Epitaxial aluminium-nitride tunnel barriers grown by nitridation with a plasma source

High critical current-density (10 to 420 kA/cm^2) superconductor-insulator-superconductor tunnel junctions with aluminium nitride barriers have been realized using a remote nitrogen plasma from an inductively coupled plasma source operated in a pressure range of 10^{-3} to 10^{-1} mbar. We find a much better reproducibility and control compared to previous work. From the current-voltage characteristics and cross-sectional TEM images it is inferred that, compared to the commonly used AlO_x barriers, the poly-crystalline AlN barriers are much more uniform in transmissivity, leading to a better quality at high critical current-densities.Comment: 3 pages, 3 figures, accepted for publication in AP

An SIS-based sideband-separating heterodyne mixer optimized for the 600 to 720 GHz band

The Atacama Large Millimeter Array (ALMA) is the largest radio astronomical enterprise ever proposed. When completed, each of its 64 constituting radio-telescopes will be able to hold 10 heterodyne receivers covering the spectroscopic windows allowed by the atmospheric transmission at the construction site, the altiplanos of the northern Chilean Andes. In contrast to the sideband-separating (2SB) receivers being developed at low frequencies, double-side-band (DSB) receivers are being developed for the highest two spectroscopic windows (bands 9 and 10). Despite of the well known advantages of 2SB mixers over their DSB counterparts, they have not been implemented at the highest-frequency bands as the involved dimensions for some of the radio frequency components are prohibitory small. However, the current state-of-the-art micromachining technology has proved that the structures necessary for this development are attainable. Here we report the design, modeling, realization, and characterization of a 2SB mixer for band 9 of ALMA (600 to 720 GHz). At the heart of the mixer, two superconductor-insulator-superconductor (SIS) junctions are used as mixing elements. The constructed instrument presents an excellent performance as shown by two important figures of merit: noise temperature of the system and side band ratio, both of them within ALMA specifications

Height and timing of growth spurt during puberty in young people living with vertically acquired HIV in Europe and Thailand.

OBJECTIVE: The aim of this study was to describe growth during puberty in young people with vertically acquired HIV. DESIGN: Pooled data from 12 paediatric HIV cohorts in Europe and Thailand. METHODS: One thousand and ninety-four children initiating a nonnucleoside reverse transcriptase inhibitor or boosted protease inhibitor based regimen aged 1-10 years were included. Super Imposition by Translation And Rotation (SITAR) models described growth from age 8 years using three parameters (average height, timing and shape of the growth spurt), dependent on age and height-for-age z-score (HAZ) (WHO references) at antiretroviral therapy (ART) initiation. Multivariate regression explored characteristics associated with these three parameters. RESULTS: At ART initiation, median age and HAZ was 6.4 [interquartile range (IQR): 2.8, 9.0] years and -1.2 (IQR: -2.3 to -0.2), respectively. Median follow-up was 9.1 (IQR: 6.9, 11.4) years. In girls, older age and lower HAZ at ART initiation were independently associated with a growth spurt which occurred 0.41 (95% confidence interval 0.20-0.62) years later in children starting ART age 6 to 10 years compared with 1 to 2 years and 1.50 (1.21-1.78) years later in those starting with HAZ less than -3 compared with HAZ at least -1. Later growth spurts in girls resulted in continued height growth into later adolescence. In boys starting ART with HAZ less than -1, growth spurts were later in children starting ART in the oldest age group, but for HAZ at least -1, there was no association with age. Girls and boys who initiated ART with HAZ at least -1 maintained a similar height to the WHO reference mean. CONCLUSION: Stunting at ART initiation was associated with later growth spurts in girls. Children with HAZ at least -1 at ART initiation grew in height at the level expected in HIV negative children of a comparable age

Neonatal Gram Negative and Candida Sepsis Survival and Neurodevelopmental Outcome at the Corrected Age of 24 Months

Objectives: To evaluate the long term neurodevelopmental outcome of premature infants exposed to either gram- negative sepsis (GNS) or neonatal Candida sepsis (NCS), and to compare their outcome with premature infants without sepsis. Methods: Historical cohort study in a population of infants born at <30 weeks gestation and admitted to the Neonatal Intensive Care Unit (NICU) of the Academic Medical Center in Amsterdam during the period 1997-2007. Outcome of infants exposed to GNS or NCS and 120 randomly chosen uncomplicated controls (UC) from the same NICU were compared. Clinical data during hospitalization and neurodevelopmental outcome data (clinical neurological status; Bayley -test results and vision/hearing test results) at the corrected age of 24 months were collected. An association model with sepsis as the central determinant of either good or adverse outcome (death or severe developmental delay) was made, corrected for confounders using multiple logistic regression analysis. Results: Of 1362 patients, 55 suffered from GNS and 29 suffered from NCS; cumulative incidence 4.2% and 2.2%, respectively. During the follow-up period the mortality rate was 34% for both GNS and NCS and 5% for UC. The adjusted Odds Ratio (OR) [95% CI] for adverse outcome in the GNS group compared to the NCS group was 1.4 [0.4-4.9]. The adjusted ORs [95% CI] for adverse outcome in the GNS and NCS groups compared to the UC group were 4.8 [1.5-15.9] and 3.2 [0.7-14.7], respectively. Conclusions: We found no statistically significant difference in outcome at the corrected age of 24 months between neonatal GNS and NCS cases. Suffering from either gram -negative or Candida sepsis increased the odds for adverse outcome compared with an uncomplicated neonatal period

