Optimization of tumor-treating field therapy for triple-negative breast cancer cells in vitro via frequency modulation.

PURPOSE: Currently, tumor-treating field (TTField) therapy utilizes a single "optimal" frequency of electric fields to achieve maximal cell death in a targeted population of cells. However, because of differences in cell size, shape, and ploidy during mitosis, optimal electric field characteristics for universal maximal cell death may not exist. This study investigated the anti-mitotic effects of modulating electric field frequency as opposed to utilizing uniform electric fields. METHODS: We developed and validated a custom device that delivers a wide variety of electric field and treatment parameters including frequency modulation. We investigated the efficacy of frequency modulating tumor-treating fields on triple-negative breast cancer cells compared to human breast epithelial cells. RESULTS: We show that frequency-modulated (FM) TTFields are as selective at treating triple-negative breast cancer (TNBC) as uniform TTFields while having a greater efficacy for combating TNBC cell growth. TTField treatment at a mean frequency of 150 kHz with a frequency range of ± 10 kHz induced apoptosis in a greater number of TNBC cells after 24 h as compared to unmodulated treatment which led to further decreased cell viability after 48 h. Furthermore, all TNBC cells died after 72 h of FM treatment while cells that received unmodulated treatment were able to recover to cell number equivalent to the control. CONCLUSION: TTFields were highly efficacious against TNBC growth, FM TTFields showed minimal effects on epithelial cells similar to unmodulated treatment.

Two-Year Outcomes with a Magnetically Levitated Cardiac Pump in Heart Failure.

BACKGROUND: In an early analysis of this trial, use of a magnetically levitated centrifugal continuous-flow circulatory pump was found to improve clinical outcomes, as compared with a mechanical-bearing axial continuous-flow pump, at 6 months in patients with advanced heart failure. METHODS: In a randomized noninferiority and superiority trial, we compared the centrifugal-flow pump with the axial-flow pump in patients with advanced heart failure, irrespective of the intended goal of support (bridge to transplantation or destination therapy). The composite primary end point was survival at 2 years free of disabling stroke (with disabling stroke indicated by a modified Rankin score of >3; scores range from 0 to 6, with higher scores indicating more severe disability) or survival free of reoperation to replace or remove a malfunctioning device. The noninferiority margin for the risk difference (centrifugal-flow pump group minus axial-flow pump group) was -10 percentage points. RESULTS: Of 366 patients, 190 were assigned to the centrifugal-flow pump group and 176 to the axial-flow pump group. In the intention-to-treat population, the primary end point occurred in 151 patients (79.5%) in the centrifugal-flow pump group, as compared with 106 (60.2%) in the axial-flow pump group (absolute difference, 19.2 percentage points; 95% lower confidence boundary, 9.8 percentage points [P<0.001 for noninferiority]; hazard ratio, 0.46; 95% confidence interval [CI], 0.31 to 0.69 [P<0.001 for superiority]). Reoperation for pump malfunction was less frequent in the centrifugal-flow pump group than in the axial-flow pump group (3 patients [1.6%] vs. 30 patients [17.0%]; hazard ratio, 0.08; 95% CI, 0.03 to 0.27; P<0.001). The rates of death and disabling stroke were similar in the two groups, but the overall rate of stroke was lower in the centrifugal-flow pump group than in the axial-flow pump group (10.1% vs. 19.2%; hazard ratio, 0.47; 95% CI, 0.27 to 0.84, P=0.02). CONCLUSIONS: In patients with advanced heart failure, a fully magnetically levitated centrifugal-flow pump was superior to a mechanical-bearing axial-flow pump with regard to survival free of disabling stroke or reoperation to replace or remove a malfunctioning device. (Funded by Abbott; MOMENTUM 3 ClinicalTrials.gov number, NCT02224755 .).

Reference Materials for Phase Equilibrium Studies. 1. Liquid-Liquid Equilibria (IUPAC Technical Report).

This article is the first of three projected IUPAC Technical Reports resulting from IUPAC Project 2011-037-2-100 (Reference Materials for Phase Equilibrium Studies). The goal of that project was to select reference systems with critically evaluated property values for the validation of instruments and techniques used in phase equilibrium studies for mixtures. This Report proposes seven systems for liquid-liquid equilibrium studies, covering the four most common categories of binary mixtures: aqueous systems of moderate solubility, non-aqueous systems, systems with low solubility, and systems with ionic liquids. For each system, the available literature sources, accepted data, smoothing equations, and estimated uncertainties are given.

