ß Phase Optimization of Solvent Cast PVDF as a Function of the Processing Method and Additive Content.

A semicrystalline polymer with high piezo-, pyro-, and ferroelectric characteristics, poly(vinylidene fluoride) (PVDF) offers exciting possibilities in various applications. The semicrystalline structure of PVDF is composed of several phases including α, ß, θ, γ, and ε phases. ß phase polymorphs of PVDF exhibit the highest piezoelectric properties, which can be enhanced through different processing methods. This study aims to investigate the ß phase transformation of PVDF through different processes/treatment methods and the processing of a PVDF polymer composite containing 0.2 wt % multiwalled carbon nanotubes and/or 20 wt % modified/unmodified barium titanate. The effects of annealing, uniaxial stretching, rolling, atmospheric plasma treatment, UV treatment, and their combinations were investigated. The transformation of α to ß phase was determined by Fourier transform infrared spectrometer, X-ray diffractometer and differential scanning calorimeter. The most remarkable ß phase transformation of PVDF films was obtained by stretching following solvent casting and hot pressing. It was observed that various process combinations, as well as the incorporation of additives, influence the ß phase content of PVDF. Alongside studying ß phase content of PVDF, the investigation extends to analyzing the tan δ and elastic and loss modulus values of rolled PVDF polymer composite films.

On Cyclic-Fatigue Crack Growth in Carbon-Fibre-Reinforced Epoxy-Polymer Composites.

The growth of cracks between plies, i.e., delamination, in continuous fibre polymer matrix composites under cyclic-fatigue loading in operational aircraft structures has always been a very important factor, which has the potential to significantly decrease the service life of such structures. Whilst current designs are based on a 'no growth' design philosophy, delamination growth can nevertheless arise in operational aircraft and compromise structural integrity. To this end, the present paper outlines experimental and data reduction procedures for continuous fibre polymer matrix composites, based on a linear elastic fracture mechanics approach, which are capable of (a) determining and computing the fatigue crack growth (FCG) rate, da/dN, curve; (b) providing two different methods for determining the mandated worst-case FCG rate curve; and (c) calculating the fatigue threshold limit, below which no significant FCG occurs. Two data reduction procedures are proposed, which are based upon the Hartman-Schijve approach and a novel simple-scaling approach. These two different methodologies provide similar worst-case curves, and both provide an upper bound for all the experimental data. The calculated FCG threshold values as determined from both methodologies are also in very good agreement.

Predictive molecular biomarkers for determining neoadjuvant chemosensitivity in muscle invasive bladder cancer.

INTRODUCTION: Identifying neoadjuvant chemotherapy (NAC) response in patients with muscle invasive bladder cancer (MIBC) has had limited success based on clinicopathological features and molecular subtyping. Identification of chemotherapy responsive cohorts would facilitate delivery to those most likely to benefit. OBJECTIVE: Develop a molecular signature that can identify MIBC NAC responders (R) and non-responders (NR) using a cohort of known NAC response phenotypes, and better understand differences in molecular pathways and subtype classifications between NAC R and NR. MATERIALS AND METHODS: Presented are the messenger RNA (mRNA) and microRNA (miRNA) differential expression profiles from initial transurethral resection of bladder tumor (TURBT) specimens of a discovery cohort of MIBC patients consisting of 7 known NAC R and 11 NR, and a validation cohort consisting of 3 R and 5 NR. Pathological response at time of cystectomy after NAC was used to classify initial TURBT specimens as R (pT0) versus NR (≥pT2). RNA and miRNA from FFPE blocks were sequenced using RNAseq and qPCR, respectively. RESULTS: The discovery cohort had 2309 genes, while the validation cohort had 602 genes and 13 miRNA differentially expressed between R and NR. Gene set enrichment analysis identified mitochondrial gene expression, DNA replication initiation, DNA unwinding in the R discovery cohort and positive regulation of vascular associated smooth muscle cell proliferation in the NR discovery cohort. Canonical correlation (CC) analysis was applied to differentiate R versus NR. 3 CCs (CC13, CC16, and CC17) had an AUC >0.65 in the discovery and validation dataset. Gene ontology enrichment showed CC13 as nucleoside triphosphate metabolic process, CC16 as cell cycle and cellular response to DNA damage, CC17 as DNA packaging complex. All patients were classified using established molecular subtypes: Baylor, UNC, CIT, Lund, MD Anderson, TCGA, and Consensus Class. The MD Anderson p53-like subtype, CIT MC4 subtype and Consensus Class stroma rich subtype had the strongest correlation with a NR phenotype, while no subtype had a strong correlation with the R phenotype. CONCLUSIONS: Our results identify molecular signatures that can be used to differentiate MIBC NAC R versus NR, salient molecular pathway differences, and highlight the utility of molecular subtyping in relation to NAC response.

