent clinical course with a minority of cases acquiring a more aggressive biological profile and resistance to conventional therapies, partially attributed to the persistent activation of nuclear factor-kappa B (NF-κB) pathway. In the last decade, several papers suggested an important role for the FK506-binding protein 51 (FKBP51), an immunophilin initially cloned in lymphocytes, in the control of NF-κB pathway in different types of human malignancies. OBJECTIVES: We aimed to investigate the possible value of FKBP51 expression as a new reliable marker of outcome in patients with MF. METHODS: We assessed by immunohistochemistry (IHC) FKBP51 expression in 44 patients with MF, representative of different stages of the disease. Immunohistochemical results were subsequently confirmed at mRNA level with quantitative PCR (qPCR) in a subset of enrolled patients. In addition, IHC and qPCR served to study the expression of some NF-κB-target genes, including the tumour necrosis factor receptor-associated factor 2 (TRAF2). RESULTS: Our results show that FKBP51 was expressed in all evaluated cases, with the highest level of expression characterizing MFs with the worst prognosis. Moreover, a significant correlation subsisted between FKBP51 and TRAF2 IHC expression scores. CONCLUSIONS: We hypothesize a role for FKBP51 as a prognostic marker for MF and suggest an involvement of this immunophilin in deregulated NF-κB pathway of this CTCL.

Continuous embryo culture elicits higher blastulation but similar cumulative delivery rates than sequential: a large prospective study.

PURPOSE: To assess whether continuous embryo culture involves better embryological and/or clinical outcomes than sequential. METHODS: Prospective study at a private IVF center. All consecutive IVF cycles (September 2013-2015) fulfilling the inclusion criteria underwent embryo culture in either Continuous-Single-Culture-Media (CSCM, n = 972) or sequential media (Quinn's Advantage, n = 514), respectively. ICSI, blastocyst culture in either standard (MINC) or undisturbed (Embryoscope) incubation, transfer (until September 2016), and pregnancy follow-up (until September 2017) were performed. When aneuploidy testing was required, trophectoderm biopsy and qPCR were performed. Sub-analyses and logistic regression corrected for confounders were performed. The primary outcomes were overall blastocyst rate per oocyte and mean blastocyst rate per cycle. The sample size was defined to reach 95 and 80% statistical power for the former and the latter outcome, respectively. Secondary outcomes were euploidy (if assessed), cumulative delivery rates, gestational age, and birthweight. RESULTS: Continuous embryo culture resulted into a higher overall blastocyst rate per inseminated oocyte than sequential (n = 2211/5841, 37.9% vs. 1073/3216, 33.4%; p < 0.01), confirmed also from a cycle-based analysis (mean blastocyst rate: 38.7% ± 29.7% vs. 34.3% ± 29.4%; p = 0.01). The continuous media (OR = 1.23), the undisturbed incubation system (OR = 1.22), the maternal age (OR = 0.92), and the sperm factor (OR = 0.85) were outlined as positive predictors of blastulation. However, the cumulative delivery rates per ended cycle (i.e., delivery achieved or no blastocyst produced or left; > 90%) were comparable in the two groups (n = 244/903, 27.0% vs. 129/475, 27.2%). The neonatal outcomes were similar. CONCLUSIONS: Continuous culture involves better embryological but similar clinical outcomes than sequential. This large prospective study supports the absence of clinical disparity among the two approaches.

High-Precision Probe of the Fully Sequential Decay Width of the Hoyle State in

The decay path of the Hoyle state in ^{12}C (E_{x}=7.654 MeV) has been studied with the ^{14}N(d,α_{2})^{12}C(7.654) reaction induced at 10.5 MeV. High resolution invariant mass spectroscopy techniques have allowed us to unambiguously disentangle direct and sequential decays of the state passing through the ground state of ^{8}Be. Thanks to the almost total absence of background and the attained resolution, a fully sequential decay contribution to the width of the state has been observed. The direct decay width is negligible, with an upper limit of 0.043% (95% C.L.). The precision of this result is about a factor 5 higher than previous studies. This has significant implications on nuclear structure, as it provides constraints to 3α cluster model calculations, where higher precision limits are needed.

