Sensitivity Analysis of Arctic Sea Ice in CMIP5 Climate Model Simulations

The representative characteristics of the simulated 20th century North Hemisphere sea ice by the CMIP5 models have been evaluated against available observations and compared with those by the CMIP3 models. In addition to the analysis of conventional parameters, such as climatological mean and seasonal cycle of sea ice area (SIA), a transient sensitivity analysis of summer SIA to the changes in Arctic regionally averaged melting season surface air temperatures (SAT) was conducted to better understand physics behind model uncertainties (e.g., Gregory et al. 2004; Zhang 2010)

Quantum Pseudorandom Scramblers

Quantum pseudorandom state generators (PRSGs) have stimulated exciting developments in recent years. A PRSG, on a fixed initial (e.g., all-zero) state, produces an output state that is computationally indistinguishable from a Haar random state. However, pseudorandomness of the output state is not guaranteed on other initial states. In fact, known PRSG constructions provably fail on some initial state. In this work, we propose and construct quantum Pseudorandom State Scramblers (PRSSs), which can produce a pseudorandom state on an arbitrary initial state. In the information-theoretical setting, we obtain a scrambler which maps an arbitrary initial state to a distribution of quantum states that is close to Haar random in total variation distance. As a result, our PRSS exhibits a dispersing property. Loosely, it can span an $\epsilon$-net of the state space. This significantly strengthens what standard PRSGs can induce, as they may only concentrate on a small region of the state space as long as the average output state approximates a Haar random state in total variation distance. Our PRSS construction develops a parallel extension of the famous Kac's walk, and we show that it mixes exponentially faster than the standard Kac's walk. This constitutes the core of our proof. We also describe a few applications of PRSSs. While our PRSS construction assumes a post-quantum one-way function, PRSSs are potentially a weaker primitive and can be separated from one-way functions in a relativized world similar to standard PRSGs

Recent Intensified Winter Coldness in the Mid-High Latitudes of Eurasia and Its Relationship with Daily Extreme Low Temperature Variability

Observational records in recent decades show a large-scale decrease in the cold-season temperature variance in the Northern Hemisphere midlatitudes under continuous global warming. However, severe low temperature events in winter frequently occurred in midlatitude Eurasia (MEA) in the last decade. Here, we define a new coldness intensity (CI) index for the near-surface based on the amplitude of daily anomalously cold temperatures in winter to demonstrate the CI of the variability of low temperature extremes. The results show that a sign-consistent mode dominates the CI variation in MEA, with a marked intensification during the last decade via empirical orthogonal function (EOF) analysis. This leading mode is significantly related to the frequency of winter extreme events. The associated circulations are characterized by a remarkable anomalous anticyclone in Northwest Eurasia, which induced substantial cold advection in MEA. The widespread intensified CI in MEA is closely linked with strong surface anticyclones and synoptic blocking in the mid-high latitudes (25 ∘ E-85 ∘ E). Coincidently, positive phase shifts of the first two leading modes of the extratropical circulation, which feature similar blocking-like anomalies in the northwestern Eurasian subarctic, jointly play an important role in the recent frequency of severe winters

Two-dimensional anisotropic Dirac materials PtN4C2 and Pt2N8C6 with quantum spin and valley Hall effects

We propose two novel two-dimensional topological Dirac materials, planar PtN4C2 and Pt2N8C6, which exhibit graphene-like electronic structures with linearly dispersive Dirac-cone states exactly at the Fermi level. Moreover, the Dirac cone is anisotropic, resulting in anisotropic Fermi velocities and making it possible to realize orientation-dependent quantum devices. Using the first-principles electronic structure calculations, we have systemically studied the structural, electronic, and topological properties. We find that spin-orbit coupling opens a sizable topological band gap so that the materials can be classified as quantum spin Hall insulators as well as quantum valley Hall insulators. Helical edge states that reside in the insulating band gap connecting the bulk conduction and valence bands are observed. Our work not only expands the Dirac cone material family, but also provides a new avenue to searching for more two-dimensional topological quantum spin and valley Hall insulators.Comment: 6 pages, 4 figure

