Large-Momentum-Transfer Atom Interferometers with µrad-Accuracy Using Bragg Diffraction.

Large-momentum-transfer (LMT) atom interferometers using elastic Bragg scattering on light waves are among the most precise quantum sensors to date. To advance their accuracy from the mrad to the µrad regime, it is necessary to understand the rich phenomenology of the Bragg interferometer, which differs significantly from that of a standard two-mode interferometer. We develop an analytic model for the interferometer signal and demonstrate its accuracy using comprehensive numerical simulations. Our analytic treatment allows the determination of the atomic projection noise limit of a LMT Bragg interferometer and provides the means to saturate this limit. It affords accurate knowledge of the systematic phase errors as well as their suppression by 2 orders of magnitude down to a few µrad using appropriate light-pulse parameters.

Momentum Entanglement for Atom Interferometry.

Compared to light interferometers, the flux in cold-atom interferometers is low and the associated shot noise is large. Sensitivities beyond these limitations require the preparation of entangled atoms in different momentum modes. Here, we demonstrate a source of entangled atoms that is compatible with state-of-the-art interferometers. Entanglement is transferred from the spin degree of freedom of a Bose-Einstein condensate to well-separated momentum modes, witnessed by a squeezing parameter of -3.1(8) dB. Entanglement-enhanced atom interferometers promise unprecedented sensitivities for quantum gradiometers or gravitational wave detectors.

Beaver effects on macroinvertebrate assemblages in two streams with contrasting morphology.

Beaver populations are increasing throughout Europe and especially in Switzerland. Beaver are major ecological engineers of fluvial systems, dramatically influencing river morphology, ecohydrology and, consequently, aquatic and terrestrial biota. This study compared macroinvertebrate assemblages and trophic structure at two beaver complexes with contrasting topography in Switzerland over an annual cycle. One complex (Marthalen) was in a low gradient open basin, whereas the other complex (Flaach) flowed through a higher gradient ravine-like basin. Both complexes were embedded in an overall agricultural landscape matrix. Water physico-chemistry differed between the two complexes with nitrogen, phosphorus, and DOC being higher at Marthalen than at Flaach. Both complexes showed strong seasonality in physico-chemistry, but retention of nutrients (N, P) was highest in summer and only at Marthalen. Both complexes also showed strong seasonality in macroinvertebrate assemblages, although assemblages differed substantially between complexes. At Marthalen, macroinvertebrate assemblages were predominantly lentic in character at 'pool' sites within the complex. At Flaach, lotic macroinvertebrate assemblages were common at most sites with some lentic taxa also being present. Dietary shifts based on carbon/nitrogen stable isotopes occurred in spring and summer among sites at both complexes (autochthonous resource use increasing over allochthonous resource use downstream), although being most pronounced at Marthalen. In contrast, similar resource use across sites occurred in winter within both complexes. Although beaver significantly influenced fluvial dynamics and macroinvertebrate assemblage structure at both complexes, this influence was most pronounced at Marthalen where beaver caused the system to become more wetland in character, e.g., via higher hydraulic residence time, than at Flaach. We conclude that topography can shape beaver effects on fluvial systems and resident biota.

Potassium channel gene associations with joint processing speed and white matter impairments in schizophrenia.

Patients with schizophrenia show decreased processing speed on neuropsychological testing and decreased white matter integrity as measured by diffusion tensor imaging, two traits shown to be both heritable and genetically associated indicating that there may be genes that influence both traits as well as schizophrenia disease risk. The potassium channel gene family is a reasonable candidate to harbor such a gene given the prominent role potassium channels play in the central nervous system in signal transduction, particularly in myelinated axons. We genotyped members of the large potassium channel gene family focusing on putatively functional single nucleotide polymorphisms (SNPs) in a population of 363 controls, 194 patients with schizophrenia spectrum disorder (SSD) and 28 patients with affective disorders with psychotic features who completed imaging and neuropsychological testing. We then performed three association analyses using three phenotypes - processing speed, whole-brain white matter fractional anisotropy (FA) and schizophrenia spectrum diagnosis. We extracted SNPs showing an association at a nominal P value of <0.05 with all three phenotypes in the expected direction: decreased processing speed, decreased FA and increased risk of SSD. A single SNP, rs8234, in the 3' untranslated region of voltage-gated potassium channel subfamily Q member 1 (KCNQ1) was identified. Rs8234 has been shown to affect KCNQ1 expression levels, and KCNQ1 levels have been shown to affect neuronal action potentials. This exploratory analysis provides preliminary data suggesting that KCNQ1 may contribute to the shared risk for diminished processing speed, diminished white mater integrity and increased risk of schizophrenia.

