Transcutaneous bilirubin reliability during and after phototherapy depending on skin color.

Measurement of transcutaneous bilirubin (TcB) is a non-invasive, widely used technique to estimate serum bilirubin (SB). However, its reliability in multiethnic populations during and after phototherapy is still controversial even in covered skin. The aim of this study was to determine the reliability of TcB in covered (cTcB) and exposed (eTcB) skin during and after phototherapy in a multiethnic population of term and preterm neonates according to Neomar's neonatal skin color scale. Prospective, observational study comparing SB and TcB. We determined SB when clinically indicated and, at the same time, measured cTcB under a photo-opaque patch and eTcB next to it with a jaundice meter (Dräger JM-105TM). All dyads TcB-SB were compared, both globally and according to skin color. We obtained data from 200 newborns (color1: 44, color2: 111, color3: 41, color4: 4) and compared 296 dyads TcB/SB. Correlation between cTcB and SB is strong during (0.74-0.83) and after (0.79-0.88) phototherapy, both globally and by color group. The SB-cTcB bias depends on gestational age during phototherapy and on skin color following phototherapy. The correlation between eTcB and SB during phototherapy is not strong (0.54), but becomes so 12 h after discontinuing phototherapy (0.78).  Conclusions: Our study supports the reliability of cTcB to assess SB during and after phototherapy, with differences among skin tones after the treatment. The use of cTcB and Neomar's scale during and mainly after phototherapy may help reduce the number of blood samples required. What is Known: • Controversies exist on the reliability of jaundice meters during and after phototherapy in covered skin. Only a few studies have analyzed their accuracy in multiethnic populations, but none has used a validated neonatal skin color scale. What is New: • We verified correlation between serum and transcutaneous bilirubin in covered skin in a multiethnic population depending on skin color based on our own validated neonatal skin color scale during and after phototherapy.

A Comprehensive Architecture for Federated Learning-Based Smart Advertising.

This paper introduces a cutting-edge data architecture designed for a smart advertising context, prioritizing efficient data flow and performance, robust security, while guaranteeing data privacy and integrity. At the core of this study lies the application of federated learning (FL) as the primary methodology, which emphasizes the authenticity and privacy of data while promptly discarding irrelevant or fraudulent information. Our innovative data model employs a semi-random role assignment strategy based on a variety of criteria to efficiently collect and amalgamate data. The architecture is composed of model nodes, data nodes, and validator nodes, where the role of each node is determined by factors such as computational capability, interconnection quality, and historical performance records. A key feature of our proposed system is the selective engagement of a subset of nodes for modeling and validation, optimizing resource use and minimizing data loss. The AROUND social network platform serves as a real-world case study, illustrating the efficacy of our data architecture in a practical setting. Both simulated and real implementations of our architecture showcase its potential to dramatically curtail network traffic and average CPU usage, while preserving the accuracy of the FL model. Remarkably, the system is capable of achieving over a 50% reduction in both network traffic and average CPU usage even when the user count escalates by twenty-fold. The click rate, user engagement, and other parameters have also been evaluated, proving that the proposed architecture's advantages do not affect the smart advertising accuracy. These findings highlight the proposed architecture's capacity to scale efficiently and maintain high performance in smart advertising environments, making it a valuable contribution to the evolving landscape of digital marketing and FL.

Identity and functional characterisation of the transporter supporting the Na+ -dependent high-affinity NO3 - uptake in Zostera marina L.

