California Water Myths

Presents eight common myths about water supply, ecosystems, and the legal and political aspects of governing California's water system and explains how each myth drives the debate, the reality, and alternatives for better informed policy discussions

Comparing Futures for the Sacramento-San Joaquin Delta

Analyzes expected changes to the hub of California's water system and presents a comparative assessment of four water management strategies for environmental sustainability and water supply reliability. Discusses policy and regulatory implications

A Multicenter, International Cohort Analysis of 1435 Cases to Support Clinical Trial Design in Acute Pancreatitis

Background: C-reactive protein level (CRP) and white blood cell count (WBC) have been variably used in clinical trials on acute pancreatitis (AP). We assessed their potential role. Methods: First, we investigated studies which have used CRP or WBC, to describe their current role in trials on AP. Second, we extracted the data of 1435 episodes of AP from our registry. CRP and WBC on admission, within 24 h from the onset of pain and their highest values were analyzed. Descriptive statistical tools as Kruskal-Wallis, Mann-Whitney U, Levene's F tests, Receiver Operating Characteristic (ROC) curve analysis and AUC (Area Under the Curve) with 95% confidence interval (CI) were performed. Results: Our literature review showed extreme variability of CRP used as an inclusion criterion or as a primary outcome or both in past and current trials on AP. In our cohort, CRP levels on admission poorly predicted mortality and severe cases of AP; AUC: 0.669 (CI:0.569-0.770); AUC:0.681 (CI: 0.601-0.761), respectively. CRP levels measured within 24 h from the onset of pain failed to predict mortality or severity; AUC: 0.741 (CI:0.627-0.854); AUC:0.690 (CI:0.586-0.793), respectively. The highest CRP during hospitalization had equally poor predictive accuracy for mortality and severity AUC:0.656 (CI:0.544-0.768); AUC:0.705 (CI:0.640-0.769) respectively. CRP within 24 h from the onset of pain used as an inclusion criterion markedly increased the combined event rate of mortality and severe AP (13% for CRP > 25 mg/l and 28% for CRP > 200 mg/l). Conclusion: CRP within 24 h from the onset of pain as an inclusion criterion elevates event rates and reduces the number of patients required in trials on AP.Peer reviewe

The peak-flux of GRB 221009A measured with GRBAlpha

The brightest gamma-ray burst ever observed, long-duration GRB 221009A, was detected by GRBAlpha nano-satellite without saturation. We present light curves of the prompt emission in 13 energy bands, from 80 keV to 950 keV, and perform a spectral analysis to calculate the peak flux and peak isotropic-equivalent luminosity. Since the satellite's attitude information is not available for the time of this GRB, more than 200 incident directions were probed in order to find the median luminosity and its systematic uncertainty. We found that the peak flux in the $80-800$ keV range (observer frame) was $F_{\rm{ph}}^{\rm{p}}=1300_{-200}^{+1200}$ ph cm$^{-2}$s$^{-1}$ or $F_{\rm{erg}}^{\rm{p}}=5.7_{-0.7}^{+3.7}\times10^{-4}$ erg cm$^{-2}$s$^{-1}$ and the fluence in the same energy range of the first GRB episode lasting 300 s, which was observable by GRBAlpha, was $S=2.2_{-0.3}^{+1.4}\times10^{-2}$ erg cm$^{-2}$ or $S^{\rm{bol}}=4.9_{-0.5}^{+0.8}\times10^{-2}$ erg cm$^{-2}$ for the extrapolated range of $0.9-8,690$ keV. We infer the isotropic-equivalent released energy of the first GRB episode to be $E_{\rm{iso}}^{\rm{bol}}=2.8_{-0.5}^{+0.8}\times10^{54}$ erg in the $1-10,000$ keV band (rest frame at $z=0.15$). The peak isotropic-equivalent luminosity in the $92-920$ keV range (rest frame) was $L_{\rm{iso}}^{\rm{p}}=3.7_{-0.5}^{+2.5}\times10^{52}$ erg s$^{-1}$ and the bolometric peak isotropic-equivalent luminosity was $L_{\rm{iso}}^{\rm{p,bol}}=8.4_{-1.5}^{+2.5}\times10^{52}$ erg s$^{-1}$ (4 s scale) in the $1-10,000$ keV range (rest frame). The peak emitted energy is $E_p^\ast=E_p(1+z)=1120\pm470$ keV. Our measurement of $L_{\rm{iso}}^{\rm{p,bol}}$ is consistent with the Yonetoku relation. It is possible that, due to the spectral evolution of this GRB and orientation of GRBAlpha at the peak time, the true values of peak flux, fluence, $L_{\rm{iso}}$, and $E_{\rm{iso}}$ are even higher. [abridged]Comment: 7 pages, 7 figures, 1 table, accepted for publication in Astronomy & Astrophysic

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.

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead