Anti-angiogenesis therapies: their potential in cancer management

Angiogenesis plays an important role in normal animal growth and development. This process is also vital for the growth of tumors. Angiogenesis inhibitors have a different mechanism of action to traditional chemotherapy agents and radiation therapy. The angiogenesis inhibitors can act synergistically with conventional treatments and tend to have non-overlapping toxicities. There are four drugs which have a proven role in treating cancer patients. Bevacizumab is a humanized monoclonal antibody that binds to and neutralizes vascular endothelial growth factor (VEGF). Sunitinib and sorafenib inhibit multiple tyrosine kinase receptors that are important for angiogenesis. Thalidomide inhibits the activity of basic fibroblast growth factor-2 (bFGF). The licensed indications and the supporting evidence are discussed. Other drugs are currently being tested in clinical trials and the most promising of these drugs are discussed. Aflibercept, also known as VEGF-trap, is a recombinant fusion protein that binds to circulating VEGF. The vascular disrupting agents act by targeting established blood vessels. These exciting new treatments have the potential to transform the management of cancer

Esthetic Smile Preferences of Dental Professionals

Title from PDF of title page, viewed December 13, 2017Thesis advisors: Shankar Rengasamy Venugopalan and Mary P. WalkerVitaIncludes bibliographical references (pages 44-48)Thesis (M.S.)--School of Dentistry. University of Missouri--Kansas City, 2017This study examined the preferences of esthetic smile characteristics between general dentists and specialists in orthodontics, periodontics, and prosthodontics using a six item pilot survey. Characteristics examined included gingival display, vertical relationship of lateral incisor to central incisor and canine, mesiodistal position of the gingival height of contour (zenith) of the maxillary lateral incisor, smile line, amount of visible buccal corridor space, and width ratio of the maxillary anterior teeth. A photograph showing an esthetically pleasing smile of a female was captured, cropped and mirrored at the midline to appear bilaterally symmetrical using Adobe Photoshop. For each characteristic, the baseline photograph was incrementally altered digitally, then all photographs of a single characteristic were displayed on each separate page of the survey. The survey was divided into two parts: Part I provided no prompting of the specific characteristic being evaluated, whereas Part II was prompted. Participants were instructed to select one photograph in each series for ‘most esthetic’ and ‘least esthetic’ in both Parts I and II. Five participants in each of the four professional categories (n=20), all either part- or full-time faculty at the UMKC School of Dentistry, were recruited though an email advertisement. Those who met the inclusion criteria completed the survey in a solitary, uninterrupted manner. Statistical analysis of the gathered data was performed with the Fisher’s Exact test and significance was set at p ≤ .05. In addition, an agreement test was used to compare between each individual’s responses for Parts I and II. Statistically significant differences between general dentists and the specialists were found only for the width ratio of the maxillary anterior teeth, and only when not prompted: generalists preferred a width ratio of 0.65 while specialists preferred 0.7. Preferences for all other characteristics were similar across disciplines. When comparing survey responses with or without prompting, generalists tended to change their selections more frequently when provided with prompting information. The results of this study suggest that specialists prefer wider smiles than generalists. In addition, specialists are more readily able to identify their preferences when evaluating the esthetic nature of smiles.Introduction -- Materials and methods -- Results -- Discussion -- Literature cited -- Appendix A. IRB letter -- Appendix B. Authorization and release for photography -- Appendix C. Email advertisement -- Appendix D. Verbal script for survey instructions -- Appendix E. Survey, Part 1 -- Appendix F. Survey, Part 2 -- Appendix G. Participant comment

Development of novel adenoviral vectors to overcome challenges observed with HAdV-5 based constructs

Recombinant vectors based on human adenovirus serotype 5 (HAdV-5) have been extensively studied in pre-clinical models and clinical trials over the last two decades. However, the thorough understanding of the HAdV-5 interaction with human subjects has uncovered major concerns about its product applicability. High vector-associated toxicity and widespread pre-existing immunity have been shown to significantly impede the effectiveness of HAdV-5 mediated gene transfer. It is therefore that the in depth knowledge attained working on HAdV-5 is currently being used to develop alternative vectors. Here, we provide a comprehensive overview of data obtained in recent years disqualifying the HAdV-5 vector for systemic gene delivery as well as novel strategies being pursued to overcome the limitations observed with particular emphasis on the ongoing vectorization efforts to obtain vectors based on alternative serotypes

A cryogenic silicon interferometer for gravitational-wave detection

The detection of gravitational waves from compact binary mergers by LIGO has opened the era of gravitational wave astronomy, revealing a previously hidden side of the cosmos. To maximize the reach of the existing LIGO observatory facilities, we have designed a new instrument able to detect gravitational waves at distances 5 times further away than possible with Advanced LIGO, or at greater than 100 times the event rate. Observations with this new instrument will make possible dramatic steps toward understanding the physics of the nearby Universe, as well as observing the Universe out to cosmological distances by the detection of binary black hole coalescences. This article presents the instrument design and a quantitative analysis of the anticipated noise floor

