Long-term benefit from immune modulation and anti-inflammatory treatment in metastatic mesothelioma.

A 64 year old male heating engineer was investigated for a persistent cough and found to have epithelioid mesothelioma with pleural effusion, lung nodules and increased thoracic lymph nodes. He declined standard of care treatment following his own research and he was enrolled in a named patient programme of IMM-101. He was advised to correct his low vitamin D3 level and to start using anti-inflammatories such as aspirin, bromelain and low dose Naltrexone. At review one year later a CT scan showed no change and he continued on the regimen. Four years after the diagnosis a CT scan showed that there was a modest but definite progression of the left malignant pleural thickening, and a new right-sided effusion, enlargement of several intrathoracic nodes which had been noted on the early scans. The chest wall lump eventually broke down and required local radiotherapy. He then developed abdominal pain and found to have peritoneal disease. Last year he obtained the cannabinoids CBD and THC which slowed down the disease and a CT scan after he had been on this for six months, showed that his disease was fairly stable with marginal progression

Using technology to deliver cancer follow-up : a systematic review

Peer reviewedPublisher PD

Expanding dispersal studies at hydrothermal vents through species identification of cryptic larval forms

Author Posting. © The Author(s), 2010. This is the author's version of the work. It is posted here by permission of Springer for personal use, not for redistribution. The definitive version was published in Marine Biology 157 (2010): 1049-1062, doi:10.1007/s00227-009-1386-8.The rapid identification of hydrothermal vent-endemic larvae to the species level is a key limitation to understanding the dynamic processes that control the abundance and distribution of fauna in such a patchy and ephemeral environment. Many larval forms collected near vents, even those in groups such as gastropods that often form a morphologically distinct larval shell, have not been identified to species. We present a staged approach that combines morphological and molecular identification to optimize the capability, efficiency, and economy of identifying vent gastropod larvae from the northern East Pacific Rise (NEPR). With this approach, 15 new larval forms can be identified to species. A total of 33 of the 41 gastropod species inhabiting the NEPR, and 26 of the 27 gastropod species known to occur specifically in the 9° 50’ N region, can be identified to species. Morphological identification efforts are improved by new protoconch descriptions for Gorgoleptis spiralis, Lepetodrilus pustulosus, Nodopelta subnoda, and Echinopelta fistulosa. Even with these new morphological descriptions, the majority of lepetodrilids and peltospirids require molecular identification. Restriction fragment length polymorphism digests are presented as an economical method for identification of five species of Lepetodrilus and six species of peltospirids. The remaining unidentifiable specimens can be assigned to species by comparison to an expanded database of 18S ribosomal DNA. The broad utility of the staged approach was exemplified by the revelation of species-level variation in daily planktonic samples and the identification and characterization of egg capsules belonging to a conid gastropod Gymnobela sp. A. The improved molecular and morphological capabilities nearly double the number of species amenable to field studies of dispersal and population connectivity.Funding was provided by as Woods Hole Oceanographic Institution Deep Ocean Exploration Institute grant to L.M and S. Beaulieu, National Science Foundation grants OCE-0424953, OCE-9712233, and OCE-9619605 to L.M, OCE-0327261 to T.S., and OCE-0002458 to K. Von Damm, and a National Defense Science and Engineering Graduate fellowship to D.A

Searching for Exoplanets Using a Microresonator Astrocomb

Detection of weak radial velocity shifts of host stars induced by orbiting planets is an important technique for discovering and characterizing planets beyond our solar system. Optical frequency combs enable calibration of stellar radial velocity shifts at levels required for detection of Earth analogs. A new chip-based device, the Kerr soliton microcomb, has properties ideal for ubiquitous application outside the lab and even in future space-borne instruments. Moreover, microcomb spectra are ideally suited for astronomical spectrograph calibration and eliminate filtering steps required by conventional mode-locked-laser frequency combs. Here, for the calibration of astronomical spectrographs, we demonstrate an atomic/molecular line-referenced, near-infrared soliton microcomb. Efforts to search for the known exoplanet HD 187123b were conducted at the Keck-II telescope as a first in-the-field demonstration of microcombs

Recurrence of complement factor H-related protein 5 nephropathy in a renal transplant.