Change Factors in the Process of Cognitive-Behavioural Therapy for Obsessive-Compulsive Disorder.

While there is a plethora of evidence for the efficacy of cognitive-behavioural therapy (CBT) in obsessive-compulsive disorder (OCD), studies on change factors of the therapeutic process that account for this success are scarce. In the present study, 155 participants with primary OCD were investigated during CBT inpatient treatment. The Yale-Brown Obsessive-Compulsive Scale-SR served as a measure of symptom severity. In addition, the following process change factors were measured: therapeutic relationship, experience of self-esteem during therapy, experience of mastery, problem actualization and clarification. All variables were assessed on a weekly basis for seven weeks. Linear mixed growth curve analyses were conducted to model the decrease of symptoms over time and to analyse whether the change factors predicted symptom reduction. The analyses revealed a linear decrease of symptoms with high inter-individual variation. Results further showed that increase in self-esteem and mastery experiences as well as the initial score on mastery experience and clarification predicted decrease on the Y-BOCS. We conclude that CBT therapists should focus on clarification in the very first sessions, and try to boost self-esteem and self-efficacy, which is related to mastery, throughout the treatment of OCD. Copyright © 2016 John Wiley & Sons, Ltd. KEY PRACTITIONER MESSAGE: Increase in mastery and self-esteem experiences are associated with symptom decrease in obsessive-compulsive disorder (OCD) during cognitive-behavioural therapy (CBT). Initial score of mastery experiences and problem clarification predict symptom decrease in OCD during CBT. CBT therapists should focus on problem clarification in the very first sessions and try to boost self-esteem and self-efficacy throughout the treatment of OCD.

Atom-Chip Fountain Gravimeter.

We demonstrate a quantum gravimeter by combining the advantages of an atom chip for the generation, delta-kick collimation, and coherent manipulation of freely falling Bose-Einstein condensates (BECs) with an innovative launch mechanism based on Bloch oscillations and double Bragg diffraction. Our high-contrast BEC interferometer realizes tens of milliseconds of free fall in a volume as little as a one centimeter cube and paves the way for measurements with sub-µGal accuracies in miniaturized, robust devices.

Mtss1 is a critical epigenetically regulated tumor suppressor in CML.

Chronic myeloid leukemia (CML) is driven by malignant stem cells that can persist despite therapy. We have identified Metastasis suppressor 1 (Mtss1/MIM) to be downregulated in hematopoietic stem and progenitor cells from leukemic transgenic SCLtTA/Bcr-Abl mice and in patients with CML at diagnosis, and Mtss1 was restored when patients achieved complete remission. Forced expression of Mtss1 decreased clonogenic capacity and motility of murine myeloid progenitor cells and reduced tumor growth. Viral transduction of Mtss1 into lineage-depleted SCLtTA/Bcr-Abl bone marrow cells decreased leukemic cell burden in recipients, and leukemogenesis was reduced upon injection of Mtss1-overexpressing murine myeloid 32D cells. Tyrosine kinase inhibitor (TKI) therapy and reversion of Bcr-Abl expression increased Mtss1 expression but failed to restore it to control levels. CML patient samples revealed higher DNA methylation of specific Mtss1 promoter CpG sites that contain binding sites for Kaiso and Rest transcription factors. In summary, we identified a novel tumor suppressor in CML stem cells that is downregulated by both Bcr-Abl kinase-dependent and -independent mechanisms. Restored Mtss1 expression markedly inhibits primitive leukemic cell biology in vivo, providing a therapeutic rationale for the Bcr-Abl-Mtss1 axis to target TKI-resistant CML stem cells in patients.

