Continuum Representation for Simulating Discrete Events of Battery Operation

A mathematical approach for representing the discrete events in the cycling studies of lithium-ion batteries as a continuum event has been proposed to generate charge/discharge curves for N number of battery cycles. Simulations of up to 5000 cycles have been performed using this technique using the solid-phase diffusion model. A nonlinear electrochemical engineering model, which describes the galvanostatic charge/open-circuit/discharge processes of a thin-film nickel electrode, has also been investigated to test and validate the computational performance of the continuum representation technique. Finally, the tested technique is implemented for an existing full-order pseudo-two-dimensional lithium-ion battery model that has several coupled and nonlinear partial differential equations in multiple domains. The continuum representation, which is expressed as a function of a dependent variable in time t, works efficiently for several cycles with very minimal model initialization efforts and computation cost. However, it is not ideal for state detection. The mathematical simulation approaches that are currently followed for the modeling of charge/discharge cycles of lithium-ion batteries involve different computational schemes. 1-10 The complexity arises because of steep variations in the dependent variables ͑concentrations and potentials͒ between charge and discharge processes, difficulty in obtaining consistent initial values for the model equations, solver failure after a certain number of cycles due to high charge/discharge cutoff voltages, thermal effects, etc. We came up with a shooting method in a spatial direction 11 based on the steadystate model equations that work well for providing consistent initialization during a charge or discharge process. Wu and White 12 devised an initialization subroutine called differential algebraic equation initialization subroutine ͑DAEIS͒ to overcome numerical inconsistency and discussed in detail the initialization problems of battery models. Consistent initial values of the dependent variables for index-1 differential algebraic equation ͑DAE͒ systems can be obtained using DAEIS. DAEIS is effective in handling a DAE system with combined continuous processes and discrete events that are frequently encountered in battery operations. Before the advancement of computation capability, Tafel approximation of the electrokinetic expression and Ohm's law in electrolyte were used to calculate initial guesses for algebraic variables. 13 In this work, the complete protocol that includes many discrete events to constitute one cycle of lithium-ion battery was reformulated as a single continuous process. Then, this continuous process was repeatedly simulated up to the desired number of cycles. This was achieved by carefully changing the model variables that directly influence the cycling parameters, for example, changing the independent variable ͑in time͒ or the dependent variable ͑in solid-phase concentration at the surface of the intercalating particles͒ and expressing the same as an additional algebraic equation in terms of the number of battery cycles. This approach was attempted to overcome the difficulties mentioned during the conventional cycle studies, and it was an efficient method for many situations. Adding an additional nonlinear algebraic equation does not contribute to the significant computation cost for the model simulation; rather, it helps in effectively handling large cycle numbers and in generating the cycle data for further analysis. The proposed mathematical representation has been demonstrated for models with different degrees of complexity and in comparison with the results from those using the conventional approach. 14-16 The combination of this continuum representation and this efficient reformulated model helps in the use of meaningful models of batteries for emerging applications such as satellites, military, hybrid electric vehicles, etc. The combination of the continuum representation and the reformulated model is helpful in a way that solving the full-order physicsbased lithium-ion battery model with less computation cost was facilitated by the reformulated version of the full-order model that does not require a large system of differential and algebraic equations to be solved for each parameter in a cycle, for example, charge or discharge. Though the objective of this investigation is to devise a continuum representation for generating cycle data using a fullorder physics-based lithium-ion battery model, two other simple electrochemical models ͑mentioned above͒ are also discussed with the intention to provide more details and insight into the proposed continuum approach that can help readers to easily adopt the approach for other interesting cases

Treatment outcomes of fixed-dose combination versus separate tablet regimens in pulmonary tuberculosis patients with or without diabetes in Qatar

Background: Tuberculosis is considered the second most common cause of death due to infectious agent. The currently preferred regimen for treatment of pulmonary tuberculosis (PTB) is isoniazid, rifampin, pyrazinamide, and ethambutol, which has been used either as separate tablets (ST) or as fixed-dose combination (FDC). To date, no studies have compared both regimens in Qatar. We aim to evaluate the safety and effectiveness of FDC and ST regimen for treating PTB, in addition to comparing safety and efficacy of FDC and ST regimens in patients with diabetes treated for TB. Methods: A retrospective observational study was conducted in two general hospitals in Qatar. Patients diagnosed with PTB received anti-tuberculosis medications (either as FDC or ST) administered by the nurse. Sputum smears were tested weekly. We assessed the time to negative sputum smear and incidence of adverse events among FDC and ST groups. Results: The study included 148 patients. FDC was used in 90 patients (61%). Effectiveness was not different between FDC and ST regimens as shown by mean time to sputum conversion (29.9 ± 18.3 vs. 35.6 ± 23 days, p = 0.12). Similarly, there was no difference in the incidence of adverse events, except for visual one that was higher in ST group. Among the 33 diabetic patients, 19 received the FDC and had faster sputum conversion compared to those who received ST (31 ± 12 vs. 49.4 ± 30.9 days, p = 0.05). Overall, diabetic patients needed longer time for sputum conversion and had more hepatotoxic and gastric adverse events compared to non-diabetics. Conclusion: ST group had higher visual side effects compared to FDC. FDC may be more effective in diabetic patients; however, further studies are required to confirm such finding.PublishedN/

