Computational Fluid Dynamics Modeling of the Burr Orbital Motion in Rotational Atherectomy with Particle Image Velocimetry Validation.

Rotational atherectomy (RA) uses a high-speed rotating burr introduced via a catheter through the artery to remove hardened atherosclerotic plaque. Current clinical RA technique lacks consensus on burr size and rotational speed. The rotating burr orbits inside the artery due to the fluid force of the blood.

Photoswitching an Isolated Donor-Acceptor Stenhouse Adduct.

Donor-acceptor Stenhouse adducts (DASAs) are a new class of photoswitching molecules with excellent fatigue resistance and synthetic tunability. Here, tandem ion mobility mass spectrometry coupled with laser excitation is used to characterize the photocyclization reaction of isolated, charge-tagged DASA molecules over the 450-580 nm range. The experimental maximum response at 530 nm agrees with multireference perturbation theory calculations for the S ← S transition maximum at 533 nm.

Clinical trials recruitment planning: A proposed framework from the Clinical Trials Transformation Initiative.

Patient recruitment is widely recognized as a key determinant of success for clinical trials. Yet a substantial number of trials fail to reach recruitment goals-a situation that has important scientific, financial, ethical, and policy implications. Further, there are important effects on stakeholders who directly contribute to the trial including investigators, sponsors, and study participants.

Conservation of pattern as a tool for inference on spatial snapshots in ecological data.

As climate change and other anthropogenic factors increase the uncertainty of vegetation ecosystem persistence, the ability to rapidly assess their dynamics is paramount. Vegetation and sessile communities form a variety of striking regular spatial patterns such as stripes, spots and labyrinths, that have been used as indicators of ecosystem current state, through qualitative analysis of simple models. Here we describe a new method for rigorous quantitative estimation of biological parameters from a single spatial snapshot.

Identification of ion-channel modulators that protect against aminoglycoside-induced hair cell death.

Aminoglycoside antibiotics are used to treat life-threatening bacterial infections but can cause deafness due to hair cell death in the inner ear. Compounds have been described that protect zebrafish lateral line hair cells from aminoglycosides, but few are effective in the cochlea. As the aminoglycosides interact with several ion channels, including the mechanoelectrical transducer (MET) channels by which they can enter hair cells, we screened 160 ion-channel modulators, seeking compounds that protect cochlear outer hair cells (OHCs) from aminoglycoside-induced death in vitro.

From E to Z and back again: reversible photoisomerisation of an isolated charge-tagged azobenzene.

Substituted azobenzenes serve as chromophores and actuators in a wide range of molecular photoswitches. Here, tandem ion mobility spectrometry coupled with laser excitation is used to investigate the photoisomerisation of selected E and Z isomers of the charge-tagged azobenzene, methyl orange. Both isomers display a weak S(nπ*) photoisomerisation response in the blue part of the spectrum peaking at 440 nm and a more intense S(ππ*) photoisomerisation response in the near-UV with maxima at 370 and 310 nm for the E and Z isomers, respectively.

Therapeutic Application of Phage Capsule Depolymerases against K1, K5, and K30 Capsulated in Mice.

Capsule depolymerase enzymes offer a promising class of new antibiotics. studies are encouraging but it is unclear how well this type of phage product will generalize in therapeutics, or whether different depolymerases against the same capsule function similarly. Here, efficacy was tested using cloned bacteriophage depolymerases against strains with three different capsule types: K1, K5, and K30.

Lithium-Catalyzed Thiol Alkylation with Tertiary and Secondary Alcohols: Synthesis of 3-Sulfanyl-Oxetanes as Bioisosteres.

3-Sulfanyl-oxetanes are presented as promising novel bioisosteric replacements for thioesters or benzyl sulfides. From oxetan-3-ols, a mild and inexpensive Li catalyst enables chemoselective C-OH activation and thiol alkylation. Oxetane sulfides are formed from various thiols providing novel motifs in new chemical space and specifically as bioisosteres for thioesters due to their similar shape and electronic properties.