The Evolving Role of PD-L1 Inhibition in Non-Small Cell Lung Cancer: A Review of Durvalumab and Avelumab.

Non-small cell lung cancer (NSCLC) was traditionally associated with a poor prognosis. Between 2010 and 2016, the 5-years overall survival for all stages combined was about 25 percent. However, the recent use of immunotherapy has led to significant improvements in progression free survival (PFS) and overall survival (OS). Immune check point inhibitors enable the host immune system to mount a lethal response against tumor cells. Both PD-1 (nivolumab, pembrolizumab, cemipilimab) and PD-L1 inhibitors (atezolizumab and durvalumab) have been approved by the FDA for use in NSCLC, either as individual agents or in combination with platinum-based chemotherapy, radiation therapy, or other agents. As the future of immunotherapy for lung cancer continues to evolve, with multiple agents approved or in various stages of clinical research, it is imperative that we understand the mechanism of action, clinical activity, ongoing clinical trials, indications for use and toxicity for individual agents in addition to having general, basic knowledge about this new class of cancer therapeutics. In this review, we focus on two of the newer PD-L1 inhibitors, durvalumab and avelumab.

Impact of Family and Social Network on Tobacco Cessation Amongst Cancer Patients.

Continued smoking after a cancer diagnosis adversely affects outcomes, including recurrence of the primary cancer and/or the development of second primary cancers. Despite this, prevalence of smoking is high in cancer survivors and higher in survivors of tobacco-related cancers. The diagnosis of cancer provides a teachable moment, and social networks, such as family, friends, and social groups, seem to play a significant role in smoking habits of cancer patients. Interventions that involve members of patients' social network, especially those who also smoke, might improve tobacco cessation rates. Very few studies have been conducted to evaluate and target patients' social networks. Yet, many studies have demonstrated that cancer survivors who received higher levels of social support were less likely to be current smokers. Clinicians should be doing as much as they can to encourage smoking cessation in both patients and relevant family members. Research aimed at influencing smoking behavioral change in the entire family is needed to increase cessation intervention success rate, which can ultimately improve the health and longevity of patients as well as their family members.

Single-Cell Sequencing in Genitourinary Malignancies.

Single-cell sequencing (SCS) is a powerful new tool that applies Next Generation Sequencing at the cellular level. SCS has revolutionized our understanding of tumor heterogeneity and the tumor microenvironment, immune infiltration, cancer stem cells (CSCs), circulating tumor cells (CTCs), and clonal evolution. The following chapter highlights the current literature on SCS in genitourinary (GU) malignancies and discusses future applications of SCS technology. The renal cell carcinoma (RCC) section highlights the use of SCS in characterizing the initial cells driving tumorigenesis, the intercellular mutational landscape of RCC, intratumoral heterogeneity (ITH) between primary and metastatic lesions, and genes driving RCC cancer stem cells (CSCs). The bladder cancer section will also illustrate molecular drivers of bladder cancer stem cells (BCSCs), SCS use in reconstructing tumor developmental history and underlying subclones, and understanding the effect of cisplatin on intratumoral heterogeneity in vitro and potential mechanisms behind platinum resistance. The final section featuring prostate cancer will discuss how SCS can be used to identify the cellular origins of benign prostatic hyperplasia and prostate cancer, the plasticity and heterogeneity of prostate cancer cells with regard to androgen dependence, and the use of SCS in CTCs to understand chemotherapy resistance and gene expression changes after androgen deprivation therapy (ADT). The studies listed in this chapter illustrate many translational applications of SCS in GU malignancies, including diagnostic, prognostic, and treatment-related approaches. The ability of SCS to resolve intratumor heterogeneity and better define the genomic landscape of tumors and CTCs will be fundamental in the new era of precision-based care.

Prognostic Molecular Signatures for Metastatic Potential in Clinically Low-Risk Stage I and II Clear Cell Renal Cell Carcinomas.

Introduction: For patients with localized node-negative (Stage I and II) clear cell renal cell carcinomas (ccRCC), current clinicopathological staging has limited predictive capability because of their low risk. Analyzing molecular signatures at the time of nephrectomy can aid in understanding future metastatic potential. Objective: Develop a molecular signature that can stratify patients who have clinically low risk ccRCC, but have high risk genetic changes driving an aggressive metastatic phenotype. Patients, Materials, and Methods: Presented is the differential expression of mRNA and miRNA in 44 Stage I and Stage II patients, 21 who developed metastasis within 5 years of nephrectomy, compared to 23 patients who remained disease free for more than 5 years. Extracted RNA from nephrectomy specimens preserved in FFPE blocks was sequenced using RNAseq. MiRNA expression was performed using the TaqMan OpenArray qPCR protocol. Results: One hundred thirty one genes and 2 miRNA were differentially expressed between the two groups. Canonical correlation (CC) analysis was applied and four CCs (CC32, CC20, CC9, and CC7) have an AUC > 0.65 in our dataset with similar predictive power in the TCGA-KIRC dataset. Gene set enrichment showed CC9 as kidney development/adhesion, CC20 as oxidative phosphorylation pathway, CC32 as RNA binding/spindle and CC7 as immune response. In a multivariate Cox model, the four CCs were able to identify high/low risk groups for metastases in the TCGA-KIRC (p < 0.05) with odds ratios of CC32 = 5.7, CC20 = 4.4, CC9 = 3.6, and CC7 = 2.7. Conclusion: These results identify molecular signatures for more aggressive tumors in clinically low risk ccRCC patients who have a higher potential of metastasis than would be expected.