[Independence in Plastic Surgery - Benefit or Barrier? Analysis of the Publication Performance in Academic Plastic Surgery Depending on Varying Organisational Structures]. / Vorteil durch Eigenständigkeit? Analyse der Publikationsleistung der universitären Plastischen Chirurgie in verschiedenen Organisationsstrukturen.

INTRODUCTION: Despite its recognition as an independent specialty, at German university hospitals the field of plastic surgery is still underrepresented in terms of independent departments with a dedicated research focus. The aim of this study was to analyse the publication performance within the German academic plastic surgery environment and to compare independent departments and dependent, subordinate organisational structures regarding their publication performance. MATERIAL AND METHODS: Organisational structures and number of attending doctors in German university hospitals were examined via a website analysis. A pubmed analysis was applied to assess the publication performance (number of publications, cumulative impact factor, impact factor/publication, number of publications/MD, number of publications/unit) between 2009 and 2013. In a journal analysis the distribution of the cumulative impact factor and number of publications in different journals as well as the development of the impact factor in the top journals were analysed. RESULTS: Out of all 35 university hospitals there exist 12 independent departments for plastic surgery and 8 subordinate organisational structures. In 15 university hospitals there were no designated plastic surgery units. The number of attending doctors differed considerably between independent departments (3.6 attending doctors/unit) and subordinate organisational structures (1.1 attending doctors/unit). The majority of publications (89.0%) and of the cumulative impact factor (91.2%) as well as most of the publications/MD (54 publications/year) and publications/unit (61 publications/year) were created within the independent departments. Only in departments top publications with an impact factor > 5 were published. In general a negative trend regarding the number of publications (- 13.4%) and cumulative impact factor (- 28.9%) was observed. 58.4% of all publications were distributed over the top 10 journals. Within the latter the majority of articles were published in English journals (60% of publications, 79.9% of the cumulative impact factor). The average impact factor of the top 10 journals increased by 13.5% from 2009 to 2013. CONCLUSION: In contrast to subordinate and dependent organisational structures, independent departments of plastic surgery are the key performers within German academic plastic surgery which, however, suffers from a general declining publication performance. Hence, the type of organisational structure has a crucial influence on the research performance.

[Normative Data of Pharyngeal and Upper Esophageal Sphincter High Resolution Manometry]. / Normwerte für die Hochauflösungsmanometrie von Pharynx und oberem Ösophagussphinkter.

BACKGROUND: High resolution manometry (HRM) can provide information about the muscular contraction of the pharynx and the upper esophageal sphincter (UES) and represents an important tool in the diagnostics of dysphagia. To compare the results of swallowing studies interindividually and to identify pathological swallows, normative data are necessary. Normative data for the use of an HRM-probe with a large diameter has already been published. As previously has been shown these probes can influence the normal contraction of the pharynx and the UES. In this study comprehensive normal values are presented for small HRM-probes in diameter (2 mm), that only minimally affect pharyngeal and UES contractions. METHOD: 29 healthy volunteers underwent pharyngeal and upper esophageal HRM. All subjects performed 10 water swallows of 2 ml in an upright position. Pressure and time dependent parameters of the velopharyngeal region, the tongue base and the UES have been evaluated. Mean and median values and different percentile ranges were calculated. RESULTS: The normative values for the key parameters were (mean±SD): maximum velopharyngeal pressure 269.9±113.1 mmHg, maximum tongue base pressure 278±93.6 mmHg, maximum UES pressure 205.8±64.0 mmHg, UES resting pressure 42.5±18.7 mmHg and relaxation time of the UES 681.6±86.8 ms. Further parameters have been measured. CONCLUSION: Time dependent values are comparable to those already published. Especially in the UES lower pressures can be measured when a small HRM-probe is used. The normative data established in this study might help to distinguish pathological from physiological swallows using HRM.

