Active impedance matching of a cryogenic radio frequency resonator for ion traps.

A combination of direct current (DC) fields and high amplitude radio frequency (RF) fields is necessary to trap ions in a Paul trap. Such high electric RF fields are usually reached with the help of a resonator in close proximity to the ion trap. Ion trap based quantum computers profit from good vacuum conditions and low heating rates that cryogenic environments provide. However, an impedance matching network between the resonator and its RF source is necessary, as an unmatched resonator would require higher input power due to power reflection. The reflected power would not contribute to the RF trapping potential, and the losses in the cable induce additional heat into the system. The electrical properties of the matching network components change during cooling, and a cryogenic setup usually prohibits physical access to integrated components while the experiment is running. This circumstance leads to either several cooling cycles to improve the matching at cryogenic temperatures or the operation of poorly matched resonators. In this work, we demonstrate an RF resonator that is actively matched to the wave impedance of coaxial cables and the signal source. The active part of the matching circuit consists of a varactor diode array. Its capacitance depends on the DC voltage applied from outside the cryostat. We present measurements of the power reflection, the Q-factor, and higher harmonic signals resulting from the nonlinearity of the varactor diodes. The RF resonator is tested in a cryostat at room temperature and cryogenic temperatures, down to 4.3 K. A superior impedance matching for different ion traps can be achieved with this type of resonator.

Side-effect management of chimeric antigen receptor (CAR) T-cell therapy.

Chimeric antigen receptor (CAR) T cells directed against the B-cell marker CD19 are currently changing the landscape for treatment of patients with refractory and/or relapsed B-cell malignancies. Due to the nature of CAR T cells as living drugs, they display a unique toxicity profile. As CAR T-cell therapy is extending towards other diseases and being more broadly employed in hematology and oncology, optimal management strategies of side-effects associated with CAR T-cell therapy are of high relevance. Cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and cytopenias constitute challenges in the treatment of patients with CAR T cells. This review summarizes the current understanding of CAR T-cell toxicity and its management.

Low-sulphate water sample preparation for LSC detection of 35S avoiding sulphate precipitation.

Information about groundwater residence times is essential for evaluating appropriate groundwater abstraction rates and aquifer vulnerabilities and hence for sustainable groundwater management in general. Naturally occurring radionuclides are suitable tools for related investigations. While the applicability of several long-lived radionuclides for the investigation of long-term processes has been demonstrated frequently, residence times of less than one year are only scarcely discussed in the literature. That is due to the rather small number of applicable radionuclides that show adequately short half-lives. A promising approach for investigating sub-yearly residence times applies radioactive sulphur. 35S is continuously produced in the upper atmosphere from where it is transferred with the rain to the groundwater. As soon as the water enters the subsurface its 35S activity concentration decreases with an 87.4 day half-life. This makes 35S suitable for investigating sub-yearly groundwater residence times. However, the low 35S activities in natural waters require sulphate pre-concentration for 35S detection by means of liquid scintillation counting (LSC). That is usually done by sulphate extraction from large water samples with an anion-exchange resin (Amberlite IRA400, Cl-form), elution from the resin with NaCl, and precipitation as BaSO4. Our study aimed at optimizing the standard sample preparation procedure by avoiding the laborious precipitation step. We suggest (i) sulphate extraction using the exchange resin Amberlite IRA67 (OH-form), (ii) elution with ammonium hydroxide, (iii) evaporation of the eluate and (iv) dissolving the resulting dry precipitate in 2 ml H2O. In contrast to the standard approach our method results in a final sample solution of low ionic strength, which allows applying the water miscible scintillation cocktail Hionic-Fluor®. Since Hionic-Fluor accepts only aqueous solutions of low ionic strength the approach is applicable for waters with high 35S/32SO42- ratios, i.e., low total sulphate sample loads (e.g. rainwater).

All-cause and cause-specific mortality following non-traumatic spinal cord injury: evidence from a population-based cohort study in Switzerland.