Maximization of the optical intra-cavity power of whispering-gallery mode resonators via coupling prism.

In this paper, a detailed description of the optical coupling into a Whispering Gallery Mode (WGM) resonator through a prism via frustrated total internal reflection (FTIR) is presented. The problem is modeled as three media with planar interfaces and closed expressions for FTIR are given. Then, the curvature of the resonator is taken into account and the mode overlap is theoretically studied. A new analytical expression giving the optimal geometry of a disc-shaped or ring-shaped resonator for maximizing the intra-cavity circulating power is presented. Such expression takes into consideration the spatial distribution of the WGM at the surface of the resonator, thus being more accurate than the currently used expressions. It also takes into account the geometry of the prism. It is shown an improvement in the geometry values used with the current expressions of about 30%. The reason why the pump laser signal can be seen in experiments under critical coupling is explained on this basis. Then, the conditions required for exciting the highest possible optical power inside the resonator are obtained. The aim is to achieve a highly-efficient up-conversion of a THz signal into the optical domain via the second-order nonlinearity of the resonator material.

Conversion from clinically isolated syndrome to multiple sclerosis: A large multicentre study.

BACKGROUND AND OBJECTIVE: We explored which clinical and biochemical variables predict conversion from clinically isolated syndrome (CIS) to clinically definite multiple sclerosis (CDMS) in a large international cohort. METHODS: Thirty-three centres provided serum samples from 1047 CIS cases with at least two years' follow-up. Age, sex, clinical presentation, T2-hyperintense lesions, cerebrospinal fluid (CSF) oligoclonal bands (OCBs), CSF IgG index, CSF cell count, serum 25-hydroxyvitamin D3 (25-OH-D), cotinine and IgG titres against Epstein-Barr nuclear antigen 1 (EBNA-1) and cytomegalovirus were tested for association with risk of CDMS. RESULTS: At median follow-up of 4.31 years, 623 CIS cases converted to CDMS. Predictors of conversion in multivariable analyses were OCB (HR = 2.18, 95% CI = 1.71-2.77, p < 0.001), number of T2 lesions (two to nine lesions vs 0/1 lesions: HR = 1.97, 95% CI = 1.52-2.55, p < 0.001; >9 lesions vs 0/1 lesions: HR = 2.74, 95% CI = 2.04-3.68, p < 0.001) and age at CIS (HR per year inversely increase = 0.98, 95% CI = 0.98-0.99, p < 0.001). Lower 25-OH-D levels were associated with CDMS in univariable analysis, but this was attenuated in the multivariable model. OCB positivity was associated with higher EBNA-1 IgG titres. CONCLUSIONS: We validated MRI lesion load, OCB and age at CIS as the strongest independent predictors of conversion to CDMS in this multicentre setting. A role for vitamin D is suggested but requires further investigation.

No evidence of association between blastocyst aneuploidy and morphokinetic assessment in a selected population of poor-prognosis patients: a longitudinal cohort study.

Recent studies involving a limited number of patients have indicated a correlation between aneuploidy and various morphokinetic parameters during preimplantation development. The results among different groups, however, have been inconsistent in identifying the parameters that are able to predict chromosomal abnormalities. The aim of this study was to investigate whether aneuploidy of human blastocysts was detectable by specific morphokinetic parameters in patients at increased risk of aneuploidy because of advanced maternal age, history of unsuccessful IVF treatments, or both. A longitudinal cohort study was conducted using 455 blastocysts from 138 patients. Morphokinetic features of preimplantation development were detected in a timelapse incubator. Blastocysts were subjected to trophectodermal biopsy and comprehensive chromosomal screening. Analyses were conducted by means of logistic mixed-effects models, with a subject-specific intercept. No statistical correlation between 16 commonly detected morphokinetic characteristics of in-vitro embryo development and aneuploidy was found. Results suggest that morphokinetic characteristics cannot be used to select euploid blastocysts in poor-prognosis patients regarded as candidates for pre-implantation genetic screening.