The oxygen status of a tumor has significant clinical implications for treatment prognosis, with well-oxygenated subvolumes responding markedly better to radiotherapy than poorly supplied regions. ...Oxygen is essential for tumor growth, yet estimation of local oxygen distribution can be difficult to ascertain in situ, due to chaotic patterns of vasculature. It is possible to avoid this confounding influence by using avascular tumor models, such as tumor spheroids, a much better approximation of realistic tumor dynamics than monolayers, where oxygen supply can be described by diffusion alone. Similar to in situ tumours, spheroids exhibit an approximately sigmoidal growth curve, often approximated and fitted by logistic and Gompertzian sigmoid functions. These describe the basic rate of growth well, but do not offer an explicitly mechanistic explanation. This work examines the oxygen dynamics of spheroids and demonstrates that this growth can be derived mechanistically with cellular doubling time and oxygen consumption rate (OCR) being key parameters. The model is fitted to growth curves for a range of cell lines and derived values of OCR are validated using clinical measurement. Finally, we illustrate how changes in OCR due to gemcitabine treatment can be directly inferred using this model.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Ultraviolet (UVR) phototherapy is widely used to treat an array of skin conditions, including psoriasis, eczema and vitiligo. For such interventions, a quantified dose is vital if the treatment is to ...be both biologically effective and to avoid the detrimental effects of over-dosing. As dose is absorbed at surface level, the orientation of patient site with respect to the UVR lamps modulates effective dose. Previous investigations have modelled this behaviour, and examined the impact of shaped anodized aluminium reflectors typically placed around lamps in phototherapy cabins. These mirrors are effective but tend to yield complex patterns of reflection around the cabin which can result in substantial dose inhomogeneity. There has been some speculation over whether using the reflective property of parabolic mirrors might improve dose delivery or homogeneity through the treatment cabin. In this work, the effects of parabolic mirrors are simulated and compared with standard shaped mirrors. Simulation results strongly suggest that parabolic reflectors reduce total irradiance relative to standard shaped reflectors, and have a negligible impact on dose homogeneity.
Investigators should properly calculate sample sizes before the start of their randomised trials and adequately describe the details in their published report. In these a-priori calculations, ...determining the effect size to detect—eg, event rates in treatment and control groups—reflects inherently subjective clinical judgments. Furthermore, these judgments greatly affect sample size calculations. We question the branding of trials as unethical on the basis of an imprecise sample size calculation process. So-called underpowered trials might be acceptable if investigators use methodological rigor to eliminate bias, properly report to avoid misinterpretation, and always publish results to avert publication bias. Some shift of emphasis from a fixation on sample size to a focus on methodological quality would yield more trials with less bias. Unbiased trials with imprecise results trump no results at all. Clinicians and patients deserve guidance now.
Rapid progress in atomic, molecular, and optical (AMO) physics techniques enabled the creation of ultracold samples of molecular species and opened opportunities to explore chemistry in the ultralow ...temperature regime. In particular, both the external and internal quantum degrees of freedom of the reactant atoms and molecules are controlled, allowing studies that explored the role of the long-range potential in ultracold reactions. The kinetics of these reactions have typically been determined using the loss of reactants as proxies. To extend such studies into the short-range, we developed an experimental apparatus that combines the production of quantum-state-selected ultracold KRb molecules with ion mass and kinetic energy spectrometry, and directly observed KRb + KRb reaction intermediates and products M.-G. Hu and Y. Liu, et al., Science, 2019, 366, 1111. Here, we present the apparatus in detail. For future studies that aim for detecting the quantum states of the reaction products, we demonstrate a photodissociation based scheme to calibrate the ion kinetic energy spectrometer at low energies.