STUDY DESIGN: Observational cohort study. OBJECTIVE: To benchmark all-cause and cause-specific mortality following NTSCI to the general population (GP). SETTING: Specialized rehabilitation centers in Switzerland. METHODS: Longitudinal data from the Swiss Spinal Cord Injury (SwiSCI) Medical Record study were probabilistically linked with cause of death (CoD) information from the Swiss National Cohort. Standardized mortality ratios (SMRs) were estimated for all-cause and cause-specific mortality. Competing risk frameworks were used to estimate the probability of death due to specific CoD. RESULTS: One thousand five hundred and one individuals were admitted for first rehabilitation with NTSCI between 1990-2011; CoD information was available for 454 individuals of the 525 individuals that died. Overall, the mortality rate for persons with NTSCI was 1.6 times greater than that of the GP. Deaths due to cardiovascular disease (39.8%), neoplasms (22%), and infection (9.9%) were most often reported. Individuals with an SCI due to a vascular etiology indicated the greatest burden of mortality from infection compared with the GP (SMR 5.4; 95% CI, 3.1 to 9.2). CONCLUSIONS: Cause-specific SMRs varied according to etiology. This supports the need for targeted clinical care and follow-up. Cardiovascular disease, neoplasms, and infection, emerged as main causes of death following NTSCI and should thus be targets for future research and differential clinical management approaches.

Diagnostic accuracy of a new ex vivo confocal laser scanning microscope compared to H&E-stained paraffin slides for micrographic surgery of basal cell carcinoma.

BACKGROUND: For safe excision of malignant skin tumours, complete negative surgical margins are mandatory. The gold standard for analysis is frozen sections or paraffin-embedded haematoxylin and eosin (H&E)-stained slides. The production of H&E-stained slides is time-consuming (>20 h) while wounds remain unclosed. An upcoming method is confocal laser scanning microscopy (CLSM), a technique that scans unfixed fresh tissue rapidly. OBJECTIVE: Evaluation of the process to generate and analyse CLSM images and assessment of the accuracy to detect basal cell carcinoma (BCC) tissue. METHODS: Digital microscopic images were generated by the Histolog Scanner v1 from 544 fresh specimens of 148 BCCs that had been stained with a 0.01% proflavine solution. CLSM images were compared to the histological diagnoses of the corresponding H&E-stained slides. RESULTS: A total of 525 images could be analysed. The sensitivity was 73% (95% CI = [65.27%; 80.47%]), and the specificity was 96% (95% CI = [93.40%; 97.60%]). Detection of BCCs in punch biopsies was certainly detected (sensitivity of 100%). The median total time to generate and evaluate a CLSM image was 5.17 min (maximum 20.17 min and minimum 2.05 min). The greatest challenge was flattening the specimen to assure complete representation of the surgical margins. CONCLUSION: Confocal laser scanning microscopy is a time-saving and very effective alternative to classical paraffin-embedded or frozen sections. Patient treatment could be improved due to shorter hospital stays or faster outpatient therapy due to reduced intervals between surgical stages. Diagnostic accuracy of the microscope used still must be improved.

Survival after non-traumatic spinal cord injury: evidence from a population-based rehabilitation cohort in Switzerland.

STUDY DESIGN: Observational cohort study. OBJECTIVE: To investigate survival and life expectancy after NTSCI in Switzerland according to etiology. SETTING: Specialized rehabilitation centers in Switzerland. METHODS: Longitudinal data from the Swiss Spinal Cord Injury (SwiSCI) medical records study were used. Adjusted hazard ratios (HRs) and life expectancies were estimated using flexible parametric survival modeling. RESULTS: One thousand four hundred and fifty individuals were admitted to first rehabilitation for NTSCI between 1990 and 2011, contributing 6137 cumulative person-years at risk and 528 deaths. With reference to persons with a degenerative disc disorder, the HR for mortality in individuals with NTSCIs from infections was 1.42 (95% CI 0.99-2.04), while risk in those with NTSCIs from vascular disorders was 1.28 (95% CI 0.97-1.68). Mortality risk was most pronounced in individuals with NTSCIs from malignant neoplasms (HR 6.32, 95% CI 4.79-8.34). Exemplified for males with an attained age of 60 years, a malignant etiology was associated with 1.7 life years remaining (LYR), as compared to 10.1 LYR for non-malignant etiologies. Males with an attained age of 60 years and a degenerative disc etiology were estimated to have 12.9 LYR. CONCLUSIONS: This study contributes an evidence base for risk factors of mortality after NTSCI, reducing a considerable knowledge gap in survival after NTSCI. Survival and life expectancy estimates were highly differential between etiological groups, indicating a need for a heterogeneous clinical approach and dynamic health-care provisions for this growing population.

