Relations of Plasma High-Sensitivity C-Reactive Protein to Various Cardiovascular Risk Factors

This study was performed to evaluate the relation of high-sensitivity C-reactive protein (hsCRP) with several cardiovascular risk factors such as age, blood pressure, smoking habit and serum lipids, body mass index, blood glucose, regular exercise, alcohol drinking, white blood cell counts in a cross-sectional survey. Plasma hsCRP was measured by immunoturbidimetry in 202 subjects, aged over 50 yr, who participated in health-check survey in a rural area of Jeollanamdo, Korea. Plasma hsCRP level was 1.9±3.0 mg/dL. There were significant associations between hsCRP levels and age, white blood cell counts, blood glucose, diastolic blood pressure, HDL-cholesterol, body mass index and smoking status. In stepwise multivariate regression analysis, white blood cell counts, age, blood glucose, smoking status and body mass index were independent correlates of hsCRP levels. In conclusion, plasma hsCRP levels were associated with several cardiovascular risk factors, and these data are compatible with the hypothesis that CRP levels may be a marker for preclinical cardiovascular disease. Further what we need now are prospective studies to evaluate the association of C-reactive protein concentrations with subsequent cardiac events

Objective and Patient-reported Assessments of Skin Grafts and Keystone Flaps—A Pilot Retrospective Cohort Study

Background:. The keystone perforator island flap provides a versatile form of reconstruction. Perceived benefits include better donor-recipient color match, less contour defect, and fewer complications. To date, there has been no high-quality evidence comparing keystone flaps to split-thickness skin grafts (SSG) from both a qualitative and quantitative point of view. Methods:. The Objective and Patient Reported Assessments of Skin grafts versus Keystone flap cohort study compares keystone flaps with SSGs for the reconstruction of skin cancer defects. Patient-reported outcome measures were collected using the EuroQol 5 dimension scale and Patient and Observer Scar Assessment Scale (POSAS) questionnaires. Objective assessments of skin quality were assessed with the Courage and Khazaka system. Cost analysis was also performed. Results:. Thirty-eight patients were studied: 20 keystone flaps and 18 SSGs. The keystone group had higher EuroQol 5 dimension scale scores (keystone median = 1.0; SSG median = 0.832; P = 0.641) indicating better general quality of life and lower POSAS scores indicating better disease/condition specific quality of life (keystone mean = 27.7; SSG mean = 35.7; P = 0.323). Observer POSAS scores were significantly lower in the keystone group compared with the SSG group (keystone mean = 10.889; SSG mean = 17.313; P < 0.001). Preservation of sensation was significantly better in keystone flaps (P = 0.006). There was an average £158/$207 (15%) saving when performing a keystone flap. Conclusion:. This pilot study demonstrates a number of possible benefits of keystone flaps over SSGs. The results demonstrate the need for further research comparing these reconstructive options. We propose a prospective, controlled study using the methods developed in this pilot study

Design and results of the ice sheet model initialisation experiments initMIP-Greenland: an ISMIP6 intercomparison

Earlier large-scale Greenland ice sheet sea-level projections (e.g. those run during the ice2sea and SeaRISE initiatives) have shown that ice sheet initial conditions have a large effect on the projections and give rise to important uncertainties. The goal of this initMIP-Greenland intercomparison exercise is to compare, evaluate, and improve the initialisation techniques used in the ice sheet modelling community and to estimate the associated uncertainties in modelled mass changes. initMIP-Greenland is the first in a series of ice sheet model intercomparison activities within ISMIP6 (the Ice Sheet Model Intercomparison Project for CMIP6), which is the primary activity within the Coupled Model Intercomparison Project Phase 6 (CMIP6) focusing on the ice sheets. Two experiments for the large-scale Greenland ice sheet have been designed to allow intercomparison between participating models of (1) the initial present-day state of the ice sheet and (2) the response in two idealised forward experiments. The forward experiments serve to evaluate the initialisation in terms of model drift (forward run without additional forcing) and in response to a large perturbation (prescribed surface mass balance anomaly); they should not be interpreted as sea-level projections. We present and discuss results that highlight the diversity of data sets, boundary conditions, and initialisation techniques used in the community to generate initial states of the Greenland ice sheet. We find good agreement across the ensemble for the dynamic response to surface mass balance changes in areas where the simulated ice sheets overlap but differences arising from the initial size of the ice sheet. The model drift in the control experiment is reduced for models that participated in earlier intercomparison exercises