Composite-light-pulse technique for high-precision atom interferometry.

We realize beam splitters and mirrors for atom waves by employing a sequence of light pulses rather than individual ones. In this way we can tailor atom interferometers with improved sensitivity and accuracy. We demonstrate our method of composite pulses by creating a symmetric matter-wave interferometer which combines the advantages of conventional Bragg- and Raman-type concepts. This feature leads to an interferometer with a high immunity to technical noise allowing us to devise a large-area Sagnac gyroscope yielding a phase shift of 6.5 rad due to the Earth's rotation. With this device we achieve a rotation rate precision of 120 nrad s(-1) Hz(-1/2) and determine the Earth's rotation rate with a relative uncertainty of 1.2%.

Concentrations of hormones, pharmaceuticals and other micropollutants in groundwater affected by septic systems in New England and New York.

Septic-system discharges can be an important source of micropollutants (including pharmaceuticals and endocrine active compounds) to adjacent groundwater and surface water systems. Groundwater samples were collected from well networks tapping glacial till in New England (NE) and sandy surficial aquifer New York (NY) during one sampling round in 2011. The NE network assesses the effect of a single large septic system that receives discharge from an extended health care facility for the elderly. The NY network assesses the effect of many small septic systems used seasonally on a densely populated portion of Fire Island. The data collected from these two networks indicate that hydrogeologic and demographic factors affect micropollutant concentrations in these systems. The highest micropollutant concentrations from the NE network were present in samples collected from below the leach beds and in a well downgradient of the leach beds. Total concentrations for personal care/domestic use compounds, pharmaceutical compounds and plasticizer compounds generally ranged from 1 to over 20 µg/L in the NE network samples. High tris(2-butoxyethyl phosphate) plasticizer concentrations in wells beneath and downgradient of the leach beds (>20 µg/L) may reflect the presence of this compound in cleaning agents at the extended health-care facility. The highest micropollutant concentrations for the NY network were present in the shoreline wells and reflect groundwater that is most affected by septic system discharges. One of the shoreline wells had personal care/domestic use, pharmaceutical, and plasticizer concentrations ranging from 0.4 to 5.7 µg/L. Estradiol equivalency quotient concentrations were also highest in a shoreline well sample (3.1 ng/L). Most micropollutant concentrations increase with increasing specific conductance and total nitrogen concentrations for shoreline well samples. These findings suggest that septic systems serving institutional settings and densely populated areas in coastal settings may be locally important sources of micropollutants to adjacent aquifer and marine systems.

Molecular wires--impact of π-conjugation and implementation of molecular bottlenecks.

In this review we highlight recent progress in the field of photochemically and thermally induced electron transport through molecular bridges as integrative parts of electron donor-bridge-acceptor conjugates. The major emphasis is hereby on the design and the modular composition of the bridges. To this end, we will demonstrate that control over attenuation factors and reorganization energies, on one hand, as well as electronic and electron-vibration couplings, on the other hand, enables tuning electron transport over distances as short as 3.5 Å and as large as 50 Å by up to nine orders of magnitude. In terms of electron transport, the maximum extreme is given by carbon-bridged oligo-p-phenylenevinylenes of different lengths, while a zinc tetraphenylporphyrin free base tetraphenylporphyrin dyad constitutes the minimum extreme.

Zinc: an underappreciated modulatory factor of brain function.

