Prediction of cerebral perfusion pressure during carotid surgery – A computational fluid dynamics approach

Background: Maintaining cerebral perfusion pressure in the brain when a carotid artery is closed during vascular surgery is critical for avoiding intraoperative hypoperfusion and risk of ischemic stroke. Here we propose and evaluate a method based on computational fluid dynamics for predicting patient-specific cerebral perfusion pressures at carotid clamping during carotid endarterectomy. Methods: The study consisted of 22 patients with symptomatic carotid stenosis who underwent carotid endarterectomy (73 ± 5 years, 59–80 years, 17 men). The geometry of the circle of Willis was obtained preoperatively from computed tomography angiography and corresponding flow rates from four-dimensional flow magnetic resonance imaging. The patients were also classified as having a present or absent ipsilateral posterior communicating artery based on computed tomography angiography. The predicted mean stump pressures from computational fluid dynamics were compared with intraoperatively measured stump pressures from carotid endarterectomy. Findings: On group level, there was no difference between the predicted and measured stump pressures (−0.5 ± 13 mmHg, P = 0.86) and the pressures were correlated (r = 0.44, P = 0.039). Omitting two outliers, the correlation increased to r = 0.78 (P < 0.001) (−1.4 ± 8.0 mmHg, P = 0.45). Patients with a present ipsilateral posterior communicating artery (n = 8) had a higher measured stump pressure than those with an absent artery (n = 12) (P < 0.001). Interpretation: The stump pressure agreement indicates that the computational fluid dynamics approach was promising in predicting cerebral perfusion pressures during carotid clamping, which may prove useful in the preoperative planning of vascular interventions.publishedVersio

Hydrodynamics of the Certas™ programmable valve for the treatment of hydrocephalus

<p>Abstract</p> <p>Background</p> <p>The new Certas™ shunt for the treatment of hydrocephalus has seven standard pressure settings that according to the manufacturer range from 36 to 238 mmH₂O, and an additional “Virtual Off” setting with an opening pressure >400 mmH₂O. Information on actual pressure response and reliability of shunt performance is important in clinical application, especially the “Virtual Off” setting as a non-surgical replacement for shunt ligation. The objective of this study was to evaluate the <it>in-vitro</it> hydrodynamic performance of the Certas™ shunt.</p> <p>Methods</p> <p>Six new Certas™ shunts with proximal and distal catheters were tested with an automated, computerized test system that raised the pressure from zero to a maximum pressure and back to zero at each valve setting. Opening pressure and flow resistance were determined.</p> <p>Results</p> <p>For settings 1–7 the measured opening pressure range was 26 to 247 mmH₂O, and the mean change in opening pressure for a one-step adjustment was between 33 and 38 mmH₂O. For setting 8 (“Virtual Off”) the measured mean opening pressure was 494 ± 34 mmH₂O (range 451 to 556 mmH₂O). The mean outflow resistance was 7.0 mmHg/ml/min (outflow conductance 17.9 μl/s/kPa).</p> <p>Conclusions</p> <p>The six shunts had similar characteristics and closely matched the manufacturer’s specifications for opening pressure at settings 1–7. The opening pressure for the “Virtual Off” setting was nearly 500 mmH₂O, which is 100 mmH₂O higher than the manufacturer’s specification of “>400” and should be functionally off for most patients with communicating hydrocephalus. Clinical studies are needed to evaluate if the CSF dynamic profile persists after implantation in patients.</p

Size-Dependent Electroluminescence and Current-Voltage Measurements of Blue InGaN/GaN µLEDs down to the Submicron Scale

Besides high-power light-emitting diodes (LEDs) with dimensions in the range of mm, micro-LEDs (μLEDs) are increasingly gaining interest today, motivated by the future applications of μLEDs in augmented reality displays or for nanometrology and sensor technology. A key aspect of this miniaturization is the influence of the structure size on the electrical and optical properties of μLEDs. Thus, in this article, investigations of the size dependence of the electro-optical properties of μLEDs, with diameters in the range of 20 to 0.65 μm, by current-voltage and electroluminescence measurements are described. The measurements indicated that with decreasing size leakage currents in the forward direction decrease. To take advantage of these benefits, the surface has to be treated properly, as otherwise sidewall damages induced by dry etching will impair the optical properties. A possible countermeasure is surface treatment with a potassium hydroxide based solution that can reduce such defects

