Advances and challenges in the high-pressure rheology of complex fluids.

Complex fluids and soft materials are ubiquitous in nature and industry. In industrial processes, these materials often get exposed to high hydrostatic pressures. Some examples include polymer melts, crude oils, gas hydrates, food systems, foams, motor oils, lubricants, etc. In spite of the relevance and utilization of hydrostatic pressure in many industrial applications, the role of pressure on the rheological properties has not been examined extensively in the literature. We review the high-pressure rheometric systems and present advantages and drawbacks of various kinds of rheometers such as capillary rheometer, sliding plate rheometer, falling ball viscometer, and rotational rheometer. By outlining the design complexities, precision, low-torque resolution limits and the inherent error sources of each type are critically evaluated. Furthermore, the high-pressure rheology data, chosen to cover a broad range of pressures and material class ranging from simple Newtonian fluids (incompressible), complex non-Newtonian fluids and compressible fluids featuring various key applications from different industries, are reviewed. The literature suggests, while effect of pressure on the rheological behavior is vital for many applications, compared to the effects of temperature on the rheological behavior, knowledge of the effect of pressure is still in its infancy.

Identification of Galtox, a new protein toxin from Photorhabdus bacterial symbionts of Heterorhabditis nematodes.

The Gram-negative bacteria Photorhabdus lives in a symbiotic relationship with the insect-pathogenic Heterorhabditis nematodes and produces numerous hydrolytic enzymes, secondary metabolites and protein toxins. Seven Photorhabdus strains were previously isolated from the Heterorhabditis nematodes collected from different geographical regions of India. The strains IARI-SGMG3, IARI-SGHR2, IARI-SGHR4, IARI-SGMS1 and IARI-SGGJ2 were identified as P. akhurstii, whereas IARI-SGLDK1 and IARI-SGHP1 were identified as P. laumondii subsp. laumondii and P. laumondii subsp. clarkeii, respectively. A new and previously unreported 35 kDa molecular weight protein toxin 'Galtox' was identified from these Photorhabdus strains. The nucleotide sequences of the toxin gene from seven Photorhabdus strains were PCR amplified, sequenced, cloned into pET protein expression vector, and the protein toxin was expressed and purified. The Galtox sequence from various strains showed variations in sequence and toxicity against Galleria mellonella. The injection of purified Galtox protein into the 4th instar larvae showed median lethal dose (LD50) values of 2.39-26.08 ng toxin/g G. mellonella bodyweight after 48 h. The protein injection killed the insects quickly and exhibited a median lethal time (LT50) of 12-60 h when injected at the rate of 3.1-31.2 ng toxin/g G. mellonella bodyweight. Galtox protein sequence analysis indicated similarity to several bacterial toxin-related protein domains, such as 6rgnA domain of Bordetella membrane targeting toxin BteA, 6gy6 domain of Xenorhabdus α-Xenorhabdolysins, 4mu6A and 4xa9a domains similar to effector protein LegC3 from Legionella pneumophila and 1cv8.1 domain of staphylococcal cysteine proteinase staphopain B. The mode of action of Galtox needs to be understood to enable its use for the management of agricultural insect-pests.

Rapid and sensitive detection of potato cyst nematode Globodera rostochiensis by loop-mediated isothermal amplification assay.

Cyst nematodes of the species Globodera rostochiensis and G. pallida are devastating parasites of the potato crop. Early detection of cyst nematodes in the field is critical for adopting an appropriate management strategy. A specific and sensitive loop-mediated isothermal amplification (LAMP) assay using four oligonucleotide primers has been developed to amplify the internal transcribed spacer region (ITS) of ribosomal DNA of potato cyst nematode G. rostochiensis. The PCN-LAMP reaction could be completed within 75 min at 68 °C followed by termination at 85 °C for 7 min. The primers exhibited specificity for G. rostochiensis and did not detect any other tested genera of plant parasitic or entomopathogenic nematodes. LAMP reaction was highly sensitive, suitable for crude genomic DNA and could successfully detect G. rostochiensis DNA up to femtogram quantity. This assay is rapid, cost effective and requires minimal instrumentation. It will facilitate the detection of G. rostochiensis at field and point-of-care labs and help in the interception of infested plant material/soil samples at quarantine stations independent of a professional nematologist. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13205-021-02830-8.

Two step yielding in soft materials.

A review is presented on the topic of two-step yielding observed in complex fluids that cover a broad variety of materials ranging from colloidal gels, attractive glasses, emulsions, suspensions, and several commercial paste-like materials. The common features in various systems displaying two-step yielding behavior are the presence of two characteristic forces between the interacting particles or two varying representative length or time scales. This focused review aims to provide physical insights, mechanistic understanding of the two-step yielding and other associated rheological consequences of this nonlinear behavior. A discussion is provided on the microstructural details with an overview of different experimental systems exhibiting double-yielding studied so far highlighting the similarities and differences among them. Particularly, the effects of continuous phase properties, dispersed particle phase factors (size, shape, softness and surface charge) and external force field (electric, magnetic, thermal and shear flows) on two-step yielding are considered.