Thromboxane biosynthesis in cancer patients and its inhibition by aspirin: a sub-study of the Add-Aspirin trial

BACKGROUND: Pre-clinical models demonstrate that platelet activation is involved in the spread of malignancy. Ongoing clinical trials are assessing whether aspirin, which inhibits platelet activation, can prevent or delay metastases. METHODS: Urinary 11-dehydro-thromboxane B2 (U-TXM), a biomarker of in vivo platelet activation, was measured after radical cancer therapy and correlated with patient demographics, tumour type, recent treatment, and aspirin use (100 mg, 300 mg or placebo daily) using multivariable linear regression models with log-transformed values. RESULTS: In total, 716 patients (breast 260, colorectal 192, gastro-oesophageal 53, prostate 211) median age 61 years, 50% male were studied. Baseline median U-TXM were breast 782; colorectal 1060; gastro-oesophageal 1675 and prostate 826 pg/mg creatinine; higher than healthy individuals (~500 pg/mg creatinine). Higher levels were associated with raised body mass index, inflammatory markers, and in the colorectal and gastro-oesophageal participants compared to breast participants (P < 0.001) independent of other baseline characteristics. Aspirin 100 mg daily decreased U-TXM similarly across all tumour types (median reductions: 77-82%). Aspirin 300 mg daily provided no additional suppression of U-TXM compared with 100 mg. CONCLUSIONS: Persistently increased thromboxane biosynthesis was detected after radical cancer therapy, particularly in colorectal and gastro-oesophageal patients. Thromboxane biosynthesis should be explored further as a biomarker of active malignancy and may identify patients likely to benefit from aspirin

GW190521: A Binary Black Hole Merger with a Total Mass of 150 M

On May 21, 2019 at 03:02:29 UTC Advanced LIGO and Advanced Virgo observed a short duration gravitational-wave signal, GW190521, with a three-detector network signal-to-noise ratio of 14.7, and an estimated false-alarm rate of 1 in 4900 yr using a search sensitive to generic transients. If GW190521 is from a quasicircular binary inspiral, then the detected signal is consistent with the merger of two black holes with masses of 85+21-14 M⊙ and 66+17-18 M⊙ (90% credible intervals). We infer that the primary black hole mass lies within the gap produced by (pulsational) pair-instability supernova processes, with only a 0.32% probability of being below 65 M⊙. We calculate the mass of the remnant to be 142+28-16 M⊙, which can be considered an intermediate mass black hole (IMBH). The luminosity distance of the source is 5.3+2.4-2.6 Gpc, corresponding to a redshift of 0.82+0.28-0.34 . The inferred rate of mergers similar to GW190521 is 0.13+0.30-0.11 Gpc-3 yr-1

A joint fermi-gbm and ligo/virgo analysis of compact binary mergers from the first and second gravitational-wave observing runs

We present results from offline searches of Fermi Gamma-ray Burst Monitor (GBM) data for gamma-ray transients coincident with the compact binary coalescences observed by the gravitational-wave (GW) detectors Advanced LIGO and Advanced Virgo during their first and second observing runs. In particular, we perform follow-up for both confirmed events and low significance candidates reported in the LIGO/Virgo catalog GWTC-1. We search for temporal coincidences between these GW signals and GBM-triggered gamma-ray bursts (GRBs). We also use the GBM Untargeted and Targeted subthreshold searches to find coincident gamma-rays below the onboard triggering threshold. This work implements a refined statistical approach by incorporating GW astrophysical source probabilities and GBM visibilities of LIGO/Virgo sky localizations to search for cumulative signatures of coincident subthreshold gamma-rays. All search methods recover the short gamma-ray burst GRB 170817A occurring ~1.7 s after the binary neutron-star merger GW170817. We also present results from a new search seeking GBM counterparts to LIGO single-interferometer triggers. This search finds a candidate joint event, but given the nature of the GBM signal and localization, as well as the high joint false alarm rate of 1.1 x 10−6 Hz, we do not consider it an astrophysical association. We find no additional coincidences

Gravitational-wave Constraints on the Equatorial Ellipticity of Millisecond Pulsars

We present a search for continuous gravitational waves from five radio pulsars, comprising three recycled pulsars (PSR J0437−4715, PSR J0711−6830, and PSR J0737−3039A) and two young pulsars: the Crab pulsar (J0534+2200) and the Vela pulsar (J0835−4510). We use data from the third observing run of Advanced LIGO and Virgo combined with data from their first and second observing runs. For the first time, we are able to match (for PSR J0437−4715) or surpass (for PSR J0711−6830) the indirect limits on gravitational-wave emission from recycled pulsars inferred from their observed spin-downs, and constrain their equatorial ellipticities to be less than 10−8. For each of the five pulsars, we perform targeted searches that assume a tight coupling between the gravitational-wave and electromagnetic signal phase evolution. We also present constraints on PSR J0711−6830, the Crab pulsar, and the Vela pulsar from a search that relaxes this assumption, allowing the gravitational-wave signal to vary from the electromagnetic expectation within a narrow band of frequencies and frequency derivatives