Comparison of a Pure Plug-Based Versus a Primary Suture-Based Vascular Closure Device Strategy for Transfemoral Transcatheter Aortic Valve Replacement: The CHOICE-CLOSURE Randomized Clinical Trial.

BACKGROUND: Transcatheter aortic valve replacement is an established treatment option for patients with severe symptomatic aortic stenosis and is most commonly performed through the transfemoral access route. Percutaneous access site closure can be achieved using dedicated plug-based or suture-based vascular closure device (VCD) strategies, but randomized comparative studies are scarce. METHODS: The CHOICE-CLOSURE trial (Randomized Comparison of Catheter-based Strategies for Interventional Access Site Closure during Transfemoral Transcatheter Aortic Valve Implantation) is an investigator-initiated, multicenter study, in which patients undergoing transfemoral transcatheter aortic valve replacement were randomly assigned to vascular access site closure using either a pure plug-based technique (MANTA, Teleflex) with no additional VCDs or a primary suture-based technique (ProGlide, Abbott Vascular) potentially complemented by a small plug. The primary end point consisted of access site- or access-related major and minor vascular complications during index hospitalization, defined according to the Valve Academic Research Consortium-2 criteria. Secondary end points included the rate of access site- or access-related bleeding, VCD failure, and time to hemostasis. RESULTS: A total of 516 patients were included and randomly assigned. The mean age of the study population was 80.5±6.1 years, 55.4% were male, 7.6% of patients had peripheral vascular disease, and the mean Society of Thoracic Surgeons score was 4.1±2.9%. The primary end point occurred in 19.4% (50/258) of the pure plug-based group and 12.0% (31/258) of the primary suture-based group (relative risk, 1.61 [95% CI, 1.07-2.44], P=0.029). Access site- or access-related bleeding occurred in 11.6% versus 7.4% (relative risk, 1.58 [95%CI: 0.91-2.73], P=0.133) and device failure in 4.7% versus 5.4% (relative risk, 0.86, [95% CI, 0.40-1.82], P=0.841) in the respective groups. Time to hemostasis was significantly shorter in the pure plug-based group (80 [32-180] versus 240 [174-316] seconds, P<0.001). CONCLUSIONS: Among patients treated with transfemoral transcatheter aortic valve replacement, a pure plug-based vascular closure technique using the MANTA VCD is associated with a higher rate of access site- or access-related vascular complications but a shorter time to hemostasis compared with a primary suture-based technique using the ProGlide VCD. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04459208.

Molecular Dynamics Study of Wetting and Adsorption of Binary Mixtures of the Lennard-Jones Truncated and Shifted Fluid on a Planar Wall.

The wetting of surfaces is strongly influenced by adsorbate layers. Therefore, in this work, sessile drops and their interaction with adsorbate layers on surfaces were investigated by molecular dynamics simulations. Binary fluid model mixtures were considered. The two components of the fluid mixture have the same pure component parameters, but one component has a stronger and the other a weaker affinity to the surface. Furthermore, the unlike interactions between both components were varied. All interactions were described by the Lennard-Jones truncated and shifted potential with a cutoff radius of 2.5σ. The simulations were carried out at constant temperature for mixtures of different compositions. The parameters were varied systematically and chosen such that cases with partial wetting as well as cases with total wetting were obtained and the relation between the varied molecular parameters and the phenomenological behavior was elucidated. Data on the contact angle as well as on the mole fraction and thickness of the adsorbate layer were obtained, accompanied by information on liquid and gaseous bulk phases and the corresponding phase equilibrium. Also, the influence of the adsorbate layer on the wetting was studied: for a sufficiently thick adsorbate layer, the wall's influence on the wetting vanishes, which is then only determined by the adsorbate layer.

Soft Interference Cancellation for Random Coding in Massive Gaussian Multiple-Access.