Zostera marina is a seagrass, a group of angiosperms that evolved from land to live submerged in seawater, an environment of high salinity, alkaline pH and usually very low NO3 - . In 2000, we reported the first physiological evidence for the Na+ -dependent high-affinity NO3 - uptake in this plant. Now, to determine the molecular identity of this process, we searched for NO3 - transporters common to other vascular plants encoded in Z. marina's genome. We cloned two candidates, ZosmaNPF6.3 and ZosmaNRT2 with its partner protein ZosmaNAR2. ZosmaNAR2 expression levels increase up to 4.5-fold in Z. marina leaves under NO3 - -deficiency, while ZosmaNRT2 and ZosmaNPF6.3 expressions were low and unaffected by NO3 - . NO3 - transport capacity, kinetic properties and H+ or Na+ -dependence were examined by heterologous expression in the Hansenula polymorpha high-affinity NO3 - transporter gene disrupted strain (∆ynt1). ZosmaNPF6.3 functions as a H+ -dependent NO3 - transporter, without functionality at alkaline pH and apparent dual kinetics (KM = 11.1 µM at NO3 - concentrations below 50 µM). ZosmaNRT2 transports NO3 - in a H+ -independent but Na+ -dependent manner (KM = 1 mM Na+ ), with low NO3 - affinity (KM = 30 µM). When ZosmaNRT2 and ZosmaNAR2 are co-expressed, a Na+ -dependent high-affinity NO3 - transport occurs (KM = 5.7 µM NO3 - ), mimicking the in vivo value. These results are discussed in the physiological context, providing evidence that ZosmaNRT2 is a Na+ -dependent high-affinity NO3 - transporter, the first of its kind to be functionally characterised in a vascular plant, that requires ZosmaNAR2 to achieve the necessary high-affinity for nitrate uptake from seawater.

Assessment of a serum calcification propensity test for the prediction of all-cause mortality among hemodialysis patients.

BACKGROUND: Vascular calcification is a major contributor to the high cardiac burden among hemodialysis patients. A novel in vitro T50-test, which determines calcification propensity of human serum, may identify patients at high risk for cardiovascular (CV) disease and mortality. We evaluated whether T50 predicts mortality and hospitalizations among an unselected cohort of hemodialysis patients. METHODS: This prospective clinical study included 776 incident and prevalent hemodialysis patients from 8 dialysis centers in Spain. T50 and fetuin-A were determined at Calciscon AG, all other clinical data were retrieved from the European Clinical Database. After their baseline T50 measurement, patients were followed for two years for the occurrence of all-cause mortality, CV-related mortality, all-cause and CV-related hospitalizations. Outcome assessment was performed with proportional subdistribution hazards regression modelling. RESULTS: Patients who died during follow-up had a significantly lower T50 at baseline as compared to those who survived (269.6 vs. 287.7 min, p = 0.001). A cross-validated model (mean c statistic: 0.5767) identified T50 as a linear predictor of all-cause-mortality (subdistribution hazard ratio (per min): 0.9957, 95% CI [0.9933;0.9981]). T50 remained significant after inclusion of known predictors. There was no evidence for prediction of CV-related outcomes, but for all-cause hospitalizations (mean c statistic: 0.5284). CONCLUSION: T50 was identified as an independent predictor of all-cause mortality among an unselected cohort of hemodialysis patients. However, the additional predictive value of T50 added to known mortality predictors was limited. Future studies are needed to assess the predictive value of T50 for CV-related events in unselected hemodialysis patients.

Safety and preliminary efficacy on cognitive performance and adaptive functionality of epigallocatechin gallate (EGCG) in children with Down syndrome. A randomized phase Ib clinical trial (PERSEUS study).

PURPOSE: Although some caregivers are using epigallocatechin gallate (EGCG) off label in hopes of improving cognition in young adults with Down syndrome (DS), nothing is known about its safety, tolerability, and efficacy in the DS pediatric population. We aimed to evaluate safety and tolerability of a dietary supplement containing EGCG and if EGCG improves cognitive and functional performance. METHODS: A total of 73 children with DS (aged 6-12 years) were randomized. Participants received 0.5% EGCG (10 mg/kg daily dose) or placebo for 6 months with 3 months follow up after treatment discontinuation. RESULTS: In total, 72 children were treated and 66 completed the study. A total of 38 participants were included in the EGCG group and 35 in the placebo group. Of 72 treated participants, 62 (86%) had 229 treatment-emergent adverse events (AEs). Of 37 participants in the EGCG group, 13 (35%) had 18 drug-related treatment-emergent AEs and 12 of 35 (34%) from the placebo group had 22 events. In the EGCG group, neither severe AEs nor increase in the incidence of AEs related to safety biomarkers were observed. Cognition and functionality were not improved compared with placebo. Secondary efficacy outcomes in girls point to a need for future work. CONCLUSION: The use of EGCG is safe and well-tolerated in children with DS, but efficacy results do not support its use in this population.

Comparison of the analgesic effect of inhaled lavender vs vanilla essential oil for neonatal frenotomy: a randomized clinical trial (NCT04867824).