Primis : design of a pivotal, randomized, phase 3 study evaluating the safety and efficacy of the nonsteroidal farnesoid X receptor agonist cilofexor in noncirrhotic patients with primary sclerosing cholangitis

BackgroundPrimary sclerosing cholangitis (PSC) is a chronic progressive liver disease leading to biliary fibrosis and cirrhosis. Cilofexor is a nonsteroidal farnesoid X receptor agonist that demonstrated significant improvements in liver biochemistry and markers of cholestasis in patients with PSC in a phase 2 study. We describe here the rationale, design, and implementation of the phase 3 PRIMIS trial, the largest placebo-controlled trial in PSC.MethodsAdults with large-duct PSC without cirrhosis are randomized 2:1 to receive oral cilofexor 100 mg once daily or placebo for up to 96 weeks during the blinded phase. Patients completing the blinded phase are eligible to receive open-label cilofexor 100 mg daily for up to 96 weeks. The primary objective is to evaluate whether cilofexor reduces the risk of fibrosis progression compared with placebo. Liver biopsy is performed at screening and Week 96 of the blinded phase for histologic assessment of fibrosis. The primary endpoint-chosen in conjunction with guidance from the U.S. Food and Drug Administration-is the proportion of patients with >= 1-stage increase in fibrosis according to Ludwig histologic classification at week 96. Secondary objectives include evaluation of changes in liver biochemistry, serum bile acids, liver fibrosis assessed by noninvasive methods, health-related quality of life, and safety of cilofexor.ConclusionThe phase 3 PRIMIS study is the largest randomized, double-blind, placebo-controlled trial in PSC to date and will allow for robust evaluation of the efficacy and safety of cilofexor in noncirrhotic patients with large-duct PSC.Trial Registration: ClinicalTrials.gov NCT03890120; registered 26/03/2019.Peer reviewe

The Nonsteroidal Farnesoid X Receptor Agonist Cilofexor (GS-9674) Improves Markers of Cholestasis and Liver Injury in Patients With Primary Sclerosing Cholangitis

Primary sclerosing cholangitis (PSC) represents a major unmet medical need. In a phase II double-blind, placebo-controlled study, we tested the safety and efficacy of cilofexor (formerly GS-9674), a nonsteroidal farnesoid X receptor agonist in patients without cirrhosis with large-duct PSC. Patients were randomized to receive cilofexor 100 mg (n = 22), 30 mg (n = 20), or placebo (n = 10) orally once daily for 12 weeks. All patients had serum alkaline phosphatase (ALP) > 1.67 × upper limit of normal and total bilirubin ≤ 2 mg/dL at baseline. Safety, tolerability, pharmacodynamic effects of cilofexor (serum C4 [7α-hydroxy-4-cholesten-3-one] and bile acids), and changes in liver biochemistry and serum fibrosis markers were evaluated. Overall, 52 patients were randomized (median age 43 years, 58% male, 60% with inflammatory bowel disease, 46% on ursodeoxycholic acid). Baseline median serum ALP and bilirubin were 348 U/L (interquartile range 288-439) and 0.7 mg/dL (0.5-1.0), respectively. Dose-dependent reductions in liver biochemistry were observed. At week 12, cilofexor 100 mg led to significant reductions in serum ALP (median reduction -21%; P = 0.029 versus placebo), gamma-glutamyl transferase (-30%; P < 0.001), alanine aminotransferase (ALT) (-49%; P = 0.009), and aspartate aminotransferase (-42%; P = 0.019). Cilofexor reduced serum C4 compared with placebo; reductions in bile acids were greatest with 100 mg. Relative reductions in ALP were similar between ursodeoxycholic acid-treated and untreated patients. At week 12, cilofexor-treated patients with a 25% or more relative reduction in ALP had greater reductions in serum alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, tissue inhibitor of metalloproteinase 1, C-reactive protein, and bile acids than nonresponders. Adverse events were similar between cilofexor and placebo-treated patients. Rates of grade 2 or 3 pruritus were 14% with 100 mg, 20% with 30 mg, and 40% with placebo. Conclusion: In this 12-week, randomized, placebo-controlled study, cilofexor was well tolerated and led to significant improvements in liver biochemistries and markers of cholestasis in patients with PSC

