High-Q Magnetic Levitation and Control of Superconducting Microspheres at Millikelvin Temperatures.

We report the levitation of a superconducting lead-tin sphere with 100 µm diameter (corresponding to a mass of 5.6 µg) in a static magnetic trap formed by two coils in an anti-Helmholtz configuration, with adjustable resonance frequencies up to 240 Hz. The center-of-mass motion of the sphere is monitored magnetically using a dc superconducting quantum interference device as well as optically and exhibits quality factors of up to 2.6×10^{7}. We also demonstrate 3D magnetic feedback control of the motion of the sphere. The setup is housed in a dilution refrigerator operating at 15 mK. By implementing a cryogenic vibration isolation system, we can attenuate environmental vibrations at 200 Hz by approximately 7 orders of magnitude. The combination of low temperature, large mass, and high quality factor provides a promising platform for testing quantum physics in previously unexplored regimes with high mass and long coherence times.

[Distal Forearm Fractures in Children and Adolescents: Frequency and Health Care Provision in Germany]. / Distale Unterarmfrakturen im Kindes- und Jugendalter: Häufigkeit und Versorgungsgeschehen in Deutschland.

BACKGROUND: Despite their frequent occurrence, there are no standardized recommendations for treating distal forearm fractures in growing children. Due to the marked remodelling capacity, conservative therapy is the first choice treatment of fractures in children. However, there are concerns that the possibilities of conservative treatments are often underestimated. Information on the health care situation in Germany on this issue is scarce. METHODS: The present study is based on routine data of a German Health Insurance fund, the Gmünder ErsatzKasse (GEK). Data on diagnoses and treatment of insured persons aged 0-15 years were analysed for the period from 01/07/2005 to 30/06/2009 regarding the frequency of distal forearm fractures and fracture treatment. RESULTS: The overall incidence rate was 56.8 per 10 000 person-years (64.5 in boys; 48.7 in girls). Most of the distal forearm fractures occurred during spring and summer months. The majority of the fractures were immobilized in a plaster cast (84.2%; n=2 609). 8.7% (n=270) of the fractures were treated with closed reduction and percutaneous osteosynthesis. 4.5% (n=138) were treated with closed reduction without any form of osteosynthesis. Only 1.4% (n=43) of the fractures were treated with open reduction. CONCLUSION: Our study shows that boys suffer distal forearm fractures more frequently than girls and that incidences tend to be higher in older children. In addition, analyses indicated seasonal differences between the age groups. In childhood, distal forearm fractures were treated more often conservatively than operatively. However, it was remarkable that fractures in the case of closed reduction were more frequently fixed with an osteosynthesis than just by immobilization in a plaster cast.

Use of psychotropic drugs in patients with autism spectrum disorders: a systematic review.

OBJECTIVE: The objective of this review was to examine prevalence and patterns of psychopharmacotherapy in individuals with autism spectrum disorder (ASD). METHOD: A systematic literature search in PubMed, CINAHL, and PsycINFO was performed, including articles published up to November 18, 2015. RESULTS: A total of 47 studies (data collection: 1976-2012), encompassing >300 000 individuals with ASD, were included. The prevalence of psychopharmacotherapy ranged from 2.7% to 80% (median (overall): 45.7%; median (children): 41.9%; median (adults): 61.5%), with psychotropic polypharmacy occurring in 5.4-54% (median: 23.0%). Regarding drug classes, antipsychotics were most frequently used, followed by attention-deficit/hyperactivity disorder (ADHD) medication and antidepressants. Both older age and psychiatric comorbidity were associated with higher prevalences of psychopharmacotherapy and psychotropic polypharmacy. There were no time trends in psychopharmacotherapy prevalence observable. CONCLUSION: Despite a lack of pharmacological treatment options for ASD core symptoms, the prevalence of psychopharmacotherapy and polypharmacy in ASD patients is considerable, which is probably due to the treatment of non-core ASD symptoms and psychiatric comorbidities. While there is some evidence for the use of antipsychotics and ADHD medication for these indications, the use of antidepressants should be limited to selected cases.

