The Roles of the Virome in Cancer

Viral infections as well as changes in the composition of the intestinal microbiota and virome have been linked to cancer. Moreover, the success of cancer immunotherapy with checkpoint inhibitors has been correlated with the intestinal microbial composition of patients. The transfer of feces—which contain mainly bacteria and their viruses (phages)—from immunotherapy responders to non-responders, known as fecal microbiota transplantation (FMT), has been shown to be able to convert some non-responders to responders. Since phages may also increase the response to immunotherapy, for example by inducing T cells cross-reacting with cancer antigens, modulating phage populations may provide a new avenue to improve immunotherapy responsiveness. In this review, we summarize the current knowledge on the human virome and its links to cancer, and discuss the potential utility of bacteriophages in increasing the responder rate for cancer immunotherapy

Ongoing transients in carbonate compensation

Uptake of anthropogenic CO2 is acidifying the oceans. Over the next 2000 years, this will modify the dissolution and preservation of sedimentary carbonate. By coupling new formulas for the positions of the calcite saturation horizon, zsat, the compensation depth, zcc, and the snowline, zsnow, to a biogeochemical model of the oceanic carbonate system, we evaluate how these horizons will change with ongoing ocean acidification. Our model is an extended Havardton-Bear-type box model, which includes novel kinetic descriptions for carbonate dissolution above, between, and below these critical depths. In the preindustrial ocean, zsat and zcc are at 3939 and 4750 m, respectively. When forced with the IS92a CO2 emission scenario, the model forecasts (1) that zsat will rise rapidly (“runaway” conditions) so that all deep water becomes undersaturated, (2) that zcc will also rise and over 1000 years will pass before it will be stabilized by the dissolution of previously deposited CaCO3, and (3) that zsnow will respond slowly to acidification, rising by ∼1150 m during a 2000 year timeframe. A further simplified model that equates the compensation and saturation depths produces quantitatively different results. Finally, additional feedbacks due to acidification on calcification and increased atmospheric CO2 on organic matter productivity strongly affect the positions of the compensation horizons and their dynamics.

Measuring patient-perceived quality of care in US hospitals using Twitter

BACKGROUND: Patients routinely use Twitter to share feedback about their experience receiving healthcare. Identifying and analysing the content of posts sent to hospitals may provide a novel real-time measure of quality, supplementing traditional, survey-based approaches. OBJECTIVE: To assess the use of Twitter as a supplemental data stream for measuring patient-perceived quality of care in US hospitals and compare patient sentiments about hospitals with established quality measures. DESIGN: 404 065 tweets directed to 2349 US hospitals over a 1-year period were classified as having to do with patient experience using a machine learning approach. Sentiment was calculated for these tweets using natural language processing. 11 602 tweets were manually categorised into patient experience topics. Finally, hospitals with ≥50 patient experience tweets were surveyed to understand how they use Twitter to interact with patients. KEY RESULTS: Roughly half of the hospitals in the US have a presence on Twitter. Of the tweets directed toward these hospitals, 34 725 (9.4%) were related to patient experience and covered diverse topics. Analyses limited to hospitals with ≥50 patient experience tweets revealed that they were more active on Twitter, more likely to be below the national median of Medicare patients (p<0.001) and above the national median for nurse/patient ratio (p=0.006), and to be a non-profit hospital (p<0.001). After adjusting for hospital characteristics, we found that Twitter sentiment was not associated with Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) ratings (but having a Twitter account was), although there was a weak association with 30-day hospital readmission rates (p=0.003). CONCLUSIONS: Tweets describing patient experiences in hospitals cover a wide range of patient care aspects and can be identified using automated approaches. These tweets represent a potentially untapped indicator of quality and may be valuable to patients, researchers, policy makers and hospital administrators

The influence of air-sea exchange on the isotopic composition of oceanic carbon: Observations and modeling

Although the carbon isotopic composition of ocean waters after they leave the surface ocean is determined by biological cycling, air-sea exchange affects the carbon isotopic composition of surface waters in two ways. The equilibrium fractionation between oceanic and atmospheric carbon increases with decreasing temperature. In Southern Ocean Surface Waters this isotopic equilibration enriches δ13C relative to the δ13C expected from uptake and release of carbon by biological processes alone. Similarly, surface waters in the subtropical gyres are depleted in δ13C due to extensive air-sea exchange at warm temperatures. Countering the tendency toward isotopic equilibration with the atmosphere (a relatively slow process), are the effects of the equilibration of CO2 itself (a much faster process). In regions where there is a net transfer of isotopically light CO2 from the ocean to the atmosphere (e.g., the equator) surface waters become enriched in 13C, whereas in regions where isotopically light CO2 is entering the ocean (e.g., the North Atlantic) surface waters become depleted in 13C. A compilation of high quality oceanic δ13C measurements along with experiments performed using a zonally averaged three-basin dynamic ocean model are used to explore these processes

Multivalent display of minimal Clostridium difficile glycan epitopes mimics antigenic properties of larger glycans