Good Reporting Practice for Thermophysical and Thermochemical Property Measurements (IUPAC Technical Report).

Scientific projects frequently involve measurements of thermophysical, thermochemical, and other related properties of chemical compounds and materials. These measured property data have significant potential value for the scientific community, but incomplete and inaccurate reporting often hampers their utilization. The present IUPAC Technical Report summarizes the needs of chemical engineers and researchers as consumers of these data and shows how publishing practices can improve information transfer. In the Report, general principles of Good Reporting Practice are developed together with examples illustrating typical cases of reporting issues. Adoption of these principles will improve the quality, reproducibility, and usefulness of experimental data, bring a better level of consistency to results, and increase the efficiency and impact of research. Closely related to Good Reporting Practice, basic elements of Good Research Practice are also introduced with a goal to reduce the number of ambiguities and unresolved problems within the thermophysical property data domain.

Early Extended Midline Strip Craniectomy for Sagittal Synostosis.

BACKGROUND: Isolated sagittal synostosis is the most common form of nonsyndromic craniosynostosis. The surgical management of this condition ranges from strip craniectomy to total cranial vault remodeling. In our unit, passive correction of sagittal synostosis utilizing open extended midline strip craniectomy with bilateral micro-barrel staving is performed before 22 weeks corrected age. The aim of this prospective study is to identify the effectiveness and morbidity associated with this technique. PATIENTS AND METHODS: Nonsyndromic patients who underwent OMEC at a tertiaryreferral-center (Alder Hey Children's Hospital, Liverpool, UK) over a 3-year period (2014-2016) were included. In particular, we looked at pre- and postoperative cranial index (CI), as well as other secondary outcomes such as rates of transfusion and reoperation. RESULTS: A total of 44 patients (12 female, 32 male) met the inclusion criteria. Median age at operation was 132 (range 99-171) days. Median operative time was 117 (range 89-171) minutes. Twenty-four patients underwent a blood transfusion. Median pre-op CI was 66 (range 61-74.7)%. The first post-op CI, taken a median of 56 (range 12-107) days postoperatively, was 78 (range 73-87)%. No patients required reoperation. There were no perioperative deaths. CONCLUSION: Early open extended midline strip craniectomy with bilateral micro-barrel staving for correction of isolated nonsyndromic sagittal synostosis is a safe and effective technique, associated with minimal morbidity, producing sustained satisfactory head shape morphology on short to medium-term follow-up.

Chemical approaches for doping nanodevice architectures.

Advanced doping technologies are key for the continued scaling of semiconductor devices and the maintenance of device performance beyond the 14 nm technology node. Due to limitations of conventional ion-beam implantation with thin body and 3D device geometries, techniques which allow precise control over dopant diffusion and concentration, in addition to excellent conformality on 3D device surfaces, are required. Spin-on doping has shown promise as a conventional technique for doping new materials, particularly through application with other dopant methods, but may not be suitable for conformal doping of nanostructures. Additionally, residues remain after most spin-on-doping processes which are often difficult to remove. In situ doping of nanostructures is especially common for bottom-up grown nanostructures but problems associated with concentration gradients and morphology changes are commonly experienced. Monolayer doping has been shown to satisfy the requirements for extended defect-free, conformal and controllable doping on many materials ranging from traditional silicon and germanium devices to emerging replacement materials such as III-V compounds but challenges still remain, especially with regard to metrology and surface chemistry at such small feature sizes. This article summarises and critically assesses developments over the last number of years regarding the application of gas and solution phase techniques to dope silicon-, germanium- and III-V-based materials and nanostructures to obtain shallow diffusion depths coupled with high carrier concentrations and abrupt junctions.

Risk assessment and comparative effectiveness of left ventricular assist device and medical management in ambulatory heart failure patients: design and rationale of the ROADMAP clinical trial.

BACKGROUND: Mechanical circulatory support is now a proven therapy for the treatment of patients with advanced heart failure and cardiogenic shock. The role for this therapy in patients with less severe heart failure is unknown. OBJECTIVE: The objective of this study is to examine the impact of mechanically assisted circulation using the HeartMate II left ventricular assist device in patients who meet current US Food and Drug Administration-defined criteria for treatment but are not yet receiving intravenous inotropic therapy. METHODS: This is a prospective, nonrandomized clinical trial of 200 patients treated with either optimal medical management or a mechanical circulatory support device. CLINICAL CONTEXT: This trial will be the first prospective clinical evaluation comparing outcomes of patients with advanced ambulatory heart failure treated with either ongoing medical therapy or a left ventricular assist device. It is anticipated to provide novel insights regarding relative outcomes with each treatment and an understanding of patient and provider acceptance of the ventricular assist device therapy. This trial will also provide information regarding the risk of events in "stable" patients with advanced heart failure and guidance for the optimal timing of left ventricular assist device therapy.

