Cost-Effectiveness Analysis of Insulin Detemir Compared to Neutral Protamine Hagedorn (NPH) in Patients with Type 1 and Type 2 Diabetes Mellitus in Spain

Introduction: An Excel® (Microsoft Corporation) model was adapted to estimate the short-term (1-year) cost effectiveness of insulin detemir (IDet) versus neutral protamine Hagedorn (NPH) insulin in patients initiating insulin treatment with type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) in Spain. Methods: Clinical benefits included the non-severe hypoglycemia rate for T1DM and T2DM, and weight change for T2DM. Three scenarios were included with different hypoglycemia rates estimated on the basis of clinical trials and observational studies. Costs, estimated from perspective of the Spanish Public Healthcare System (Euros 2014), included insulin treatment and non-severe hypoglycemia management costs. Non-severe hypoglycemia, defined as a self-managed event, implied the use of extra glucose testing strips and a general practitioner visit during the week following the event for 25% of patients. An average disutility value was associated to non-severe hypoglycemia events and, for T2DM, to one body mass index unit gain to calculate quality-adjusted life years (QALYs). Results: For the three scenarios a range of 0.025–0.076 QALYs for T1DM and 0.014–0.051 QALYs for T2DM were gained for IDet versus NPH due to non-severe hypoglycemia and weight gain avoidance, in return of an incremental cost of €145–192 for T1DM and €128–206 for T2DM. This resulted in the IDet versus NPH incremental cost-effectiveness ratio (ICER) ranging between €1910/QALY and €7682/QALY for T1DM and €2522/QALY and €15,009/QALY for T2DM. Conclusion: IDet was a cost-effective alternative to NPH insulin in the first year of treatment of patients with T1DM and patients with T2DM in Spain, with ICERs under the threshold value commonly accepted in Spain (€30,000/QALY)

Structural and temporal patterns of the first global trading market

Little is known about the structural patterns and dynamics of the first global trading market (FGTM), which emerged during the sixteenth century as a result of the Iberian expansion, let alone how it compares to today's global financial markets. Here we build a representative network of the FGTM using information contained in 8725 (handwritten) Bills of Exchange from that time-which were (human) interpreted and digitalized into an online database. We show that the resulting temporal network exhibits a hierarchical, highly clustered and disassortative structure, with a power-law dependence on the connectivity that remains remarkably robust throughout the entire period investigated. Temporal analysis shows that, despite major turnovers in the number and nature of the links-suggesting fast adaptation in response to the geopolitical and financial turmoil experienced at the time-the overall characteristics of the FGTM remain robust and virtually unchanged. The methodology developed here demonstrates the possibility of building and analysing complex trading and finance networks originating from pre-statistical eras, enabling us to highlight the striking similarities between the structural patterns of financial networks separated by centuries in time.This research was supported by FCT-Portugal through grant nos FCT-TECH/0002/2007 (A.S.R. and A.P.), SFRH/BD/77389/2011 (F.L.P.), SFRH/BPD/76278/2011 (A.S.R.), PTDC/MAT-STA/3358/2014 (F.L.P., F.C.S. and J.M.P.), PTDC/EEI-SII/5081/2014 (F.L.P., F.C.S. and J.M.P.), UID/BIA/04050/2013 (J.M.P.) and UID/CEC/50021/2013 (F.C.S.), and by the European Science Foundation through grant no. DynCoopNet-06-TECT-FP-004 (A.S.R. and A.P.)

JNK interacting protein 1 (JIP-1) protects LNCaP prostate cancer cells from growth arrest and apoptosis mediated by 12-0-tetradecanoylphorbol-13-acetate (TPA)