Paraneoplastic cerebellar degeneration: Yo antibody alters mitochondrial calcium buffering capacity.

AIM: Neurodegeneration is associated with dysfunction of calcium buffering capacity and thereby sustained cellular and mitochondrial calcium overload. Paraneoplastic cerebellar degeneration (PCD), characterized by progressive Purkinje neurone degeneration following paraneoplastic Yo antibody internalization and binding to cerebellar degeneration-related protein CDR2 and CDR2L, has been linked to intracellular calcium homeostasis imbalance due to calbindin D28k malfunction. Therefore, we hypothesized that Yo antibody internalization affects not only calbindin calcium binding capacity, but also calcium-sensitive mitochondrial-associated signalling, causing mitochondrial calcium overload and thereby Purkinje neurone death. METHODS: Immunohistochemically, we evaluated cerebellar organotypic slice cultures of rat brains after inducing PCD through the application of Yo antibody-positive PCD patient sera or purified antibodies against CDR2 and CDR2L how pharmacologically biased mitochondrial signalling affected PCD pathology. RESULTS: We found that Yo antibody internalization into Purkinje neurons caused depletion of Purkinje neurone calbindin-immunoreactivity, cannabinoid 1 receptor over-activation and alterations in the actions of the mitochondria permeability transition pore (MPTP), voltage-dependent anion channels, reactive oxygen species (ROS) and Na+ /Ca2+ exchangers (NCX). The pathological mechanisms caused by Yo antibody binding to CDR2 or CDR2L differed between the two targets. Yo-CDR2 binding did not alter the mitochondrial calcium retention capacity, cyclophilin D-independent opening of MPTP or activity of NCX. CONCLUSION: These findings suggest that minimizing intracellular calcium overload toxicity either directly with cyclosporin-A or indirectly with cannabidiol or the ROS scavenger butylated hydroxytoluene promotes mitochondrial calcium homeostasis and may therefore be used as future neuroprotective therapy for PCD patients.

Performance characteristics of optical coherence tomography in assessment of Barrett's esophagus and esophageal cancer: systematic review.

Optical coherence tomography (OCT) can generate high-resolution images of the esophagus that allows cross-sectional visualization of esophageal wall layers. We conducted a systematic review to assess the utility of OCT for diagnosing of esophageal intestinal metaplasia (IM; Barrett's esophagus BE)), dysplasia, cancer and staging of early esophageal cancer. English language human observational studies and clinical trials published in PubMed and Embase were included if they assessed any of the following: (i) in-vivo features and accuracy of OCT at diagnosing esophageal IM, sub-squamous intestinal metaplasia (SSIM), dysplasia, or cancer, and (ii) accuracy of OCT in staging esophageal cancer. Twenty-one of the 2,068 retrieved citations met inclusion criteria. In the two prospective studies that assessed accuracy of OCT at identifying IM, sensitivity was 81%-97%, and specificity was 57%-92%. In the two prospective studies that assessed accuracy of OCT at identifying dysplasia and early cancer, sensitivity was 68%-83%, and specificity was 75%-82%. Observational studies described significant variability in the ability of OCT to accurately identify SSIM. Two prospective studies that compared the accuracy of OCT at staging early squamous cell carcinoma to histologic resection specimens reported accuracy of >90%. Risk of bias and applicability concerns was rated as low among the prospective studies using the QUADAS-2 questionnaire. OCT may identify intestinal metaplasia and dysplasia, but its accuracy may not meet recommended thresholds to replace 4-quadrant biopsies in clinical practice. OCT may be more accurate than EUS at staging early esophageal cancer, but randomized trials and cost-effective analyses are lacking.

Growth and evolution of nickel germanide nanostructures on Ge(001).

