A comparison of in-sample forecasting methods

In-sample forecasting is a recent continuous modification of well-known forecasting methods based on aggregated data. These aggregated methods are known as age-cohort methods in demography, economics, epidemiology and sociology and as chain ladder in non-life insurance. Data is organized in a two-way table with age and cohort as indices, but without measures of exposure. It has recently been established that such structured forecasting methods based on aggregated data can be interpreted as structured histogram estimators. Continuous in-sample forecasting transfers these classical forecasting models into a modern statistical world including smoothing methodology that is more efficient than smoothing via histograms. All in-sample forecasting estimators are collected and their performance is compared via a finite sample simulation study. All methods are extended via multiplicative bias correction. Asymptotic theory is being developed for the histogram-type method of sieves and for the multiplicatively corrected estimators. The multiplicative bias corrected estimators improve all other known in-sample forecasters in the simulation study. The density projection approach seems to have the best performance with forecasting based on survival densities being the runner-up

Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection.

BackgroundWe reported previously on the emergence and clinical implications of simian immunodeficiency virus (SIVmac251) mutants with a K65R mutation in reverse transcriptase (RT), and the role of CD8+ cell-mediated immune responses in suppressing viremia during tenofovir therapy. Because of significant sequence differences between SIV and HIV-1 RT that affect drug susceptibilities and mutational patterns, it is unclear to what extent findings with SIV can be extrapolated to HIV-1 RT. Accordingly, to model HIV-1 RT responses, 12 macaques were inoculated with RT-SHIV, a chimeric SIV containing HIV-1 RT, and started on prolonged tenofovir therapy 5 months later.ResultsThe early virologic response to tenofovir correlated with baseline viral RNA levels and expression of the MHC class I allele Mamu-A*01. For all animals, sensitive real-time PCR assays detected the transient emergence of K70E RT mutants within 4 weeks of therapy, which were then replaced by K65R mutants within 12 weeks of therapy. For most animals, the occurrence of these mutations preceded a partial rebound of plasma viremia to levels that remained on average 10-fold below baseline values. One animal eventually suppressed K65R viremia to undetectable levels for more than 4 years; sequential experiments using CD8+ cell depletion and tenofovir interruption demonstrated that both CD8+ cells and continued tenofovir therapy were required for sustained suppression of viremia.ConclusionThis is the first evidence that tenofovir therapy can select directly for K70E viral mutants in vivo. The observations on the clinical implications of the K65R RT-SHIV mutants were consistent with those of SIVmac251, and suggest that for persons infected with K65R HIV-1 both immune-mediated and drug-dependent antiviral activities play a role in controlling viremia. These findings suggest also that even in the presence of K65R virus, continuation of tenofovir treatment as part of HAART may be beneficial, particularly when assisted by antiviral immune responses

CP Violation in \tau ->\nu\pi K_S and D->\pi K_S: The Importance of K_S-K_L Interference

The $B$-factories have measured CP asymmetries in the $\tau\to\pi K_S\nu$ and $D\to K_S\pi$ modes. The $K_S$ state is identified by its decay to two pions at a time that is close to the $K_S$ lifetime. Within the Standard Model and many of its extensions, the asymmetries in these modes come from CP violation in $K^0-\bar{K}^0$ mixing. We emphasize that the interference between the amplitudes of intermediate $K_S$ and $K_L$ is as important as the pure $K_S$ amplitude. Consequently, the measured asymmetries depend on the times over which the relevant decay rates are integrated and on features of the experiment.Comment: 4 pages, 4 figure

Designing allostery-inspired response in mechanical networks

Recent advances in designing metamaterials have demonstrated that global mechanical properties of disordered spring networks can be tuned by selectively modifying only a small subset of bonds. Here, using a computationally efficient approach, we extend this idea to tune more general properties of networks. With nearly complete success, we are able to produce a strain between any two target nodes in a network in response to an applied source strain on any other pair of nodes by removing only ∼1% of the bonds. We are also able to control multiple pairs of target nodes, each with a different individual response, from a single source, and to tune multiple independent source/target responses simultaneously into a network. We have fabricated physical networks in macroscopic 2D and 3D systems that exhibit these responses. This work is inspired by the long-range coupled conformational changes that constitute allosteric function in proteins. The fact that allostery is a common means for regulation in biological molecules suggests that it is a relatively easy property to develop through evolution. In analogy, our results show that long-range coupled mechanical responses are similarly easy to achieve in disordered networks

Synaptic Integration of Adult-Born Hippocampal Neurons Is Locally Controlled by Astrocytes.