The divalent cation, zinc is the second most abundant metal in the human body and is indispensable for life. Zinc concentrations must however, be tightly regulated as deficiencies are associated with multiple pathological conditions while an excess can be toxic. Zinc plays an important role as a cofactor in protein folding and function, e.g. catalytic interactions, DNA recognition by zinc finger proteins and modulation ion channel activity. There are 24 mammalian proteins specific for zinc transport that are subdivided in two groups with opposing functions: ZnT proteins reduce cytosolic zinc concentration while ZIP proteins increase it. The mammalian brain contains a significant amount of zinc, with 5-15% concentrated in synaptic vesicles of glutamatergic neurons alone. Accumulated in these vesicles by the ZnT3 transporter, zinc is released into the synaptic cleft at concentrations from nanomolar at rest to high micromolar during active neurotransmission. Low concentrations of zinc modulate the activity of a multitude of voltage- or ligand-gated ion channels, indicating that this divalent cation must be taken into account in the analysis of the pathophysiology of CNS disorders including epilepsy, schizophrenia and Alzheimer's disease. In the context of the latest findings, we review the role of zinc in the central nervous system and discuss the relevance of the most recent association between the zinc transporter, ZIP8 and schizophrenia. An enhanced understanding of zinc transporters in the context of ion channel modulation may offer new avenues in identifying novel therapeutic entities that target neurological disorders.

Secondary prophylaxis in an adult patient with severe haemophilia A. Factor VIII consumption and effectiveness.

UNLABELLED: Primary prophylaxis has been proven as the gold standard for preserving joint function in severe haemophilia. Secondary prophylaxis in children has also been shown to have a more beneficial effect on joint protection as on-demand treatment. The outcome of delayed secondary prophylaxis started in adulthood is rarely studied. The case of a man (age: 47 years) with severe haemophilia A demonstrates the successful switch from on-demand therapy to prophylaxis with subsequent reduction of annual bleeding rate and number of days of work lost. The small increase of factor VIII consumption (16%) and the decrease of bleeding rate are compared with data from two recently published prospective studies. CONCLUSION: An optimal dosing schedule needs to be discussed and larger and longer prospective studies targeting the benefits of secondary prophylaxis with factor VIII started in adulthood are necessary.

Comparison of bacterial adhesion and cellular proliferation on newly developed three-dimensional scaffolds manufactured by rapid prototyping technology.

Scaffolds used in the field of tissue engineering should facilitate the adherence, spreading, and ingrowth of cells as well as prevent microbial adherence. For the first time, this study simultaneously deals with microbial and tissue cell adhesion to rapid prototyping-produced 3D-scaffolds. The cell growth of human osteosarcoma cells (CAL-72) over a time period of 3-11 days were examined on three scaffolds (PLGA, PLLA, PLLA-TCP) and compared to the adhesion of salivary microorganisms and representative germs of the oral flora (Porphyromonas gingivalis, Prevotella nigrescens, Candida albicans, Enterococcus faecalis, Streptococcus mutans, and Streptococcus sanguinis). Scanning electron microscopy (SEM), cell proliferation measurements, and determination of the colony forming units (CFU) were performed. The cell proliferation rates on PLLA and PLLA-TCP after 3, 7, and 11 days of cultivation were higher than on PLGA. On day 3 the proliferation rates on PLLA and PLLA-TCP, and on day 5 on PLLA-TCP, proved to be significantly higher compared to that of the control (culture plate). The strain which showed the most CFUs on all of the investigated scaffolds was P. gingivalis, followed by E. faecalis. No significant CFU differences were determined examining P. gingivalis among the biomaterials. In contrast, E. faecalis was significantly more adherent to PLGA and PLLA compared to PLLA-TCP. The lowest CFU values were seen with C. albicans and P. nigrescens. Salivary born aerobic and anaerobic microorganisms adhered significantly more to PLGA compared to PLLA-TCP. These results supported by SEM point out the high potential of PLLA-TCP in the field of tissue engineering.

Malignant melanoma and Wiedemann-Beckwith syndrome in childhood.

Patients with Wiedemann-Beckwith syndrome (WBS, MIM 130650), a congenital overgrowth syndrome, have a known increased tumor risk especially for embryonic tumors. WBS belongs to the "imprinting" syndromes caused by overexpression of IGF2 and/or loss of CDKN1C on chromosome 11p15.5. A 13-year-old boy with WBS developed a spitzoid malignant melanoma (Clark level V, Breslow index 4.8 mm) on the right cheek. Genetic analyses of the patient's blood showed hypermethylation at the H19 locus on chromosome 11p. The (epi)genetic changes of the WBS locus might have played a role in the pathogenesis of melanoma development.