Recombinant inbred lines derived from wide crosses in Pisum.

Genomic resources are becoming available for Pisum but to link these to phenotypic diversity requires well marked populations segregating for relevant traits. Here we describe two such resources. Two recombinant inbred populations, derived from wide crosses in Pisum are described. One high resolution mapping population involves cv Caméor, for which the first pea whole genome assembly was obtained, crossed to JI0281, a basally divergent P. sativum sativum landrace from Ethiopia. The other is an inter sub-specific cross between P. s. sativum and the independently domesticated P. s. abyssinicum. The corresponding genetic maps provide information on chromosome level sequence assemblies and identify structural differences between the genomes of these two Pisum subspecies. In order to visualise chromosomal translocations that distinguish the mapping parents, we created a simplified version of Threadmapper to optimise it for interactive 3-dimensional display of multiple linkage groups. The genetic mapping of traits affecting seed coat roughness and colour, plant height, axil ring pigmentation, leaflet number and leaflet indentation enabled the definition of their corresponding genomic regions. The consequence of structural rearrangement for trait analysis is illustrated by leaf serration. These analyses pave the way for identification of the underlying genes and illustrate the utility of these publicly available resources. Segregating inbred populations derived from wide crosses in Pisum, together with the associated marker data, are made publicly available for trait dissection. Genetic analysis of these populations is informative about chromosome scale assemblies, structural diversity in the pea genome and has been useful for the fine mapping of several discrete and quantitative traits.

Assessment of Autism Spectrum Disorder in Deaf Adults with Intellectual Disability: Feasibility and Psychometric Properties of an Adapted Version of the Autism Diagnostic Observation Schedule (ADOS-2).

This study describes the adaptation of the autism diagnostic observation schedule (ADOS-2) to assess autism spectrum disorder (ASD) in adults with intellectual disability (ID) and hearing loss who communicate primarily visually. This adapted ADOS-2 was applied to residents of specialized therapeutic living communities (n = 56). The internal consistency of the adapted ADOS-2 was excellent for the Social Affect of modules 2 and 3 and acceptable for Restricted and Repetitive Behaviors subscale of module 2, but poor for module 3. Interrater reliability was comparable to standard ADOS-2 modules 1-3. Results suggest that autism symptoms of deaf adults with ID can be reliably identified by an adapted ADOS-2, provided adequate expertise in deafness, ID, ASD and proficiency in signed language by the administrator.

Screening for autism spectrum disorder in deaf adults with intellectual disability: Feasibility and accuracy of two autism screening instruments.

BACKGROUND: There is a lack of autism screening instruments for deaf or hard of hearing (DHH) adults with intellectual disability. AIMS: This study examined the diagnostic validity of the Pervasive Developmental Disorder in Mental Retardation Scale and the Diagnostic Behavioral Assessment for autism spectrum disorder - Revised in this rare population. METHODS AND PARTICIPANTS: 56 DHH adults with intellectual disability living in three specialized therapeutic communities were examined, 9 of whom met criteria for autism. OUTCOMES AND RESULTS: With minimal adaptions regarding item interpretation, both tools showed good diagnostic and high convergent validity. Items probing for difficulties in reciprocal social interaction and restricted interests were discriminant between individuals with and without autism. CONCLUSION: These data suggest that both autism screening tools are feasible and psychometrically sound when used with appropriate adaptations for DHH adults with intellectual disability.

A protocol for wide-scope non-target analysis of contaminants in small amounts of biota using bead beating tissuelyser extraction and LC-HRMS.