Adult neurogenesis is regulated by the neurogenic niche, through mechanisms that remain poorly defined. Here, we investigated whether niche-constituting astrocytes influence the maturation of adult-born hippocampal neurons using two independent transgenic approaches to block vesicular release from astrocytes. In these models, adult-born neurons but not mature neurons showed reduced glutamatergic synaptic input and dendritic spine density that was accompanied with lower functional integration and cell survival. By taking advantage of the mosaic expression of transgenes in astrocytes, we found that spine density was reduced exclusively in segments intersecting blocked astrocytes, revealing an extrinsic, local control of spine formation. Defects in NMDA receptor (NMDAR)-mediated synaptic transmission and dendrite maturation were partially restored by exogenous D-serine, whose extracellular level was decreased in transgenic models. Together, these results reveal a critical role for adult astrocytes in local dendritic spine maturation, which is necessary for the NMDAR-dependent functional integration of newborn neurons

Decontamination of filtering facepiece respirators using a low-temperature-steam–2%-formaldehyde sterilization process during a pandemic: a safe alternative for re-use

Background The coronavirus disease 2019 pandemic has caused problems with respirator supplies. Re-use may minimize the impact of the shortage, but requires the availability of an efficient and safe decontamination method. Aim To determine whether low-temperature-steam–2%-formaldehyde (LTSF) sterilization is effective, preserves the properties of filtering facepiece (FFP) respirators and allows safe re-use. Methods Fourteen unused FFP2, FFP3 and N95 respirator models were subjected to two cycles of decontamination cycles. After the second cycle, each model was inspected visually and accumulated residual formaldehyde levels were analysed according to EN 14180. After one and two decontamination cycles, the fit factor (FF) of each model was tested, and penetration tests with sodium chloride aerosols were performed on five models. Findings Decontamination physically altered three of the 14 models. All of the residual formaldehyde values were below the permissible threshold. Irregular decreases and increases in FF were observed after each decontamination cycle. In the sodium chloride aerosol penetration test, three models obtained equivalent or superior results to those of the FFP classification with which they were marketed, both at baseline and after one and two cycles of decontamination, and two models had lower filtering capacity. Conclusion One and two decontamination cycles using LTSF did not alter the structure of most (11/14) respirators tested, and did not degrade the fit or filtration capacity of any of the analysed respirators. The residual formaldehyde levels complied with EN 14180. This reprocessing method could be used in times of shortage of personal protective equipment

The Physics of Heavy Flavours at SuperB

This is a review of the SuperB project, covering the accelerator, detector, and highlights of the broad physics programme. SuperB is a flavour factory capable of performing precision measurements and searches for rare and forbidden decays of $B_{u,d,s}$, $D$, $\tau$ and $\Upsilon({\mathrm{nS}})$ particles. These results can be used to test fundamental symmetries and expectations of the Standard Model, and to constrain many different hypothesised types of new physics. In some cases these measurements can be used to place constraints on the existence of light dark matter and light Higgs particles with masses below $10GeV/c^2$. The potential impact of the measurements that will be made by SuperB on the field of high energy physics is also discussed in the context of data taken at both high energy in the region around the \Upsilon({\mathrm{4S}})$, and near charm threshold.Comment: 49 pages, topical review submitted to J. Phys

Observation of Bs->Ds(*)+Ds(*)- using e+e- collisions and a determination of the Bs-Bsbar width difference \Delta\Gamma_s