Multiphoton Quantum Optics and Quantum State Engineering

We present a review of theoretical and experimental aspects of multiphoton quantum optics. Multiphoton processes occur and are important for many aspects of matter-radiation interactions that include the efficient ionization of atoms and molecules, and, more generally, atomic transition mechanisms; system-environment couplings and dissipative quantum dynamics; laser physics, optical parametric processes, and interferometry. A single review cannot account for all aspects of such an enormously vast subject. Here we choose to concentrate our attention on parametric processes in nonlinear media, with special emphasis on the engineering of nonclassical states of photons and atoms. We present a detailed analysis of the methods and techniques for the production of genuinely quantum multiphoton processes in nonlinear media, and the corresponding models of multiphoton effective interactions. We review existing proposals for the classification, engineering, and manipulation of nonclassical states, including Fock states, macroscopic superposition states, and multiphoton generalized coherent states. We introduce and discuss the structure of canonical multiphoton quantum optics and the associated one- and two-mode canonical multiphoton squeezed states. This framework provides a consistent multiphoton generalization of two-photon quantum optics and a consistent Hamiltonian description of multiphoton processes associated to higher-order nonlinearities. Finally, we discuss very recent advances that by combining linear and nonlinear optical devices allow to realize multiphoton entangled states of the electromnagnetic field, that are relevant for applications to efficient quantum computation, quantum teleportation, and related problems in quantum communication and information.Comment: 198 pages, 36 eps figure

Global Norms, Local Activism, and Social Movement Outcomes: Global Human Rights and Resident Koreans in Japan

The authors integrate social movement outcomes research and the world society approach to build a theoretical model to examine the impact of global and local factors on movement outcomes. Challenging the current research on policy change, which rarely examines the effects of global norms and local activism in one analysis, they argue (1) that global regimes empower and embolden local social movements and increase pressure on target governments from below, and (2) that local activists appeal to international forums with help from international activists to pressure the governments from above. When the pressures from the top and the bottom converge, social movements are more likely to succeed. Furthermore, these pressures are stronger in countries integrated into global society and on issues with strong global norms. The empirical analysis of social movements by resident Koreans in Japan advocating for four types of human rights—civil, political, social/economic, and cultural—demonstrates that the movements produced more successes as Japan\u27s involvement in the international human rights regime expanded since the late 1970s, and that activism on issues with strong global norms achieved greater successes. The analysis also shows that lack of cohesive domestic activism can undercut the chances of social movements\u27 success even with strong global norms on the issue

Future Sea Level Change Under Coupled Model Intercomparison Project Phase 5 and Phase 6 Scenarios From the Greenland and Antarctic Ice Sheets

Projections of the sea level contribution from the Greenland and Antarctic ice sheets (GrIS and AIS) rely on atmospheric and oceanic drivers obtained from climate models. The Earth System Models participating in the Coupled Model Intercomparison Project phase 6 (CMIP6) generally project greater future warming compared with the previous Coupled Model Intercomparison Project phase 5 (CMIP5) effort. Here we use four CMIP6 models and a selection of CMIP5 models to force multiple ice sheet models as part of the Ice Sheet Model Intercomparison Project for CMIP6 (ISMIP6). We find that the projected sea level contribution at 2100 from the ice sheet model ensemble under the CMIP6 scenarios falls within the CMIP5 range for the Antarctic ice sheet but is significantly increased for Greenland. Warmer atmosphere in CMIP6 models results in higher Greenland mass loss due to surface melt. For Antarctica, CMIP6 forcing is similar to CMIP5 and mass gain from increased snowfall counteracts increased loss due to ocean warming

BLOOM: A 176B-Parameter Open-Access Multilingual Language Model

Large language models (LLMs) have been shown to be able to perform new tasks based on a few demonstrations or natural language instructions. While these capabilities have led to widespread adoption, most LLMs are developed by resource-rich organizations and are frequently kept from the public. As a step towards democratizing this powerful technology, we present BLOOM, a 176B-parameter open-access language model designed and built thanks to a collaboration of hundreds of researchers. BLOOM is a decoder-only Transformer language model that was trained on the ROOTS corpus, a dataset comprising hundreds of sources in 46 natural and 13 programming languages (59 in total). We find that BLOOM achieves competitive performance on a wide variety of benchmarks, with stronger results after undergoing multitask prompted finetuning. To facilitate future research and applications using LLMs, we publicly release our models and code under the Responsible AI License