The Trump presidency, climate change, and the prospect of a disorderly energy transition

This article reflects on the implications of the Trump presidency for global anthropogenic climate change and efforts to address it. Existing commentary, predicated on liberal institutionalist reasoning, has argued that neither Trump’s promised rollback of domestic climate-related funding and regulations, nor withdrawal from the Paris framework, will be as impactful as often feared. While broadly concurring, I nonetheless also in this article take a wider view, to argue that the Trump administration is likely to exacerbate several existing patterns and trends. I discuss four in particular: the general inadequacy of global greenhouse gas emissions reduction targets and implementation efforts; the inadequacy of contemporary climate financing; the embrace between populist conservatism and opposition to action on climate change; and not least, the current global oil and gas boom which, crucially, is being led by the US. I submit that these patterns and trends, and the Trump administration’s likely contributions to them, do not augur well for climate change mitigation, let alone for an orderly transition to a low-carbon global economy. Given current directions of travel, I suggest, this coming transition is likely to be deeply conflict-laden – probably violently so – and to have consequences that will reverberate right across mid-twentieth-century international order

Development of Advanced Thin Films by PECVD for Photovoltaic Applications

Compared to wafer based solar cells, thin film solar cells greatly reduce material cost and thermal budget due to low temperature process. Monolithically manufacturing allows large area fabrication and continuous processing. In this work, several photovoltaic thin films have been developed by rf-PECVD including a-Si:H and μc-Si, both intrinsic and doped on Corning 4 inch glass substrate at low temperature. The conductivity of n type and p type μc-Si at 180ºC was 17S/cm and 7.1E-2S/cm, respectively. B dopants either in a-Si:H or μc-Si films require higher plasma power to get active doping. The B2H6-to-SiH4 flow ratio for p type μc-Si lies from 0.01 to 0.025. Chamber conditions have critical effect on film quality. Repeatable and superior results require a well-established cleaning passivation procedure. Moreover, μc-Si films have been deposited from pure silane on glass substrate by modified rf-ICP-CVD. The deposition rate has been dramatically increased to 5Å/s due to little H2 dilution with crystalline fraction was around 69%, and 6.2Å/s with crystalline fraction 45%. Microstructure started to form at 150ºC with a thin incubation layer on the glass substrate, and became fully dense conical conglomerates around 300nm where conductivity and crystallinity saturated. Additionally, a-SiGe:H films have been developed by modified rf-ICP-CVD. The optical band gaps have been varied from 1.25 to 1.63eV by changing SiH4-to-GeH4 ratio. Also high temperature resulted in low bandgap. Cross-section TEM showed some microcrystllites appeared near interface region. Heterojunction solar cells on p type c-Si wafer have been fabricated using films developed in this thesis. Interference fringes in EQE disappeared on either textured substrate or cells with lift-off contacts. Maximum EQE was 87% around 700nm. I-V curves have also been studied where the interesting kink suggests a counter-diode has formed between emitter region and contacts

Enhanced metabolism and negative regulation of ER stress support higher erythropoietin production in HEK293 cells

Recombinant protein production can cause severe stress on cellular metabolism, resulting in limited titer and product quality. To investigate cellular and metabolic characteristics associated with these limitations, we compare HEK293 clones producing either erythropoietin (EPO) (secretory) or GFP (non-secretory) protein at different rates. Transcriptomic and functional analyses indicate significantly higher metabolism and oxidative phosphorylation in EPO producers compared with parental and GFP cells. In addition, ribosomal genes exhibit specific expression patterns depending on the recombinant protein and the production rate. In a clone displaying a dramatically increased EPO secretion, we detect higher gene expression related to negative regulation of endoplasmic reticulum (ER) stress, including upregulation of ATF6B, which aids EPO production in a subset of clones by overexpression or small interfering RNA (siRNA) knockdown. Our results offer potential target pathways and genes for further development of the secretory power in mammalian cell factories

Tuberculostearic Acid-Containing Phosphatidylinositols as Markers of Bacterial Burden in Tuberculosis