It is necessary to treat neonatal pain because it may have short- and long-term adverse effects. Frenotomy is a painful procedure where sucking, a common strategy to relieve pain, cannot be used because the technique is performed on the tongue. In a previous randomized clinical trial, we demonstrated that inhaled lavender essential oil (LEO) reduced the signs of pain during neonatal frenotomy. We aimed to find out whether inhaled vanilla essential oil (VEO) is more effective in reducing pain during frenotomy than LEO. Randomized clinical trial with neonates who underwent a frenotomy for type 3 tongue-ties between May and October 2021. Pain was assessed using pre and post-procedure heart rate (HR) and oxygen saturation (SatO2), crying time, and NIPS score. Neonates were randomized into "experimental" and "control" group. In both groups, we performed swaddling, administered oral sucrose, and let the newborn suck for 2 min. We placed a gauze pad with one drop of LEO (control group) or of VEO (experimental group) under the neonate's nose for 2 min prior to and during the frenotomy. We enrolled 142 neonates (71 per group). Both groups showed similar NIPS scores (2.02 vs 2.38) and crying times (15.3 vs 18.7 s). We observed no differences in HR increase or in SatO2 decrease between both groups. We observed no side effects in either of the groups. CONCLUSIONS: We observed no appreciable difference between LEO and VEO; therefore, we cannot conclude which of them was more effective in treating pain in neonates who underwent a frenotomy. TRIAL REGISTRATION:  This clinical trial is registered with www. CLINICALTRIALS: gov with NCT04867824. WHAT IS KNOWN: • Pain management is one of the most important goals of neonatal care as it can have long-term neurodevelopmental effects. • Lavender essential oil can help relieve pain due to its sedative, antispasmodic, and anticolic properties. WHAT IS NEW: • Lavender and vanilla essential oils are safe, beneficial, easy to use, and cheap in relieving pain in neonates who undergo a frenotomy for type 3 tongue-ties.

Reliability of transcutaneous bilirubin determination based on skin color determined by a neonatal skin color scale of our own.

Measurement of transcutaneous bilirubin (TcB) is widely used to estimate serum bilirubin (SB). However, its reliability depending on skin tone is still controversial. Ethnic classification does not correlate well with skin tone. We aimed to determine the reliability of transcutaneous bilirubin in a multiethnic population based on skin color according to our neonatal skin color scale. We conducted a prospective, observational study comparing SB and TcB among different skin colors. With the blood sample routinely obtained at 48-72 h for the screening of inborn errors of metabolism, we determined SB and TcB with a jaundice meter. We obtained data from 1359 newborns (color 1 337, color 2 750, color 3 249, color 4 23) and analyzed 1549 dyads SB/TcB. Correlation between TcB and serum bilirubin was very good (R2 = 0.908-0.956), globally and by color group, with slight differences between darker and lighter skin colors. Bland-Altman plots showed different mean bias depending on skin color. Conclusions: Our study not only supports the reliability of TcB to assess SB regardless of skin color, but also supports the fact that TcB tends to overestimate SB in a higher degree in dark-skinned neonates. This may help reduce the number of blood samples for newborns. What is Known: • Jaundice meters are extensively used to diagnose neonatal hyperbilirubinemia, although controversies exist on their reliability depending on skin color. • Only a few studies have analyzed their accuracy in multiethnic populations, but none has used a validated neonatal skin color scale. What is New: • We verified correlation between serum and transcutaneous bilirubin in a multiethnic population depending on skin color after classifying our neonates into color groups with our own validated neonatal skin color scale.

Exploring the opportunities for alignment of regulatory postauthorization requirements and data required for performance-based managed entry agreements.

