Combining Radiotherapy With Anti-angiogenic Therapy and Immunotherapy; A Therapeutic Triad for Cancer?

Radiotherapy has been used for the treatment of cancer for over a century. Throughout this period, the therapeutic benefit of radiotherapy has continuously progressed due to technical developments and increased insight in the biological mechanisms underlying the cellular responses to irradiation. In order to further improve radiotherapy efficacy, there is a mounting interest in combining radiotherapy with other forms of therapy such as anti-angiogenic therapy or immunotherapy. These strategies provide different opportunities and challenges, especially with regard to dose scheduling and timing. Addressing these issues requires insight in the interaction between the different treatment modalities. In the current review, we describe the basic principles of the effects of radiotherapy on tumor vascularization and tumor immunity and vice versa. We discuss the main strategies to combine these treatment modalities and the hurdles that have to be overcome in order to maximize therapeutic effectivity. Finally, we evaluate the outstanding questions and present future prospects of a therapeutic triad for cancer

Current- and wave- generated bedforms on mixed sand-clay intertidal flats : a new bedform phase diagram and implications for bed roughness and preservation potential

Funding: This work was supported by the United Kingdom’s Natural Environment Research Council (NERC) under Grant NE/I027223/1 (COHBED). JM, Julie Hope, and Daniel Parsons were partially funded by a Horizon 2020 European Research Council Consolidator Award (GEOSTICK, Grant 725955). The GEOSTICK project also kindly contributed the article processing fees. Andrew Manning’s contribution toward this research was partly supported by the National Science Foundation grants OCE-1924532 and OCE-1736668, TKI-MUSA project 11204950-000-ZKS-0002, and the HR Wallingford company research project FineScale (Grant Nos. ACK3013_62). DP received funding from the MASTS pooling initiative (The Marine Alliance for Science and Technology for Scotland) and their support is gratefully acknowledged. MASTS is funded by the Scottish Funding Council (Grant reference HR09011) and contributing institutions.The effect of bedforms on frictional roughness felt by the overlying flow is crucial to the regional modelling of estuaries and coastal seas. Bedforms are also a key marker of palaeoenvironments. Experiments have shown that even modest biotic and abiotic cohesion in sand inhibits bedform formation, modifies bedform size, and slows bedform development, but this has rarely been tested in nature. The present study used a comprehensive dataset recorded over a complete spring–neap cycle on an intertidal flat to investigate bedform dynamics controlled by a wide range of wave and current conditions, including the effects of wave–current angle and bed cohesion. A detailed picture of different bedform types and their relationship to the flow, be they equilibrium, non-equilibrium, or relict, was produced, and captured in a phase diagram that integrates wave-dominated, current-dominated, and combined wave–current bedforms. This bedform phase diagram incorporates a substantially wider range of flow conditions than previous phase diagrams, including bedforms related to near-orthogonal wave–current angles, such as ladderback ripples. Comparison with laboratory-derived bedform phase diagrams indicates that washed-out ripples, lunate interference ripples and upper-stage plane beds replace the subaqueous dune field; such bedform distributions may be a key characteristic of intertidal flats. The field data also provide a means of predicting the dimensions of these bedforms, which can be transferred to other areas and grain sizes. We show that an equation for the prediction of equilibrium bedform size is sufficient to predict the roughness, even though the bedforms are highly variable in character and only in equilibrium with the flow for approximately half the time. Whilst the effect of cohesive clay is limited under more active spring conditions, clay does play a role in reducing the bedform dimensions under more quiescent neap conditions. We also investigated which combinations of waves, currents, and bed clay contents in the intertidal zone have the highest potential for bedform preservation in the geological record. This shows that combined wave–current bedforms have the lowest preservation potential and equilibrium current ripples have the highest preservation potential, even in the presence of moderate and storm waves. Hence, the absence of wave ripples and combined-flow bedforms and their primary stratification in sedimentary successions cannot be taken as evidence that waves were absent at the time of deposition.Publisher PDFPeer reviewe

Chlorhexidine hexametaphosphate as a wound care material coating: antimicrobial efficacy, toxicity and effect on healing.