In 2017, Polyanskiy showed that the trade-off between power and bandwidth efficiency for massive Gaussian random access is governed by two fundamentally different regimes: low power and high power. For both regimes, tight performance bounds were found by Zadik et al., in 2019. This work utilizes recent results on the exact block error probability of Gaussian random codes in additive white Gaussian noise to propose practical methods based on iterative soft decoding to closely approach these bounds. In the low power regime, this work finds that orthogonal random codes can be applied directly. In the high power regime, a more sophisticated effort is needed. This work shows that power-profile optimization by means of linear programming, as pioneered by Caire et al. in 2001, is a promising strategy to apply. The proposed combination of orthogonal random coding and iterative soft decoding even outperforms the existence bounds of Zadik et al. in the low power regime and is very close to the non-existence bounds for message lengths around 100 and above. Finally, the approach of power optimization by linear programming proposed for the high power regime is found to benefit from power imbalances due to fading which makes it even more attractive for typical mobile radio channels.

Functional implications of Cav 2.3 R-type voltage-gated calcium channels in the murine auditory system - novel vistas from brainstem-evoked response audiometry.

Voltage-gated Ca2+ channels (VGCCs) are considered to play a key role in auditory perception and information processing within the murine inner ear and brainstem. In the past, Cav 1.3 L-type VGCCs gathered most attention as their ablation causes congenital deafness. However, isolated patch-clamp investigation and localization studies repetitively suggested that Cav 2.3 R-type VGCCs are also expressed in the cochlea and further components of the ascending auditory tract, pointing to a potential functional role of Cav 2.3 in hearing physiology. Thus, we performed auditory profiling of Cav 2.3+/+ controls, heterozygous Cav 2.3+/- mice and Cav 2.3 null mutants (Cav 2.3-/- ) using brainstem-evoked response audiometry. Interestingly, click-evoked auditory brainstem responses (ABRs) revealed increased hearing thresholds in Cav 2.3+/- mice from both genders, whereas no alterations were observed in Cav 2.3-/- mice. Similar observations were made for tone burst-related ABRs in both genders. However, Cav 2.3 ablation seemed to prevent mutant mice from total hearing loss particularly in the higher frequency range (36-42 kHz). Amplitude growth function analysis revealed, i.a., significant reduction in ABR wave WI and WIII amplitude in mutant animals. In addition, alterations in WI -WIV interwave interval were observed in female Cav 2.3+/- mice whereas absolute latencies remained unchanged. In summary, our results demonstrate that Cav 2.3 VGCCs are mandatory for physiological auditory information processing in the ascending auditory tract.

Spatiotemporal parameters in sprinters with unilateral and bilateral transfemoral amputations and functional impairments.

PURPOSE: Although sprinters with unilateral (UTF) and bilateral transfemoral (BTF) amputations and functional impairments (FIs) without amputation were allocated into different classifications because of the recent revision of the International Paralympic Committee Athletics Rules and Regulations, it is unclear whether running mechanics differ among the three groups. The aim of this study was to investigate the differences in the spatiotemporal parameters of the three groups during 100-m sprint in official competitions. METHODS: Using publicly available Internet broadcasts, we analyzed 11 elite-level sprinters with UTF amputation, 4 sprinters with BTF amputation, and 5 sprinters with FI without amputation. The best personal times for nearly all individuals were included. For each sprinter's race, the average speed, step frequency, and step length were calculated using the number of steps in conjunction with the official race time. RESULTS: Although there were no significant differences in the average speed among the UTF, BTF, and FI groups (7.95 ± 0.22, 7.90 ± 0.42, and 7.93 ± 0.14 m/s, respectively, p = 0.87), those with BTF amputation showed significantly lower step frequency (UTF: 4.20 ± 0.20 Hz, BTF: 3.71 ± 0.32 Hz, FI: 4.20 ± 0.10 Hz, p < 0.05) and longer step length (UTF: 1.90 ± 0.08 m, BTF: 2.14 ± 0.02 m, FI: 1.89 ± 0.06 m, p < 0.05) than the other two groups. CONCLUSION: These results suggest that the step characteristics during sprinting are not the same among sprinters with UTF amputation, BTF amputations, or FI without amputations.

Three-dimensional phase field modeling of inhomogeneous gas-liquid systems using the PeTS equation of state.