Cold Waves in East China and Their Response to Two Types of Arctic Amplification

Cold waves occur frequently in East China, with their cold air source in the Arctic. Changes in the Arctic are often linked with Arctic amplification. The circulation anomaly associated with Arctic amplification is often represented by Arctic Oscillation (AO). In recent years, storms have frequently invaded the central Arctic region, resulting in dramatic changes in Arctic environment. In this paper, based on correlation studies, composite analysis, and case studies, the remote effects of the old and storm-induced Arctic amplification are compared, especially with regard to their impact on cold waves in East China. The results show that the AO can shed light on the interannual variation of cold events intermittently, although it cannot explain the increasing trend of cold waves in the southern part of East China. However, this long-term trend correlates well with storm activity. Cyclones are becoming more active in the western Arctic and anticyclones are intensifying in the eastern Arctic. In this scenario, the storm-induced warm advection could enhance the ridge over northeast Eurasia, the Siberian High expands southeastward, and cold air accumulates in northeast Asia, which cools the northern part of East China directly. The circulation around the Siberian High leads to a northeast wind in the southern part of East China, which plays a vital role in snowstorms. This study could improve our understanding of the global effects of Arctic changes and could enhance the prediction skill of cold waves

Weakened cyclones, intensified anticyclones and recent extreme cold winter weather events in Eurasia

Extreme cold winter weather events over Eurasia have occurred more frequently in recent years in spite of a warming global climate. To gain further insight into this regional mismatch with the global mean warming trend, we analyzed winter cyclone and anticyclone activities, and their interplay with the regional atmospheric circulation pattern characterized by the semi-permanent Siberian high. We found a persistent weakening of both cyclones and anticyclones between the 1990s and early 2000s, and a pronounced intensification of anticyclone activity afterwards. It is suggested that this intensified anticyclone activity drives the substantially strengthening and northwestward shifting/expanding Siberian high, and explains the decreased midlatitude Eurasian surface air temperature and the increased frequency of cold weather events. The weakened tropospheric midlatitude westerlies in the context of the intensified anticyclones would reduce the eastward propagation speed of Rossby waves, favoring persistence and further intensification of surface anticyclone systems

Evaluating the impact of school-based influenza vaccination programme on absenteeism and outbreaks at schools in Hong Kong: a retrospective cohort study protocol

Abstract Introduction Seasonal influenza causes annual school breaks and student absenteeism in Hong Kong schools and kindergartens. This proposal aims to conduct a retrospective cohort study to evaluate the impact of a school-based influenza vaccination (SIV) programme on absenteeism and outbreaks at schools in Hong Kong. Methods The study will compare schools that implemented the SIV programme with schools that did not. The data will be sourced from school records, encompassing absenteeism records, outbreak reports, and vaccination rates. We will recruit 1000 students from 381 schools and kindergartens in 18 districts of Hong Kong starting June 2024. The primary outcome measures will include absenteeism rates due to influenza and school influenza outbreaks. Secondary outcomes will consist of vaccination coverage rates and the impact of the SIV programme on hospitalisations due to influenza-like illness. A t-test will be conducted to compare the outcomes between schools with and without the SIV programme. Ethics and dissemination The school completed signing the participants’ informed consent form before reporting the data to us. Our study has been approved by the Hospital Authority Hong Kong West Cluster IRB Committee (IRB No: UW 17–111) and was a subtopic of the research “The estimated age-group specific influenza vaccine coverage rates in Hong Kong and the impact of the school outreach vaccination program”. Trial registration This study will be retrospectively registered