Sports-Related Maxillofacial Injuries.

BACKGROUND: Sports-related maxillofacial injuries contribute a significant proportion of the workload in a maxillofacial unit. The aim of this study was to identify the incidence of maxillofacial sports-related injuries, treatments required, and assess the impact of the injury on future sport participation. METHOD: A retrospective review was carried out on all maxillofacial trauma referrals from September 1, 2009 to August 31, 2010. Patient records were reviewed and the following variables were recorded: age, sex, sport involved, injury sustained, mechanism of injury, treatment, subsequent participation, and interval before return to sport. RESULTS: The study population included 162 patients with sports-related facial injuries. The most common sporting injuries were as follows: Gaelic football 35.3% (N = 57), soccer 22.3% (N = 36), rugby 12.4% (N = 20), and equine sports 12.4% (N = 20). The most common injury sustained was zygomatic complex fracture 36.4% (N = 59). Mandibular fracture occurred in 20% (N = 33), orbit fracture in 14.2% (N = 23), and nasal bone fracture in 12.3% (N = 20). The most common mechanism of injury was from a clash of heads (23.4%) followed by an elbow to the face (17.2%). The majority of patients (84%) resumed participation in their chosen sport at mean interval of 7.3 weeks (range 1-18 weeks). CONCLUSIONS: This study identified a significant number of sporting facial injuries, which presented over 1 year. In total, 113 patients underwent a surgical procedure for the management of their injuries. This study highlights the need to educate all players regarding use of personal protective equipment and adherence to the rules of sports.

New oral anticoagulants and their implications for dental patients.

Anticoagulation therapy is used in several conditions to prevent or treat thromboembolism. Over the last 40 years, warfarin has been the oral anticoagulant of choice and has been considered the mainstay of treatment. However, its use is limited by a narrow therapeutic index and complex pharmacodynamics, necessitating regular monitoring and dose adjustments. Recently, two new oral anticoagulants--dabigatran etexilate (a direct thrombin inhibitor) and rivaroxiban (a factor Xa inhibitor)--have been approved for use in North America and Europe. Unlike warfarin, dabigatran and rivaroxiban are relatively small molecules that work as anticoagulants by targeting specific single steps of the coagulation cascade. Their advantages, relative to warfarin, include: predictable pharmacokinetics; limited food and drug interactions; rapid onset of action; and, short half-life. They require no monitoring. However, they lack a specific reversal agent. The number of patients taking dabigatran and rivaroxaban is increasing. Therefore, it is inevitable that dentists will be required to perform invasive procedures on this cohort of patients. This paper outlines the various properties of the new oral anticoagulants and the most recent guidelines regarding the management of these dental patients taking these medications.

Prevention of osteoradionecrosis in patients with head and neck cancer treated with radiation therapy.

BACKGROUND: Osteoradionecrosis is a long-term, serious side effect of head and neck radiation therapy and is associated with significant morbidity and quality of life issues. METHODS: This paper sought to determine consensus on the prevention and management of osteoradionecrosis by an international panel of multidisciplinary professionals expert in the management of patients with head and neck cancer using a Delphi methodology. Unique to this work is our direct inclusion of the views of patients and carers in our findings. RESULTS: This study reached consensus on the importance of pre and post oral health assessment and education for patients with head and neck cancer. This was also noted by the patients and carers who took part in the study. CONCLUSIONS: This work highlights the need for a standardized oral health assessment tool and multidisciplinary care of patients to prevent and manage osteoradionecrosis.

Efficacy and selectivity of tumor-treating field therapy for triple-negative breast cancer cells via in-house delivery device.