AIM: In this study, chlorhexidine hexametaphosphate (CHX-HMP) is investigated as a persistent antimicrobial coating for wound care materials. MATERIALS & METHODS: CHX-HMP was used as a wound care material coating and compared with chlorhexidine digluconate materials with respect to antimicrobial efficacy, toxicity and wound closure. RESULTS: Antimicrobial efficacy at day 1, 3 and 7 was observed with experimental and commercial materials. CHX-HMP coated materials had less toxic effect on human placental cells than commercial chlorhexidine dressings. CHX-HMP in pluronic gel did not delay healing but reduced wound colonization by E. faecalis. CONCLUSION: CHX-HMP could become a useful component of wound care materials with sustained antimicrobial efficacy, lower toxicity than chlorhexidine digluconate materials, and reduction in wound colonization without affecting closure

Current- and Wave-Generated Bedforms on Mixed Sand–Clay Intertidal Flats:A New Bedform Phase Diagram and Implications for Bed Roughness and Preservation Potential

The effect of bedforms on frictional roughness felt by the overlying flow is crucial to the regional modelling of estuaries and coastal seas. Bedforms are also a key marker of palaeoenvironments. Experiments have shown that even modest biotic and abiotic cohesion in sand inhibits bedform formation, modifies bedform size, and slows bedform development, but this has rarely been tested in nature. The present study used a comprehensive dataset recorded over a complete spring–neap cycle on an intertidal flat to investigate bedform dynamics controlled by a wide range of wave and current conditions, including the effects of wave–current angle and bed cohesion. A detailed picture of different bedform types and their relationship to the flow, be they equilibrium, non-equilibrium, or relict, was produced, and captured in a phase diagram that integrates wave-dominated, current-dominated, and combined wave–current bedforms. This bedform phase diagram incorporates a substantially wider range of flow conditions than previous phase diagrams, including bedforms related to near-orthogonal wave–current angles, such as ladderback ripples. Comparison with laboratory-derived bedform phase diagrams indicates that washed-out ripples, lunate interference ripples and upper-stage plane beds replace the subaqueous dune field; such bedform distributions may be a key characteristic of intertidal flats. The field data also provide a means of predicting the dimensions of these bedforms, which can be transferred to other areas and grain sizes. We show that an equation for the prediction of equilibrium bedform size is sufficient to predict the roughness, even though the bedforms are highly variable in character and only in equilibrium with the flow for approximately half the time. Whilst the effect of cohesive clay is limited under more active spring conditions, clay does play a role in reducing the bedform dimensions under more quiescent neap conditions. We also investigated which combinations of waves, currents, and bed clay contents in the intertidal zone have the highest potential for bedform preservation in the geological record. This shows that combined wave–current bedforms have the lowest preservation potential and equilibrium current ripples have the highest preservation potential, even in the presence of moderate and storm waves. Hence, the absence of wave ripples and combined-flow bedforms and their primary stratification in sedimentary successions cannot be taken as evidence that waves were absent at the time of deposition

"Now he walks and walks, as if he didn't have a home where he could eat": food, healing, and hunger in Quechua narratives of madness

In the Quechua-speaking peasant communities of southern Peru, mental disorder is understood less as individualized pathology and more as a disturbance in family and social relationships. For many Andeans, food and feeding are ontologically fundamental to such relationships. This paper uses data from interviews and participant observation in a rural province of Cuzco to explore the significance of food and hunger in local discussions of madness. Carers’ narratives, explanatory models, and theories of healing all draw heavily from idioms of food sharing and consumption in making sense of affliction, and these concepts structure understandings of madness that differ significantly from those assumed by formal mental health services. Greater awareness of the salience of these themes could strengthen the input of psychiatric and psychological care with this population and enhance knowledge of the alternative treatments that they use. Moreover, this case provides lessons for the global mental health movement on the importance of openness to the ways in which indigenous cultures may construct health, madness, and sociality. Such local meanings should be considered by mental health workers delivering services in order to provide care that can adjust to the alternative ontologies of sufferers and carers