Recently, an equation of state (EoS) for the Lennard-Jones truncated and shifted (LJTS) fluid has become available. As it describes metastable and unstable states well, it is suited for predicting density profiles in vapor-liquid interfaces in combination with density gradient theory (DGT). DGT is usually applied to describe interfaces in Cartesian one-dimensional scenarios. In the present work, the perturbed LJ truncated and shifted (PeTS) EoS is implemented into a three-dimensional phase field (PF) model which can be used for studying inhomogeneous gas-liquid systems in a more general way. The results are compared with the results from molecular dynamics simulations for the LJTS fluid that are carried out in the present work and good agreement is observed. The PF model can therefore be used to overcome the scale limit of molecular simulations. A finite element approach is applied for the implementation of the PF model. This requires the first and second derivatives of the PeTS EoS which are calculated using hyper-dual numbers. Several tests and examples of applications of the new PeTS PF model are discussed.

Does inside passing contribute to the high incidence of groin injuries in soccer? A biomechanical analysis.

Groin injuries are common in soccer and often cause time-loss from training. While groin injuries have been linked to full effort kicking, the role of inside passing is unclear. Therefore, the purpose of this study was to investigate hip joint kinematics and muscle force, stress and contraction velocity for adductor longus and gracilis during inside passing. 3D kinematics of ten soccer players (23.4 yrs; 77.5 kg; 1.81 m) were captured with a motion capture system inside a Footbonaut. Muscle force and contraction velocity were determined with AnyBody Modelling System. Gracilis muscle forces were 9% lower compared to adductor longus (p = 0.005), but muscle stress was 183% higher in gracilis (p = 0.005). Contraction velocity reveals eccentric contraction of gracilis in the last quarter of the swing phase. Considering the combination of eccentric contraction, high muscle stress and the repetitive nature of inside passing, gracilis accumulates high loads in matches and training. These results indicate that the high incidence of groin injuries in soccer could be linked to isolated pass training. Practitioners need to be aware of the risk and refrain from sudden increases in the amount of pass training. This gives the musculoskeletal system time to adapt and might avoid career threatening injuries.

Restricted attention to social cues in schizophrenia patients.

Deficits of psychosocial functioning are a robust finding in schizophrenia. Research on social cognition may open a new avenue for the development of effective interventions. As a correlate of social perceptive information processing deficits, schizophrenia patients (SZP) show deviant gaze behavior (GB) while viewing emotional faces. As understanding of a social environment requires gathering complex social information, our study aimed at investigating the gaze behavior of SZP related to social interactions and its impact on the level of social and role functioning. GB of 32 SZP and 37 healthy control individuals (HCI) was investigated with a high-resolution eye tracker during an unguided viewing of 12 complex pictures of social interaction scenes. Regarding whole pictures, SZP showed a shorter scanpath length, fewer fixations and a shorter mean distance between fixations. Furthermore, SZP exhibited fewer and shorter fixations on faces, but not on the socially informative bodies nor on the background, suggesting a cue-specific abnormality. Logistic regression with bootstrapping yielded a model including two GB parameters; a subsequent ROC curve analysis indicated an excellent ability of group discrimination (AUC .85). Face-related GB aberrations correlated with lower social and role functioning and with delusional thinking, but not with negative symptoms. Training of spontaneous integration of face-related social information seems promising to enable a holistic perception of social information, which may in turn improve social and role functioning. The observed ability to discriminate SZP from HCI warrants further research on the predictive validity of GB in psychosis risk prediction.

Gender-Specific Hippocampal Dysrhythmia and Aberrant Hippocampal and Cortical Excitability in the APPswePS1dE9 Model of Alzheimer's Disease.

