The Fallacy of Nuclear Primacy

"The United States is easily deterred by any nuclear armed state, even by the most primitive and diminutive of nuclear arsenals." Bruce G. Blair is the President of the World Security Institute. Chen Yali is the editor in chief of Washington Observer

The Oil Weapon: Myth of China's Vulnerability

The geopolitical canvass on which China plots its strategy for energy security displays a ubiquitous presence of one country: the United States. Chinese energy security planners must reckon with America's ravenous consumption of imported oil, its strategic alliances with other heavy importers of oil in Asia, its overseas military operations in the heart of the world's leading oil producing region, its naval dominion over the world's oil transportation routes, and the global domination of U.S. oil companies or multinational oil companies heavily capitalized by American investment. This is the context in which China pursues its energy security, sometimes blandly described as 'conservation and diversification of supply', which masks the nation's real struggle to satisfy its rapidly growing energy needs without exposing its energy lifelines to external forces that may, intentionally or not, betray China's interests

Retrospective, matched cohort study of the effectiveness of common COPD drug treatments on 30-day readmissions

Introduction: Chronic Obstructive Pulmonary Disease (COPD) is a prevalent lung disease that represents an important public health challenge. Pharmacological treatment of COPD continues to be a challenge in the US, especially in rural areas. Hospitals with high 30-day readmissions may face penalties under HRRP.Research Question: Are common pharmacological treatments effective in controlling early hospital readmission?Methods: In this study, we conducted a phase IV drug trial of combination treatments: budesonide/formoterol and fluticasone/salmeterol. We utilized Cerner health facts database to compare 30-day readmission rates among patients prescribed these COPD treatments. Using propensity score matching and chi-square analysis on patient demographics and hospital-associated variables, we tested for differences in readmission rates. Covariates used: drug type, race, marital status, payer type, gender, and hospital location.Results: Overall there were no significant differences in 30 day readmission rates between treatments. However, the combination of budesonide/formoterol was found to have a lower readmission rate than fluticasone/salmeterol in COPD patients in urban hospital settings, self-payers, Medicare/Medicaid patients, and Caucasians.Conclusions: Identifying treatments that have lower 30-day readmission among patients could influence clinical decisions as providers make choices regarding patient care such as hospital length of stay and discharge options. However, due to the observational nature we cannot conclude with certainty that medication was the only factor responsible for any differences observed in this study. Further studies are needed which could provide information to guide further research for therapeutics and tools to better patient management post discharge

Molecular dynamics simulations of apo and holo forms of fatty acid binding protein 5 and cellular retinoic acid binding protein II reveal highly mobile protein, retinoic acid ligand, and water molecules

Structural and dynamic properties from a series of 300 ns molecular dynamics, MD, simulations of two intracellular lipid binding proteins, iLBPs, (Fatty Acid Binding Protein 5, FABP5, and Cellular Retinoic Acid Binding Protein II, CRABP-II) in both the apo form and when bound with retinoic acid reveal a high degree of protein and ligand flexibility. The ratio of FABP5 to CRABP-II in a cell may determine whether it undergoes natural apoptosis or unrestricted cell growth in the presence of retinoic acid. As a result, FABP5 is a promising target for cancer therapy. The MD simulations presented here reveal distinct differences in the two proteins and provide insight into the bindingmechanism. CRABP-II is a much larger, more flexible protein that closes upon ligand binding, where FABP5 transitions to an open state in the holo form. The traditional understanding obtained from crystal structures of the gap between two β-sheets of the β-barrel common to iLBPs and the α-helix cap that forms the portal to the binding pocket is insufficient for describing protein conformation (open vs. closed) or ligand entry and exit. When the high degree of mobility between multiple conformations of both the ligand and protein are examined via MD simulation, a new mode of ligand motion that improves understanding of binding dynamics is revealed

Search for bursts in air shower data

There have been reports in recent years of the possible observation of bursts in air shower data. If such events are truly of an astrophysical nature then, they represent an important new class of phemonenon since no other bursts have been observed above the MeV level. The spectra of conventional gamma ray bursts are unknown at higher energies but their observed spectra at MeV energies appear generally to exhibit a steepening in the higher MeV range and are thus unlikely to extrapolate to measurable fluxes at air shower energies. An attempt has been made to look for deviations from randomness in the arrival times of air showers above approx. 10 to the 14th power eV with a number of systems and results so far are presented here. This work will be continued for a substantial period of ime with a system capable of recording bursts with multiple events down to a spacing of 4 microns. Earlier data have also been searched for the possible association of air shower events with a glitch of the Vela pulsar

Advancing the future of physical activity guidelines in Canada: an independent expert panel interpretation of the evidence

The Canadian Society for Exercise Physiology, in partnership with the Public Health Agency of Canada, has initiated a review of their physical activity guidelines to promote healthy active living for Canadian children, youth, adults and older adults; previous guidelines were released in 2002, 2002, 1998 and 1999 respectively. Several background papers from this project were published recently and provide foundation evidence upon which to base new guidelines. Furthermore, comprehensive systematic reviews were completed to ensure a rigorous evaluation of evidence informing the revision of physical activity guidelines for asymptomatic populations. The overall guideline development process is being guided and assessed by the AGREE II instrument. A meeting of experts was convened to present the evidence complied to inform the guideline revisions. An independent expert panel was assembled to review the background materials and systematic reviews; listen to the presentations and discussions at the expert meeting; ask for clarification; and produce the present paper representing their interpretation of the evidence including grading of the evidence and their identification of needs for future research. The paper includes also their recommendations for evidence-informed physical activity guidelines