This work describes a robust and powerful method for wide-scope target and non-target analysis of xenobiotics in biota samples based on bead beating tissuelyser extraction, solid phase extraction (SPE) clean-up and further detection by liquid chromatography coupled to high resolution mass spectrometry (LC-HRMS). Unlike target methodologies, non-target methods usually aim at determining a wide range of still unknown substances with different physicochemical properties. Therefore, losses during the extraction process were minimised. Apart from that, the reduction of possible interferences showed to be necessary to expand the number of compounds that can be detected. This was achieved with an additional SPE clean-up step carried out with mixed-bed multi-layered cartridges. The method was validated with a set of 27 compounds covering a wide range of physicochemical properties, and further applied to the analysis of krill and fish samples.•The bead beating extraction was efficient for a wide range of organic pollutants in small quantities of biota samples.•Multi-layered solid phase extraction clean-up yield a wide xenobiotics coverage reducing matrix effects.•Method validation with 27 compounds led to a suitable method for non-target analysis of organic pollutants in biota.

Factors affecting the chemical durability of glass used in the pharmaceutical industry.

Delamination, or the generation of glass flakes in vials used to contain parenteral drug products, continues to be a persistent problem in the pharmaceutical industry. To understand all of the factors that might contribute to delamination, a statistical design of experiments was implemented to describe this loss of chemical integrity for glass vials. Phase I of this study focused on the effects of thermal exposure (prior to product filling) on the surface chemistry of glass vials. Even though such temperatures are below the glass transition temperature for the glass, and parenteral compounds are injected directly into the body, data must be collected to show that the glass was not phase separating. Phase II of these studies examined the combined effects of thermal exposure, glass chemistry, and exposure to pharmaceutically relevant molecules on glass delamination. A variety of tools was used to examine the glass and the solution contained in the vial including: scanning electron microscopy and dynamic secondary ion mass spectroscopy for the glass; and visual examination, pH measurements, laser particle counting, and inductively coupled plasma-optical emission spectrometry for the analysis of the solution. The combined results of phase I and II showed depyrogenation does not play a significant role in delamination. Terminal sterilization, glass chemistry, and solution chemistry are the key factors in the generation of glass flakes. Dissolution of silica may be an effective indicator that delamination will occur with a given liquid stored in glass. Finally, delamination should not be defined by the appearance of visible glass particulates. There is a mechanical component in the delamination process whereby the flakes must break away from the interior vial surface. Delamination should be defined by the observation of flakes on the interior surface of the vial, which can be detected by several other analytical techniques.

Inadvertent neuraxial block placement at or above the L1-L2 interspace in the super-obese parturient: a retrospective study.

BACKGROUND: Increasing body mass index (BMI) increases the difficulty of neuraxial procedures. We hypothesized that it may put patients at risk for inappropriately high dural puncture. The accuracy of anesthesiologists' estimates of the interspinous level in super-obese parturients has not been studied. We evaluated the frequency of inadvertently high epidural and/or intrathecal catheter placement (at or above the L1/L2 interspace) in parturients of BMI ≥50 kg/m2. METHODS: Inclusion criteria for this retrospective study were women with a BMI ≥50 kg/m2 who delivered by cesarean with an epidural or intrathecal catheter. The primary outcome was the percentage of catheters placed at or above L1/L2, determined by reviewing the retained foreign object radiograph. Secondary outcomes were agreement between the estimated and actual catheter location and subgroup analysis of catheters placed under ultrasound guidance. RESULTS: After excluding 15 cases for which the catheter location could not be determined and 10 cases for which the estimated level of insertion was not recorded, 125 cases were included. Inadvertent high placement occurred in 26/125 (21%, 95% confidence interval (CI) 15% to 29%) patients. There was poor agreement between the estimated and actual catheter location (27% accurate, unweighted κ-statistic 0.02). Eleven of 39 catheters placed with ultrasound (28%, 95% CI 17% to 44%) were at or above L1/L2 compared with 15/86 catheters placed without ultrasound (17%, 95% CI 11% to 27%, P=0.17). There were no neurological complications. CONCLUSIONS: A high rate of inadvertently high epidural or intrathecal catheter placement occurs in super-obese parturients. Ultrasound did not prevent this.