Complement factor H-related protein 5 (CFHR5) nephropathy is a familial renal disease endemic in Cyprus. It is characterized by persistent microscopic hematuria, synpharyngitic macroscopic hematuria and progressive renal impairment. Isolated glomerular accumulation of complement component 3 (C3) is typical with variable degrees of glomerular inflammation. Affected individuals have a heterozygous internal duplication in the CFHR5 gene, although the mechanism through which this mutation results in renal disease is not understood. Notably, the risk of progressive renal failure in this condition is higher in males than females. We report the first documented case of recurrence of CFHR5 nephropathy in a renal transplant in a 53-year-old Cypriot male. Strikingly, histological changes of CFHR5 nephropathy were evident in the donor kidney 46 days post-transplantation. This unique case demonstrates that renal-derived CFHR5 protein cannot prevent the development of CFHR5 nephropathy

Protracted timescales of lower crustal growth at the fast-spreading East Pacific Rise

Author Posting. © The Author(s), 2011. This is the author's version of the work. It is posted here by permission of Nature Publishing Group for personal use, not for redistribution. The definitive version was published in Nature Geoscience 5 (2012): 275-278, doi:10.1038/ngeo1378.Formation of the oceanic crust at mid-ocean ridges is a fundamental component of plate tectonics. A majority of the crust at many ridges is composed of plutonic rocks that form by crystallization of mantle-derived magmas within the crust. Recent application of U/Pb dating to samples from in-situ oceanic crust has begun to provide exciting new insight into the timing, duration and distribution of magmatism during formation of the plutonic crust1-4. Previous studies have focused on samples from slow-spreading ridges, however, the time scales and processes of crustal growth are expected to vary with plate spreading rate. Here we present the first high-precision dates from plutonic crust formed at the fast-spreading East Pacific Rise (EPR). Individual zircon minerals yielded dates from 1.420–1.271 million years ago, with uncertainties of ± 0.006–0.081 million years. Within individual samples, zircons record a range of dates of up to ~0.124 million years, consistent with protracted crystallization or assimilation of older zircons from adjacent rocks. The variability in dates is comparable to data from the Vema lithospheric section on the Mid-Atlantic Ridge (MAR)3, suggesting that time scales of magmatic processes in the lower crust may be similar at slow- and fast-spreading ridges.This research was partially funded by NSF grant OCE-0727914 (SAB), a Cardiff University International Collaboration Award (CJL) and NERC grant NE/C509023/1 (CJM).2012-07-2

There Is No Safe Dose of Prions

Understanding the circumstances under which exposure to transmissible spongiform encephalopathies (TSEs) leads to infection is important for managing risks to public health. Based upon ideas in toxicology and radiology, it is plausible that exposure to harmful agents, including TSEs, is completely safe if the dose is low enough. However, the existence of a threshold, below which infection probability is zero has never been demonstrated experimentally. Here we explore this question by combining data and mathematical models that describe scrapie infections in mice following experimental challenge over a broad range of doses. We analyse data from 4338 mice inoculated at doses ranging over ten orders of magnitude. These data are compared to results from a within-host model in which prions accumulate according to a stochastic birth-death process. Crucially, this model assumes no threshold on the dose required for infection. Our data reveal that infection is possible at the very low dose of a 1000 fold dilution of the dose that infects half the challenged animals (ID50). Furthermore, the dose response curve closely matches that predicted by the model. These findings imply that there is no safe dose of prions and that assessments of the risk from low dose exposure are right to assume a linear relationship between dose and probability of infection. We also refine two common perceptions about TSE incubation periods: that their mean values decrease linearly with logarithmic decreases in dose and that they are highly reproducible between hosts. The model and data both show that the linear decrease in incubation period holds only for doses above the ID50. Furthermore, variability in incubation periods is greater than predicted by the model, not smaller. This result poses new questions about the sources of variability in prion incubation periods. It also provides insight into the limitations of the incubation period assay