We have made the first observation of Bs->Ds(*)+Ds(*)- decays using 23.6 fb-1 of data recorded by the Belle experiment running on the Upsilon(5S) resonance. The branching fractions are measured to be B(B^0_s\ra D^+_s D^-_s) = (1.0\,^{+0.4}_{-0.3}\,^{+0.3}_{-0.2})%, B(B^0_s\ra D^{*\pm}_s D^{\mp}_s) = (2.8\,^{+0.8}_{-0.7}\,\pm 0.7)%, and B(B^0_s\ra D^{*+}_s D^{*-}_s) = (3.1\,^{+1.2}_{-1.0}\,\pm 0.8)%; the sum is B(B^0_s\ra D^{(*)+}_s D^{(*)-}_s) = (6.9\,^{+1.5}_{-1.3}\,\pm 1.9)%. Assuming Bs->Ds(*)+Ds(*)- saturates decays to CP-even final states, the branching fraction determines the ratio \Delta\Gamma_s/cos(\phi), where \Delta\Gamma_s is the difference in widths between the two Bs-Bsbar mass eigenstates, and \phi is a CP-violating weak phase. Taking CP violation to be negligibly small, we obtain \Delta\Gamma_s/\Gamma_s = 0.147^{+0.036}_{-0.030}(stat.)^{+0.044}_{-0.042}(syst.), where \Gamma_s is the mean decay width.Comment: 13 pages, 2 figures, 2 tables. v2: text added for clarification, version published in Phys. Rev. Letter

Measurement of CP violating asymmetries in B^0 -> K^+K^- K^0_S decays with a time-dependent Dalitz approach

We report a measurement of $CP$ violating asymmetries in $B^0(\overline{B}^0) \to K^+ K^- K^0_S$ decays with a time-dependent Dalitz approach. This analysis is based on a data sample of $657\times 10^6$ $B\overline{B}$ pairs accumulated at the $\Upsilon(4S)$ resonance with the Belle detector at the KEKB asymmetric-energy $e^+e^-$ collider. As the result of an unbinned maximum likelihood fit to the selected candidates, the mixing-induced and direct $CP$ violation parameters, $\phi^{\rm eff}_1$ and ${\cal A}_{CP}$ are obtained for $B^0 \to \phi(1020) K^0_S$, $B^0 \to f_0(980) K^0_S$ and other $B^0 \to K^+ K^- K^0_S$ decays. We find four solutions that describe the data. There are \{eqnarray*} \phi_1^{\rm eff}(B^0\to \phi(1020) K^0_S) & = & (32.2 \pm 9.0 \pm 2.6 \pm 1.4)^{\circ}; \phi_1^{\rm eff}(B^0\to \phi(1020) K^0_S) & = & (26.2 \pm 8.8 \pm 2.7 \pm 1.2)^{\circ};\\ \phi_1^{\rm eff}(B^0\to \phi(1020) K^0_S) & = & (27.3 \pm 8.6 \pm 2.8 \pm 1.3)^{\circ}\; {\rm and}\\ \phi_1^{\rm eff}(B^0\to \phi(1020) K^0_S) & = & (24.3 \pm 8.0 \pm 2.9 \pm 5.2)^{\circ}.{eqnarray*}\ The values for the $CP$ violating phase in $B^0\to \phi(1020) K^0_S$ are similar but other properties of the Dalitz plot are quite different for the four solutions. These four solutions have consistent $\phi^{\rm eff}_1$ values for all three $B$ meson decay channels and none of them deviates significantly from the values measured in $B \to (c\bar{c}) K^0$ decays with the currently available statistics. In addition, we find no significant direct $CP$ violation.Comment: submitted to PR

Search for CP violation in the decays D(s)+→KS0π+D^+_{(s)} \to K_S^0\pi^+ and D(s)+→KS0K+D^+_{(s)} \to K_S^0K^+

We have searched for CP violation in the charmed meson decays $D^{+}_{(s)}\to K^0_S\pi^+$ and $D^{+}_{(s)}\to K^0_S K^+$ using 673 fb$^{-1}$ of data collected with the Belle detector at the KEKB asymmetric-energy $e^+e^-$ collider. No evidence for CP violation is observed. We report the most sensitive CP asymmetry measurements to date for these decays: $A_{CP}^{D^+\to K^0_S\pi^+}=(-0.71\pm0.19\pm0.20)$, $A_{CP}^{D^+_s\to K^0_S\pi^+}=(+5.45\pm2.50\pm0.33)$, $A_{CP}^{D^+\to K^0_S K^+}=(-0.16\pm0.58\pm0.25)$, and $A_{CP}^{D^+_s\to K^0_S K^+}=(+0.12\pm0.36\pm0.22)$, where the first uncertainties are statistical and the second are systematic