Bisphosphonate-related osteonecrosis of jaw (BRONJ): diagnostic criteria and possible pathogenic mechanisms of an unexpected anti-angiogenic side effect.

Recently, bisphosphonates (BPs) have been widely used in medical practice as anti-resorptive agents owing to their anti-osteoclatic action. In addition, these compounds are also used for their analgesic action and their potential anti-tumour effect. Patients treated with BPs may subsequently develop osteonecrosis of the jaw or maxillary bone after minor local trauma including dental work, recently labelled as bisphosphonate osteonecrosis of jaw (BRONJ). However, the etiopathogenic mechanisms of this pathological condition are poorly understood. Although, several pathways have been proposed for BRONJ occurrence, no single model can explain all morphological changes observed at the macro- and microscopic level. Recent research suggests that BPs may promote an anti-angiogenic effect which contributes directly to the clinical features associated with BRONJ. Remarkably, the anti-angiogenic effect promoting BRONJ might be in keeping with the anti-neoplastic action of BPs. The current review, presents clinical diagnostic criteria. In addition, based on our own experience we describe the histopathological criteria for diagnosis of BRONJ and the possible pathways which may lead to this frustrating pathological condition

Preparing for Climatic Change: The Water, Salmon, and Forests of the Pacific Northwest

The impacts of year-to-year and decade-to-decade climatic variations on some of the Pacific Northwest’s key natural resources can be quantified to estimate sensitivity to regional climatic changes expected as part of anthropogenic global climatic change. Warmer, drier years, often associated with El Niño events and/or the warm phase of the Pacific Decadal Oscillation, tend to be associated with below-average snowpack, streamflow, and flood risk, below-average salmon survival, below-average forest growth, and above-average risk of forest fire. During the 20th century, the region experienced a warming of 0.8 ◦C. Using output from eight climate models, we project a further warming of 0.5–2.5 ◦C (central estimate 1.5 ◦C) by the 2020s, 1.5–3.2 ◦C (2.3◦C) by the 2040s, and an increase in precipitation except in summer. The foremost impact of a warming climate will be the reduction of regional snowpack, which presently supplies water for ecosystems and human uses during the dry summers. Our understanding of past climate also illustrates the responses of human management systems to climatic stresses, and suggests that a warming of the rate projected would pose significant challenges to the management of natural resources. Resource managers and planners currently have few plans for adapting to or mitigating the ecological and economic effects of climatic change

Preparing for Climatic Change: The Water, Salmon, and Forests of the Pacific Northwest

The impacts of year-to-year and decade-to-decade climatic variations on some of the Pacific Northwest’s key natural resources can be quantified to estimate sensitivity to regional climatic changes expected as part of anthropogenic global climatic change. Warmer, drier years, often associated with El Niño events and/or the warm phase of the Pacific Decadal Oscillation, tend to be associated with below-average snowpack, streamflow, and flood risk, below-average salmon survival, below-average forest growth, and above-average risk of forest fire. During the 20th century, the region experienced a warming of 0.8 ◦C. Using output from eight climate models, we project a further warming of 0.5–2.5 ◦C (central estimate 1.5 ◦C) by the 2020s, 1.5–3.2 ◦C (2.3◦C) by the 2040s, and an increase in precipitation except in summer. The foremost impact of a warming climate will be the reduction of regional snowpack, which presently supplies water for ecosystems and human uses during the dry summers. Our understanding of past climate also illustrates the responses of human management systems to climatic stresses, and suggests that a warming of the rate projected would pose significant challenges to the management of natural resources. Resource managers and planners currently have few plans for adapting to or mitigating the ecological and economic effects of climatic change

Making the most of data:An information selection and assessment framework to improve water systems operations