Nickel germanide is deemed an excellent material system for low resistance contact formation for future Ge device modules integrated into mainstream, Si-based integrated circuit technologies. In this study, we present a multi-technique experimental study on the formation processes of nickel germanides on Ge(001). We demonstrate that room temperature deposition of ∼1 nm of Ni on Ge(001) is realized in the Volmer-Weber growth mode. Subsequent thermal annealing results first in the formation of a continuous NixGey wetting layer featuring well-defined terrace morphology. Upon increasing the annealing temperature to 300 °C, we observed the onset of a de-wetting process, characterized by the appearance of voids on the NixGey terraces. Annealing above 300 °C enhances this de-wetting process and the surface evolves gradually towards the formation of well-ordered, rectangular NixGey 3D nanostructures. Annealing up to 500 °C induces an Ostwald ripening phenomenon, with smaller nanoislands disappearing and larger ones increasing their size. Subsequent annealing to higher temperatures drives the Ni-germanide diffusion into the bulk and the consequent formation of highly ordered, {111} faceted Ni-Ge nanocrystals featuring an epitaxial relationship with the substrate Ni-Ge (101); (010) || Ge(001); (110).

Changes of salivary estrogen levels for detecting the fertile period.

OBJECTIVES: Is the saliva test, Geratherm ovu control, as accurate as the established urinary luteinizing hormone (LH) test for detecting ovulation and the following the fertile period? STUDY DESIGN: The voluntary participants were 74 healthy women with regular menstrual cycles and not using any hormonal contraceptives. The women used Geratherm ovu control, a small plastic hand-held microscope, for detecting the fertile period. A drop of saliva from sublingual was put onto the lens of the microscope. Three results were possible: non-fertile (dot pattern), transitional and fertile (ferning pattern). The participants performed the saliva test from the 5th till the 22nd day of the menstrual cycle and noted the respective result in a table. In addition to Geratherm ovu control, the EXACTO test for determining urinary LH concentration and the time of peak fertility was also performed. RESULTS: Positive LH shows a sharp increase beginning on the 10th cycle day with a maximum on the 17th cycle day. The curve for positive saliva and questionable positive saliva (one curve) is almost parallel with the curve for positive LH, reaching a maximum on the 16th cycle day. There is a high level of conformity for the same test results from the 5th (100%) till the 14th (84%) cycle day and from the 18th (80%) till the 22nd (96%) cycle day which corresponds to the pre- and post-ovulatory period. CONCLUSION: The saliva and the LH test both detect the fertile window of a menstrual cycle. Caused by the different hormones (estrogen for the saliva and LH for the LH test) leading to the respective positive test results, saliva turns positive 24h before LH. Consequently, the saliva test can be used as an ovulation test and help women maximize their chances of conceiving. There is also a high congruence between LH and saliva in the pre- and post-ovulatory period, indicating that the saliva test can also be used for contraception purposes.

[Technique of Autologous Chondrocyte Implantation for Severe Radiocarpal Arthrosis: Status Quo after 24 Months]. / Technik der autologen Chondrozytenimplantation bei ausgeprägter Radiokarpalarthrose: Status quo nach 24 Monaten.

We illustrate the operative technique of autologous chondrocyte implantation (ACI) to restore a 4° cartilage damage of the radius surface in the case of a 22-year-old patient, and report on the clinical and radiological results at 6 and 24 months postoperatively.

[Bisphosphonate-associated osteonecrosis of the jaw]. / Bisphosphonat-assoziierte Kiefernekrosen.

BACKGROUND: Bisphosphonates (BP) are used in the treatment of severe osteoporosis and metastasis of malignant diseases. A possible relationship between the occurrence of osteonecrosis of the jaw and BP therapy was first described in 2003. Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is difficult to treat. In some cases the condition of the patients is so compromised that only minimally invasive surgery is possible. Histopathologically, osteonecrosis shows the features of chronic sequestered osteomyelitis, which can be found in different areas of the upper and lower jaw. Sometimes extensive resections of the jaw are necessary. Thus, BRONJ can cause mutilation, impairment of function and esthetics in the orofacial system and, thereby, compromise the life quality of the patients. Triggering factors are often tooth extraction without surgical plastic wound closure of the alveoli, but can also be associated with bruises from denture or other minor wounds. OBJECTIVES: The purpose of this article is to present results from our own patient collective, including therapy regime, success rate, and therapy recommendations. METHODS: The patient populations at three German hospitals were analyzed using a standard questionnaire. The patients in the study group, entered into a follow-up system for early detection of possible BRONJ, were evaluated for treatement outcome. RESULTS: The success rate for prophylactic surgery in asymptomatic patients was very high at 96 %. In the group with symptomatic BRONJ, the outcome was significantly lower (76.4 %). CONCLUSIONS: Because of the complex symptoms, close cooperation between oncologists, dentists, and maxillofacial surgeons is required in the treatment of BRONJ. Before starting therapy with bisphosphonates and during the therapy, dental treatment and monitoring of the patient' oral health is necessary.

