Albumin concentrations are primarily determined by the body cell mass and the systemic inflammatory response in cancer patients with weight loss

The association between hypoalbuminemia and poor prognosis in patients with cancer is well recognized. However, the factors that contribute to the fall in albumin concentrations are not well understood. In the present study, we examined the relationship between circulating albumin concentrations, weight loss, the body cell mass (measured using total body potassium), and the presence of an inflammatory response (measured using C- reactive protein) in male patients (n=40) with advanced lung or gastrointestinal cancer. Albumin concentrations were significantly correlated with the percent ideal body weight (r=0.390, p lt 0.05), extent of reported weight loss (r=-0.492, p lt 0.01), percent predicted total body potassium (adjusted for age, height, and weight, r=0.686, p lt 0.001), and logo C-reactive protein concentrations (r=-0.545, p lt 0.001). On multiple regression analysis, the percent predicted total body potassium and log(10) C-reactive protein concentrations accounted for 63% of the variation in albumin concentrations (r(2) = 0.626, p lt 0.001). The interrelationship between albumin, body cell mass, and the inflammatory response is consistent with the concept that the presence of an ongoing inflammatory response contributes to the progressive loss of these vital protein components of the body and the subsequent death of patients with advanced cancer

Scan-rescan reproducibility of neurite microstructure estimates using NODDI

In this work we provide a preliminary assessment of the reproducibility of the Neurite Orientation Dispersion and Density Imaging (NODDI), a recent diffusion MRI technique for directly quantifying microstructural indices of neurites in vivo, in the human brain. It is important to assess the reproducibility of such a technique to verify the precision of the method, which has implications for translation to clinical studies. NODDI outputs indices which reflect the functional and computational complexity of various regions of the brain and thus can provide useful information, non-invasively, for understanding pathology of the brain. We compare the parameter maps derived from diffusion MRI data acquired using the NODDI protocol from a normal subject, at two separate imaging sessions. We show that the NODDI indices have reproducibility comparable to that of the DTI indices. We additionally show that the clinically feasible NODDI protocol maintains good reproducibility of parameter estimates, comparable to that of a more comprehensive protocol

Ranking diffusion-MRI models with in-vivo human brain data

Diffusion MRI microstructure imaging provides a unique non-invasive probe into the microstructure of biological tissue. Its analysis relies on mathematical models relating microscopic tissue features to the MR signal. This work aims to determine which compartment models of diffusion MRI are best at describing the signal from in-vivo brain white matter. Recent work shows that three compartment models, including restricted intra-axonal, glial compartments and hindered extra-cellular diffusion, explain best multi b-value data sets from fixed rat brain tissue. Here, we perform a similar experiment using in-vivo human data. We compare one, two and three compartment models, ranking them with standard model selection criteria. Results show that, as with fixed tissue, three compartment models explain the data best, although simpler models emerge for the in-vivo data. We also find that splitting the scanning into shorter sessions has little effect on the models fitting and that the results are reproducible. The full ranking assists the choice of model and imaging protocol for future microstructure imaging applications in the brain

Influence of LAR and VAR on Para-Aminopyridine Antimalarials Targetting Haematin in Chloroquine-Resistance

Antimalarial chloroquine (CQ) prevents haematin detoxication when CQ-base concentrates in the acidic digestive vacuole through protonation of its p-aminopyridine (pAP) basic aro- matic nitrogen and sidechain diethyl-N. CQ export through the variant vacuolar membrane export channel, PFCRT, causes CQ-resistance in Plasmodium falciparum but 3-methyl CQ (sontochin SC), des-ethyl amodiaquine (DAQ) and bis 4-aminoquinoline piperaquine (PQ) are still active. This is determined by changes in drug accumulation ratios in parasite lipid (LAR) and in vacuolar water (VAR). Higher LAR may facilitate drug binding to and blocking PFCRT and also aid haematin in lipid to bind drug. LAR for CQ is only 8.3; VAR is 143,482. More hydrophobic SC has LAR 143; VAR remains 68,523. Similarly DAQ with a phenol sub- stituent has LAR of 40.8, with VAR 89,366. In PQ, basicity of each pAP is reduced by distal piperazine N, allowing very high LAR of 973,492, retaining VAR of 104,378. In another bis quinoline, dichlorquinazine (DCQ), also active but clinically unsatisfactory, each pAP retains basicity, being insulated by a 2-carbon chain from a proximal nitrogen of the single linking piperazine. While LAR of 15,488 is still high, the lowest estimate of VAR approaches 4.9 million. DCQ may be expected to be very highly lysosomotropic and therefore potentially hepatotoxic. In 11 pAP antimalarials a quadratic relationship between logLAR and logRe- sistance Index (RI) was confirmed, while log (LAR/VAR) vs logRI for 12 was linear. Both might be used to predict the utility of structural modifications

Deep residual networks for automatic segmentation of laparoscopic videos of the liver