African societies are dependent on rainfall for agricultural and other water‐dependent activities, yet rainfall is extremely variable in both space and time and reoccurring water shocks, such as ...drought, can have considerable social and economic impacts. To help improve our knowledge of the rainfall climate, we have constructed a 30 year (1983–2012), temporally consistent rainfall data set for Africa known as TARCAT (Tropical Applications of Meteorology using SATellite and ground‐based observations (TAMSAT) African Rainfall Climatology And Time series) using archived Meteosat thermal infrared imagery, calibrated against rain gauge records collated from numerous African agencies. TARCAT has been produced at 10 day (dekad) scale at a spatial resolution of 0.0375°. An intercomparison of TARCAT from 1983 to 2010 with six long‐term precipitation data sets indicates that TARCAT replicates the spatial and seasonal rainfall patterns and interannual variability well, with correlation coefficients of 0.85 and 0.70 with the Climate Research Unit and Global Precipitation Climatology Centre gridded‐gauge analyses respectively in the interannual variability of the Africa‐wide mean monthly rainfall. The design of the algorithm for drought monitoring leads to TARCAT underestimating the Africa‐wide mean annual rainfall on average by −0.37 mm d−1 (21%) compared to other data sets. As the TARCAT rainfall estimates are historically calibrated across large climatically homogeneous regions, the data can provide users with robust estimates of climate related risk, even in regions where gauge records are inconsistent in time.
Key Points
Development of a satellite‐based 30 year rainfall data set for AfricaThe data set has been designed to be temporally consistentThe data set skillfully captures interannual and decadal variability
Use of control (comparison) groups is a powerful research tool. In case-control studies, controls estimate the frequency of an exposure in the population under study. Controls can be taken from known ...or unknown study populations. A known group consists of a defined population observed over a period, such as passengers on a cruise ship. When the study group is known, a sample of the population can be used as controls. If no population roster exists, then techniques such as random-digit dialling can be used. Sometimes, however, the study group is unknown, for example, motor-vehicle crash victims brought to an emergency department, who may come from far away. In this situation, hospital controls, neighbourhood controls, and friend, associate, or relative controls can be used. In general, one well-selected control group is better than two or more. When the number of cases is small, the ratio of controls to cases can be raised to improve the ability to find important differences. Although no ideal control group exists, readers need to think carefully about how representative the controls are. Poor choice of controls can lead to both wrong results and possible medical harm.
Molecular genetics has linked mitochondrial dysfunction to the pathogenesis of Parkinson's disease by the discovery of rare, inherited mutations in gene products that associate with the mitochondria. ...Mutations in PTEN-induced kinase-1 (PINK1), which encodes a mitochondrial kinase, and PARKIN, encoding an E3 ubiquitin ligase, are the most frequent causes of recessive Parkinson's disease. Recent functional studies have revealed that PINK1 recruits PARKIN to mitochondria to initiate mitophagy, an important autophagic quality control mechanism that rids the cell of damaged mitochondria. PINK1 is post-translationally processed into a cleaved form whose levels are tightly regulated, although the significance of this processing is unknown. Here we demonstrate that the mitochondrial protease presenilin-associated rhomboid-like (PARL) can affect the proteolytic processing of PINK1 and that normal PINK1 localization and stability requires PARL's catalytic activity. PARL deficiency impairs PARKIN recruitment to mitochondria, suggesting PINK1's processing and localization are important in determining its interaction with PARKIN. We sequenced the PARL gene in Parkinson's disease patients and discovered a novel missense mutation in a functional domain of PARL's N-terminus. This PARL mutant is not sufficient to rescue PARKIN recruitment, suggesting that impaired mitophagy may be an underlying mechanism of disease pathogenesis in patients with PARL mutations.
Electric guitar playing is ubiquitous in practically all modern music genres. In the hands of an experienced player, electric guitars can sound as expressive and distinct as a human voice. Unlike ...other more quantised instruments where pitch is a discrete function, guitarists can incorporate micro-tonality and, as a result, vibrato and sting-bending are idiosyncratic hallmarks of a player. Similarly, a wide variety of techniques unique to the electric guitar have emerged. While the mechano-acoustics of stringed instruments and vibrating strings are well studied, there has been comparatively little work dedicated to the underlying physics of unique electric guitar techniques and strings, nor the mechanical factors influencing vibrato, string-bending, fretting force and whammy-bar dynamics. In this work, models for these processes are derived and the implications for guitar and string design discussed. The string-bending model is experimentally validated using a variety of strings and vibrato dynamics are simulated. The implications of these findings on the configuration and design of guitars is also discussed.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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