Advances in Environmental monitoring systems are making a wide range of data available at increasingly higher temporal and spatial resolution. This creates an opportunity to enhance real-time understanding of water systems conditions and to improve prediction of their future evolution, ultimately increasing our ability to make better decisions. Yet, many water systems are still operated using very simple information systems, typically based on simple statistical analysis and the operator’s experience. In this work, we propose a framework to automatically select the most valuable information to inform water systems operations supported by quantitative metrics to operationally and economically assess the value of this information. The Hoa Binh reservoir in Vietnam is used to demonstrate the proposed framework in a multiobjective context, accounting for hydropower production and flood control. First, we quantify the expected value of perfect information, meaning the potential space for improvement under the assumption of exact knowledge of the future system conditions. Second, we automatically select the most valuable information that could be actually used to improve the Hoa Binh operations. Finally, we assess the economic value of sample information on the basis of the resulting policy performance. Results show that our framework successfully select information to enhance the performance of the operating policies with respect to both the competing objectives, attaining a 40% improvement close to the target trade-off selected as potentially good compromise between hydropower production and flood control

Climate change and mountain water resources: overview and recommendations for research, management and policy

Mountains are essential sources of freshwater for our world, but their role in global water resources could well be significantly altered by climate change. How well do we understand these potential changes today, and what are implications for water resources management, climate change adaptation, and evolving water policy? To answer above questions, we have examined 11 case study regions with the goal of providing a global overview, identifying research gaps and formulating recommendations for research, management and policy. <br><br> After setting the scene regarding water stress, water management capacity and scientific capacity in our case study regions, we examine the state of knowledge in water resources from a highland-lowland viewpoint, focusing on mountain areas on the one hand and the adjacent lowland areas on the other hand. Based on this review, research priorities are identified, including precipitation, snow water equivalent, soil parameters, evapotranspiration and sublimation, groundwater as well as enhanced warming and feedback mechanisms. In addition, the importance of environmental monitoring at high altitudes is highlighted. We then make recommendations how advancements in the management of mountain water resources under climate change could be achieved in the fields of research, water resources management and policy as well as through better interaction between these fields. <br><br> We conclude that effective management of mountain water resources urgently requires more detailed regional studies and more reliable scenario projections, and that research on mountain water resources must become more integrative by linking relevant disciplines. In addition, the knowledge exchange between managers and researchers must be improved and oriented towards long-term continuous interaction

Generalized Toric Codes Coupled to Thermal Baths

We have studied the dynamics of a generalized toric code based on qudits at finite temperature by finding the master equation coupling the code's degrees of freedom to a thermal bath. As a consequence, we find that for qutrits new types of anyons and thermal processes appear that are forbidden for qubits. These include creation, annihilation and diffusion throughout the system code. It is possible to solve the master equation in a short-time regime and find expressions for the decay rates as a function of the dimension $d$ of the qudits. Although we provide an explicit proof that the system relax to the Gibbs state for arbitrary qudits, we also prove that above a certain crossing temperature, qutrits initial decay rate is smaller than the original case for qubits. Surprisingly this behavior only happens with qutrits and not with other qudits with $d>3$.Comment: Revtex4 file, color figures. New Journal of Physics' versio

Topological Color Codes and Two-Body Quantum Lattice Hamiltonians

Topological color codes are among the stabilizer codes with remarkable properties from quantum information perspective. In this paper we construct a four-valent lattice, the so called ruby lattice, governed by a 2-body Hamiltonian. In a particular regime of coupling constants, degenerate perturbation theory implies that the low energy spectrum of the model can be described by a many-body effective Hamiltonian, which encodes the color code as its ground state subspace. The gauge symmetry $\mathbf{Z}_{2}\times\mathbf{Z}_{2}$ of color code could already be realized by identifying three distinct plaquette operators on the lattice. Plaquettes are extended to closed strings or string-net structures. Non-contractible closed strings winding the space commute with Hamiltonian but not always with each other giving rise to exact topological degeneracy of the model. Connection to 2-colexes can be established at the non-perturbative level. The particular structure of the 2-body Hamiltonian provides a fruitful interpretation in terms of mapping to bosons coupled to effective spins. We show that high energy excitations of the model have fermionic statistics. They form three families of high energy excitations each of one color. Furthermore, we show that they belong to a particular family of topological charges. Also, we use Jordan-Wigner transformation in order to test the integrability of the model via introducing of Majorana fermions. The four-valent structure of the lattice prevents to reduce the fermionized Hamiltonian into a quadratic form due to interacting gauge fields. We also propose another construction for 2-body Hamiltonian based on the connection between color codes and cluster states. We discuss this latter approach along the construction based on the ruby lattice.Comment: 56 pages, 16 figures, published version