Pre-eclampsia through the eyes of the obstetrician and anesthesiologist.

Due to the high risk of morbidity and mortality from unrecognized and untreated pre-eclampsia, clinicians should have a high index of suspicion to evaluate, treat and monitor patients presenting with signs concerning for pre-eclampsia. Early blood pressure management and seizure prophylaxis during labor are critical for maternal safety. Intrapartum, special anesthetic considerations should be employed to ensure the safety of the parturient and fetus. Patients who have pre-eclampsia should be aware that they are at high risk for the future development of cardiovascular disease.

UNIFOLIATA regulates leaf and flower morphogenesis in pea.

BACKGROUND: The vegetative phenotype of the pea mutant unifoliata (uni) is a simplification of the wild-type compound leaf to a single leaflet. Mutant uni plants are also self-sterile and the flowers resemble known floral meristem and organ identity mutants. In Antirrhinum and Arabidopsis, mutations in the floral meristem identity gene FLORICAULA/LEAFY (FLO/LFY) affect flower development alone, whereas the tobacco FLO/LFY homologue, NFL, is expressed in vegetative tissues, suggesting that NFL specifies determinacy in the progenitor cells for both flowers and leaves. In this paper, we characterised the pea homologue of FLO/LFY. RESULTS: The pea cDNA homologue of FLO/LFY, PEAFLO, mapped to the uni locus in recombinant-inbred mapping populations and markers based on PEAFLO cosegregated with uni in segregating sibling populations. The characterisation of two spontaneous uni mutant alleles, one containing a deletion and the other a point mutation in the PEAFLO coding sequences, predicted that PEAFLO corresponds to UNI and that the mutant vegetative phenotype was conferred by the defective PEAFLO gene. CONCLUSIONS: The uni mutant demonstrates that there are shared regulatory processes in the morphogenesis of leaves and flowers and that floral meristem identity genes have an extended role in plant development. Pleiotropic regulatory genes such as UNI support the hypothesis that leaves and flowers derive from a common ancestral sporophyll-like structure. The regulation of indeterminancy during leaf and flower morphogenesis by UNI may reflect a primitive function for the gene in the pre-angiosperm era.

Biomimetic Remineralization of Carious Lesions by Self-Assembling Peptide.

Caries is the most common disease in the world. Great efforts have been undertaken for prevention and to identify a regenerative treatment solution for dental caries. Self-assembling ß-sheet forming peptides have previously shown to form 3-dimensional fiber networks supporting tissue regeneration. In particular, the self-assembling peptide P11-4 has shown potential in the treatment and prevention of dental caries. It has previously been shown that application of monomeric P11-4 solution to early carious lesions can increase net mineral gain by forming de novo hydroxyapatite crystals. The hypothesis for the mode of action was that monomeric self-assembling peptide P11-4 diffuses into the subsurface lesion body and assembles therein into higher order fibrils, facilitating mineralization of the subsurface volume by mimicking the natural biomineralization of the tooth enamel, and it remains within the lesion body as a scaffold built-in by the newly formed hydroxyapatite. The aim of the present study was to investigate the mechanism of action of the self-assembling peptide P11-4 supporting mineralization of carious enamel. By various analytical methods, it could be shown that the self-assembling peptide P11-4 diffuses into the subsurface lesion, assembles into higher formed aggregates throughout the whole volume of the lesion, and supports nucleation of de novo hydroxyapatite nanocrystals and consequently results in increased mineral density within the subsurface carious lesion. The results showed that the application of self-assembling peptide P11-4 can facilitate the subsurface regeneration of the enamel lesion by supporting de novo mineralization in a similar mode of action as has been shown for the natural formation of dental enamel.

Endothelial dysfunction in patients with chronic heart failure: systemic effects of lower-limb exercise training.