Personalized medicine and Hispanic health: improving health outcomes and reducing health disparities - a National Heart, Lung, and Blood Institute workshop report.

Persons of Hispanic/Latino descent may represent different ancestries, ethnic and cultural groups and countries of birth. In the U.S.

Flower resource and land management drives hoverfly communities and bee abundance in seminatural and agricultural grasslands.

Pollination is a key ecosystem service, and appropriate management, particularly in agricultural systems, is essential to maintain a diversity of pollinator guilds. However, management recommendations frequently focus on maintaining plant communities, with the assumption that associated invertebrate populations will be sustained. We tested whether plant community, flower resources, and soil moisture would influence hoverfly (Syrphidae) abundance and species richness in floristically-rich seminatural and floristically impoverished agricultural grassland communities in Wales (U.

Transmissible Viral Vaccines.

Genetic engineering now enables the design of live viral vaccines that are potentially transmissible. Some designs merely modify a single viral genome to improve on the age-old method of attenuation whereas other designs create chimeras of viral genomes. Transmission has the benefit of increasing herd immunity above that achieved by direct vaccination alone but also increases the opportunity for vaccine evolution, which typically undermines vaccine utility.

Arresting Evolution.

Evolution in the form of selective breeding has long been harnessed as a useful tool by humans. However, rapid evolution can also be a danger to our health and a stumbling block for biotechnology. Unwanted evolution can underlie the emergence of drug and pesticide resistance, cancer, and weeds.

Divergent Synthesis of Cyclopropane-Containing Lead-Like Compounds, Fragments and Building Blocks through a Cobalt Catalyzed Cyclopropanation of Phenyl Vinyl Sulfide.

Cyclopropanes provide important design elements in medicinal chemistry and are widely present in drug compounds. Here we describe a strategy and extensive synthetic studies for the preparation of a diverse collection of cyclopropane-containing lead-like compounds, fragments and building blocks exploiting a single precursor. The bifunctional cyclopropane ()-ethyl 2-(phenylsulfanyl)-cyclopropane-1-carboxylate was designed to allow derivatization through the ester and sulfide functionalities to topologically varied compounds designed to fit in desirable chemical space for drug discovery.

A review of immune therapy in cancer and a question: can thermal therapy increase tumor response?

Immune therapy is a successful cancer treatment coming into its own. This is because checkpoint molecules, adoptive specific lymphocyte transfer and chimeric antigen T-cell (CAR-T) therapy are able to induce more durable responses in an increasing number of malignancies compared to chemotherapy. In addition, immune therapies are able to treat bulky disease, whereas standard cytotoxic therapies cannot treat large tumour burdens.

Single operation palladium catalysed C(sp)-H functionalisation of tertiary aldehydes: investigations into transient imine directing groups.

Simple amine and diamine derivatives can promote the palladium catalysed direct β-C-H arylation of aliphatic aldehydes transient imine formation. Trifluoroacetate was shown to be crucial in promoting the reaction. Sub-stoichiometric quantities of simple -tosylethylenediamine was shown to form a bidentate directing group with an imine linkage.

Dynamics of π*-resonances in anionic clusters of para-toluquinone.

Frequency-resolved photoelectron spectroscopy applied to mass-selected cluster anions is an insightful approach to characterise the dynamics of π*-resonances with microsolvation. Here, the technique is demonstrated with monomer, dimer and trimer radical anions of para-toluquinone (pTQ) over a ∼1 eV excitation window above the detachment threshold. The pTQ spectra show similar resonances and dynamics to para-benzoquinone, a prototype electrophore.

Measuring the role of seagrasses in regulating sediment surface elevation.

Seagrass meadows provide numerous ecosystem services and their rapid global loss may reduce human welfare as well as ecological integrity. In common with the other 'blue carbon' habitats (mangroves and tidal marshes) seagrasses are thought to provide coastal defence and encourage sediment stabilisation and surface elevation. A sophisticated understanding of sediment elevation dynamics in mangroves and tidal marshes has been gained by monitoring a wide range of different sites, located in varying hydrogeomorphological conditions over long periods.

