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Mechanical Characterization of Compact Rolled-up Microtubes Using In Situ Scanning Electron Microscopy Nanoindentation and Finite Element Analysis
Self-assembled Swiss-roll microstructures (SRMs) are widely explored to build up microelectronic devices such as capacitors, transistors, or inductors as well as sensors and lab-in-a-tube systems. These devices often need to be transferred to a special position on a microchip or printed circuit board for the final application. Such a device transfer is typically conducted by a pick-and-place process exerting enormous mechanical loads onto the 3D components that may cause catastrophic failure of the device. Herein, the mechanical deformation behavior of SRMs using experiments and simulations is investigated. SRMs using in situ scanning electron microscopy (SEM) combined with nanoindentation are characterized. This allows us to mimic and characterize mechanical loads as they occur in a pick-and-place process. The deformation response of SRMs depends on three geometrical factors, i.e., the number of windings, compactness of consecutive windings, and inner diameter of the microtube. Nonlinear finite element analysis (FEA) showing good agreement with experiments is performed. It is believed that the insights into the mechanical loading of 3D self-assembled architectures will lead to novel techniques suitable for a new generation of pick-and-place machines operating at the microscale. © 2021 The Authors. Advanced Engineering Materials published by Wiley-VCH Gmb
Comparison of indirect radiation dose estimates with directly measured radiation dose for patients and operators during complex endovascular procedures
BackgroundA great deal of attention has been directed at the necessity and potential for deleterious outcomes as a result of radiation exposure during diagnostic evaluations and interventional procedures. We embarked on this study in an attempt to accurately determine the amount of radiation exposure given to patients undergoing complex endovascular aortic repair. These measured doses were then correlated with radiation dose estimates provided by the imaging equipment manufacturers that are typically used for documentation and analysis of radiation-induced risk.MethodsConsecutive patients undergoing endovascular thoracoabdominal aneurysm (eTAAA) repair were prospectively studied with respect to radiation dose. Indirect parameters as cumulative air kerma (CAK), kerma area product (KAP), and fluoroscopy time (FT) were recorded concurrently with direct measurements of dose (peak skin dose [PSD]) and radiation exposure patterns using radiochromatic film placed in the back of the patient during the procedure. Simultaneously, operator exposure was determined using high-sensitivity electronic dosimeters. Correlation between the indirect and direct parameters was calculated. The observed radiation exposure pattern was reproduced in phantoms with over 200 dosimeters located in mock organs, and effective dose has been calculated in an in vitro study. Scatter plots were used to evaluate the relationship between continuous variables and Pearson coefficients.ResultseTAAA repair was performed in 54 patients over 5 months, of which 47 had the repair limited to the thoracoabdominal segment. Clinical follow-up was complete in 98% of the patients. No patients had evidence of radiation-induced skin injury. CAK exceeded 15 Gy in 3 patients (the Joint Commission on Accreditation of Healthcare Organizations [JCAHO] threshold for sentinel events); however, the direct measurements were well below 15 Gy in all patients. PSD was measured by quantifying the exposure of the radiochromatic film. PSD correlated weakly with FT but better with CAK and KAP (r = 0.55, 0.80, and 0.76, respectively). The following formula provides the best estimate of actual PSD = 0.677 + 0.257 CAK. The average effective dose was 119.68 mSv (for type II or III eTAAA) and 76.46 mSv (type IV eTAAA). The operator effective dose averaged 0.17 mSv/case and correlated best with the KAP (r = 0.82, P < .0001).ConclusionFT cannot be used to estimate PSD, and CAK and KAP represent poor surrogate markers for JCAHO-defined sentinel events. Even when directly measured PSDs were used, there was a poor correlation with clinical event (no skin injuries with an average PSD >2 Gy). The effective radiation dose of an eTAAA is equivalent to two preoperative computed tomography scans. The maximal operator exposure is 50 mSv/year, thus, a single operator could perform up to 294 eTAAA procedures annually before reaching the recommended maximum operator dose
