Solving Partial Differential Equations with Monte Carlo / Random Walk on an Analog-Digital Hybrid Computer

Current digital computers are about to hit basic physical boundaries with respect to integration density, clock frequencies, and particularly energy consumption. This requires the application of new computing paradigms, such as quantum and analog computing in the near future. Although neither quantum nor analog computer are general purpose computers they will play an important role as co-processors to offload certain classes of compute intensive tasks from classic digital computers, thereby not only reducing run time but also and foremost power consumption. In this work, we describe a random walk approach to the solution of certain types of partial differential equations which is well suited for combinations of digital and analog computers (hybrid computers). The experiments were performed on an Analog Paradigm Model-1 analog computer attached to a digital computer by means of a hybrid interface. At the end we give some estimates of speedups and power consumption obtainable by using future analog computers on chip.Comment: 9 pages, 7 figures. Proceeding for the MikroSystemTechnik Kongress 2023 (VDE Verlag MST Kongress 2023

Experimental Investigation on Heat Transfer Enhancement with Passive Inserts in Flat Tubes in due Consideration of an Efficiency Assessment

This paper presents results of an experimental investigation on pressure drop and heat transfer for a wide range of Reynolds and Prandtl numbers ranging from 8 < Pr < 60 and 40 < Re < 3500, for flat tubes without and with passive inserts. For three different kinds of passive insert designs, the impact on heat and momentum transfer due to coaction of the total set of passive inserts with different shape and amount was investigated. Experimental results were analyzed regarding two main aspects: Heat transfer mechanisms and pressure drop induced by friction and form drag forces due to the presence of different shapes. After heat and momentum transfer mechanisms for each passive insert design were analyzed, heat transfer and pressure drop enhancement were compared to each other, leading to an efficiency discussion. Different concepts for efficiency evaluation, which are cited in literature, were applied to the presented experimental data. Pros and cons of the different concepts are discussed. Finally, we propose an equation for evaluation of total performance, which fully respects the energetic and exergetic aspects of heat transfer and pressure drop enhancement

Muscular involvement assessed by MRI correlates to motor function measurement values in oculopharyngeal muscular dystrophy

Oculopharyngeal muscular dystrophy (OPMD) is a progressive skeletal muscle dystrophy characterized by ptosis, dysphagia, and upper and lower extremity weakness. We examined eight genetically confirmed OPMD patients to detect a MRI pattern and correlate muscle involvement, with validated clinical evaluation methods. Physical assessment was performed using the Motor Function Measurement (MFM) scale. We imaged the lower extremities on a 1.5T scanner. Fatty replacement was graded on a 4-point visual scale. We found prominent affection of the adductor and hamstring muscles in the thigh, and soleus and gastrocnemius muscles in the lower leg. The MFM assessment showed relative mild clinical impairment, mostly affecting standing and transfers, while distal motor capacity was hardly affected. We observed a high (negative) correlation between the validated clinical scores and our visual imaging scores suggesting that quantitative and more objective muscle MRI might serve as outcome measure for clinical trials in muscular dystrophie

Thermal Transients to Accelerate Cyclic Aging of Lithium‐Ion Batteries

Cyclic aging tests of lithium-ion batteries are very time-consuming. Therefore, it is necessary to reduce the testing time by tightening the testing conditions. However, the acceleration with this approach is limited without altering the aging mechanisms. In this paper, we investigate whether and how thermal transients accelerate the aging. The tests are performed on NMC/graphite pouch cells by applying temperatures in a range of 5 °C to 45 °C to the cell surface. The results show, that an accelerated capacity loss can be achieved in comparison to the reference cell at a steady-state temperature of 25 °C. However, capacity difference analysis (CDA) prognoses a covering layer for the transient cells, which is confirmed upon post-mortem analysis. We suspect the origin to lie in the dynamics of temperature fields and current distribution during temperature changes when charging. More specifically, areas of higher temperature in the cell lead to high local current densities and plating. Subsequently, high temperatures promote the reaction of the plated lithium with electrolyte. The results show that thermal transients are a critical condition for lifetime and safety and should be treated with caution as they can occur during real life operation

Systematic substrate identification indicates a central role for the metalloprotease ADAM10 in axon targeting and synapse function