Alzheimer's disease (AD) is a multifactorial disorder leading to progressive memory loss and eventually death. In this study an APPswePS1dE9 AD mouse model has been analyzed using implantable video-EEG radiotelemetry to perform long-term EEG recordings from the primary motor cortex M1 and the hippocampal CA1 region in both genders. Besides motor activity, EEG recordings were analyzed for electroencephalographic seizure activity and frequency characteristics using a Fast Fourier Transformation (FFT) based approach. Automatic seizure detection revealed severe electroencephalographic seizure activity in both M1 and CA1 deflection in APPswePS1dE9 mice with gender-specific characteristics. Frequency analysis of both surface and deep EEG recordings elicited complex age, gender, and activity dependent alterations in the theta and gamma range. Females displayed an antithetic decrease in theta (θ) and increase in gamma (γ) power at 18-19 weeks of age whereas related changes in males occurred earlier at 14 weeks of age. In females, theta (θ) and gamma (γ) power alterations predominated in the inactive state suggesting a reduction in atropine-sensitive type II theta in APPswePS1dE9 animals. Gender-specific central dysrhythmia and network alterations in APPswePS1dE9 point to a functional role in behavioral and cognitive deficits and might serve as early biomarkers for AD in the future.

EEG Radiotelemetry in Small Laboratory Rodents: A Powerful State-of-the Art Approach in Neuropsychiatric, Neurodegenerative, and Epilepsy Research.

EEG radiotelemetry plays an important role in the neurological characterization of transgenic mouse models of neuropsychiatric and neurodegenerative diseases as well as epilepsies providing valuable insights into underlying pathophysiological mechanisms and thereby facilitating the development of new translational approaches. We elaborate on the major advantages of nonrestraining EEG radiotelemetry in contrast to restraining procedures such as tethered systems or jacket systems containing recorders. Whereas a main disadvantage of the latter is their unphysiological, restraining character, telemetric EEG recording overcomes these disadvantages. It allows precise and highly sensitive measurement under various physiological and pathophysiological conditions. Here we present a detailed description of a straightforward successful, quick, and efficient technique for intraperitoneal as well as subcutaneous pouch implantation of a standard radiofrequency transmitter in mice and rats. We further present computerized 3D-stereotaxic placement of both epidural and deep intracerebral electrodes. Preoperative preparation of mice and rats, suitable anaesthesia, and postoperative treatment and pain management are described in detail. A special focus is on fields of application, technical and experimental pitfalls, and technical connections of commercially available radiotelemetry systems with other electrophysiological setups.

Normative Spatiotemporal Parameters During 100-m Sprints in Amputee Sprinters Using Running-Specific Prostheses.

The aim of this study was to develop a normative sample of step frequency and step length during maximal sprinting in amputee sprinters. We analyzed elite-level 100-m races of 255 amputees and 93 able-bodied sprinters, both men and women, from publicly-available Internet broadcasts. For each sprinter's run, the average forward velocity, step frequency, and step length over the 100-m distance were analyzed by using the official record and number of steps in each race. The average forward velocity was greatest in able-bodied sprinters (10.04 ± 0.17 m/s), followed by bilateral transtibial (8.77 ± 0.27 m/s), unilateral transtibial (8.65 ± 0.30 m/s), and transfemoral amputee sprinters (7.65 ± 0.38 m/s) in men. Differences in velocity among 4 groups were associated with step length (able-bodied vs transtibial amputees) or both step frequency and step length (able-bodied vs transfemoral amputees). Although we also found that the velocity was greatest in able-bodied sprinters (9.10 ± 0.14 m/s), followed by unilateral transtibial (7.08 ± 0.26 m/s), bilateral transtibial (7.06 ± 0.48 m/s), and transfemoral amputee sprinters (5.92 ± 0.33 m/s) in women, the differences in the velocity among the groups were associated with both step frequency and step length. Current results suggest that spatiotemporal parameters during a 100-m race of amputee sprinters is varied by amputation levels and sex.

Randomized, controlled trial of ultrasound-assisted catheter-directed thrombolysis for acute intermediate-risk pulmonary embolism.