Performance-based managed entry agreements (PB-MEAs) might allow patient access to new medicines, but practical hurdles make competent authorities for pricing and reimbursement (CAPR) reluctant to implement PB-MEAs. We explored if the feasibility of PB-MEAs might improve by better aligning regulatory postauthorization requirements with the data generation of PB-MEAs and by active collaboration and data sharing. Reviewers from seven CAPRs provided structured assessments of the information available at the European Medicines Agency (EMA) Web site on regulatory postauthorization requirements for fifteen recently authorized products. The reviewers judged to what extent regulatory postauthorization studies could help implement PB-MEAs by addressing uncertainty gaps. Study domains assessed were: patient population, intervention, comparators, outcomes, time horizon, anticipated data quality, and anticipated robustness of analysis. Reviewers shared general comments about PB-MEAs for each product and on cooperation with other CAPRs. Reviewers rated regulatory postauthorization requirements at least partly helpful for most products and across domains except the comparator domain. One quarter of responses indicated that public information provided by the EMA was insufficient to support the implementation of PB-MEAs. Few PB-MEAs were in place for these products, but the potential for implementation of PB-MEAs or collaboration across CAPRs was seen as more favorable. Responses helped delineate a set of conditions where PB-MEAs may help reduce uncertainty. In conclusion, PB-MEAs are not a preferred option for CAPRs, but we identified conditions where PB-MEAs might be worth considering. The complexities of implementing PB-MEAs remain a hurdle, but collaboration across silos and more transparency on postauthorization studies could help overcome some barriers.

Managing the Cloud Continuum: Lessons Learnt from a Real Fog-to-Cloud Deployment.

The wide adoption of the recently coined fog and edge computing paradigms alongside conventional cloud computing creates a novel scenario, known as the cloud continuum, where services may benefit from the overall set of resources to optimize their execution. To operate successfully, such a cloud continuum scenario demands for novel management strategies, enabling a coordinated and efficient management of the entire set of resources, from the edge up to the cloud, designed in particular to address key edge characteristics, such as mobility, heterogeneity and volatility. The design of such a management framework poses many research challenges and has already promoted many initiatives worldwide at different levels. In this paper we present the results of one of these experiences driven by an EU H2020 project, focusing on the lessons learnt from a real deployment of the proposed management solution in three different industrial scenarios. We think that such a description may help understand the benefits brought in by a holistic cloud continuum management and also may help other initiatives in their design and development processes.

Degradation of Fatty Acid Phase-Change Materials (PCM): New Approach for Its Characterization.

The use of adequate thermal energy storage (TES) systems is an efficient way to achieve thermal comfort in buildings reducing the cooling and heating demand. Besides, deploy phase change materials (PCM) to meet and enhance the TES needs is highly effective and widely studied. In this paper, a study of the degradation of two fatty acids is presented, capric and myristic acids, in order to evaluate whether their thermo-physical properties are affected throughout time during service. This was carried out by means of two different types of thermal treatments: degradation at constant temperature (thermal stability test), 60 °C during 100 h and 500 h, and degradation with heating and cooling cycling (thermal cycling stability), between a temperature range from 15 °C to 70 °C with 0.5 °C/min ramp during 500 and 1000 cycles. Despite no significant changes were measured for myristic acid, experimental results revealed a decrease of melting enthalpy of 6.6% in capric acid thermally treated for 500 h. Evidences of chemical degradation were found that might explain the decrease in thermophysical properties during use.

EMA Review of Axicabtagene Ciloleucel (Yescarta) for the Treatment of Diffuse Large B-Cell Lymphoma.

On June 28, 2018, the Committee for Advanced Therapies and the Committee for Medicinal Products for Human Use adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Yescarta for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma and primary mediastinal large B-cell lymphoma, after two or more lines of systemic therapy. Yescarta, which was designated as an orphan medicinal product and included in the European Medicines Agency's Priority Medicines scheme, was granted an accelerated review timetable. The active substance of Yescarta is axicabtagene ciloleucel, an engineered autologous T-cell immunotherapy product whereby a patient's own T cells are harvested and genetically modified ex vivo by retroviral transduction using a retroviral vector to express a chimeric antigen receptor (CAR) comprising an anti-CD19 single chain variable fragment linked to CD28 costimulatory domain and CD3-zeta signaling domain. The transduced anti-CD19 CAR T cells are expanded ex vivo and infused back into the patient, where they can recognize and eliminate CD19-expressing cells. The benefits of Yescarta as studied in ZUMA-1 phase II (NCT02348216) were an overall response rate per central review of 66% (95% confidence interval, 56%-75%) at a median follow-up of 15.1 months in the intention to treat population and a complete response rate of 47% with a significant duration. The most common adverse events were cytokine release syndrome, neurological adverse events, infections, pyrexia, diarrhea, nausea, hypotension, and fatigue. IMPLICATIONS FOR PRACTICE: Yescarta (axicabtagene ciloleucel) was the first chimeric antigen receptor T-cell therapy to be submitted for evaluation to the European Medicines Agency and admitted into the "priority medicine" scheme; it was granted accelerated assessment on the basis of anticipated clinical benefit in relapsed/refractory diffuse large B-cell lymphoma, a condition of unmet medical need. Indeed, Yescarta showed an overall response rate of 66% and a complete response rate of 47% with a significant duration and a manageable toxicity that compared very favorably with historical controls. Here the analysis of benefits and risks is presented, and specific challenges with this important novel product are highlighted, providing further insights and reflections for future medical research.