Effects of temporal variation in temperature and density dependence on insect population dynamics

Understanding the effects of environmental variation on insect populations is important in light of predictions about increasing climatic variability. This paper uses the univoltine western corn rootworm (WCR, Diabrotica virgifera virgifera LeConte) as a case study and employs deterministic and stochastic modeling to evaluate how insect population dynamics is shaped by density-dependent survival and annual variation in temperature, which are key in regulating insect populations. Field data showed that larval survival varied significantly between years but was constant for a range of densities. Survival dropped only beyond a threshold density, a feature resembling generalized Ricker functions used in modeling density-dependent survival due to scramble competition for resources. We used soil temperature data for 20 yr to model annual variation in developmental time and survival. The deterministic model, where the developmental time was same across years, showed that though survival was high and did not change for a range of densities (i.e., density-independent survival), predicted densities were large enough that strong density dependence could occur in the field (i.e., predicted densities fall in the region where survival drops sharply) and that populations could exhibit stable equilibrium, cycles, etc. Interestingly, populations with lower density-independent survival were less likely to produce stable equilibrium compared to populations with higher density-independent survival. We found that population densities were at stable equilibrium when both mean developmental time and fertility were relatively low or when developmental time and fertility were relatively high. This in turn implies that, in warmer regions, where mean developmental time will be lower, stability is more likely for insect populations with low fertility; species in warmer regions will experience cyclical and unstable dynamics when fertility is high. While increase in the mean developmental time reduces overall survival, increasing variation in developmental time could increase mean survival, a consequence of the Jensen’s inequality, since survival was a concave decreasing function of developmental time. Hence, both mean and variability in temperature affect the dynamics of insect populations. Finally, we found that stochastic variation in soil temperature produced large variation in predicted population densities that could potentially enhance or diminish the effect of density dependence

Targeting B-Raf inhibitor resistant melanoma with novel cell penetrating peptide disrupters of PDE8A – C-Raf

Background: Recent advances in the treatment of melanoma that involve immunotherapy and B-Raf inhibition have revolutionised cancer care for this disease. However, an un-met clinical need remains in B-Raf inhibitor resistant patients where first-generation B-Raf inhibitors provide only short-term disease control. In these cases, B-Raf inhibition leads to paradoxical activation of the C-Raf – MEK – ERK signalling pathway, followed by metastasis. PDE8A has been shown to directly interact with and modulate the cAMP microdomain in the vicinity of C-Raf. This interaction promotes C-Raf activation by attenuating the PKA-mediated inhibitory phosphorylation of the kinase. Methods: We have used a novel cell-penetrating peptide agent (PPL-008) that inhibits the PDE8A – C-Raf complex in a human malignant MM415 melanoma cell line and MM415 melanoma xenograft mouse model to investigate ERK MAP kinase signalling. Results: We have demonstrated that the PDE8A – C-Raf complex disruptor PPL-008 increased inhibitory C-Raf-S259 phosphorylation and significantly reduced phospho-ERK signalling. We have also discovered that the ability of PPL-008 to dampen ERK signalling can be used to counter B-Raf inhibitor-driven paradoxical activation of phospho-ERK in MM415 cells treated with PLX4032 (Vemurafenib). PPL-008 treatment also significantly retarded the growth of these cells. When applied to a MM415 melanoma xenograft mouse model, PPL-008C penetrated tumour tissue and significantly reduced phospho-ERK signalling in that domain. Conclusion: Our data suggests that the PDE8A-C-Raf complex is a promising therapeutic treatment for B-Raf inhibitor resistant melanoma

Factors affecting use of unscheduled care for people with advanced cancer:a retrospective cohort study in Scotland

BACKGROUND: People with advanced cancer frequently attend unscheduled care, but little is known about the factors influencing presentations. Most research focuses on accident and emergency (A&amp;E) and does not consider GP out-of-hours (GPOOH).AIM: To describe the frequency and patterns of unscheduled care use by people with cancer in their last year of life and to examine the associations of demographic and clinical factors with unscheduled care attendance.DESIGN AND SETTING: Retrospective cohort study of all 2443 people who died from cancer in Tayside, Scotland, during 2012-2015. Clinical population datasets were linked to routinely collected clinical data using the Community Health Index (CHI) number.METHOD: Anonymised CHI-linked data were analysed in SafeHaven, with descriptive analysis, using binary logistic regression for adjusted associations.RESULTS: Of the people who died from cancer, 77.9% (n = 1904) attended unscheduled care in the year before death. Among unscheduled care users, most only attended GPOOH (n = 1070, 56.2%), with the rest attending A&amp;E only (n = 204, 10.7%), or both (n = 630, 33.1%). Many attendances occurred in the last week (n =1360, 19.7%), last 4 weeks (n = 2541, 36.7%), and last 12 weeks (n = 4174, 60.3%) of life. Age, sex, deprivation, and cancer type were not significantly associated with unscheduled care attendance. People living in rural areas were less likely to attend unscheduled care: adjusted odds ratio (aOR) 0.64 (95% confidence interval = 0.50 to 0.82). Pain was the commonest coded clinical reason for presenting (GPOOH: n = 482, 10.5%; A&amp;E: n = 336, 28.8%). Of people dying from cancer, n = 514, 21.0%, were frequent users (≥5 attendances/year), and accounted for over half (n = 3986, 57.7%) of unscheduled care attendances.CONCLUSION: Unscheduled care attendance by people with advanced cancer was substantially higher than previously reported, increased dramatically towards the end of life, was largely independent of demographic factors and cancer type, and was commonly for pain and palliative care.</p