MOTIVATION: For primary and metastatic liver cancer patients undergoing liver resection, a laparoscopic approach can reduce recovery times and morbidity while offering equivalent curative results; however, only about 10% of tumours reside in anatomical locations that are currently accessible for laparoscopic resection. Augmenting laparoscopic video with registered vascular anatomical models from pre-procedure imaging could support using laparoscopy in a wider population. Segmentation of liver tissue on laparoscopic video supports the robust registration of anatomical liver models by filtering out false anatomical correspondences between pre-procedure and intra-procedure images. In this paper, we present a convolutional neural network (CNN) approach to liver segmentation in laparoscopic liver procedure videos. METHOD: We defined a CNN architecture comprising fully-convolutional deep residual networks with multi-resolution loss functions. The CNN was trained in a leave-one-patient-out cross-validation on 2050 video frames from 6 liver resections and 7 laparoscopic staging procedures, and evaluated using the Dice score. RESULTS: The CNN yielded segmentations with Dice scores ≥0.95 for the majority of images; however, the inter-patient variability in median Dice score was substantial. Four failure modes were identified from low scoring segmentations: minimal visible liver tissue, inter-patient variability in liver appearance, automatic exposure correction, and pathological liver tissue that mimics non-liver tissue appearance. CONCLUSION: CNNs offer a feasible approach for accurately segmenting liver from other anatomy on laparoscopic video, but additional data or computational advances are necessary to address challenges due to the high inter-patient variability in liver appearance

Adaptive remodeling of the bacterial proteome by specific ribosomal modification regulates Pseudomonas infection and niche colonisation

Post-transcriptional control of protein abundance is a highly important, underexplored regulatory process by which organisms respond to their environments. Here we describe an important and previously unidentified regulatory pathway involving the ribosomal modification protein RimK, its regulator proteins RimA and RimB, and the widespread bacterial second messenger cyclic-di-GMP (cdG). Disruption of rimK affects motility and surface attachment in pathogenic and commensal Pseudomonas species, with rimK deletion significantly compromising rhizosphere colonisation by the commensal soil bacterium P. fluorescens, and plant infection by the pathogens P. syringae and P. aeruginosa. RimK functions as an ATP-dependent glutamyl ligase, adding glutamate residues to the C-terminus of ribosomal protein RpsF and inducing specific effects on both ribosome protein complement and function. Deletion of rimK in P. fluorescens leads to markedly reduced levels of multiple ribosomal proteins, and also of the key translational regulator Hfq. In turn, reduced Hfq levels induce specific downstream proteomic changes, with significant increases in multiple ABC transporters, stress response proteins and non-ribosomal peptide synthetases seen for both ΔrimK and Δhfq mutants. The activity of RimK is itself controlled by interactions with RimA, RimB and cdG. We propose that control of RimK activity represents a novel regulatory mechanism that dynamically influences interactions between bacteria and their hosts; translating environmental pressures into dynamic ribosomal changes, and consequently to an adaptive remodeling of the bacterial proteome

Upper atmospheres and ionospheres of planets and satellites

The upper atmospheres of the planets and their satellites are more directly exposed to sunlight and solar wind particles than the surface or the deeper atmospheric layers. At the altitudes where the associated energy is deposited, the atmospheres may become ionized and are referred to as ionospheres. The details of the photon and particle interactions with the upper atmosphere depend strongly on whether the object has anintrinsic magnetic field that may channel the precipitating particles into the atmosphere or drive the atmospheric gas out to space. Important implications of these interactions include atmospheric loss over diverse timescales, photochemistry and the formation of aerosols, which affect the evolution, composition and remote sensing of the planets (satellites). The upper atmosphere connects the planet (satellite) bulk composition to the near-planet (-satellite) environment. Understanding the relevant physics and chemistry provides insight to the past and future conditions of these objects, which is critical for understanding their evolution. This chapter introduces the basic concepts of upper atmospheres and ionospheres in our solar system, and discusses aspects of their neutral and ion composition, wind dynamics and energy budget. This knowledge is key to putting in context the observations of upper atmospheres and haze on exoplanets, and to devise a theory that explains exoplanet demographics.Comment: Invited Revie

Conceptualising production, productivity and technology in pharmacy practice: a novel framework for policy, education and research.

CONTEXT AND BACKGROUND: People and health systems worldwide face serious challenges due to shifting disease demographics, rising population demands and weaknesses in healthcare provision, including capacity shortages and lack of impact of healthcare services. These multiple challenges, linked with the global push to achieve universal health coverage, have made apparent the importance of investing in workforce development to improve population health and economic well-being. In relation to medicines, health systems face challenges in terms of access to needed medicines, optimising medicines use and reducing risk. In 2017, the International Pharmaceutical Federation (FIP) published global policy on workforce development ('the Nanjing Statements') that describe an envisioned future for professional education and training. The documents make clear that expanding the pharmacy workforce benefits patients, and continually improving education and training produces better clinical outcomes. AIMS AND PURPOSE: The opportunities for harnessing new technologies in pharmacy practice have been relatively ignored. This paper presents a conceptual framework for analysing production methods, productivity and technology in pharmacy practice that differentiates between dispensing and pharmaceutical care services. We outline a framework that may be employed to study the relationship between pharmacy practice and productivity, shaped by educational and technological inputs. METHOD AND RESULTS: The analysis is performed from the point of view of health systems economics. In relation to pharmaceutical care (patient-oriented practice), pharmacists are service providers; however, their primary purpose is not to deliver consultations, but to maximise the quantum of health gain they secure. Our analysis demonstrates that 'technology shock' is clearly beneficial compared with orthodox notions of productivity or incremental gain implementations. Additionally, the whole process of providing professional services using 'pharmaceutical care technologies' is governed by local institutional frames, suggesting that activities may be structured differently in different places and countries. DISCUSSION AND CONCLUSION: Addressing problems with medication use with the development of a pharmaceutical workforce that is sufficient in quantity and competence is a long-term issue. As a result of this analysis, there emerges a challenge about the profession's relationship with existing and emerging technical innovations. Our novel framework is designed to facilitate policy, education and research by providing an analytical approach to service delivery. By using this approach, the profession could develop examples of good practice in both developed and developing countries worldwide