BACKGROUND: In patients with acute pulmonary embolism, systemic thrombolysis improves right ventricular (RV) dilatation, is associated with major bleeding, and is withheld in many patients at risk. This multicenter randomized, controlled trial investigated whether ultrasound-assisted catheter-directed thrombolysis (USAT) is superior to anticoagulation alone in the reversal of RV dilatation in intermediate-risk patients. METHODS AND RESULTS: Fifty-nine patients (63±14 years) with acute main or lower lobe pulmonary embolism and echocardiographic RV to left ventricular dimension (RV/LV) ratio ≥1.0 were randomized to receive unfractionated heparin and an USAT regimen of 10 to 20 mg recombinant tissue plasminogen activator over 15 hours (n=30; USAT group) or unfractionated heparin alone (n=29; heparin group). Primary outcome was the difference in the RV/LV ratio from baseline to 24 hours. Safety outcomes included death, major and minor bleeding, and recurrent venous thromboembolism at 90 days. In the USAT group, the mean RV/LV ratio was reduced from 1.28±0.19 at baseline to 0.99±0.17 at 24 hours (P<0.001); in the heparin group, mean RV/LV ratios were 1.20±0.14 and 1.17±0.20, respectively (P=0.31). The mean decrease in RV/LV ratio from baseline to 24 hours was 0.30±0.20 versus 0.03±0.16 (P<0.001), respectively. At 90 days, there was 1 death (in the heparin group), no major bleeding, 4 minor bleeding episodes (3 in the USAT group and 1 in the heparin group; P=0.61), and no recurrent venous thromboembolism. CONCLUSIONS: In patients with pulmonary embolism at intermediate risk, a standardized USAT regimen was superior to anticoagulation with heparin alone in reversing RV dilatation at 24 hours, without an increase in bleeding complications. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01166997.

Absolute terahertz power measurement of a time-domain spectroscopy system.

We report on, to the best of our knowledge, the first absolute terahertz (THz) power measurement of a photoconductive emitter developed for time-domain spectroscopy (TDS). The broadband THz radiation emitted by a photoconductor optimized for the excitation with 1550-nm femtosecond pulses was measured by an ultrathin pyroelectric thin-film (UPTF) detector. We show that this detector has a spectrally flat transmission between 100 GHz and 5 THz due to special conductive electrodes on both sides of the UPTF. Its flat responsivity allows the calibration with a standard detector that is traceable to the International System of Units (SI) at the THz detector calibration facility of PTB. Absolute THz power in the range from below 1 µW to above 0.1 mW was measured.

Altered theta oscillations and aberrant cortical excitatory activity in the 5XFAD model of Alzheimer's disease.

Alzheimer's disease (AD) is an age-related neurodegenerative disorder characterized by impairment of memory function. The 5XFAD mouse model was analyzed and compared with wild-type (WT) controls for aberrant cortical excitability and hippocampal theta oscillations by using simultaneous video-electroencephalogram (EEG) monitoring. Seizure staging revealed that 5XFAD mice exhibited cortical hyperexcitability whereas controls did not. In addition, 5XFAD mice displayed a significant increase in hippocampal theta activity from the light to dark phase during nonmotor activity. We also observed a reduction in mean theta frequency in 5XFAD mice compared to controls that was again most prominent during nonmotor activity. Transcriptome analysis of hippocampal probes and subsequent qPCR validation revealed an upregulation of Plcd4 that might be indicative of enhanced muscarinic signalling. Our results suggest that 5XFAD mice exhibit altered cortical excitability, hippocampal dysrhythmicity, and potential changes in muscarinic signaling.

Limited effects of an eIF2αS51A allele on neurological impairments in the 5xFAD mouse model of Alzheimer's disease.

Alzheimer's disease (AD) has been associated with increased phosphorylation of the translation initiation factor 2α (eIF2α) at serine 51. Increased phosphorylation of eIF2α alters translational control and may thereby have adverse effects on synaptic plasticity, learning, and memory. To analyze if increased levels of p-eIF2α indeed promote AD-related neurocognitive impairments, we crossed 5xFAD transgenic mice with an eIF2α(S51A) knock-in line that expresses the nonphosphorylatable eIF2α variant eIF2α(S51A). Behavioral assessment of the resulting mice revealed motor and cognitive deficits in 5xFAD mice that were, with the possible exception of locomotor hyperactivity, not restored by the eIF2α(S51A) allele. Telemetric intracranial EEG recordings revealed no measurable effects of the eIF2α(S51A) allele on 5xFAD-associated epileptic activity. Microarray-based transcriptome analyses showed clear transcriptional alterations in 5xFAD hippocampus that were not corrected by the eIF2α(S51A) allele. In contrast to prior studies, our immunoblot analyses did not reveal increased levels of p-eIF2α in the hippocampus of 5xFAD mice, suggesting that elevated p-eIF2α levels are not a universal feature of AD models. Collectively, our data indicate that 5xFAD-related pathologies do not necessarily require hyperphosphorylation of eIF2α to emerge; they also show that heterozygosity for the nonphosphorylatable eIF2α(S51A) allele has limited effects on 5xFAD-related disease manifestations.