The association between donor and recipient statin use and infections after allogeneic hematopoietic cell transplantation.

Recent studies have reported that statin use may be associated with improved outcomes in patients with sepsis or respiratory viral infections. In the setting of allogeneic hematopoietic cell transplantation (HCT), it has been shown that donor and recipient statin use is associated with reduced risks of GVHD. We assessed in retrospective analysis whether donor or recipient statin use impacts infection risk after allogeneic HCT (n=1191). Although recipient statin use was associated with the increased incidence of Gram-negative bacteremia (adjusted hazard ratio (aHR) 2.22, (95% confidence interval (CI) 1.2-4.2), P=0.01) without affecting mortality, donor statin use was associated with an increased incidence of respiratory viral infections in recipients (aHR 2.84 (95% CI 1.3-6.0), P=0.007). The overall incidence of invasive fungal infections and CMV reactivation and CMV disease were not impacted by recipient or donor statin use. In conclusion, this study suggests that recipient or donor statin use may be associated with an increased incidence of some infections without adversely affecting mortality.

Impact of radical operative treatment on the quality of life in women with vulvar cancer--a retrospective study.

OBJECTIVES: For patients undergoing vulva surgery the quality of life (QoL) is generally accepted as an important outcome parameter in addition to long-term survival, mortality and complication rates. Less radical operative treatment can reduce morbidity and thereby improve quality of life. This study focuses on outcome in terms of QoL in patients comparing wide local excision (WLE) with radical vulvectomy and waiver of lymphonodectomy (LNE) with inguinofemoral lymphonodectomy. METHODS: In a retrospective single-center study from 2000 to 2010, 199 patients underwent surgery for vulvar cancer. To assess QoL, the EORTC QLQ-C30 and a tumor-specific module questionnaire were sent to all patients in the follow-up period. RESULTS: Women who underwent WLE have a superior QoL with regard to global health status and physical, role, emotional and cognitive functioning than those who underwent radical vulvectomy. Less radical surgery also implies less fatigue, nausea/vomiting, pain, insomnia, appetite loss, diarrhea and financial difficulties. After radical vulvectomy 89% of patients have sexual complications. CONCLUSION: Radical operative treatment, such as radical vulvectomy, causes deterioration in the QoL of these patients. An individualized, less radical surgery must be the aim in the treatment of vulvar cancer.

Caloric restriction increases serum testosterone concentrations in obese male subjects by two distinct mechanisms.

The concentration of serum testosterone is mainly regulated by the testicular function, which is under control of the central hypothalamic-pituitary-gonadal axis. A certain amount of testosterone is converted into ß-estradiol by adipose tissue. Obesity in men is often associated with decreased androgen levels. The aim of the present study was to examine the effect of caloric restriction on serum testosterone levels in obese men. Dietary intervention study was performed with a very low calorie diet (800 kcal/d) for 12 weeks. Thirteen obese human male subjects (median body mass index: 42.7 kg/m2) were included. Body composition was assessed by impedance analysis. Insulin sensitivity was estimated by leptin-to-adiponectin ratio (LAR). Testosterone (T), ß-estradiol, albumin, sex hormone-binding globulin (SHBG), LH, and FSH serum concentrations were measured by enzyme immunoassays. Statistical analysis was performed on baseline and values after 3 months. Caloric restriction significantly increased total testosterone (6.97 nmol/l to 13.21 nmol/l; p=0.001) and SHBG (22.11 nmol/l to 42.12 nmol/l; p=0.001) concentrations in serum. This is caused by a significant improvement of the testicular function (LH/T: 0.36-0.20; p=0.005) and a significant reduction of the T/ß-estradiol conversion rate (73.59-104.29; p=0.003). There was a significant negative correlation of improvement of testicular function and LAR (rs=-0.683 (p=0.042)). In obese men caloric restriction significantly increases the serum testosterone concentration. This is achieved by 2 distinct mechanisms, that is, improvement of testicular function and reduced conversion of testosterone to ß-estradiol by aromatase activity of the adipose tissue.