Validation of a neonatal skin color scale.

Ethnic classification does not correlate well with skin tone. As there are no neonatal skin color scales, we aimed to create and validate one of our own. After creating the scale and briefly training our staff, we conducted a prospective, observational study to assess reproducibility and correlation of each scale color with the melanin and erythema indexes and transcutaneous bilirubin. The reliability of our color scale was measured using Kappa agreement (and its 95% confidence interval) and the concordance index by comparing inter-observer classification of neonatal skin color. We also calculated inter-rater agreement with the intraclass correlation coefficient (ICC). The Kendall tau-b correlation coefficient was used to test the correlation between our color scale and the Mexameter® MX 18. We obtained data from 258 newborns. Inter-observer agreement on color assignment was 83.2%. Median melanin index was significantly different among the 4 color groups, whereas erythema index and transcutaneous bilirubin were not.Conclusions: Our proposed neonatal skin color scale correlates well with the melanin index at 24 h of life, increasing from colors 1 to 4, and the only chromophore different among our four color groups is melanin. Scale color assignment is reproducible. Therefore, it can be used to classify neonatal skin color. Further research is warranted to assess the clinical relevance of these findings. What is known: • Classifying neonates by skin color is difficult because to date there are no skin color scales available based on real skin tone regardless of ethnicity or country of origin. • Skin color differs among individuals from a given ethnic group and depends, among others, on melanin and hemoglobin. What is new: • We created a neonatal skin color scale based on real skin color. • We conducted a study to validate it, and confirmed a good inter-observer agreement in color assignment as well as a good correlation between each color in the scale and the median melanin level.

The fourth edition of the European Network for Health Technology Assessment Forum: highlights and outcomes.

The European Network for Health Technology Assessment (EUnetHTA) organizes an annual Forum with stakeholders to receive feedback on its activities, processes, and outputs produced. The fourth edition of the EUnetHTA Forum brought together representatives of HTA bodies, patient organizations, healthcare professionals (HCPs), academia, payers, regulators, and industry. The aim of this paper is to provide an overview of the highlights presented at the 2019 EUnetHTA Forum, reporting the main items and themes discussed in the plenary panel and breakout sessions. The leading topic was the concept of unmet medical need seen from different stakeholders' perspectives. Breakout sessions covered the joint production of assessment reports and engagement with payers, patients, and HCPs. Synergies, pragmatism, and inclusiveness across Member States and stakeholders were emphasized as leading factors to put in place a collaboration that serves the interest of patients and public health in a truly European spirit.

An Enantioselective Approach to 4-Substituted Proline Scaffolds: Synthesis of (S)-5-(Tert-Butoxy Carbonyl)-5-Azaspiro[2.4]heptane-6-Carboxylic Acid.

A catalytic and enantioselective preparation of the (S)-4-methyleneproline scaffold is described. The key reaction is a one-pot double allylic alkylation of an imine analogue of glycine in the presence of a chinchonidine-derived catalyst under phase transfer conditions. These 4-methylene substituted proline derivatives are versatile starting materials often used in medicinal chemistry. In particular, we have transformed tert-butyl (S)-4-methyleneprolinate (12) into the N-Boc-protected 5-azaspiro[2.4]heptane-6-carboxylic acid (1), a key element in the industrial synthesis of antiviral ledipasvir.

Unmet Medical Need: An Introduction to Definitions and Stakeholder Perceptions.