Rheology of starch dispersions at high temperatures.

In the food industry, many food products experience extreme processing conditions of high temperature and high shear stresses. The measurements of sample behavior for water-based formulations above 100°C is extremely challenging due to changes in material composition from the boiling of volatile ingredients. We have developed a high-sensitivity, pressurized starch pasting cell (up to 5 bar) which utilizes a design free of mechanical bearings and seals, resulting in an order-of-magnitude improvement in torque sensitivity (1 µN.m in oscillatory and 10 µN.m in shear flows) compared to traditional pressure cells. A pressurized atmosphere in the cell suppresses boiling of the volatile components, allowing the characterization of the structure-property relationships of the sample over a range of testing conditions (-5 to 150°C) which simulate industrial processing and storage conditions. This cell is employed to investigate the pasting properties of a commercial starch dispersed in water. In situ gelatinization of starch dispersions of varying starch particle weight fractions (ϕ) subjected to a high temperature (120°C) at elevated pressure and at a fixed shear rate is studied. A phase transition, from an initial flowable starch slurry to a paste, takes place during which the viscosity evolves by several orders of magnitude. Typical parameters associated with the viscosity evolution during gelatinization such as onset temperature, peak temperature, and peak viscosity are analyzed to probe the impact of high temperature on the gelation process and the rheological properties of the final starch paste. Furthermore, yield stresses of the final paste, measured at 120°C, are examined for varying ϕ through traditional rheological methods such as flow ramps, oscillatory shear, and stress growth, demonstrating the capabilities of this cell for studies of steady shear and nonlinear viscoelastic behavior of the starch pastes. The yield stress values are found to be in good agreement when comparing various testing methods. Yield stresses range from 0.25 to 6.5 Pa for ϕ between 0.05 and 0.15, with 0.05 being the minimum starch weight fraction for which there is any measurable yield stress. The yield stress and the paste viscosity both scale with starch particle weight fraction as (ϕ - ϕc ) m , where ϕc = 0.04 as no yield stress is observed for ϕ ≤ 0.04. The exponent, m, for yield stress is found to be in the range of 1.15-1.4 depending on the analytical method used and the definition of yield stress while for peak and breakdown viscosities it is noted to be 1.6 and 1.1, respectively. The Herschel-Bulkley model is found to fit the flow curves well. The starch pastes are found to exhibit shear-thinning and significant thixotropic behavior.

Clinical, Economic, and Humanistic Burden Associated With Delayed Diagnosis of Axial Spondyloarthritis: A Systematic Review.

INTRODUCTION: Few studies have evaluated the impact of delayed diagnosis of axial spondyloarthritis (axSpA) on the overall burden of disease. The objective of this review was to evaluate the available literature on the clinical, economic, and humanistic burden of delayed diagnosis in patients with axSpA. METHODS: This systematic literature review was conducted and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We searched the MEDLINE and Embase databases for English-language publications of original research articles (up to July 12, 2018) and conference abstracts (January 1, 2014, to July 12, 2018) reporting studies of adult patients with delayed diagnosis of axSpA associated with clinical, economic, or humanistic burden. Retrieved publications were screened for eligibility by two independent reviewers; discrepancies were resolved by a third independent reviewer. Data were extracted by one reviewer and validated by a second independent reviewer. RESULTS: A total of 1391 publications were retrieved, of which 21 met the inclusion criteria and were included in the analysis. Of these, 15 reported data on clinical burden, nine on economic burden, and six on humanistic burden, with eight studies reporting a combination of clinical, economic, and/or humanistic burden. Patients with a delayed diagnosis of axSpA generally had higher disease activity, worse physical function, and more structural damage than those who received an earlier diagnosis. Patients with a delayed diagnosis also had a greater likelihood of work disability and higher direct and indirect healthcare costs than those who received an earlier diagnosis. Delayed diagnosis was associated with a greater likelihood for depression, negative psychological impacts, and worse quality of life. CONCLUSIONS: Delayed axSpA diagnosis was associated with more functional impairment, higher healthcare costs, and worse quality of life, highlighting the importance of early recognition of axSpA to reduce extensive burden on patients and society. Plain language summary available for this article.

Rheological predictions of sensory attributes of lotions.