Treatment of aortic stenosis with a self-expanding transcatheter valve: the International Multi-centre ADVANCE Study.

AIM: Transcatheter aortic valve implantation has become an alternative to surgery in higher risk patients with symptomatic aortic stenosis. The aim of the ADVANCE study was to evaluate outcomes following implantation of a self-expanding transcatheter aortic valve system in a fully monitored, multi-centre 'real-world' patient population in highly experienced centres. METHODS AND RESULTS: Patients with severe aortic stenosis at a higher surgical risk in whom implantation of the CoreValve System was decided by the Heart Team were included. Endpoints were a composite of major adverse cardiovascular and cerebrovascular events (MACCE; all-cause mortality, myocardial infarction, stroke, or reintervention) and mortality at 30 days and 1 year. Endpoint-related events were independently adjudicated based on Valve Academic Research Consortium definitions. A total of 1015 patients [mean logistic EuroSCORE 19.4 ± 12.3% [median (Q1,Q3), 16.0% (10.3, 25.3%)], age 81 ± 6 years] were enrolled. Implantation of the CoreValve System led to a significant improvement in haemodynamics and an increase in the effective aortic valve orifice area. At 30 days, the MACCE rate was 8.0% (95% CI: 6.3-9.7%), all-cause mortality was 4.5% (3.2-5.8%), cardiovascular mortality was 3.4% (2.3-4.6%), and the rate of stroke was 3.0% (2.0-4.1%). The life-threatening or disabling bleeding rate was 4.0% (2.8-6.3%). The 12-month rates of MACCE, all-cause mortality, cardiovascular mortality, and stroke were 21.2% (18.4-24.1%), 17.9% (15.2-20.5%), 11.7% (9.4-14.1%), and 4.5% (2.9-6.1%), respectively. The 12-month rates of all-cause mortality were 11.1, 16.5, and 23.6% among patients with a logistic EuroSCORE ≤10%, EuroSCORE 10-20%, and EuroSCORE >20% (P< 0.05), respectively. CONCLUSION: The ADVANCE study demonstrates the safety and effectiveness of the CoreValve System with low mortality and stroke rates in higher risk real-world patients with severe aortic stenosis.

AGAMOUS terminates floral stem cell maintenance in Arabidopsis by directly repressing WUSCHEL through recruitment of Polycomb Group proteins.

Floral stem cells produce a defined number of floral organs before ceasing to be maintained as stem cells. Therefore, floral stem cells offer an ideal model to study the temporal control of stem cell maintenance within a developmental context. AGAMOUS (AG), a MADS domain transcription factor essential for the termination of floral stem cell fate, has long been thought to repress the stem cell maintenance gene WUSCHEL (WUS) indirectly. Here, we uncover a role of Polycomb Group (PcG) genes in the temporally precise repression of WUS expression and termination of floral stem cell fate. We show that AG directly represses WUS expression by binding to the WUS locus and recruiting, directly or indirectly, PcG that methylates histone H3 Lys-27 at WUS. We also show that PcG acts downstream of AG and probably in parallel with the known AG target KNUCKLES to terminate floral stem cell fate. Our studies identify core components of the network governing the temporal program of floral stem cells.

Heat-shock protein 90 inhibition in autoimmunity to type VII collagen: evidence that nonmalignant plasma cells are not therapeutic targets.