BACKGROUND: Despite increasing informal and formal use of unmet medical need (UMN) in drug development, regulation, and assessment, there is no insight into its definitions in use. This study aims to provide insight into the current definitions in use and to provide a starting point for a multi-stakeholder discussion on alignment. METHODS: A scoping and a gray literature review were performed to locate definitions of UMN in literature and on stakeholder websites. These definitions were categorized and then discussed among the multi-stakeholder author group via semistructured group discussions and open session workshops with a broader stakeholder audience. Issues with the formation of a common definition and mechanisms for use were discussed. RESULTS: The reviews yielded 16 definitions. Differences were evident, but all included 1 or more of the following elements: (adequacy of) available treatments (16 of 16: 100%), disease severity or burden (6 of 16: 38%), and patient population size (1 of 16: 6%). The stakeholder discussions led to a suggestion for a definition including the first 2 items and, depending on context, population size. The discussions also showed that quantification of UMN is highly dependent on the scope and the value framework in which it is used based on different stakeholder preferences and responsibilities. CONCLUSION: We encourage stakeholders that want to promote alignment on the concept of UMN to prospectively discuss the scope in which they want to apply the concept, what elements they find important for consideration in each case, and how they would measure UMN within the broader regulatory or value framework applicable.

Molecular Characterization of ZosmaNRT2, the Putative Sodium Dependent High-Affinity Nitrate Transporter of Zostera marina L.

One of the most important adaptations of seagrasses during sea colonization was the capacity to grow at the low micromolar nitrate concentrations present in the sea. In contrast to terrestrial plants that use H+ symporters for high-affinity NO3- uptake, seagrasses such as Zostera marina L. use a Na+-dependent high-affinity nitrate transporter. Interestingly, in the Z. marina genome, only one gene (Zosma70g00300.1; NRT2.1) is annotated to this function. Analysis of this sequence predicts the presence of 12 transmembrane domains, including the MFS domains of the NNP transporter family and the "nitrate signature" that appears in all members of the NNP family. Phylogenetic analysis shows that this sequence is more related to NRT2.5 than to NRT2.1, sharing a common ancestor with both monocot and dicot plants. Heterologous expression of ZosmaNRT2-GFP together with the high-affinity nitrate transporter accessory protein ZosmaNAR2 (Zosma63g00220.1) in Nicotiana benthamiana leaves displayed four-fold higher fluorescence intensity than single expression of ZosmaNRT2-GFP suggesting the stabilization of NRT2 by NAR2. ZosmaNRT2-GFP signal was present on the Hechtian-strands in the plasmolyzed cells, pointing that ZosmaNRT2 is localized on the plasma membrane and that would be stabilized by ZosmaNAR2. Taken together, these results suggest that Zosma70g00300.1 would encode a high-affinity nitrate transporter located at the plasma membrane, equivalent to NRT2.5 transporters. These molecular data, together with our previous electrophysiological results support that ZosmaNRT2 would have evolved to use Na+ as a driving ion, which might be an essential adaptation of seagrasses to colonize marine environments.

[Gender meanings of the risk of sexually transmitted infections/HIV transmission among young people]. / Percepción del riesgo de infecciones de transmisión sexual/VIH en jóvenes desde una perspectiva de género.

AIM: To identify the links between social representations used by young people to construct their gender identity, sexuality, and the risk management for sexually transmitted infections. SETTING: Different settings of Primary Health Care in Girona. PARTICIPANTS: Young people aged between 16 and 21 years (32 participants) living in Girona. METHOD: A qualitative study with a social constructionist perspective. A theoretical sampling was carried out and the triangular group and individual interview techniques were used for data collection. The data was interpreted using discourse analysis. RESULTS: Among girls, the ideology of romantic love was associated with dependence on their partner, resulting in a loss of autonomy in the negotiation of condom use. Boys represented sexual desire as an irrepressible urge that causes a loss of self-control through hormonal impulses, which was used to justify their carelessness in relation to condom use. These perspectives explain why girls are subject to sexist prejudices when they have sex just for physical pleasure in the absence of a stable affective bond, whereas boys in the same situation experience enhanced prestige among their peers that reinforces their male identity. The discourse on trust among couples often results in the rejection of condom use, because condoms encapsulate various meanings that are not compatible with faithfulness. CONCLUSIONS: These results show the need for awareness among Primary Care professionals of the influence of psychosocial processes among young people, specifically those related to the construction of gender identity and of male and female sexuality in the management of risks associated with sexual activity.