Совершенствование механизмов формирования доходов бюджета АРК

Целью нашей работы является исследование механизмов формирования доходов бюджета Автономной Республики Крым и разработка мероприятий по их совершенствованию

Individual risk calculator to predict lymph node metastases in patients with submucosal (T1b) esophageal adenocarcinoma:a multicenter cohort study

Background Lymph node metastasis (LNM) is possible after endoscopic resection of early esophageal adenocarcinoma (EAC). This study aimed to develop and internally validate a prediction model that estimates the individual risk of metastases in patients with pT1b EAC. Methods A nationwide, retrospective, multicenter cohort study was conducted in patients with pT1b EAC treated with endoscopic resection and/or surgery between 1989 and 2016. The primary end point was presence of LNM in surgical resection specimens or detection of metastases during follow-up. All resection specimens were histologically reassessed by specialist gastrointestinal pathologists. Subdistribution hazard regression analysis was used to develop the prediction model. The discriminative ability of this model was assessed using the c-statistic. Results 248 patients with pT1b EAC were included. Metastases were seen in 78 patients, and the 5-year cumulative incidence was 30.9 % (95 % confidence interval [CI] 25.1 %-36.8 %). The risk of metastases increased with submucosal invasion depth (subdistribution hazard ratio [SHR] 1.08, 95 %CI 1.02-1.14, for every increase of 500 μm), lymphovascular invasion (SHR 2.95, 95 %CI 1.95-4.45), and for larger tumors (SHR 1.23, 95 %CI 1.10-1.37, for every increase of 10 mm). The model demonstrated good discriminative ability (c-statistic 0.81, 95 %CI 0.75-0.86). Conclusions A third of patients with pT1b EAC experienced metastases within 5 years. The probability of developing post-resection metastases was estimated with a personalized predicted risk score incorporating tumor invasion depth, tumor size, and lymphovascular invasion. This model requires external validation before implementation into clinical practice

Design, Synthesis, and Structure−Activity Relationship Exploration of 1-Substituted 4-Aroyl-3-hydroxy-5-phenyl-1H-pyrrol-2(5H)-one Analogues as Inhibitors of the Annexin A2−S100A10 Protein Interaction

This research was supported by grants from Cancer Research UK. H.K.M. was funded by a Biotechnology and Biological Sciences Research Council studentship.S100 proteins are small adaptors that regulate the activity of partner proteins by virtue of direct protein interactions. Here, we describe the first small molecule blockers of the interaction between S100A10 and annexin A2. Molecular docking yielded candidate blockers that were screened for competition of the binding of an annexin A2 peptide to S100A10. Several inhibitory clusters were identified with some containing compounds with potency in the lower micromolar range. We chose 3-hydroxy-1-(2-hydroxypropyl)-5-(4-isopropylphenyl)-4-(4-methylbenzoyl)-1H-pyrrol-2(5H)-one (1a) as a starting point for structure-activity studies. These confirmed the hypothetical binding mode from the virtual screen for this series of molecules. Selected compounds disrupted the physiological complex of annexin A2 and S100A10, both in a broken cell preparation and inside MDA-MB-231 breast cancer cells. Thus, this class of compounds has promising properties as inhibitors of the interaction between annexin A2 and S100A10 and may help to elucidate the cellular function of this protein interaction.Peer reviewe

Lymphovascular invasion quantification could improve risk prediction of lymph node metastases in patients with submucosal (T1b) esophageal adenocarcinoma

AIM: To quantify lymphovascular invasion (LVI) and to assess the prognostic value in patients with pT1b esophageal adenocarcinoma. METHODS: In this nationwide, retrospective cohort study, patients were included if they were treated with surgery or endoscopic resection for pT1b esophageal adenocarcinoma. Primary endpoint was the presence of metastases, lymph node metastases, or distant metastases, in surgical resection specimens or during follow‐up. A prediction model to identify risk factors for metastases was developed and internally validated. RESULTS: 248 patients were included. LVI was distributed as follows: no LVI (n = 196; 79.0%), 1 LVI focus (n = 16; 6.5%), 2–3 LVI foci (n = 21; 8.5%) and ≥4 LVI foci (n = 15; 6.0%). Seventy‐eight patients had metastases. The risk of metastases was increased for tumors with 2–3 LVI foci [subdistribution hazard ratio (SHR) 3.39, 95% confidence interval (CI) 2.10–5.47] and ≥4 LVI foci (SHR 3.81, 95% CI 2.37–6.10). The prediction model demonstrated a good discriminative ability (c‐statistic 0.81). CONCLUSION: The risk of metastases is higher when more LVI foci are present. Quantification of LVI could be useful for a more precise risk estimation of metastases. This model needs to be externally validated before implementation into clinical practice