Therapeutic Drug Monitoring for Slow Response to Tuberculosis Treatment in a State Control Program, Virginia, USA

TOC summary: Diabetes was associated with increased risk for slow response and low rifampin levels

Tuberculosis chemotherapy: current drug delivery approaches

Tuberculosis is a leading killer of young adults worldwide and the global scourge of multi-drug resistant tuberculosis is reaching epidemic proportions. It is endemic in most developing countries and resurgent in developed and developing countries with high rates of human immunodeficiency virus infection. This article reviews the current situation in terms of drug delivery approaches for tuberculosis chemotherapy. A number of novel implant-, microparticulate-, and various other carrier-based drug delivery systems incorporating the principal anti-tuberculosis agents have been fabricated that either target the site of tuberculosis infection or reduce the dosing frequency with the aim of improving patient outcomes. These developments in drug delivery represent attractive options with significant merit, however, there is a requisite to manufacture an oral system, which directly addresses issues of unacceptable rifampicin bioavailability in fixed-dose combinations. This is fostered by the need to deliver medications to patients more efficiently and with fewer side effects, especially in developing countries. The fabrication of a polymeric once-daily oral multiparticulate fixed-dose combination of the principal anti-tuberculosis drugs, which attains segregated delivery of rifampicin and isoniazid for improved rifampicin bioavailability, could be a step in the right direction in addressing issues of treatment failure due to patient non-compliance

Rare pathogenic variants in WNK3 cause X-linked intellectual disability

This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this recordData availability: All data are available upon request. The sequence variants in WNK3 (NM_004656.3) reported in the paper have been deposited in ClinVar database. Their respective accession numbers (SCV002107163 to SCV002107168) are indicated in Tables 1 and S1.Purpose WNK3 kinase (PRKWNK3) has been implicated in the development and function of the brain via its regulation of the cation-chloride cotransporters, but the role of WNK3 in human development is unknown. Method We ascertained exome or genome sequences of individuals with rare familial or sporadic forms of intellectual disability (ID). Results We identified a total of 6 different maternally-inherited, hemizygous, 3 loss-of-function or 3 pathogenic missense variants (p.Pro204Arg, p.Leu300Ser, p.Glu607Val) in WNK3 in 14 male individuals from 6 unrelated families. Affected individuals had identifier with variable presence of epilepsy and structural brain defects. WNK3 variants cosegregated with the disease in 3 different families with multiple affected individuals. This included 1 large family previously diagnosed with X-linked Prieto syndrome. WNK3 pathogenic missense variants localize to the catalytic domain and impede the inhibitory phosphorylation of the neuronal-specific chloride cotransporter KCC2 at threonine 1007, a site critically regulated during the development of synaptic inhibition. Conclusion Pathogenic WNK3 variants cause a rare form of human X-linked identifier with variable epilepsy and structural brain abnormalities and implicate impaired phospho-regulation of KCC2 as a pathogenic mechanism.Estonian Research CouncilNational Natural Science Foundation of ChinaRoyal SocietySouth Carolina Department of Disabilities and Special Needs (SCDDSN)National Institute of Neurological Disorders and Stroke (NINDS

Solid-State Characterization of Nevirapine

The purpose of this investigation is to characterize nevirapine from commercial samples and samples crystallized from different solvents under various conditions. The solid-state behavior of nevirapine samples was investigated using a variety of complementary techniques such as microscopy (optical, polarized, hot stage microscopy), differential scanning calorimeter, thermogravimetric analysis, Fourier transform infrared spectroscopy and powder X-ray diffractometry. The commercial samples of nevirapine had the same polymorphic crystalline form with an anhedral crystal habit. Intrinsic dissolution of nevirapine was similar for both the commercial batches. Powder dissolution showed pH dependency, with maximum dissolution in acidic pH and there was no significant effect of particle size. The samples recrystallized from different solvent systems with varying polarity yielded different crystal habits. Stirring and degrees of supersaturation influenced the size and shape of the crystals. The recrystallized samples did not produce any new polymorphic form, but weak solvates with varying crystal habit were produced. Recrystallized samples showed differences in the x-ray diffractograms. However, all the samples had the same internal crystal lattice as revealed from their similar melting points and heat of fusion. The intrinsic dissolution rate of recrystallized samples was lower than the commercial sample. It was found that the compression pressure resulted in desolvation and partial conversion of the crystal form. After compression, the recrystallized samples showed similar x-ray diffractograms to the commercial sample. Amorphous form showed slightly higher aqueous solubility than the commercial crystalline form