One-fourth of the global human population is estimated to be infected with strains of the Mycobacterium tuberculosis complex (MTBC), the causative agent of tuberculosis (TB). Using lipidomic approaches, we show that tuberculostearic acid (TSA)-containing phosphatidylinositols (PIs) are molecular markers for infection with clinically relevant MTBC strains and signify bacterial burden. For the most abundant lipid marker, detection limits of ∼10$^{2}$ colony forming units (CFUs) and ∼10$^{3}$ CFUs for bacterial and cell culture systems were determined, respectively. We developed a targeted lipid assay, which can be performed within a day including sample preparation─roughly 30-fold faster than in conventional methods based on bacterial culture. This indirect and culture-free detection approach allowed us to determine pathogen loads in infected murine macrophages, human neutrophils, and murine lung tissue. These marker lipids inferred from mycobacterial PIs were found in higher levels in peripheral blood mononuclear cells of TB patients compared to healthy individuals. Moreover, in a small cohort of drug-susceptible TB patients, elevated levels of these molecular markers were detected at the start of therapy and declined upon successful anti-TB treatment. Thus, the concentration of TSA-containing PIs can be used as a correlate for the mycobacterial burden in experimental models and in vitro systems and may prospectively also provide a clinically relevant tool to monitor TB severity

Cerebrospinal fluid markers before and after shunting in patients with secondary and idiopathic normal pressure hydrocephalus

<p>Abstract</p> <p>Background</p> <p>The aim of this study was to explore biochemical changes in the cerebrospinal fluid (CSF) induced by shunt surgery and the relationship between these changes and clinical improvement.</p> <p>Methods</p> <p>We measured clinical symptoms and analysed lumbar CSF for protein content, neurodegeneration and neurotransmission markers in patients with secondary (SNPH, n = 17) and idiopathic NPH (INPH, n = 18) before and 3 months after shunt surgery. Patients were divided into groups according to whether or not there was improvement in clinical symptoms after surgery.</p> <p>Results</p> <p>Preoperatively, the only pathological findings were elevated neurofilament protein (NFL), significantly more so in the SNPH patients than in the INPH patients, and elevated albumin content. Higher levels of NFL correlated with worse gait, balance, wakefulness and neuropsychological performance. Preoperatively, no differences were seen in any of the CSF biomarkers between patients that improved after surgery and those that did not improve. Postoperatively, a greater improvement in gait and balance performance correlated with a more pronounced reduction in NFL. Levels of albumin, albumin ratio, neuropeptide Y, vasoactive intestinal peptide and ganglioside GD3 increased significantly after shunting in both groups. In addition, Gamma amino butyric acid increased significantly in SNPH and tau in INPH.</p> <p>Conclusion</p> <p>We conclude that a number of biochemical changes occur after shunt surgery, but there are no marked differences between the SNPH and INPH patients. The results indicate that NFL may be a marker that can predict a surgically reversible state in NPH.</p

HIV-1 Enhancing Effect of Prostatic Acid Phosphatase Peptides Is Reduced in Human Seminal Plasma

We recently reported that HIV-1 infection can be inhibited by innate antimicrobial components of human seminal plasma (SP). Conversely, naturally occurring peptidic fragments from the SP-derived prostatic acid phosphatase (PAP) have been reported to form amyloid fibrils called “SEVI” and enhance HIV-1 infection in vitro. In order to understand the biological consequence of this proviral effect, we extended these studies in the presence of human SP. PAP-derived peptides were agitated to form SEVI and incubated in the presence or absence of SP. While PAP-derived peptides and SEVI alone were proviral, the presence of 1% SP ablated their proviral activity in several different anti-HIV-1 assays. The anti-HIV-1 activity of SP was concentration dependent and was reduced following filtration. Supraphysiological concentrations of PAP peptides and SEVI incubated with diluted SP were degraded within hours, with SP exhibiting proteolytic activity at dilutions as high as 1∶200. Sub-physiological concentrations of two prominent proteases of SP, prostate-specific antigen (PSA) and matriptase, could degrade physiological and supraphysiological concentrations of PAP peptides and SEVI. While human SP is a complex biological fluid, containing both antiviral and proviral factors, our results suggest that PAP peptides and SEVI may be subject to naturally occurring proteolytic components capable of reducing their proviral activity