Ovulation detection in saliva, is it possible.

BACKGROUND/AIMS: The new mini-microscope Geratherm® ovu control was evaluated for its recognition of saliva ferning in a collective of 47 patients taking part in an artificial reproductive technology program on the day of follicular puncture. METHODS: The ferning phenomenon was evaluated by patients and laboratory staff according to the criteria: no ferning, slight ferning and good ferning. RESULTS: Geratherm® ovu control showed a specificity of 78% and a sensitivity of 80% in relation to rising E2 levels under follicle-stimulating hormone/human chorionic gonadotrophin. A comparison of the evaluations of the saliva test carried out by patients and by laboratory staff resulted in a high and substantial agreement of 89.4% (κ). CONCLUSION: Evaluations performed by ovu control were similar to those achieved with a highly sophisticated inverted microscope.

Central FoxO3a and FoxO6 expression is down-regulated in obesity induced diabetes but not in aging.

BACKGROUND: Recent data suggest that insulin-like growth factor (IGF)-1 resistance in neurons prolongs longevity. In C. elegans this effect is mediated via DAF-16 the ortholog of the mammalian FoxO transcription factors. 3 different FoxO transcription factors (FoxOs) are expressed in rodent CNS: FoxO1, FoxO3a and FoxO6. METHODS: To define whether the different FoxOs are region-, sex- and age-specifically expressed, we analyzed FoxO mRNA levels in different brain regions from 6, 16, 60 and 100 weeks old mice using realtime-PCR. In addition, we fed mice a high fat diet (HFD) to experimentally induce obesity and diabetes and analyzed FoxO mRNA in the different brain regions. RESULTS: Interestingly, FoxO1 was predominantly expressed in the hippocampus whereas FoxO3a was quantitatively the most abundant FoxO in the neocortex. During aging, FoxO1 expression peaked in all brain regions at 16 weeks and FoxO6 showed its highest expression at 60 weeks in the parietal and occipital cortex. In 6 weeks old mice FoxO6 expression was higher in male compared to female mice in the hippocampus and all cortical regions. Surprisingly, in HFD animals FoxO3a was significantly less expressed in the cerebellum and all cortical regions compared to control animals. Even more dramatic, FoxO6 expression dropped about 80% in all brain regions in response to HFD. CONCLUSION: Thus, FoxOs in the CNS showed a highly distinct expression, which in addition was age- and sex-dependent. In contrast to FoxO1, FoxO3a and FoxO6 were specifically diminished in the CNS of HFD animals possibly contributing to the reduced lifespan observed in these animals.

Modelling the effect of environmental factors on the hyphal growth of the basidiomycete Physisporinus vitreus.

The present work investigated the effects of environmental factors on the growth of fungal colonies of the white-rot basidiomycetes Physisporinus vitreus using a lattice-free discrete modeling approach called the fungal growth model (FGM), in which hyphae and nutrients are considered as discrete structures. A discrete modeling approach enables the underlying mechanistic rule concerning the basic architecture and dynamics of fungal networks to be studied on the scale of a single colony. By comparing simulations of the FGM with laboratory experiments of fungal colonies growing on malt extract agar we show that the combined effects of water activity, temperature and pH on the radial growth rate of fungal mycelia on the macroscopic scale may be explained by a power law for the costs of hyphal maintenance and expansion on the microscopic scale. Information about the response of the fungal mycelium at the micro- scopic level to environmental conditions is essential for simulating its behavior in complex structure substrates such as wood, where the effect of the fungus on the wood (i.e. the degradation of the cell wall) changes the local environmental condition (e.g. the permeability of the substrate and therefore the water activity in a colonized wood cell lumen). Using a combination of diffusion and moisture processes with the FGM may increase our understanding of the colonization strategy of P. vitreus and help to optimize its growth behavior for biotechnological applications such as bioincising.