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

State of the climate in 2018

In 2018, the dominant greenhouse gases released into Earth’s atmosphere—carbon dioxide, methane, and nitrous oxide—continued their increase. The annual global average carbon dioxide concentration at Earth’s surface was 407.4 ± 0.1 ppm, the highest in the modern instrumental record and in ice core records dating back 800 000 years. Combined, greenhouse gases and several halogenated gases contribute just over 3 W m−2 to radiative forcing and represent a nearly 43% increase since 1990. Carbon dioxide is responsible for about 65% of this radiative forcing. With a weak La Niña in early 2018 transitioning to a weak El Niño by the year’s end, the global surface (land and ocean) temperature was the fourth highest on record, with only 2015 through 2017 being warmer. Several European countries reported record high annual temperatures. There were also more high, and fewer low, temperature extremes than in nearly all of the 68-year extremes record. Madagascar recorded a record daily temperature of 40.5°C in Morondava in March, while South Korea set its record high of 41.0°C in August in Hongcheon. Nawabshah, Pakistan, recorded its highest temperature of 50.2°C, which may be a new daily world record for April. Globally, the annual lower troposphere temperature was third to seventh highest, depending on the dataset analyzed. The lower stratospheric temperature was approximately fifth lowest. The 2018 Arctic land surface temperature was 1.2°C above the 1981–2010 average, tying for third highest in the 118-year record, following 2016 and 2017. June’s Arctic snow cover extent was almost half of what it was 35 years ago. Across Greenland, however, regional summer temperatures were generally below or near average. Additionally, a satellite survey of 47 glaciers in Greenland indicated a net increase in area for the first time since records began in 1999. Increasing permafrost temperatures were reported at most observation sites in the Arctic, with the overall increase of 0.1°–0.2°C between 2017 and 2018 being comparable to the highest rate of warming ever observed in the region. On 17 March, Arctic sea ice extent marked the second smallest annual maximum in the 38-year record, larger than only 2017. The minimum extent in 2018 was reached on 19 September and again on 23 September, tying 2008 and 2010 for the sixth lowest extent on record. The 23 September date tied 1997 as the latest sea ice minimum date on record. First-year ice now dominates the ice cover, comprising 77% of the March 2018 ice pack compared to 55% during the 1980s. Because thinner, younger ice is more vulnerable to melting out in summer, this shift in sea ice age has contributed to the decreasing trend in minimum ice extent. Regionally, Bering Sea ice extent was at record lows for almost the entire 2017/18 ice season. For the Antarctic continent as a whole, 2018 was warmer than average. On the highest points of the Antarctic Plateau, the automatic weather station Relay (74°S) broke or tied six monthly temperature records throughout the year, with August breaking its record by nearly 8°C. However, cool conditions in the western Bellingshausen Sea and Amundsen Sea sector contributed to a low melt season overall for 2017/18. High SSTs contributed to low summer sea ice extent in the Ross and Weddell Seas in 2018, underpinning the second lowest Antarctic summer minimum sea ice extent on record. Despite conducive conditions for its formation, the ozone hole at its maximum extent in September was near the 2000–18 mean, likely due to an ongoing slow decline in stratospheric chlorine monoxide concentration. Across the oceans, globally averaged SST decreased slightly since the record El Niño year of 2016 but was still far above the climatological mean. On average, SST is increasing at a rate of 0.10° ± 0.01°C decade−1 since 1950. The warming appeared largest in the tropical Indian Ocean and smallest in the North Pacific. The deeper ocean continues to warm year after year. For the seventh consecutive year, global annual mean sea level became the highest in the 26-year record, rising to 81 mm above the 1993 average. As anticipated in a warming climate, the hydrological cycle over the ocean is accelerating: dry regions are becoming drier and wet regions rainier. Closer to the equator, 95 named tropical storms were observed during 2018, well above the 1981–2010 average of 82. Eleven tropical cyclones reached Saffir–Simpson scale Category 5 intensity. North Atlantic Major Hurricane Michael’s landfall intensity of 140 kt was the fourth strongest for any continental U.S. hurricane landfall in the 168-year record. Michael caused more than 30 fatalities and $25 billion (U.S. dollars) in damages. In the western North Pacific, Super Typhoon Mangkhut led to 160 fatalities and$6 billion (U.S. dollars) in damages across the Philippines, Hong Kong, Macau, mainland China, Guam, and the Northern Mariana Islands. Tropical Storm Son-Tinh was responsible for 170 fatalities in Vietnam and Laos. Nearly all the islands of Micronesia experienced at least moderate impacts from various tropical cyclones. Across land, many areas around the globe received copious precipitation, notable at different time scales. Rodrigues and Réunion Island near southern Africa each reported their third wettest year on record. In Hawaii, 1262 mm precipitation at Waipā Gardens (Kauai) on 14–15 April set a new U.S. record for 24-h precipitation. In Brazil, the city of Belo Horizonte received nearly 75 mm of rain in just 20 minutes, nearly half its monthly average. Globally, fire activity during 2018 was the lowest since the start of the record in 1997, with a combined burned area of about 500 million hectares. This reinforced the long-term downward trend in fire emissions driven by changes in land use in frequently burning savannas. However, wildfires burned 3.5 million hectares across the United States, well above the 2000–10 average of 2.7 million hectares. Combined, U.S. wildfire damages for the 2017 and 2018 wildfire seasons exceeded $40 billion (U.S. dollars)