PURPOSE: Triple-negative breast cancer continues to be one of the leading causes of death in women, making up 7% of all cancer deaths. Tumor-treating electric fields are low-energy, low-frequency oscillating electric fields that induce an anti-proliferative effect on mitotic cells in glioblastoma multiforme, non-small cell lung cancer, and ovarian cancer. Little is known about effects of tumor-treating fields on triple-negative breast cancer and known research for tumor-treating fields only utilizes low (< 3 V/cm) electric field intensities. METHODS: We have developed an in-house field delivery device capable of high levels of customization to explore a much wider variety of electric field and treatment parameters. Furthermore, we investigated the selectivity of tumor-treating field treatment between triple-negative breast cancer and human breast epithelial cells. RESULTS: Tumor-treating fields show greatest efficacy against triple-negative breast cancer cell lines between 1 and 3 V/cm electric field intensities while having little effect on epithelial cells. CONCLUSION: These results provide a clear therapeutic window for tumor-treating field delivery to triple-negative breast cancer.

Complete genomes of Pasteurella multocida isolates from porcine, bovine, and cervine samples found in New Zealand farms.

Here, we present complete genome assemblies of Pasteurella multocida strains isolated from porcine, bovine, and cervine farms as part of bacteriology incursion investigations to identify pathogens that might present a sanitary risk to New Zealand.

Molecular characterisation of the Australian and New Zealand livestock Chlamydia pecorum strains confirms novel but clonal ST23 in association with ovine foetal loss.

Chlamydia pecorum is a veterinary pathogen associated with abortions and perinatal mortality in sheep. Recent studies investigating foetal and perinatal lamb mortality in sheep from Australia and New Zealand identified C. pecorum clonal sequence type (ST)23 strains in aborted and stillborn lambs. Presently, there is limited genotypic information on C. pecorum strains associated with reproductive disease, although whole genome sequencing (WGS) of one abortigenic ST23 C. pecorum strain identified unique features, including a deletion in the CDS1 locus of the chlamydial plasmid. We applied WGS on two ST23 strains detected in aborted and stillborn lambs from Australia and used phylogenetic and comparative analyses to compare these to the other available C. pecorum genomes. To re-evaluate the genetic diversity of contemporary strains, we applied C. pecorum genotyping, and chlamydial plasmid sequencing to a range of C. pecorum positive samples and isolates from ewes, aborted foetuses and stillborn lambs, cattle and a goat from diverse geographical regions across Australia and New Zealand.The two new C. pecorum genomes are nearly identical to the genome of the Australian abortigenic strain including the unique deletion in the chlamydial plasmid. Genotyping revealed that these novel C. pecorum ST23 strains are widespread and associated with sheep abortions on Australian and New Zealand farms. In addition, a goat C. pecorum strain (denoted ST 304) from New Zealand was also characterised. This study expands the C. pecorum genome catalogue and describes a comprehensive molecular characterisation of the novel livestock ST23 strains associated with foetal and lamb mortality.

Enhanced dosimetry procedures and assessment for EBT2 radiochromic film.

PURPOSE: Quantitatively determine an optimum image analysis procedure to mitigate inhomogeneities within the EBT2 film and from scanning for accurate absolute dose measurement deposited by an external radiation therapy beam. Multichannel dosimetry procedures were conceived, described, and quantitatively tested against single and dual channel dosimetry. METHODS: A solid water(TM) block was placed on CT imaging and treatment tables in a configuration that avoids bulky compressive devices. CT markers helped register the CT to the treatment plan and the radiation dose distribution from the radiochromic film. The CT images were digitally rotated and resampled to match the spatial resolution of the scanned dosimetric distribution and treatment plan. The ECLIPSE treatment plan planes were digitally translated through digital triangulation of the treatment isocenter to the CT markers in the CT image. A 6 MV photon beam, conforming to the treatment plan, irradiated the EBT2 film sandwiched between solid water(TM) slabs. The exposed radiochromic film images were rotated and translated to the CT images using coincident markers in the CT image that are associated with "tattoos" marked on the radiochromic film. The exposed radiochromic film gray-levels from a flatbed scanner in reflection mode were converted to dose using calibration films. The test dose distribution was scanned and averaged six times to reduce temporal noise. This study generated dose distributions using the red channel alone, green channel alone, ratio of the red to blue channel, ratio of the green to blue channel, a hybrid approach combining the green to blue ratio for higher doses (>80 cGy) with the red to blue ratio (<80 cGy), multichannel averaging and optimized autonomous multichannel correction. Single channel, multichannel, and channel ratio methods for processing the exposed radiochromic film were compared to the treatment plan via gamma analysis. The ellipsoidal decision surface was defined by its axes of 3% of the maximum dose and 3 mm in the horizontal and vertical directions. RESULTS: The multichannel dosimetry procedures provided excellent agreement with calculation of the dose distribution as determined by the gamma analysis. The green channel mostly performed as well or better than the red channel. The green to blue channel ratio for doses when combined with red to blue ratio ("Hybrid") achieved a high level performance. In addition, new registration procedures were developed and tested for aiding the comparison of calculated and experimentally determined dose distributions. CONCLUSIONS: This study described, developed, and tested new processing methods for reducing inaccuracies in absolute dose determination due to inhomogeneities within the film and from scanning. This study found better performance using optimized multichannel following averaging of all color channels. Combining the channel ratios in a hybrid approach also achieved high performance. Averaging the test films reduced temporal noise that severely degraded the blue channel. This methodology avoided using cumbersome, registered correction matrices. Novel registration and digital rotation of CT images enabled quantitative testing and helped improve contact between the radiochromic film and phantom.