The prevalence of OSA in snorers presenting with various chief complaints: a pilot study.

AIMS: The incidence of obstructive sleep apnea (OSA) in snoring patients is reported in the literature to range from 20% to 70%. The aim of this study was to obtain exact data on the percent of snorers who have OSA, and to classify them as having normal, mild, moderate, or severe sleep apnea. METHODOLOGY: There were 273 patients who came into the senior author's office with sleep disorder breathing problems. They suffered with various sleep problems. All 273 patients also had a snoring problem. None of the 273 patients had ever had a sleep test, or polysomnograph (PSG). All 273 required a PSG for evaluation of their sleep problem. They were referred to a certified sleep lab local to them. When the results of the PSG came back, the authors were able to classify them as having normal, mild, moderate, or severe sleep apnea. RESULTS: The results of the 273 PSGs showed the following: 12 patients (4%) had PSGs of apnoea-hypopnoea index (AHI)<5 (normal), 57 patients (21%) had PSGs with AHIs 5-<15 (mild), 79 patients (29%) had PSGs with AHIs 15-<30 (moderate), 119 patients (44%) had PSGs 30 or >30 (severe), and 6 patients (2%) had PSGs >100 (severe). CONCLUSIONS: Based on this study, of 273 patients who snored, the incidence of OSA is high. Ninety-six percent of the patients suffered with mild to severe sleep apnea. This malady, which can be very serious and degenerating, could be much more prevalent than previously believed. Additional research is needed to verify these figures.

Longitudinal study of cephalometric soft tissue profile traits between the ages of 6 and 18 years.

OBJECTIVE: To study the longitudinal changes in 19 soft tissue cephalometric traits (according to the Bergman cephalometric soft tissue facial analysis). MATERIALS AND METHODS: Cephalograms and photographs of 40 subjects (20 male, 20 female, from the Burlington Growth Centre) that were obtained at ages 6, 9, 12, 14, 16, and 18 years were used. Subjects were orthodontically untreated whites and had Class I dentoskeletal relationships (ideal overjet and overbite). Images were obtained with the lips in a relaxed position or lightly touching. RESULTS: Three groups of soft tissue traits were identified: (1) traits that increased in size with growth (nasal projection, lower face height, chin projection, chin-throat length, upper and lower lip thickness, upper lip length, and lower lip-chin length); (2) traits that decreased in size with growth (interlabial gap and mandibular sulcus contour [only in females]); and (3) traits that remained relatively constant during growth (facial profile angle, nasolabial angle, lower face percentage, chin-throat/lower face height percentage, lower face-throat angle, upper incisor exposure, maxillary sulcus contour, and upper and lower lip protrusion). CONCLUSION: Current findings identify areas of growth and change in individuals with Class I skeletal and dental relationships with ideal overjet and overbite and should be considered during treatment planning of orthodontic and orthognathic patients.

Enhancement of transdermal delivery of progesterone using medium-chain mono and diglycerides as skin penetration enhancers.

We evaluated whether medium-chain mono and diglycerides (MCG) can be utilized to optimize the transdermal delivery of progesterone (PGT). MCG was studied at 10-70% (w/w) in propylene glycol (a polar solvent) or Myvacet oil (nonpolar solvent); PGT was used at 1% (w/w). The topical (to the skin) and transdermal (across the skin) delivery of PGT were evaluated in vitro using porcine ear skin. When incorporated in propylene glycol, MCG at 10% enhanced the topical and transdermal delivery of PGT by 2.5- and 7-fold, respectively. At 20-50%, topical delivery was further enhanced while transdermal delivery gradually returned towards baseline. At 70%, MCG enhanced neither the delivery to viable skin nor the transdermal delivery of PGT. Similar concentration-dependent effects were observed when MCG was incorporated in Myvacet oil, but their magnitudes were 2- to 3-fold smaller. The relative safety of MCG was assessed in cultured fibroblasts and compared to propylene glycol (regarded as safe) and sodium lauryl sulfate (moderate-to-severe irritant). Both MCG and propylene glycol were substantially less cytotoxic than sodium lauryl sulfate. We conclude that formulations containing 10% MCG in propylene glycol may be a simple and safe method to improve the transdermal delivery of progesterone and promote its use in hormone replacement therapy.