Standardization and Scaling of a Community-Based Palliative Care Model.

Background: Although limited, the descriptions of Community-Based Palliative Care (CBPC) demonstrates variability in team structures, eligibility, and standardization across care settings.

Objective: In 2014, Four Seasons Compassion for Life, a nonprofit hospice and palliative care (PC) organization in Western North Carolina (WNC), was awarded a Centers for Medicare and Medicaid Services Health Care Innovation (CMMI) Award to expand upon their existing innovative model to implement, evaluate, and demonstrate CBPC in the United States. The objective of this article is to describe the processes and challenges of scaling and standardizing the CBPC model.

Preoperative sentinel lymph node identification, biopsy and localisation using contrast enhanced ultrasound (CEUS) in patients with breast cancer: a systematic review and meta-analysis.

Aim: To evaluate whether contrast-enhanced ultrasound (CEUS)-guided core biopsy of the sentinel lymph node (SLN) could identify metastatic nodes preoperatively and reduce the number of surgical SLN biopsies in patients with breast cancer and normal axillary B-mode ultrasound; and to establish whether CEUS SLN identification and localisation is a viable alternative to standard lymphatic mapping using isotope and blue dye.

Materials And Methods: A search of several electronic databases was performed and identified studies were assessed using QUADAS-2 for methodological quality. Pooled estimates of sensitivity and specificity for identification of nodal metastases were calculated.

Photoisomerization of Protonated Azobenzenes in the Gas Phase.

Because of their high photoisomerization efficiencies, azobenzenes and their functionalized derivatives are used in a broad range of molecular photoswitches. Here, the photochemical properties of the trans isomers of protonated azobenzene (ABH) and protonated 4-aminoazobenzene (NHABH) cations are investigated in the gas phase using a tandem ion mobility spectrometer. Both cations display a strong photoisomerization response across their S ← S bands, with peaks in their photoisomerization yields at 435 and 525 nm, respectively, red-shifted with respect to the electronic absorption bands of the unprotonated AB and NHAB molecules.

One Size Does Not Fit All: Disease Profiles of Serious Illness Patients Receiving Specialty Palliative Care.

Introduction: Understanding the symptom profiles of seriously ill patients who receive palliative care, especially noncancer diagnoses where the data are sparse and are critical to better targeting our resources to the needs of patients.

Methods: We performed a retrospective, multicohort study of patients evaluated during their first consultative palliative care visit in a community-based palliative care registry. We placed into one of seven major disease categories based on clinician-reported primary diagnosis for consultation.

Protomer-Specific Photochemistry Investigated Using Ion Mobility Mass Spectrometry.

The utility of tandem ion mobility mass spectrometry coupled with electronic spectroscopy to investigate protomer-specific photochemistry is demonstrated by measuring the photoisomerization response for protomers of protonated 4-dicyanomethylene-2-methyl-6-para-dimethylaminostyryl-4H-pyran (DCM) molecules. The target DCMH species has three protomers that are distinguished by their different collision cross sections with He, N, and CO buffer gases, trends in abundance with ion source conditions, and from their photoisomerization responses. The trans-DCMH protomers with the proton located either on the tertiary amine N atom or on a cyano group N atom exhibit distinct S← S photoisomerization responses, with the maxima in their photoisomerization action spectra occurring at 420 and 625 nm, respectively, consistent with predictions from accompanying electronic structure calculations.

Reduced Protein Expression in a Virus Attenuated by Codon Deoptimization.

A general means of viral attenuation involves the extensive recoding of synonymous codons in the viral genome. The mechanistic underpinnings of this approach remain unclear, however. Using quantitative proteomics and RNA sequencing, we explore the molecular basis of attenuation in a strain of bacteriophage T7 whose major capsid gene was engineered to carry 182 suboptimal codons.