12-0-tetradecanoylphorbol-13-acetate (TPA) stimulates protein kinase C (PKC) which mediates apoptosis in androgen-sensitive LNCaP human prostate cancer cells. The downstream signals of PKC that mediate TPA-induced apoptosis in LNCaP cells are unclear. In this study, we found that TPA activates the c-Jun NH2-terminal kinase (JNK)/c-Jun/AP-1 pathway. To explore the possible role that the JNK/c-Jun/AP-1 signal pathway has on TPA-induced apoptosis in LNCaP cells, we stably transfected the scaffold protein, JNK interacting protein 1 (JIP-1), which binds to JNK inhibiting its ability to phosphorylate c-Jun. TPA (10(-9)-10(-7) mol l(-1)) caused phosphorylation of JNK in both wild-type and JIP-1-transfected (LNCaP-JIP-1) cells. It resulted in phosphorylation and upregulation of expression of c-Jun protein in the wild-type LNCaP cells, but not in the JIP-1-transfected LNCaP cells. In addition, upregulation of AP-1 reporter activity by TPA (10(-9) mol l(-1)) occurred in LNCaP cells but was abrogated in LNCaP-JIP-1 cells. Thus, TPA stimulated c-Jun through JNK, and JIP-1 effectively blocked JNK. TPA (10(-12)-10(-8) mol l(-1)) treatment of LNCaP cells caused their growth inhibition, cell cycle arrest, upregulation of p53 and p21waf1, and induction of apoptosis. All of these effects were significantly attenuated when LNCaP-JIP-1 cells were similarly treated with TPA. A previous study showed that c-Jun/AP-1 blocked androgen receptor (AR) signaling by inhibiting AR binding to AR response elements (AREs) of target genes including prostate-specific antigen (PSA). Therefore, we hypothesised that TPA would not be able to disrupt the AR signal pathway in LNCaP-JIP-1 cells. Contrary to expectation, TPA (10(-9)-10(-8) mol l(-1)) inhibited DHT-induced AREs reporter activity and decreased levels of PSA in the LNCaP-JIP-1 cells. Taken together, TPA, probably by stimulation of PKC, phosphorylates JNK, which phosphorylates and increases expression of c-Jun leading to AP-1 activity. Growth control of prostate cancer cells can be mediated through the JNK/c-Jun pathway, but androgen responsiveness of these cells can be independent of this pathway, suggesting that androgen independence in progressive prostate cancer may not occur through activation of this pathway

Mass Calibration of Optically Selected des Clusters Using a Measurement of CMB-cluster Lensing with SPTpol Data

We use cosmic microwave background (CMB) temperature maps from the 500 deg 2 SPTpol survey to measure the stacked lensing convergence of galaxy clusters from the Dark Energy Survey (DES) Year-3 redMaPPer (RM) cluster catalog. The lensing signal is extracted through a modified quadratic estimator designed to be unbiased by the thermal Sunyaev-Zel'dovich (tSZ) effect. The modified estimator uses a tSZ-free map, constructed from the SPTpol 95 and 150 GHz data sets, to estimate the background CMB gradient. For lensing reconstruction, we employ two versions of the RM catalog: a flux-limited sample containing 4003 clusters and a volume-limited sample with 1741 clusters. We detect lensing at a significance of 8.7σ(6.7σ) with the flux (volume)-limited sample. By modeling the reconstructed convergence using the Navarro-Frenk-White profile, we find the average lensing masses to be M 200m = (1.62 -0.25+0.32 [stat] ± 0.04 [sys.]) and (1.28 -0.18+0.14 [stat] ± 0.03[sys.])× 10 14 M ⊙ for the volume- and flux-limited samples, respectively. The systematic error budget is much smaller than the statistical uncertainty and is dominated by the uncertainties in the RM cluster centroids. We use the volume-limited sample to calibrate the normalization of the mass-richness scaling relation, and find a result consistent with the galaxy weak-lensing measurements from DES

Dark energy survey year 1 results: Redshift distributions of the weak-lensing source galaxies

We describe the derivation and validation of redshift distribution estimates and their uncertainties for the populations of galaxies used as weak-lensing sources in the Dark Energy Survey (DES) Year 1 cosmological analyses. The Bayesian Photometric Redshift (BPZ) code is used to assign galaxies to four redshift bins between z ≈ 0.2 and ≈1.3, and to produce initial estimates of the lensing-weighted redshift distributions nPZi(z) ∝ dni/dz for members of bin i. Accurate determination of cosmological parameters depends critically on knowledge of ni, but is insensitive to bin assignments or redshift errors for individual galaxies. The cosmological analyses allow for shifts ni (z) = nPZi(z - Δzi) to correct themean redshift of ni(z) for biases in nPZi. The Δzi are constrained by comparison of independently estimated 30-band photometric redshifts of galaxies in the Cosmic Evolution Survey (COSMOS) field to BPZ estimates made from the DES griz fluxes, for a sample matched in fluxes, pre-seeing size, and lensing weight to the DES weak-lensing sources. In companion papers, the Δzi of the three lowest redshift bins are further constrained by the angular clustering of the source galaxies around red galaxies with secure photometric redshifts at 0.15 < z < 0.9. This paper details the BPZ and COSMOS procedures, and demonstrates that the cosmological inference is insensitive to details of the ni(z) beyond the choice of Δzi. The clustering and COSMOS validation methods produce consistent estimates of Δzi in the bins where both can be applied, with combined uncertainties of σΔzi = 0.015, 0.013, 0.011, and 0.022 in the four bins. Repeating the photo-z procedure instead using the Directional Neighbourhood Fitting algorithm, or using the ni(z) estimated from the matched sample in COSMOS, yields no discernible difference in cosmological inferences

