Factors Influencing the One- and Two-Year Growth Response in Children Treated with Growth Hormone: Analysis from an Observational Study

To assess gender-, pubertal-, age-related differences in change from baseline height standard deviation score (ΔHSDS), data from 5,797 growth hormone (GH) naïve pediatric patients (<18 years) with growth hormone deficiency (GHD), multiple pituitary hormone deficiency (MPHD), Turner syndrome (TS), small for gestational age (SGA), Noonan syndrome (NS), and idiopathic short stature (ISS) were obtained from the ANSWER (American Norditropin Studies: Web-enabled Research) Program registry. For patients with SGA, ΔHSDS at year 1 was significantly greater for males versus females (P = .016), but no other gender differences were observed. For patients with GHD, ΔHSDS was greater in prepubertal than in pubertal patients. Younger patients for both genders (<11 years for boys; <10 years for girls) showed a greater ΔHSDS (P < .05 for GHD, MPHD, and ISS). Overall, positive ΔHSDSs were observed in all patients, with greater growth responses in younger prepubertal children, emphasizing the importance of starting GH treatment early

Experimental certification of millions of genuinely entangled atoms in a solid

Quantum theory predicts that entanglement can also persist in macroscopic physical systems, albeit difficulties to demonstrate it experimentally remain. Recently, significant progress has been achieved and genuine entanglement between up to 2900 atoms was reported. Here we demonstrate 16 million genuinely entangled atoms in a solid-state quantum memory prepared by the heralded absorption of a single photon. We develop an entanglement witness for quantifying the number of genuinely entangled particles based on the collective effect of directed emission combined with the nonclassical nature of the emitted light. The method is applicable to a wide range of physical systems and is effective even in situations with significant losses. Our results clarify the role of multipartite entanglement in ensemble-based quantum memories as a necessary prerequisite to achieve a high single-photon process fidelity crucial for future quantum networks. On a more fundamental level, our results reveal the robustness of certain classes of multipartite entangled states, contrary to, e.g., Schr\"odinger-cat states, and that the depth of entanglement can be experimentally certified at unprecedented scales.Comment: 11 pages incl. Methods and Suppl. Info., 4 figures, 1 table. v2: close to published version. See also parallel submission by Zarkeshian et al (1703.04709

Effect of 4 years of growth hormone therapy in children with Noonan syndrome in the American Norditropin Studies: Web-Enabled Research (ANSWER) Program® registry.

BACKGROUND: Noonan syndrome (NS) is a genetic disorder characterized by phenotypic features, including facial dysmorphology, cardiovascular anomalies, and short stature. Growth hormone (GH) has been approved by the United States Food and Drug Administration for short stature in children with NS. The objective of this analysis was to assess the height standard deviation score (HSDS) and change in HSDS (ΔHSDS) for up to 4 years (Y4) of GH therapy in children with NS. METHODS: The American Norditropin Studies: Web-Enabled Research (ANSWER) Program®, a US-based registry, collects long-term efficacy and safety information on patients treated with Norditropin® (somatropin rDNA origin, Novo Nordisk A/S) at the discretion of participating physicians. A total of 120 children (90 boys, 30 girls) with NS, naïve to previous GH treatment, were included in this analysis. RESULTS: The mean (SD) baseline age of subjects (n = 120) was 9.2 (3.8) years. Mean (SD) HSDS increased from -2.65 (0.73) at baseline to -1.32 (1.11) at Y4 (n = 17). Subjects showed continued increase in HSDS from baseline to Y4 without significant differences between genders at Y1 or Y2. The mean (SD) GH dose was 47 (11) mcg/kg/day at baseline and 59 (16) mcg/kg/day at Y4. There was a negative correlation between baseline age and ΔHSDS at Y1 (R = -0.3156; P = 0.0055) and Y2 (R = -0.3394; P = 0.017). ΔHSDS at Y1 was significantly correlated with ΔHSDS at Y2 (n = 37; R = 0.8527, P \u3c 0.0001) and Y3 (n = 20; R = 0.5145; P = 0.0203), but not Y4 (n = 12; R = 0.4066, P = 0.1896). CONCLUSIONS: GH treatment-naïve patients with NS showed continued increases in HSDS during 4 years of treatment with GH with no significant differences between genders up to 2 years. Baseline age was negatively correlated with ΔHSDS at Y1 and Y2. Whether long-term therapy in NS results in continued increase in HSDS to adult height remains to be investigated. TRIAL REGISTRATION: ClinicalTrials.gov NCT01009905

Identification of factors associated with good response to growth hormone therapy in children with short stature: results from the ANSWER Program®

<p>Abstract</p> <p>Objective</p> <p>To identify factors associated with growth in children on growth hormone (GH) therapy using data from the American Norditropin Studies: Web-enabled Research (ANSWER) Program^®registry.</p> <p>Methods</p> <p>GH-naïve children with GH deficiency, multiple pituitary hormone deficiency, idiopathic short stature, Turner syndrome, or a history of small for gestational age were eligible (N = 1,002). Using a longitudinal statistical approach, predictive factors were identified in patients with GHD for change from baseline in height standard deviation score (ΔHSDS) following 2 years of treatment.</p> <p>Results</p> <p>Gradual increases in ΔHSDS over time were observed for all diagnostic categories. Significant predictive factors of ΔHSDS, ranked by significance were: height velocity (HV) at 4 months > baseline age > baseline HSDS > baseline body mass index (BMI) SDS > baseline insulin-like growth factor I (IGF-I) SDS; gender was not significant. HV at 4 months and baseline BMI SDS were positively correlated, whereas baseline age, HSDS, and IGF-I SDS were negatively correlated with ΔHSDS.</p> <p>Conclusions</p> <p>These results may help guide GH therapy based on pretreatment characteristics and early growth response.</p

Mentoring New Faculty: An Appreciative Approach

During this period of dramatic social and institutional change in higher education, positive induction and ongoing support for early-career and faculty members new to the campus community is essential. Disparities remain in the recruitment, development, retention, and promotion of diverse faculty, in large part because of the lack of mentoring. The purpose of this article is to enhance approaches for supporting early-career and otherwise new faculty members. Based upon the principles and processes of Appreciative Inquiry, the Appreciative Mentoring Model is presented. Each of the Appreciative Inquiry “D-phases” is described in detail together with research-based best practices that can be employed in mentoring. Prompts, questions, and specific examples designed to support the growing need for a more collaborative, fluid, dynamic, and transformative approach to mentoring are provided.

Ice thickness monitoring for cryo-EM grids by interferometry imaging

While recent technological developments contributed to breakthrough advances in single particle cryo-electron microscopy (cryo-EM), sample preparation remains a significant bottleneck for the structure determination of macromolecular complexes. A critical time factor is sample optimization that requires the use of an electron microscope to screen grids prepared under different conditions to achieve the ideal vitreous ice thickness containing the particles. Evaluating sample quality requires access to cryo-electron microscopes and a strong expertise in EM. To facilitate and accelerate the selection procedure of probes suitable for high-resolution cryo-EM, we devised a method to assess the vitreous ice layer thickness of sample coated grids. The experimental setup comprises an optical interferometric microscope equipped with a cryogenic stage and image analysis software based on artificial neural networks (ANN) for an unbiased sample selection. We present and validate this approach for different protein complexes and grid types, and demonstrate its performance for the assessment of ice quality. This technique is moderate in cost and can be easily performed on a laboratory bench. We expect that its throughput and its versatility will contribute to facilitate the sample optimization process for structural biologists