Phenotypic characterization of PNPase knockdown in C. elegans

The multifunctional exoribonuclease protein PNPase is implicated as a potential target for cancer therapy as well as causing mitochondrial disorders in humans, but there has yet to be a whole animal knockdown model created. In this study, C. elegans was used to investigate the effect of knocking down pnpt-1, the gene that encodes PNPase. It was discovered that pnpt-1 knockdown significantly extends lifespan via an increase in superoxide production similar to other known mitochondrial lifespan extension pathways. Additionally, mitochondrial networks, size and respiration are affected indication of other mitochondrial dysfunction.. PNPase is also known to transport small RNAs into the mitochondria which in turn can affect mitochondria RNA splicing and translation of proteins involved in respiration. Further investigation showed a significant accumulation of polycistronic mitochondrial transcripts in knockdown animals. Lastly, this model has shown that PNPase knockdown is functionally comparable across species and is a viable model for future studies

Ultrasound Matrix Imaging. I. The focused reflection matrix and the F-factor

This is the first article in a series of two dealing with a matrix approach \alex{for} aberration quantification and correction in ultrasound imaging. Advanced synthetic beamforming relies on a double focusing operation at transmission and reception on each point of the medium. Ultrasound matrix imaging (UMI) consists in decoupling the location of these transmitted and received focal spots. The response between those virtual transducers form the so-called focused reflection matrix that actually contains much more information than a raw ultrasound image. In this paper, a time-frequency analysis of this matrix is performed, which highlights the single and multiple scattering contributions as well as the impact of aberrations in the monochromatic and broadband regimes. Interestingly, this analysis enables the measurement of the incoherent input-output point spread function at any pixel of this image. A focusing criterion can then be built, and its evolution used to quantify the amount of aberration throughout the ultrasound image. In contrast to the standard coherence factor used in the literature, this new indicator is robust to multiple scattering and electronic noise, thereby providing a highly contrasted map of the focusing quality. As a proof-of-concept, UMI is applied here to the in-vivo study of a human calf, but it can be extended to any kind of ultrasound diagnosis or non-destructive evaluation.Comment: 14 pages, 3 figure

Ultrasound Matrix Imaging. II. The distortion matrix for aberration correction over multiple isoplanatic patches

This is the second article in a series of two which report on a matrix approach for ultrasound imaging in heterogeneous media. This article describes the quantification and correction of aberration, i.e. the distortion of an image caused by spatial variations in the medium speed-of-sound. Adaptive focusing can compensate for aberration, but is only effective over a restricted area called the isoplanatic patch. Here, we use an experimentally-recorded matrix of reflected acoustic signals to synthesize a set of virtual transducers. We then examine wave propagation between these virtual transducers and an arbitrary correction plane. Such wave-fronts consist of two components: (i) An ideal geometric wave-front linked to diffraction and the input focusing point, and; (ii) Phase distortions induced by the speed-of-sound variations. These distortions are stored in a so-called distortion matrix, the singular value decomposition of which gives access to an optimized focusing law at any point. We show that, by decoupling the aberrations undergone by the outgoing and incoming waves and applying an iterative strategy, compensation for even high-order and spatially-distributed aberrations can be achieved. As a proof-of-concept, ultrasound matrix imaging (UMI) is applied to the in-vivo imaging of a human calf. A map of isoplanatic patches is retrieved and is shown to be strongly correlated with the arrangement of tissues constituting the medium. The corresponding focusing laws yield an ultrasound image with an optimal contrast and a transverse resolution close to the ideal value predicted by diffraction theory. UMI thus provides a flexible and powerful route towards computational ultrasound.Comment: 17 pages, 8 figure

Cancers of Unknown Primary

Cancers of unknown primary (CUP) are a heterogeneous group of histologically proven metastatic tumors whose primary site can\u27t be determined after a standard diagnostic and pathologic work-up. This chapter in Cancer Concepts: A Guidebook for the Non-Oncologist presents provides an overview of cancers of unknown primary, including initial evaluation and principles of treatment.https://escholarship.umassmed.edu/cancer_concepts/1016/thumbnail.jp