Impact of TSH during the first trimester of pregnancy on obstetric and foetal complications: Usefulness of 2.5 mIU/L cut-off value.

OBJECTIVE: An association of pregnancy outcomes with subclinical hypothyroidism has been reported; however, there still exists a strong controversy regarding whether subclinical hypothyroidism ought to be dealt with or not. The objective of the study was to evaluate the association of foetal-maternal complications with first trimester maternal Thyrotropin (TSH) values. DESIGN: A retrospective study in a single tertiary care hospital was performed. PATIENTS: A total of 1981 pregnant women were studied during 2012. MEASUREMENTS: Thyrotropin (TSH) universal screening was performed between 9 and 12 weeks of gestation. Outcomes included foetal-maternal complications and newborn health parameters. RESULTS: Median TSH was 1.72 (0.99-2.61) mIU/L. The incidence of perinatal loss, miscarriage and stillbirth was 7.2%, 5.9% and 1.1%, respectively. Median TSH of women with and without miscarriage was 1.97 (1.29-3.28) vs 1.71 (0.96-2.58) mIU/L (P = .009). Incidence of pre-eclampsia was 3.2%; TSH in these women was 2.10 (1.40-2.74) vs 1.71 (0.98-2.59) mIU/L in those without (P = .027). TSH in women with dystocia in labour was 1.76 (1.00-2.53) vs 1.68 (0.94-2.59) mIU/L in those who gave birth with normal progression (P = .044). Women with TSH 2.5-5.1 mIU/L had a higher risk of perinatal loss [OR 1.589 (1.085-2.329)], miscarriage [OR 1.702 (1.126-2.572)] and premature birth [OR 1.39 (1.013-1.876)], adjusted by mother's age. There was no association with the other outcomes analysed. CONCLUSIONS: There is a positive association between maternal TSH in the first trimester of pregnancy and the incidence of perinatal loss and miscarriage. The TSH cut-off value of 2.5 mIU/L identified women with higher adverse pregnancy outcomes.

Molecules Designed to Contain Two Weakly Coupled Spins with a Photoswitchable Spacer.

Controlling the charges and spins of molecules lies at the heart of spintronics. A photoswitchable molecule consisting of two independent spins separated by a photoswitchable moiety was designed in the form of new ligand H4 L, which features a dithienylethene photochromic unit and two lateral coordinating moieties, and yields molecules with [MM⋅⋅⋅MM] topology. Compounds [M4 L2 (py)6 ] (M=Cu, 1; Co, 2; Ni, 3; Zn, 4) were prepared and studied by single-crystal X-ray diffraction (SCXRD). Different metal centers can be selectively distributed among the two chemically distinct sites of the ligand, and this enables the preparation of many double-spin systems. Heterometallic [MM'⋅⋅⋅M'M] analogues with formulas [Cu2 Ni2 L2 (py)6 ] (5), [Co2 Ni2 L2 (py)6 ] (6), [Co2 Cu2 L2 (py)6 ] (7), [Cu2 Zn2 L2 (py)6 ] (8), and [Ni2 Zn2 L2 (py)6 ] (9) were prepared and analyzed by SCXRD. Their composition was established unambiguously. All complexes exhibit two weakly interacting [MM'] moieties, some of which embody two-level quantum systems. Compounds 5 and 8 each exhibit a pair of weakly coupled S=1/2 spins that show quantum coherence in pulsed Q-band EPR spectroscopy, as required for quantum computing, with good phase memory times (TM =3.59 and 6.03 µs at 7 K). Reversible photoswitching of all the molecules was confirmed in solution. DFT calculations on 5 indicate that the interaction between the two spins of the molecule can be switched on and off on photocyclization.

A Useful Allene for the Stereoselective Synthesis of Protected Quaternary 2-Amino-2-vinyl-1,3-diols.

Treatment of readily available allene 1 with Cy2BH followed by addition of an aldehyde led to quaternary protected 2-amino-2-vinyl-1,3-diols in high yield and excellent stereochemical purity. The choice of benzoyl as N-protecting group is critical since the observed N- to O-Bz transfer during the process prevents later undesired isomerizations in the adducts and keeps all heteroatoms protected.