Synthetic cell-surface glycans are promising vaccine candidates against Clostridium difficile. The complexity of large, highly antigenic and immunogenic glycans is a synthetic challenge. Less complex antigens providing similar immune responses are desirable for vaccine development. Based on molecular-level glycan-antibody interaction analyses, we here demonstrate that the C. difficile surface polysaccharide-I (PS-I) can be resembled by multivalent display of minimal disaccharide epitopes on a synthetic scaffold that does not participate in binding. We show that antibody avidity as a measure of antigenicity increases by about five orders of magnitude when disaccharides are compared with constructs containing five disaccharides. The synthetic, pentavalent vaccine candidate containing a peptide T-cell epitope elicits weak but highly specific antibody responses to larger PS-I glycans in mice. This study highlights the potential of multivalently displaying small oligosaccharides to achieve antigenicity characteristic of larger glycans. The approach may result in more cost-efficient carbohydrate vaccines with reduced synthetic effort

Overestimate of Committed Warming

Palaeoclimate variations are an essential component in constraining future projections of climate change as a function of increasing anthropogenic greenhouse gases. The Earth System Sensitivity (ESS) describes the multi-millennial response of Earth (in terms of global mean temperature) to a doubling of CO2 concentrations. A recent study used a correlation of inferred temperatures and radiative forcing from greenhouse gases over the past 800,000 years to estimate the ESS from present day CO2 is about 9 degrees C, and to imply a long-term commitment of 3-7 degrees C even if greenhouse gas levels remain at present-day concentrations. However, we demonstrate that the methodology of ref. 2 does not reliably estimate the ESS in the presence of orbital forcing of ice age cycles and therefore conclude that the inferred present-day committed warming is considerably overestimated

Cross Reactive Material 197 glycoconjugate vaccines contain privileged conjugation sites

Production of glycoconjugate vaccines involves the chemical conjugation of glycans to an immunogenic carrier protein such as Cross-Reactive-Material-197 (CRM197). Instead of using glycans from natural sources recent vaccine development has been focusing on the use of synthetically defined minimal epitopes. While the glycan is structurally defined, the attachment sites on the protein are not. Fully characterized conjugates and batch-to-batch comparisons are the key to eventually create completely defined conjugates. A variety of glycoconjugates consisting of CRM197 and synthetic oligosaccharide epitopes was characterised using mass spectrometry techniques. The primary structure was assessed by combining intact protein MALDI-TOF-MS, LC-MALDI-TOF-MS middle-down and LC-ESI-MS bottom-up approaches. The middle-down approach on CNBr cleaved glycopeptides provided almost complete sequence coverage, facilitating rapid batch-to-batch comparisons, resolving glycan loading and identification of side products. Regions close to the N- and C-termini were most efficiently conjugated.Full Tex

Destabilization of the thermohaline circulation by transient perturbations to the hydrological cycle

We reconsider the problem of the stability of the thermohaline circulation as described by a two-dimensional Boussinesq model with mixed boundary conditions. We determine how the stability properties of the system depend on the intensity of the hydrological cycle. We define a two-dimensional parameters' space descriptive of the hydrology of the system and determine, by considering suitable quasi-static perturbations, a bounded region where multiple equilibria of the system are realized. We then focus on how the response of the system to finite-amplitude surface freshwater forcings depends on their rate of increase. We show that it is possible to define a robust separation between slow and fast regimes of forcing. Such separation is obtained by singling out an estimate of the critical growth rate for the anomalous forcing, which can be related to the characteristic advective time scale of the system.Comment: 37 pages, 8 figures, submitted to Clim. Dy

Derivation of Del180 from sediment core log data\u27 Implications for millennial-scale climate change in the Labrador Sea

Sediment core logs from six sediment cores in the Labrador Sea show millennial-scale climate variability during the last glacial by recording all Heinrich events and several major Dansgaard-Oeschger cycles. The same millennial-scale climate change is documented for surface water δ18O records of Neogloboquadrina pachyderma (left coiled); hence the surface water δ18O record can be derived from sediment core logging by means of multiple linear regression, providing a paleoclimate proxy record at very high temporal resolution (70 years). For the Labrador Sea, sediment core logs contain important information about deepwater current velocities and also reflect the variable input of ice-rafted debris from different sources as inferred from grain-size analysis, the relation of density and P wave velocity, and magnetic susceptibility. For the last glacial, faster deepwater currents, which correspond to highs in sediment physical properties, occurred during iceberg discharge and lasted from several centuries to a few millennia. Those enhanced currents might have contributed to increased production of intermediate waters during times of reduced production of North Atlantic Deep Water. Hudson Strait might have acted as a major supplier of detrital carbonate only during lowered sea level (greater ice extent). During coldest atmospheric temperatures over Greenland, deepwater currents increased during iceberg discharge in the Labrador Sea, then surface water freshened shortly thereafter, while the abrupt atmospheric temperature rise happened after a larger time lag of ≥ 1 kyr. The correlation implies a strong link and common forcing for atmosphere, sea surface, and deep water during the last glacial at millennial timescales but decoupling at orbital timescales