The role of biophysical cohesion on subaqueous bed form size

Biologically active, fine-grained sediment forms abundant sedimentary deposits on Earth's surface, and mixed mud-sand dominates many coasts, deltas, and estuaries. Our predictions of sediment transport and bed roughness in these environments presently rely on empirically based bed form predictors that are based exclusively on biologically inactive cohesionless silt, sand, and gravel. This approach underpins many paleoenvironmental reconstructions of sedimentary successions, which rely on analysis of cross-stratification and bounding surfaces produced by migrating bed forms. Here we present controlled laboratory experiments that identify and quantify the influence of physical and biological cohesion on equilibrium bed form morphology. The results show the profound influence of biological cohesion on bed form size and identify how cohesive bonding mechanisms in different sediment mixtures govern the relationships. The findings highlight that existing bed form predictors require reformulation for combined biophysical cohesive effects in order to improve morphodynamic model predictions and to enhance the interpretations of these environments in the geological record

Genome-wide association study identifies 30 loci associated with bipolar disorder.

Bipolar disorder is a highly heritable psychiatric disorder. We performed a genome-wide association study (GWAS) including 20,352 cases and 31,358 controls of European descent, with follow-up analysis of 822 variants with P < 1 × 10-4 in an additional 9,412 cases and 137,760 controls. Eight of the 19 variants that were genome-wide significant (P < 5 × 10-8) in the discovery GWAS were not genome-wide significant in the combined analysis, consistent with small effect sizes and limited power but also with genetic heterogeneity. In the combined analysis, 30 loci were genome-wide significant, including 20 newly identified loci. The significant loci contain genes encoding ion channels, neurotransmitter transporters and synaptic components. Pathway analysis revealed nine significantly enriched gene sets, including regulation of insulin secretion and endocannabinoid signaling. Bipolar I disorder is strongly genetically correlated with schizophrenia, driven by psychosis, whereas bipolar II disorder is more strongly correlated with major depressive disorder. These findings address key clinical questions and provide potential biological mechanisms for bipolar disorder

Urbanization and seasonality strengthens the CO2 capacity of the Red River Delta, Vietnam

Tropical rivers are dynamic CO2 sources. Regional patterns in the partial pressure of CO2 (pCO2) and relationships with other a/biotic factors in densely populated and rapidly developing river delta regions of Southeast Asia are still poorly constrained. Over one year, at 21 sites across the river system in the Red River Delta (RRD), Vietnam, we calculated pCO2 levels from temperature, pH, and total alkalinity and inter-linkages between pCO2 and phytoplankton, water chemistry and seasonality were then assessed. The smaller, more urbanized, and polluted Day River had an annual median pCO2 of 5000 ± 3300 µatm and the larger Red River of 2675 ± 2271 µatm. pCO2 was 1.6 and 3.2 times higher during the dry season in the Day and Red rivers respectively than the rainy season. Elevated pCO2 levels in the Day River during the dry season were also 2.4-fold higher than the median value (2811 ±  3577 µatm) of calculated and direct pCO2 measurements in >20 sub/tropical rivers. By further categorizing the river data into Hanoi City vs. other less urban-populated provinces, we found significantly higher nutrients, organic matter content, and riverine cyanobacteria during the dry season in the Day River across Hanoi City. Forward selection also identified riverine cyanobacteria and river discharge as the main predictors explaining pCO2 variation in the RRD. After accounting for the shared effects (14%), river discharge alone significantly explained 12% of the pCO2 variation, cyanobacteria uniquely a further 21%, while 53% of the pCO2 variance was unexplained by either. We show that the urbanization of rivers deltas could result in increased sources of riverine pCO2, water pollution, and harmful cyanobacterial blooms