Habitat‐dependent occupancy and movement in a migrant songbird highlights the importance of mangroves and forested lagoons in Panama and Colombia
Climate change is predicted to impact tropical mangrove forests due to decreased rainfall, sea‐level rise, and increased seasonality of flooding. Such changes are likely to influence habitat quality for migratory songbirds occupying mangrove wetlands during the tropical dry season. Overwintering habitat quality is known to be associated with fitness in migratory songbirds, yet studies have focused primarily on territorial species. Little is known about the ecology of nonterritorial species that may display more complex movement patterns within and among habitats of differing quality. In this study, we assess within‐season survival and movement at two spatio‐temporal scales of a nonterritorial overwintering bird, the prothonotary warbler (Protonotaria citrea), that depends on mangroves and tropical lowland forests. Specifically, we (a) estimated within‐patch survival and persistence over a six‐week period using radio‐tagged birds in central Panama and (b) modeled abundance and occupancy dynamics at survey points throughout eastern Panama and northern Colombia as the dry season progressed. We found that site persistence was highest in mangroves; however, the probability of survival did not differ among habitats. The probability of warbler occupancy increased with canopy cover, and wet habitats were least likely to experience local extinction as the dry season progressed. We also found that warbler abundance is highest in forests with the tallest canopies. This study is one of the first to demonstrate habitat‐dependent occupancy and movement in a nonterritorial overwintering migrant songbird, and our findings highlight the need to conserve intact, mature mangrove, and lowland forests
Short-Term Hurricane Impacts on a Neotropical Community of Marked Birds and Implications for Early-Stage Community Resilience
Populations in fragmented ecosystems risk extirpation through natural disasters, which must be endured rather than avoided. Managing communities for resilience is thus critical, but details are sketchy about the capacity for resilience and its associated properties in vertebrate communities. We studied short-term resilience in a community of individually marked birds, following this community through the catastrophic destruction of its forest habitat by Hurricane Iris in Belize, Central America. We sampled for 58 d immediately before the storm, 28 d beginning 11 d after Hurricane Iris, and for 69 d approximately one year later. Our data showed that the initial capacity for resilience was strong. Many banded individuals remained after the storm, although lower post-hurricane recapture rates revealed increased turnover among individuals. Changes occurred in community dynamics and in abundances among species and guilds. Survivors and immigrants both were critical components of resilience, but in a heterogeneous, species-specific manner. Delayed effects, including higher fat storage and increased species losses, were evident one year later
Variation of the fine structure constant in QSO spectra from coherent dark matter oscillations
We consider the problem of the evolution of the fine structure coefficient
alpha under the assumption that the scalar field coupling to the Maxwell term
satisfies the condition mt>>1 for coherent dark matter oscillations. In this
case we find that the coupling scale f in the leading order coupling
-(phi/4f)F^2 affects the cosmological evolution of alpha according to
ln(alpha/alpha_0) xi(m_{Pl}/f)ln(tanh(t/2 tau)/tanh(t_0/2 tau)). A fit to the
QSO observations by Murphy et al. yields f/xi= 2.12^{+0.58}_{-0.37} 10^5m_{Pl}.
Here m_{Pl} is the reduced Planck mass, and xi^2=rho_phi/rho_m parametrizes the
contribution of phi to the matter density in the universe.Comment: 6 pages, accepted for publication in the MNRA
A phase I study of a dual PI3-kinase/mTOR inhibitor BEZ235 in adult patients with relapsed or refractory acute leukemia
Background
Combined inhibition of phosphatidylinositol 3-kinase (PI3K) and the mammalian target of rapamycin (mTOR) complexes may be an efficient treatment for acute leukemia. The primary objective of this phase I single center open label study was to determine the maximum tolerated dose (MTD) and recommended phase II dose (RP2D) of the dual pan-class I PI3K and mTOR inhibitor BEZ235 in patients with advanced leukemia.