Reflection matrix approach for quantitative imaging of scattering media

We present a physically intuitive matrix approach for wave imaging and characterization in scattering media. The experimental proof-of-concept is performed with ultrasonic waves, but this approach can be applied to any field of wave physics for which multi-element technology is available. The concept is that focused beamforming enables the synthesis, in transmit and receive, of an array of virtual transducers which map the entire medium to be imaged. The inter-element responses of this virtual array form a focused reflection matrix from which spatial maps of various characteristics of the propagating wave can be retrieved. Here we demonstrate: (i) a local focusing criterion that enables the image quality and the wave velocity to be evaluated everywhere inside the medium, including in random speckle, and (ii) an highly resolved spatial mapping of the prevalence of multiple scattering, which constitutes a new and unique contrast for ultrasonic imaging. The approach is demonstrated for a controllable phantom system, and for in vivo imaging of the human abdomen. More generally, this matrix approach opens an original and powerful route for quantitative imaging in wave physics.Comment: 18 pages, 6 figure

Anaerobiosis influences virulence properties of Pseudomonas aeruginosa cystic fibrosis isolates and the interaction with Staphylococcus aureus

The airways of individuals with cystic fibrosis (CF) are abundantly colonised by Staphylococcus aureus and Pseudomonas aeruginosa. Co-infecting hypoxic regions of static mucus within CF airways, together with decreases in pulmonary function, mucus plugging and oxygen consumption by host neutrophils gives rise to regions of anoxia. This study determined the impact of anaerobiosis upon S. aureus-P. aeruginosa interactions in planktonic co-culture and mixed species biofilms in vitro. Whilst anoxia reduced the ability for P. aeruginosa CF isolates to dominate over S. aureus, this occurred in an isolate dependent manner. Investigations into the underlying mechanisms suggest that the anti-staphylococcal compound facilitating P. aeruginosa dominance under normoxia and anoxia is greater than 3 kDa in size and is heat-stable. Not all interspecies interactions studied were antagonistic, as S. aureus exoproducts were shown to restore and enhance P. aeruginosa motility under normoxia and anoxia in an isolate dependent manner. Collectively, this study suggests changes in oxygen availability within regions of the CF lung is likely to influence interspecies interactions and in turn, potentially influence disease progression

Sentinel Lymph Node Biopsy Does Not Improve Disease-Specific Survival in Elderly Patients with Intermediate Thickness Melanoma

Objective: To determine whether sentinel lymph node biopsy (SLNB) is associated with improved disease-specific survival among elderly patients with intermediate-thickness melanoma Design: Retrospective cohort study of prospectively-maintained tumor registry Setting: Single institution tertiary care center. P atients: Adults ≥ 70 years of age, who underwent surgical intervention for melanoma from 2000-2013. Main Outcome Measures: The primary outcomes were overall survival (OS) and disease-free survival (DFS). Other clinicopathologic variables measured included age, gender, anatomic site, histologic type, tumor thickness, presence of adverse features, receipt and result of SLNB, and receipt of completion lymph node dissection (CLND). Results: Ninety-one patients (mean age 80 years, 54% male) underwent wide excision of an intermediate-thickness melanoma. Forty-nine patients (54%) received a SLNB. Seven of these biopsies (14%) were positive, and five patients (71%) went on to receive CLND. Five-year OS was 41% in patients who did not receive SLNB and 52% in patients who did receive SLNB (Fig. 1A). However, 5-year DFS was 79% in patients who did not receive SLNB and 77% in patients who did receive SLNB (Fig. 1B). Conclusions: Among elderly patients with intermediate-thickness melanoma, patients who received SLNB had higher 5-year OS than those who did not receive SLNB. However, the 5-year DFS is similar between the two groups, which suggests that the OS differences are related to non-melanoma factors. Routine SLNB for intermediate-thickness melanoma patients may not significantly change the outcome for this age group, and clinical decision-making should consider individual patient comorbidities and goals of care