Complex behavior of 33 commercial lotions was investigated in order to identify correlations between laboratory instrumental measurements and sensory attributes of these products. Sensory attributes were evaluated by trained panelists. Six attributes were identified as potentially related to rheology, which belong to three main sensory categories: appearance, pickup, and rub out. Potential rheological predictors were extracted from the data of rotational rheometry. Yield stress and instantaneous viscosity maximum (IVM) were determined in stress ramp. Alternative definitions of yield stress based on step-shear and oscillatory strain sweeps were also considered along with linear viscoelastic moduli, G' and G″. Statistical analysis has shown all these definitions of yield stress and IVM are in fact closely correlated and that IVM is the best overall predictor of most attributes although G'/G″ ratio also is significant for rub out attributes. However, integrity of shape, the main appearance attribute, is even better predicted by an imitative slump-like test in which image analysis is used to quantify sample spreading on a flat surface.

Relative value assessment: characterizing the benefit of oncology therapies through diverse survival metrics from a US perspective.

OBJECTIVES: The introduction of innovative, high-cost oncology treatments, coupled with mounting budgetary pressures, necessitates value trade-offs across cancer types. Defining value is critical to informing decision-making. A cost-value analysis tool was used to assess relative clinical value from a US perspective using multiple outcome metrics for a variety of metastatic cancers. METHODS: Literature published (January 1, 2000-August 31, 2016) was reviewed to identify outcome metrics for approved treatments for metastatic cancers. Data were extracted or derived for median and mean overall survival (OS), landmark survival rates, and other survival metrics, and compared across treatments vs their respective trial comparators, with and without considering costs. RESULTS: Reported survival metrics varied by agent within cancer type. For treatment of prostate cancer, abiraterone yielded the highest improvement in 1-year survival rate (13.7%, previously treated), whereas enzalutamide yielded the highest median OS improvement (4.8 months, previously treated) and sipuleucel-T, the highest mean OS improvement (3.6 months, previously untreated) vs their respective trial comparators. For treatment of non-small cell lung cancer vs their respective trial comparators, nivolumab yielded the highest improvement in mean OS (11.9 months) and 3-year survival rate (12.6%), each in previously treated squamous disease, whereas afatinib yielded the highest median OS improvement (4.1 months, previously untreated EGFR del19 and L858R mutants). Cost-value analysis results varied with the applied survival metric. CONCLUSIONS: Although median OS is the traditional gold standard oncology efficacy metric, it fails to capture long-term survival benefits-the ultimate goal of cancer treatment-offered by new treatment modalities. Diverse metrics are needed for comprehensive value assessments of cancer therapies.

Indirect treatment comparison of dabrafenib plus trametinib versus vemurafenib plus cobimetinib in previously untreated metastatic melanoma patients.

BACKGROUND: Metastatic melanoma is an aggressive form of skin cancer with a high mortality rate and the fastest growing global incidence rate of all malignancies. The introduction of BRAF/MEK inhibitor combinations has yielded significant increases in PFS and OS for melanoma. However, at present, no direct comparisons between different BRAF/MEK combinations have been conducted. In light of this, an indirect treatment comparison was performed between two BRAF/MEK inhibitor combination therapies for metastatic melanoma, dabrafenib plus trametinib and vemurafenib plus cobimetinib, in order to understand the relative efficacy and toxicity profiles of these therapies. METHODS: A systematic literature search identified two randomized trials as suitable for indirect comparison: the coBRIM trial of vemurafenib plus cobimetinib versus vemurafenib and the COMBI-v trial of dabrafenib plus trametinib versus vemurafenib. The comparison followed the method of Bucher et al. and analyzed both efficacy (overall survival [OS], progression-free survival [PFS], and overall response rate [ORR]) and safety outcomes (adverse events [AEs]). RESULTS: The indirect comparison revealed similar efficacy outcomes between both therapies, with no statistically significant difference between therapies for OS (hazard ratio [HR] 0.94, 95% confidence interval [CI] 0.68 - 1.30), PFS (HR 1.05, 95% CI 0.79 - 1.40), or ORR (risk ratio [RR] 0.90, 95% CI 0.74 - 1.10). Dabrafenib plus trametinib differed significantly from vemurafenib plus cobimetinib with regard to the incidence of treatment-related AE (RR 0.92, 95% CI 0.87 - 0.97), any AE grade ≥3 (RR 0.71, 95% CI 0.60 - 0.85) or dose interruption/modification (RR 0.77, 95% CI 0.60 - 0.99). Several categories of AEs occurred significantly more frequently with vemurafenib plus cobimetinib, while some occurred significantly more frequently with dabrafenib plus trametinib. For severe AEs (grade 3 or above), four occurred significantly more frequently with vemurafenib plus cobimetinib and no severe AE occurred significantly more frequently with dabrafenib plus trametinib. CONCLUSIONS: This indirect treatment comparison suggested that dabrafenib plus trametinib had comparable efficacy to vemurafenib plus cobimetinib but was associated with reduced adverse events.