Methods
Herein patients > 18 years of age who had relapsed or showed refractory leukemia were treated with BEZ235 (orally at 300–400 mg BID (cohort − 1/1)) to assess safety, tolerability, preliminary efficacy and pharmacokinetic (PK). Adverse events data and serious adverse events were analyzed and haematological and clinical biochemistry toxicities were assessed from laboratory test parameters. Response was assessed for the first time at the end of cycle 1 (day 29) and after every subsequent cycle. Pharmacokinetic and pharmacodynamic analyses of BEZ235 were also included (BEZ235 plasma levels, phosphorylation of AKT, S6 and 4EBP1). On statistics this trial is a multiple ascending dose study in which a following variant of the 3 + 3 rule (“Rolling Six”), a minimum of 6 and a maximum of 12 patients was recruited for the dose escalation and another 5 were planned for the expansion phase.
Results
Twenty-four patients with ALL (n = 11) or AML (n = 12) or CML-BP (n = 1) were enrolled. All patients had failed one (n = 5) or more lines of therapy (n = 5) and 14 patients were in refractory / refractory relapse. No formal MTD was defined, stomatitis and gastrointestinal toxicity at 400 mg BID dose was considered incompatible with prolonged treatment. The RP2D of BEZ235 was defined as 300 mg BID. Four of 24 patients showed clinical benefit. Twenty-two of 24 patients discontinued because of progression, (median time to progression 27 days (4d-112d). There was no association between PK parameters and efficacy or tolerability.
Conclusions
Combined inhibition of PI3K and mTOR inhibits a clinically meaningful driver pathway in a small subset of patients with ALL, with no benefit in patients with AML
Ultrahigh energy cosmic rays from collisional annihilation revisited
We re-examine collisional annihilation of superheavy dark matter particles in
dark matter density spikes in the galactic halo as a possible source of
ultrahigh energy cosmic rays. We estimate the possible flux in a way that does
not depend on detailed assumptions about the density profiles of dark matter
clumps. The result confirms that collisional annihilation is compatible with
annihilation cross sections below the unitarity bounds for superheavy dark
matter if the particles can form dense cores in dark matter substructure, and
it provides estimates for core sizes and densities. The ensuing clumpy source
distribution in the galactic halo will be tested within a few years of
operation of the Pierre Auger observatory.Comment: 9 pages, new section included, introduction shortened, to appear in
Can. J. Phy
Clinical relevance of heparin-PF4 complex antibody in DVT after total joint replacement
<p>Abstract</p> <p>Background</p> <p>Antibodies to the heparin-platelet factor-4 (HPF-4) complex (HIT antibodies) have been observed in patients with heparin-induced thrombocytopenia (HIT). These antibodies are thought to be involved in thrombosis through activation of platelet/endothelial cells. This prospective study was conducted to determine the incidence of post-operative HIT antibodies to assess the associated risk of deep vein thrombosis (DVT) in patients undergoing total knee arthroplasty (TKA) or total hip arthroplasty (THA).</p> <p>Methods</p> <p>We studied 104 patients who underwent unilateral primary TKA (n = 44) and primary THA (n = 60) with short-duration prophylaxis (1–2 days of a fixed dose of unfractionated heparin). HIT antibodies were assayed using a sandwich-type ELISA before the operation and after heparin treatment (post-operative day 7).</p> <p>Results</p> <p>In the clinical outcome, the incidence of symptomatic DVT was 15.4% (16/104, TKA; 10, THA 6) and pulmonary embolism (PE) was not observed. The total seroconversion rate of HIT antibodies at post-operative day 7 was 34.6% (36/104). Among 36 seroconverted patients, 11 (30.6%) developed symptomatic DVT and 5 out of 68 of the non-seroconverted patients (7.4%) developed symptomatic DVT. The incidence for DVT was significantly higher in the seroconverted patients compared with that of the non-seroconverted patients (odds ratio 5.5, 95%CI: 1.7–17.6 <it>p </it>= 0.0028). Furthermore, in the patients with symptomatic DVT, the titer of HIT antibodies at post-operative day 7 was significantly higher compared with those without symptomatic DVT.</p> <p>Conclusion</p> <p>Our data therefore suggest that seroconversion for HIT antibodies generated by heparin is associated with a risk of DVT in patients undergoing total joint replacement.</p
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