Metzincin metalloproteases have major roles in intercellular communication by modulating the function of membrane proteins. One of the proteases is the a-disintegrin-and-metalloprotease 10 (ADAM10) which acts as alpha-secretase of the Alzheimer\u27s disease amyloid precursor protein. ADAM10 is also required for neuronal network functions in murine brain, but neuronal ADAM10 substrates are only partly known. With a proteomic analysis of Adam10-deficient neurons we identified 91, mostly novel ADAM10 substrate candidates, making ADAM10 a major protease for membrane proteins in the nervous system. Several novel substrates, including the neuronal cell adhesion protein NrCAM, are involved in brain development. Indeed, we detected mistargeted axons in the olfactory bulb of conditional ADAM10-/- mice, which correlate with reduced cleavage of NrCAM, NCAM and other ADAM10 substrates. In summary, the novel ADAM10 substrates provide a molecular basis for neuronal network dysfunctions in conditional ADAM10-/- mice and demonstrate a fundamental function of ADAM10 in the brain

Natriuretic peptide vs. clinical information for diagnosis of left ventricular systolic dysfunction in primary care

<p>Abstract</p> <p>Background</p> <p>Screening of primary care patients at risk for left ventricular systolic dysfunction by a simple blood-test might reduce referral rates for echocardiography. Whether or not natriuretic peptide testing is a useful and cost-effective diagnostic instrument in primary care settings, however, is still a matter of debate.</p> <p>Methods</p> <p>N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, clinical information, and echocardiographic data of left ventricular systolic function were collected in 542 family practice patients with at least one cardiovascular risk factor. We determined the diagnostic power of the NT-proBNP assessment in ruling out left ventricular systolic dysfunction and compared it to a risk score derived from a logistic regression model of easily acquired clinical information.</p> <p>Results</p> <p>23 of 542 patients showed left ventricular systolic dysfunction. Both NT-proBNP and the clinical risk score consisting of dyspnea at exertion and ankle swelling, coronary artery disease and diuretic treatment showed excellent diagnostic power for ruling out left ventricular systolic dysfunction. AUC of NT-proBNP was 0.83 (95% CI, 0.75 to 0.92) with a sensitivity of 0.91 (95% CI, 0.71 to 0.98) and a specificity of 0.46 (95% CI, 0.41 to 0.50). AUC of the clinical risk score was 0.85 (95% CI, 0.79 to 0.91) with a sensitivity of 0.91 (95% CI, 0.71 to 0.98) and a specificity of 0.64 (95% CI, 0.59 to 0.67). 148 misclassifications using NT-proBNP and 55 using the clinical risk score revealed a significant difference (McNemar test; p < 0.001) that was based on the higher specificity of the clinical risk score.</p> <p>Conclusion</p> <p>The evaluation of clinical information is at least as effective as NT-proBNP testing in ruling out left ventricular systolic dysfunction in family practice patients at risk. If these results are confirmed in larger cohorts and in different samples, family physicians should be encouraged to rely on the diagnostic power of the clinical information from their patients.</p

Changes in heart failure medications in patients hospitalised and discharged

BACKGROUND: To date, evidence-based recommendations help doctors to manage patients with heart failure (HF). However, the implementation of these recommendations in primary care is still problematic as beneficial drugs are infrequently prescribed. The aim of the study was to determine whether admission to hospital increases usage of beneficial HF medication and if this usage is maintained directly after discharge. METHODS: The study was conducted from November 2002 until January 2004. In 77 patients hospitalised with heart failure (HF), the medication prescribed by the referring general practitioner (GP) and drug treatment directed by the hospital physicians was documented. Information regarding the post-discharge (14 d) therapy by the GP was evaluated via a telephone interview. Ejection fraction values, comorbidity and specifics regarding diagnostic or therapeutic intervention were collected by chart review. RESULTS: When compared to the referring GPs, hospital physicians prescribed more ACE-inhibitors (58.4% vs. 76.6%; p = 0.001) and beta-blockers of proven efficacy in HF (metoprolol, bisoprolol, carvedilol; 58.4% vs. 81.8%). Aldosterone antagonists were also administered more frequently in the hospital setting compared to general practice (14.3% vs. 37.7%). The New York Heart Association classification for heart failure did not influence whether aldosterone antagonists were administered either in primary or secondary care. Fourteen days after discharge, there was no significant discontinuity in discharge medication. CONCLUSION: Patients suffering from HF were more likely to receive beneficial medication in hospital than prior to admission. The treatment regime then remained stable two weeks after discharge. We suggest that findings on drug continuation in different cardiovascular patients might be considered validated for patients with HF

Toxoplasma gondii Actively Inhibits Neuronal Function in Chronically Infected Mice