Acute tubulointerstitial nephritis related to antituberculous drug therapy.

BACKGROUND: Acute tubulointerstitial nephritis (ATIN) as a complication of antituberculous therapy has been most commonly reported due to rifampicin therapy. This reaction typically occurs following re-exposure to the drug. This study undertook to investigate the clinicopathological features of ATIN related to antituberculous therapy. METHODS: We performed a retrospective study of all adult patients with a biopsy-proven diagnosis of ATIN on chemotherapy for tuberculosis. The patients presented with acute renal failure at our institution during 1995 - 2007. The demographic, clinical, biochemical and histopathological features were studied. The patient outcome and management were analyzed. RESULTS: 41 patients had histologically proven ATIN. 23 (56%) were female. The mean age at presentation was 42 years. The most common regimen included rifampicin used intermittently to treat pulmonary tuberculosis. The average duration of antituberculosis therapy was 19 days before presentation and the duration of the acute illness averaged 5 days. The most common clinical manifestation included gastro-intestinal symptoms occurring in 35 (85%) patients with associated hepatitis biochemically in 20 (53%) patients. No skin rashes were observed and eosinophilia was only present in two patients. Hematuria was observed universally without any significant proteinuria. Anemia was present in 37 (90%) patients, with associated thrombocytopenia in 15 (37%). Rifampicin was discontinued in 37 (90%) cases. Nine (22%) patients required dialysis. One patient failed to recover renal function and 4 (10%) patients died. Mortality was related to overwhelming tuberculosis infection. The main factor predicting the need for dialysis was duration of oliguria. CONCLUSION: ATIN is a rare, but serious complication of repeat antituberculous therapy mainly due to re-exposure to rifampicin. Although the renal prognosis is generally good the disease does carry significant morbidity and mortality risks. A high index of suspicion is needed in re-treatment patients. A suggested screening test is for microhematuria with urine dipstix.

Left ventricular mass, abdominal circumference and age: the Fels longitudinal study.

PURPOSE: To determine the relationship of abdominal circumference with increased left ventricular mass (LVM) from young adulthood into old age. METHODS: Cross-sectional echocardiographic images were taken from 182 men and 220 women in the Fels Longitudinal Study 20 to 75 years of age to determine left ventricular mass. Left ventricular mass was divided by stature raised to the power of 2.7 (LVM/ht2.7) in order to minimize the impact of heart size variation from body size without overcompensating for the adverse effect of obesity. Abdominal circumference was measured and BMI calculated from stature and weight and categories of overweight, obesity and abdominal obesity were determined using published cut points. Regression models were used to describe the relationships of age, abdominal circumference, BMI and self-reported physical activity to LVM/ht2.7. RESULTS: Age, abdominal circumference and BMI were each positively and significantly related to an increased LVM/ht2.7 in men and women (p < 0.05). In the men, multivariate models indicated that abdominal circumference and BMI were both significantly related to an increased LVM/ht2.7, but the inclusion of BMI in these models for the women reduced the association of abdominal circumference and physical activity below significant levels. In the men, there was also a quadratic association of abdominal circumference with LVM/ht2.7 that was significant along with BMI and physical activity. Sex-specific logistic regressions with BMI and abdominal circumference obesity categories did not change or improve the initial findings in men or women. CONCLUSIONS: In women, increases in abdominal fatness as reflected in abdominal circumference at any age are linearly related to an increase in LVM/ht2.7, but the relationship of overall fatness as reflected in BMI with LVM/ht2.7 is stronger. In men, both abdominal fatness and overall fatness at any age are linearly related to an increase LVM/ht2.7. However, the significant curvilinear association of abdominal circumference and a linear association of BMI and physical activity with LVM/ht2.7 indicate the possible positive covariate relationship of overall muscle mass with LVM/ht2.7. This reflects the physiological changes with age and demonstrate, in part, the complexity of the interpretations of the inter associations of body composition, the cardiovascular system and the aging process, but the impact among the elderly and the known inadequacy of BMI at these ages remains an area for continued clinical study.