Blocking heat-shock protein 90 (Hsp90) induces death of malignant plasma cells by activation of the unfolded protein response, a signaling pathway activated by accumulation of misfolded proteins within the endoplasmic reticulum. We hypothesized that nontransformed plasma cells are also hypersensitive to Hsp90 inhibition because of their high amount of protein biosynthesis. To investigate this hypothesis, 2 different Hsp90 inhibitors, the geldanamycin derivative 17-DMAG and the nontoxic peptide derivative TCBL-145, were applied to mice with experimental epidermolysis bullosa acquisita, an autoimmune bullous disease characterized by autoantibodies against type VII collagen of the dermal-epidermal junction. Both inhibitors ameliorated clinical disease of type VII collagen-immunized mice, suppressed auto-antibody production, and reduced dermal neutrophilic infiltrate. Interestingly, total plasma cell numbers, type VII collagen-specific plasma cells, and germinal center B cells were unaffected by anti-Hsp90 treatment in vivo. However, T-cell proliferation was potently inhibited, as evidenced by the reduced response of isolated lymph node cells from immunized mice to in vitro restimulation with anti-CD3/CD28 antibody or autoantigen in the presence of Hsp90 inhibitors. Our results suggest that Hsp90 blockade has no impact on normal or autoreactive plasma cells in vivo and indentify T cells as targets of anti-Hsp90 treatment in autoimmunity to type VII collagen.

Traceable terahertz power measurement from 1 THz to 5 THz.

The metrology institute in Germany, the Physikalisch-Technische Bundesanstalt (PTB), calibrates the spectral responsivity of THz detectors at 2.52 THz traceable to International System of Units. The Terahertz detector calibration facility is equipped with a standard detector calibrated against a cryogenic radiometer at this frequency. In order to extend this service to a broader spectral range in the THz region a new standard detector was developed. This detector is based on a commercial thermopile detector. Its absorber was modified and characterized by spectroscopic methods with respect to its absorptance and reflectance from 1 THz to 5 THz and at the wavelength of a helium-neon laser in the visible spectral range. This offers the possibility of tracing back the THz power responsivity scale to the more accurate responsivity scale in the visible spectral range and thereby to reduce the uncertainty of detector calibrations in the THz range significantly.

Sensitive and specific assays for routine serological diagnosis of epidermolysis bullosa acquisita.

BACKGROUND: Epidermolysis bullosa acquisita (EBA) is a severe autoimmune subepidermal blistering disease characterized by autoantibodies against the N-terminal collagenous domain (NC1) of type VII collagen (Col VII). OBJECTIVE: Development of reliable assays for the detection of anti-Col VII-NC1 antibodies. METHODS: NC1 was expressed in human HEK293 cells and used as target antigen in an enzyme-linked immunosorbent assay (ELISA) and in an immunofluorescence assay (IFA). These two assays were probed in a large cohort of patients with EBA (n = 73), bullous pemphigoid (BP, n = 72), anti-p200 pemphigoid (n = 24), anti-laminin 332 mucous membrane pemphigoid (MMP, n = 15), pemphigus vulgaris (PV, n = 24), and healthy control subjects (n = 254). RESULTS: The cut-off for the ELISA was optimized for accuracy by receiver-operating characteristics (area under the curve [AUC] = 0.9952). IgG reactivity against NC1 was detected in 69 of 73 EBA (94.5%) and 5 control sera (2 healthy controls and 3 BP patients), resulting in a specificity of 98.7%. The IFA showed a sensitivity of 91.8% and specificity of 99.8%. Reproducibility of the ELISA was demonstrated by an intra-class correlation coefficient of 0.97. IgG subclass analyses by ELISA revealed IgG1, IgG2, IgG3, and IgG4 anti-NC1 reactivity in 83.6%, 85.3%, 37.7%, and 83.6% of EBA sera, respectively. LIMITATIONS: The novel assays were not evaluated prospectively and their use in monitoring serum levels during the disease course was not tested. CONCLUSION: The two assays are highly specific and sensitive to diagnose EBA. Their diagnostic competence was demonstrated in a large cohort of well-characterized EBA sera.