OBJECTIVES: We sought to analyze the systemic effects of lower-limb exercise training (ET) on radial artery endothelial function in patients with chronic heart failure (CHF). BACKGROUND: Local ET has the potential to improve local endothelial dysfunction in patients with CHF. However, it remains unclear whether the systemic effects can be achieved by local ET. METHODS: Twenty-two male patients with CHF were prospectively randomized to either ET on a bicycle ergometer (ET group, n = 11; left ventricular ejection fraction [LVEF] 26 +/- 3%) or an inactive control group (group C, n = 11; LVEF 24 +/- 2%). At the beginning of the study and after four weeks, endothelium-dependent and -independent vasodilation of the radial artery was determined by intra-arterial infusion of acetylcholine (ACh-7.5, 15 and 30 microg/min) and nitroglycerin (0.2 mg/min). The mean internal diameter (ID) of the radial artery was assessed using a high resolution ultrasound system (NIUS-02, Asulab Research Laboratories, Neuchâtel, Switzerland) with a 10-MHz probe. RESULTS: After four weeks of ET, patients showed a significant increase in the baseline-corrected mean ID in response to ACh (30 microg/min), from 33 +/- 10 to 127 +/- 25 microm (p < 0.001 vs. control group at four weeks). In the control group, the response to ACh (30 microg/min) remained unchanged. Endothelium-independent vasodilation was similar in both groups at the beginning of the study and at four weeks. In the training group, increases in agonist-mediated, endothelium-dependent vasodilation correlated to changes in functional work capacity (r = 0.63, p < 0.05). CONCLUSIONS: In patients with stable CHF, bicycle ergometer ET leads to a correction of endothelial dysfunction of the upper extremity, indicating a systemic effect of local ET on endothelial function.

Oxygen-isotope effect on the In-plane penetration depth in underdoped La2-xSrxCuO4 single crystals

We report measurements of the oxygen-isotope effect (OIE) on the in-plane penetration depth lambda(ab)(0) in underdoped La2-xSrxCuO4 single crystals. A highly sensitive magnetic torque sensor with a resolution of Deltatau approximately 10(-12) N m was used for the magnetic measurements on microcrystals with a mass of approximately 10 &mgr;g. The OIE on lambda(-2)(ab)(0) is found to be -10(2)% for x = 0.080 and -8(1)% for x = 0.086. It arises mainly from the oxygen-mass dependence of the in-plane effective mass m(*)(ab). The present results suggest that lattice vibrations are important for the occurrence of high temperature superconductivity.

Beta2-adrenergic receptor polymorphisms at codon 16, cardiovascular phenotypes and essential hypertension in whites and African Americans.

Beta2-adrenergic receptors (beta2-AR) contribute to cardiovascular regulation by influencing several functions and previous studies suggest that a decreased function of the beta2-AR may be involved in essential hypertension. Beta2-AR are polymorphic and certain polymorphisms of these receptors are of functional importance. We focus here on the Arg16-->Gly16 beta2-AR polymorphism, which shows enhanced agonist-promoted downregulation of the receptor and which, in two recent studies, yielded opposite results in terms of association with essential hypertension: an increased frequency of the Gly16 variant in African-Caribbean hypertensives and of the Arg16 variant in offspring of Norwegian white hypertensive parents. In the current study, we genotyped 243 subjects, including both African-American and white individuals, for codon 16 polymorphism and assessed blood pressure and cardiovascular function using impedance cardiography and pressor sensitivity to phenylephrine. We found similar patterns of cardiovascular function and expression of hypertension with the two genotypes of codon 16. There was no statistically significant difference in the overall allelic distribution of the two genotypes: among African-Americans, 51% of the hypertensives and 50% of the normotensives carried the Arg16 allele, whereas among the white subjects 40% of the hypertensives and 47% of the normotensives were carriers of the Arg16 allele. Although we observed a statistically significant increase in the Arg16/Gly16 heterozygotes in the African-American population, the Gly16 allele was not significantly increased in the African-Americans compared to whites. These findings indicate that the codon 16 polymorphisms are not associated with hypertension in a mixed American study population nor do they appear to substantially impact on a variety of hemodynamic variables.