Upon infection with the obligate intracellular parasite Toxoplasma gondii, fast replicating tachyzoites infect a broad spectrum of host cells including neurons. Under the pressure of the immune response, tachyzoites convert into slow-replicating bradyzoites, which persist as cysts in neurons. Currently, it is unclear whether T. gondii alters the functional activity of neurons, which may contribute to altered behaviour of T. gondii–infected mice and men. In the present study we demonstrate that upon oral infection with T. gondii cysts, chronically infected BALB/c mice lost over time their natural fear against cat urine which was paralleled by the persistence of the parasite in brain regions affecting behaviour and odor perception. Detailed immunohistochemistry showed that in infected neurons not only parasitic cysts but also the host cell cytoplasm and some axons stained positive for Toxoplasma antigen suggesting that parasitic proteins might directly interfere with neuronal function. In fact, in vitro live cell calcium (Ca2+) imaging studies revealed that tachyzoites actively manipulated Ca2+ signalling upon glutamate stimulation leading either to hyper- or hypo-responsive neurons. Experiments with the endoplasmatic reticulum Ca2+ uptake inhibitor thapsigargin indicate that tachyzoites deplete Ca2+ stores in the endoplasmatic reticulum. Furthermore in vivo studies revealed that the activity-dependent uptake of the potassium analogue thallium was reduced in cyst harbouring neurons indicating their functional impairment. The percentage of non-functional neurons increased over time In conclusion, both bradyzoites and tachyzoites functionally silence infected neurons, which may significantly contribute to the altered behaviour of the host

Radiological progression of cerebral metastases after radiosurgery: assessment of perfusion MRI for differentiating between necrosis and recurrence

To assess the capability of perfusion MRI to differentiate between necrosis and tumor recurrence in patients showing radiological progression of cerebral metastases treated with stereotactic radiosurgery (SRS). From 2004 to 2006 dynamic susceptibility-weighted contrast-enhanced perfusion MRI scans were performed on patients with cerebral metastasis showing radiological progression after SRS during follow-up. Several perfusion MRI characteristics were examined: a subjective visual score of the relative cerebral blood volume (rCBV) map and quantitative rCBV measurements of the contrast-enhanced areas of maximal perfusion. For a total of 34 lesions in 31 patients a perfusion MRI was performed. Diagnoses were based on histology, definite radiological decrease or a combination of radiological and clinical follow-up. The diagnosis of tumor recurrence was obtained in 20 of 34 lesions, and tumor necrosis in 14 of 34. Regression analyses for all measures proved statistically significant (χ2 = 11.6–21.6, P < 0.001–0.0001). Visual inspection of the rCBV map yielded a sensitivity and specificity of 70.0 respectively 92.9%. The optimal cutoff point for maximal tumor rCBV relative to white matter was 2.00 (improving the sensibility to 85.0%) and 1.85 relative to grey matter (GM), improving the specificity to 100%, with a corresponding sensitivity of 70.0%. Perfusion MRI seems to be a useful tool in the differentiation of necrosis and tumor recurrence after SRS. For the patients displaying a rCBV-GM greater than 1.85, the diagnosis of necrosis was excluded. Salvage treatment can be initiated for these patients in an attempt to prolong survival

Clinical and virological characteristics of hospitalised COVID-19 patients in a German tertiary care centre during the first wave of the SARS-CoV-2 pandemic: a prospective observational study

Purpose: Adequate patient allocation is pivotal for optimal resource management in strained healthcare systems, and requires detailed knowledge of clinical and virological disease trajectories. The purpose of this work was to identify risk factors associated with need for invasive mechanical ventilation (IMV), to analyse viral kinetics in patients with and without IMV and to provide a comprehensive description of clinical course. Methods: A cohort of 168 hospitalised adult COVID-19 patients enrolled in a prospective observational study at a large European tertiary care centre was analysed. Results: Forty-four per cent (71/161) of patients required invasive mechanical ventilation (IMV). Shorter duration of symptoms before admission (aOR 1.22 per day less, 95% CI 1.10-1.37, p < 0.01) and history of hypertension (aOR 5.55, 95% CI 2.00-16.82, p < 0.01) were associated with need for IMV. Patients on IMV had higher maximal concentrations, slower decline rates, and longer shedding of SARS-CoV-2 than non-IMV patients (33 days, IQR 26-46.75, vs 18 days, IQR 16-46.75, respectively, p < 0.01). Median duration of hospitalisation was 9 days (IQR 6-15.5) for non-IMV and 49.5 days (IQR 36.8-82.5) for IMV patients. Conclusions: Our results indicate a short duration of symptoms before admission as a risk factor for severe disease that merits further investigation and different viral load kinetics in severely affected patients. Median duration of hospitalisation of IMV patients was longer than described for acute respiratory distress syndrome unrelated to COVID-19