Galaxy-galaxy lensing with the DES-CMASS catalogue: measurement and constraints on the galaxy-matter cross-correlation

The DMASS sample is a photometric sample from the DES Year 1 data set designed to replicate the properties of the CMASS sample from BOSS, in support of a joint analysis of DES and BOSS beyond the small overlapping area. In this paper, we present the measurement of galaxy–galaxy lensing using the DMASS sample as gravitational lenses in the DES Y1 imaging data. We test a number of potential systematics that can bias the galaxy–galaxy lensing signal, including those from shear estimation, photometric redshifts, and observing conditions. After careful systematic tests, we obtain a highly significant detection of the galaxy–galaxy lensing signal, with total S/N = 25.7. With the measured signal, we assess the feasibility of using DMASS as gravitational lenses equivalent to CMASS, by estimating the galaxy-matter cross-correlation coefficient rcc. By jointly fitting the galaxy–galaxy lensing measurement with the galaxy clustering measurement from CMASS, we obtain rcc=1.09+0.12−0.11 for the scale cut of 4h−1Mpc and rcc=1.06+0.13−0.12 for 12h−1Mpc in fixed cosmology. By adding the angular galaxy clustering of DMASS, we obtain rcc = 1.06 ± 0.10 for the scale cut of 4h−1Mpc and rcc = 1.03 ± 0.11 for 12h−1Mpc⁠. The resulting values of rcc indicate that the lensing signal of DMASS is statistically consistent with the one that would have been measured if CMASS had populated the DES region within the given statistical uncertainty. The measurement of galaxy–galaxy lensing presented in this paper will serve as part of the data vector for the forthcoming cosmology analysis in preparation

Dark Energy Survey Year 3 Results: Galaxy mock catalogs for BAO analysis

The calibration and validation of scientific analysis in simulations is a fundamental tool to ensure unbiased and robust results in observational cosmology. In particular, mock galaxy catalogs are a crucial resource to achieve these goals in the measurement of baryon acoustic oscillation (BAO) in the clustering of galaxies. Here we present a set of 1952 galaxy mock catalogs designed to mimic the Dark Energy Survey Year 3 BAO sample over its full photometric redshift range 0.6 < zphoto < 1.1. The mocks are based upon 488 ICE-COLA fast N-body simulations of full-sky light cones and were created by populating halos with galaxies, using a hybrid halo occupation distribution – halo abundance matching model. This model has ten free parameters, which were determined, for the first time, using an automatic likelihood minimization procedure. We also introduced a novel technique to assign photometric redshift for simulated galaxies, following a two-dimensional probability distribution with VIMOS Public Extragalactic Redshift Survey data. The calibration was designed to match the observed abundance of galaxies as a function of photometric redshift, the distribution of photometric redshift errors, and the clustering amplitude on scales smaller than those used for BAO measurements. An exhaustive analysis was done to ensure that the mocks reproduce the input properties. Finally, mocks were tested by comparing the angular correlation function w(θ), angular power spectrum Cℓ, and projected clustering ξp(r⊥) to theoretical predictions and data. The impact of volume replication in the estimate of the covariance is also investigated. The success in accurately reproducing the photometric redshift uncertainties and the galaxy clustering as a function of redshift render this mock creation pipeline as a benchmark for future analyses of photometric galaxy surveys

Dark Energy Survey Year 1 Results: Tomographic cross-correlations between Dark Energy Survey galaxies and CMB lensing from South Pole Telescope+Planck

We measure the cross-correlation between redMaGiC galaxies selected from the Dark Energy Survey (DES) year 1 data and gravitational lensing of the cosmic microwave background (CMB) reconstructed from South Pole Telescope (SPT) and Planck data over 1289 deg2. When combining measurements across multiple galaxy redshift bins spanning the redshift range of 0.1