Structured use of the median in the analytical measurement process.

In the pharmaceutical industry, the process of measuring a product's attributes can be very complicated and the potential for an analytical mistake can be quite high. Often, an unexpected result leads to an investigation to assess the possibility that a mistake was made in the laboratory. Traditionally, the data generated in these investigations has been used, along with various outlier tests, to attempt to negate the original data. Sometimes, historical estimates of the S.D. of the analytical method are not available for use in outlier testing and the power of the outlier tests to detect true mistakes without such historical estimates is often very low due to the small amount of data available. This leads to a great deal of inconsistency in the amount of data that is further generated and how the data is ultimately handled in making a decision. Recently, FDA demands for consistent and objective laboratory investigations have raised concerns about these practices. An alternative approach, involving a systematic investigation strategy and data handling via the structured use of the median, is proposed in this paper. The operating characteristics of the traditional and proposed approaches are compared to show their similarity and the advantages of the proposed approach. It is strongly believed by the authors that the structured use of the median will lead to more consistent investigations and data handling, which will benefit industry, the FDA and ultimately, the consumer, by allowing more accurate decisions to be made more efficiently.

Evaluation of key sources of variability in the measurement of pharmaceutical drug products by near infrared reflectance spectroscopy.

Potential sources of variability in the measurement of solid oral drug products by near infrared reflectance spectroscopy were evaluated with statistical experimental design. Spectra were collected for two different tablet types according to the data collection and treatment parameters defined by the experimental design. Each tablet had three different dose-levels. Libraries were constructed using second-derivative spectra. Key figures-of-merit generated during internal and external library validation were used to calculate which parameters most strongly influence the library performance for dose-level discrimination. These responses and their corresponding experimental conditions were evaluated with the screening model in the JMP program. Segment value used for the second-derivative calculation was an an influential factor and had a complex effect. Orientation on the sampling platform also had an influential effect for embossed tablets. Collection of spectra over fewer days decreased variability within the library. More frequent reference spectrum collection improved the performance of libraries to a small degree. A larger sample population increased the range of spectral variability within a dose-level but apparently not the overall performance of the library. The number of scans averaged per spectrum was not an influential factor in this study. These results are summarized and used to recommend an approach to dose-level discrimination.

Statistical approaches to determine analytical variability and specifications: application of experimental design and variance component analysis.

Assessment of analytical variability is recognized as an important factor for the establishment of specifications. Estimation of the variance for an analytical procedure can be accomplished using a variety of approaches. The approach of variance component analysis was applied retrospectively, as well as prospectively, to estimate analytical variance. The prospective approach also included the use of experimental design. Recent new drug substance examples illustrating these approaches are presented. In these examples, the analytical property of potency was evaluated. Factors examined in the experimental design include laboratory, day, analyst, instrument and column. Process variability can also be determined by variance component analysis. For a stable drug substance, combining the analytical and process variances provides an estimate on the total variance for the analytical property of potency. With the total variability statistically derived, an appropriate specification that is consistent with process and analytical capability can be established.

[Familial Mediterranean fever. Case of a 48-year-old patient with recurrent abdominal pain]. / Familiäres Mittelmeerfieber. Ein Fall eines 48 Jahre alten Patienten mit rezidivierenden Bauchschmerzen.

A 48 year-old male patient from Turkey underwent laparotomy 13 years before admission to one unit because of persistent pain in the upper abdomen and fever. Subsequently, he was repeatedly admitted to surgical departments with recurrent upper abdominal pain and fever. The patient was admitted for medical investigation to our department with fever and left pleuritic pain. During this observation period he repeatedly had attacks of fever lasting for one day with leucocytosis. The diagnosis of familial Mediterranean fever was made. Therapy with colchicine (1.5 mg/day) led to complete remission, maintained over the follow-up period of 2 years to date.