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.

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.

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.

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.

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.

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.

[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.

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.

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.

Cooling-by-measurement and mechanical state tomography via pulsed optomechanics.

Observing a physical quantity without disturbing it is a key capability for the control of individual quantum systems. Such back-action-evading or quantum non-demolition measurements were first introduced in the 1970s for gravitational wave detection, and now such techniques are an indispensable tool throughout quantum science. Here we perform measurements of the position of a mechanical oscillator using pulses of light with a duration much shorter than a period of mechanical motion. Utilizing this back-action-evading interaction, we demonstrate state preparation and full state tomography of the mechanical motional state. We have reconstructed states with a position uncertainty reduced to 19 pm, limited by the quantum fluctuations of the optical pulse, and we have performed 'cooling-by-measurement' to reduce the mechanical mode temperature from an initial 1,100 to 16 K. Future improvements to this technique will allow for quantum squeezing of mechanical motion, even from room temperature, and reconstruction of non-classical states exhibiting negative phase-space quasi-probability.

Mid-infrared optical frequency combs at 2.5 µm based on crystalline microresonators.

The mid-infrared spectral range (λ~2-20 µm) is of particular importance as many molecules exhibit strong vibrational fingerprints in this region. Optical frequency combs--broadband optical sources consisting of equally spaced and mutually coherent sharp lines--are creating new opportunities for advanced spectroscopy. Here we demonstrate a novel approach to create mid-infrared optical frequency combs via four-wave mixing in a continuous-wave pumped ultra-high Q crystalline microresonator made of magnesium fluoride. Careful choice of the resonator material and design made it possible to generate a broadband, low-phase noise Kerr comb at λ=2.5 µm spanning 200 nm (≈10 THz) with a line spacing of 100 GHz. With its distinguishing features of compactness, efficient conversion, large mode spacing and high power per comb line, this novel frequency comb source holds promise for new approaches to molecular spectroscopy and is suitable to be extended further into the mid-infrared.

[Sepsis in a woman with severe portosystemic encephalopathy. An uncommon complication of drug therapy]. / Sepsis bei einer Patientin mit portosystemischer Enzephalopathie.

HISTORY: A 60-year-old woman was referred to our hospital, because she was unarousable. She was known to have an impaired liver function due to long-lasting alkohol abuse. Third-party medical history did not explain the patient's condition. TREATMENT AND COURSE: The history and laboratory findings suggested hepatic coma, therefore treatment with ornithin-aspartat, rifaximin, lactulose and antibiotics was started. Lactate concentration indicated severe hypoxic damage. The clinical examinations and circulatory parameters lead to the diagnosis of sepsis, which was suspected to be caused by spontaneous bacterial peritonitis. Computed tomography of the abomen demonstrated colitis but no other pathologic intestinal finding. Inspite of intensive therapy with antibiotics, fluids and catecholamines the patient died 3 days after admission. Autopsy revealed the cause of sepsis: a tablet, swallowed with its blister package had led to a perforation of the terminal ileum. CONCLUSION: Apart from the most cause of peritonitis in patients with liver cirrhosis - the spontaneous bacterial peritonitis - a secondary cause must also be taken into account as a reason for sepsis. A well prepared history could possibly show the direction for detection of the cause.

Detection of tumour necrosis factor-alpha in dogs with lymphoma(*).

Tumour necrosis factor-alpha (TNF-α) production by malignant lymphoblasts has been identified in vitro and in vivo in mice and humans, respectively. The goals of this study were (1) to evaluate a novel single-sample TNF-α assay and (2) to determine whether TNF-α is increased in dogs with lymphoma prior to and following treatment. Canine TNF-α was analysed concurrently using the novel Siemens Immulite® single-sample automated ELISA and the previously validated Quantikine® standard ELISA. Serum from dogs with lymphoma and from breed-, age- and gender-matched control dogs was evaluated at two time points. Three of 25 (12%) dogs with lymphoma had detectable TNF-α at diagnosis, whereas none had detectable TNF-α following complete or partial remission. TNF-α was not detectable in control dogs. Despite 91% homology between human and canine TNF-α, the Immulite® automated ELISA failed to detect canine TNF-α. Serum TNF-α appears to have limited value as a tumour marker in dogs with lymphoma.

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.

Oesophagoscopy and detection of viral nucleic acids in oesophageal biopsies--A contribution to BVDV diagnosis.

The endoscopic appearance of the oesophagus of animals infected with bovine virus diarrhoea virus (BVDV) but without signs of acute mucosal disease (MD) was investigated for any common or 'early warning' lesions. Thirty-seven BVDV-infected animals [36 persistently infected (PI) and one transiently infected] were examined clinically and endoscopically for typical erosions of the oronasal and oesophageal mucosa, respectively. During oesophagoscopy, mucosal biopsies were taken and tested for pestivirus-specific nucleic acids by reverse transcription polymerase chain reaction (RT-PCR). The results were compared with those of RT-PCR with various sample materials (blood, nasal and conjunctival swabs and faecal samples) usually used for routine diagnosis of BVDV infection. The average age of the 36 PI animals was 13.5 months, eight animals were 24 months or older. None of the PI animals had clinically visible erosions of the oronasal mucous membranes. During oesophagoscopy, all animals showed a reddening but unexpectedly no erosions or ulcerations of the oesophageal mucosa. Although in 21 of 36 PI animals all samples tested positive, the oesophageal biopsies were with no exception constantly RT-PCR positive in contrast to all other materials investigated. Remarkably, in the transiently infected animal all samples tested negative except for the oesophageal biopsy. Hence, this infection would have been missed by conventional diagnostic sampling.

Severe heart failure from light chain cardiomyopathy (cardiac amyloidosis).

Primary (AL)amyloidosis is characterized by clonal production of immunoglobulin with subsequent deposition in several organs. We describe the clinical features of a 66-year old female who was referred to our department for congestive heart failure. One year before, she was examined and found to have diastolic dysfunction of the left ventricle. We could evaluate the diagnosis of primary amyloid cardiomyopathy by echocardiography, Doppler echocardiography and laboratory findings and confirmed the diagnosis by biopsy of the rectum mucosa. Clinical outcome was poor, because therapy is poor.

Superior vena cava syndrome: relief with a modified saphenojugular bypass graft.

Superior vena cava (SVC) syndrome is a disabling and potentially life-threatening complication. SVC revascularization can be achieved by means of endovascular or direct surgical reconstructions. In the patient on whom we report, these two options were not possible, and a peripheral venous bypass grafting procedure was done with a technical innovation. Right upper-extremity swelling developed in a 55-year-old woman after radiation therapy for lung carcinoma. A left subclavian vein Port-A-Cath induced extensive thrombosis of the left innominate, axillosubclavian, and jugular veins. She was referred to our institution with very symptomatic SVC syndrome after two failed endovascular interventions. The occlusion of both innominate veins and chronic thrombus extending into the left axillosubclavian and internal jugular veins was confirmed by means of a venogram. A third endovascular attempt failed. The presternal skin had severe radiation-induced damage precluding direct SVC reconstruction. A bypass grafting procedure from the right internal jugular to the femoral vein was performed with spliced bilateral greater saphenous veins tunneled inside an externally supported expanded polytetrafluoroethylene graft. Postoperatively, the patient had no symptoms, and graft patency was confirmed by means of duplex ultrasound scanning. A saphenojugular bypass grafting procedure can offer prompt and durable relief of SVC syndrome when endovascular or direct surgical reconstructions are not possible. This rarely used peripheral venous bypass grafting procedure was modified by tunneling the vein graft inside an externally supported polytetrafluoroethylene graft to prevent kinking or compression.