Corrigendum to "Covid-19 and the aviation industry: The interrelationship between the spread of the Covid-19 pandemic and the frequency of flights on the EU Market" [Ann. Tour. Res., Volume 91, November 2021, 103298].

[This corrects the article DOI: 10.1016/j.annals.2021.103298.].

Protein stability and structure in HIC: hydrogen exchange experiments and COREX calculations.

Hydrogen exchange mass spectrometry (HXMS) coupled to proteolytic digestion has been used to probe the conformation of bovine ß-lactoglobulin (BLG), bovine α-lactalbumin (BLA), and human serum albumin (HSA) in solution and while adsorbed to the hydrophobic interaction chromatography media Phenyl Sepharose 6FF. All three proteins show evidence of EX1 exchange kinetics, indicating a loss of stability on the surface. HX protection patterns for all three proteins also indicate that the unfolded form is only partially solvent exposed. The hydrogen-deuterium exchange patterns of BLG and BLA on the surface suggest a structure that resembles each protein's respective solution phase molten globule state. The low stability of Domain II of HSA observed on Phenyl Sepharose 6FF also suggests a link to solution stability because Domain II is frequently cited as the least stable domain in solution unfolding pathways. COREX, an algorithm used to compute protein folding stabilities, correctly predicts solution hydrogen-deuterium exchange patterns for BLG and offers insight into its adsorbed phase stabilities but is unreliable for BLA predictions. The results of this work demonstrate a link between solution-phase local stability patterns and the nature of partially unfolded states that proteins can adopt on HIC surfaces.

Pair correlation function integrals: computation and use.

We describe a method for extending radial distribution functions obtained from molecular simulations of pure and mixed molecular fluids to arbitrary distances. The method allows total correlation function integrals to be reliably calculated from simulations of relatively small systems. The long-distance behavior of radial distribution functions is determined by requiring that the corresponding direct correlation functions follow certain approximations at long distances. We have briefly described the method and tested its performance in previous communications [R. Wedberg, J. P. O'Connell, G. H. Peters, and J. Abildskov, Mol. Simul. 36, 1243 (2010); Fluid Phase Equilib. 302, 32 (2011)], but describe here its theoretical basis more thoroughly and derive long-distance approximations for the direct correlation functions. We describe the numerical implementation of the method in detail, and report numerical tests complementing previous results. Pure molecular fluids are here studied in the isothermal-isobaric ensemble with isothermal compressibilities evaluated from the total correlation function integrals and compared with values derived from volume fluctuations. For systems where the radial distribution function has structure beyond the sampling limit imposed by the system size, the integration is more reliable, and usually more accurate, than simple integral truncation.

Tumors and diseases of the joint.

A variety of different diseases affect the synovium, including infection, noninfectious immunologic inflammatory conditions, degenerative arthroses, crystal deposits, trauma, and tumors. Tumors of the synovium are relatively uncommon. Any mesenchymal tumor may arise in the synovium, but most recapitulate its normal counterpart including synoviocytes, blood vessels, fat, and fibrous tissue. These tumors can arise in any synovial lined structures both within joints and in extraarticular locations. Most synovial tumors are benign. Malignant tumors are rare but important to recognize because many are aggressive and must be treated appropriately. Among common nonneoplastic conditions that affect the synovium and surrounding structures are crystal deposits such as monosodium urate crystals, calcium pyrophosphate dihydrate crystals, and hydroxyapatite crystals. These crystal deposits may be asymptomatic or cause severe pain or chronic joint destruction. Their accurate identification is important to guide appropriate therapy.