Report 12: The global impact of COVID-19 and strategies for mitigation and suppression

The world faces a severe and acute public health emergency due to the ongoing COVID-19 global pandemic. How individual countries respond in the coming weeks will be critical in influencing the trajectory of national epidemics. Here we combine data on age-specific contact patterns and COVID-19 severity to project the health impact of the pandemic in 202 countries. We compare predicted mortality impacts in the absence of interventions or spontaneous social distancing with what might be achieved with policies aimed at mitigating or suppressing transmission. Our estimates of mortality and healthcare demand are based on data from China and high-income countries; differences in underlying health conditions and healthcare system capacity will likely result in different patterns in low income settings. We estimate that in the absence of interventions, COVID-19 would have resulted in 7.0 billion infections and 40 million deaths globally this year. Mitigation strategies focussing on shielding the elderly (60% reduction in social contacts) and slowing but not interrupting transmission (40% reduction in social contacts for wider population) could reduce this burden by half, saving 20 million lives, but we predict that even in this scenario, health systems in all countries will be quickly overwhelmed. This effect is likely to be most severe in lower income settings where capacity is lowest: our mitigated scenarios lead to peak demand for critical care beds in a typical low-income setting outstripping supply by a factor of 25, in contrast to a typical high-income setting where this factor is 7. As a result, we anticipate that the true burden in low income settings pursuing mitigation strategies could be substantially higher than reflected in these estimates. Our analysis therefore suggests that healthcare demand can only be kept within manageable levels through the rapid adoption of public health measures (including testing and isolation of cases and wider social distancing measures) to suppress transmission, similar to those being adopted in many countries at the current time. If a suppression strategy is implemented early (at 0.2 deaths per 100,000 population per week) and sustained, then 38.7 million lives could be saved whilst if it is initiated when death numbers are higher (1.6 deaths per 100,000 population per week) then 30.7 million lives could be saved. Delays in implementing strategies to suppress transmission will lead to worse outcomes and fewer lives saved. We do not consider the wider social and economic costs of suppression, which will be high and may be disproportionately so in lower income settings. Moreover, suppression strategies will need to be maintained in some manner until vaccines or effective treatments become available to avoid the risk of later epidemics. Our analysis highlights the challenging decisions faced by all governments in the coming weeks and months, but demonstrates the extent to which rapid, decisive and collective action now could save millions of lives

Report 8: Symptom progression of COVID-19

The COVID-19 epidemic was declared a Public Health Emergency of International Concern (PHEIC) by WHO on 30th January 2020 [1]. As of 8 March 2020, over 107,000 cases had been reported. Here, we use published and preprint studies of clinical characteristics of cases in mainland China as well as case studies of individuals from Hong Kong, Japan, Singapore and South Korea to examine the proportional occurrence of symptoms and the progression of symptoms through time. We find that in mainland China, where specific symptoms or disease presentation are reported, pneumonia is the most frequently mentioned, see figure 1. We found a more varied spectrum of severity in cases outside mainland China. In Hong Kong, Japan, Singapore and South Korea, fever was the most frequently reported symptom. In this latter group, presentation with pneumonia is not reported as frequently although it is more common in individuals over 60 years old. The average time from reported onset of first symptoms to the occurrence of specific symptoms or disease presentation, such as pneumonia or the use of mechanical ventilation, varied substantially. The average time to presentation with pneumonia is 5.88 days, and may be linked to testing at hospitalisation; fever is often reported at onset (where the mean time to develop fever is 0.77 days)