A cohort study of post-weaning multisystemic wasting syndrome and PCV2 in 178 pigs from birth to 14 weeks on a single farm in England

Our hypothesis was that pigs that develop post-weaning multisystemic wasting syndrome (PMWS) are detectable from an early age with signs of weight loss and other clinical and serological abnormalities. Therefore, the objective of this study was to investigate the temporally varying and fixed events linked with the clinical incidence of PMWS by comparing affected and unaffected pigs in a cohort of 178 male piglets. Piglets were enrolled at birth and examined each week. Samples of blood were collected at regular intervals. The exposures measured were porcine circovirus type 2 (PCV2) antibody titres in all 178 and PCV2 antigen in a subset of 75 piglets. We also observed piglet health and measured their weight, and a post-mortem examination was performed by an external laboratory on all pigs between 6 and 14 weeks of age that died. From the cohort, 14 (8%) pigs died from PMWS and 4% from other causes. A further 37 pigs between 6 and 14 weeks of age died from PMWS (30) and ileitis and other causes (7). PMWS was only apparent in pigs from 1 to 2 weeks before death when they wasted rapidly. There were no other characteristic clinical signs and no obvious gross clinical lesions post-mortem. There was no strong link with PCV2 antibody throughout life but PCV2 antigen level was higher from 4 to 6 weeks of age in pigs that died from PMWS compared with pigs that died from other causes

Is the evidence for dark energy secure?

Several kinds of astronomical observations, interpreted in the framework of the standard Friedmann-Robertson-Walker cosmology, have indicated that our universe is dominated by a Cosmological Constant. The dimming of distant Type Ia supernovae suggests that the expansion rate is accelerating, as if driven by vacuum energy, and this has been indirectly substantiated through studies of angular anisotropies in the cosmic microwave background (CMB) and of spatial correlations in the large-scale structure (LSS) of galaxies. However there is no compelling direct evidence yet for (the dynamical effects of) dark energy. The precision CMB data can be equally well fitted without dark energy if the spectrum of primordial density fluctuations is not quite scale-free and if the Hubble constant is lower globally than its locally measured value. The LSS data can also be satisfactorily fitted if there is a small component of hot dark matter, as would be provided by neutrinos of mass 0.5 eV. Although such an Einstein-de Sitter model cannot explain the SNe Ia Hubble diagram or the position of the `baryon acoustic oscillation' peak in the autocorrelation function of galaxies, it may be possible to do so e.g. in an inhomogeneous Lemaitre-Tolman-Bondi cosmology where we are located in a void which is expanding faster than the average. Such alternatives may seem contrived but this must be weighed against our lack of any fundamental understanding of the inferred tiny energy scale of the dark energy. It may well be an artifact of an oversimplified cosmological model, rather than having physical reality.Comment: 12 pages, 5 figures; to appear in a special issue of General Relativity and Gravitation, eds. G.F.R. Ellis et al; Changes: references reformatted in journal style - text unchange

Susceptibility and dilution effects of the kagome bi-layer geometrically frustrated network. A Ga-NMR study of SrCr_(9p)Ga_(12-9p)O_(19)

We present an extensive gallium NMR study of the geometrically frustrated kagome bi-layer compound SrCr_(9p)Ga_(12-9p)O_(19) (Cr^3+, S=3/2) over a broad Cr-concentration range (.72<p<.95). This allows us to probe locally the kagome bi-layer susceptibility and separate the intrinsic properties due to the geometric frustration from those related to the site dilution. Our major findings are: 1) The intrinsic kagome bi-layer susceptibility exhibits a maximum in temperature at 40-50 K and is robust to a dilution as high as ~20%. The maximum reveals the development of short range antiferromagnetic correlations; 2) At low-T, a highly dynamical state induces a strong wipe-out of the NMR intensity, regardless of dilution; 3) The low-T upturn observed in the macroscopic susceptibility is associated to paramagnetic defects which stem from the dilution of the kagome bi-layer. The low-T analysis of the NMR lineshape suggests that the defect can be associated with a staggered spin-response to the vacancies on the kagome bi-layer. This, altogether with the maximum in the kagome bi-layer susceptibility, is very similar to what is observed in most low-dimensional antiferromagnetic correlated systems; 4) The spin glass-like freezing observed at T_g=2-4 K is not driven by the dilution-induced defects.Comment: 19 pages, 19 figures, revised version resubmitted to PRB Minor modifications: Fig.11 and discussion in Sec.V on the NMR shif

Projection Postulate and Atomic Quantum Zeno Effect

The projection postulate has been used to predict a slow-down of the time evolution of the state of a system under rapidly repeated measurements, and ultimately a freezing of the state. To test this so-called quantum Zeno effect an experiment was performed by Itano et al. (Phys. Rev. A 41, 2295 (1990)) in which an atomic-level measurement was realized by means of a short laser pulse. The relevance of the results has given rise to controversies in the literature. In particular the projection postulate and its applicability in this experiment have been cast into doubt. In this paper we show analytically that for a wide range of parameters such a short laser pulse acts as an effective level measurement to which the usual projection postulate applies with high accuracy. The corrections to the ideal reductions and their accumulation over n pulses are calculated. Our conclusion is that the projection postulate is an excellent pragmatic tool for a quick and simple understanding of the slow-down of time evolution in experiments of this type. However, corrections have to be included, and an actual freezing does not seem possible because of the finite duration of measurements.Comment: 25 pages, LaTeX, no figures; to appear in Phys. Rev.

Monetary Policy Rules and Directions of Causality: a Test for the Euro Area

Using a VAR model in first differences with quarterly data for the euro zone, the study aims to ascertain whether decisions on monetary policy can be interpreted in terms of a “monetary policy rule” with specific reference to the so-called nominal GDP targeting rule (Hall and Mankiw, 1994; McCallum, 1988; Woodford, 2012). The results obtained indicate a causal relation proceeding from deviation between the growth rates of nominal gross domestic product (GDP) and target GDP to variation in the three-month market interest rate. The same analyses do not, however, appear to confirm the existence of a significant inverse causal relation from variation in the market interest rate to deviation between the nominal and target GDP growth rates. Similar results were obtained on replacing the market interest rate with the European Central Bank refinancing interest rate. This confirmation of only one of the two directions of causality does not support an interpretation of monetary policy based on the nominal GDP targeting rule and gives rise to doubt in more general terms as to the applicability of the Taylor rule and all the conventional rules of monetary policy to the case in question. The results appear instead to be more in line with other possible approaches, such as those based on post Keynesian analyses of monetary theory and policy and more specifically the so-called solvency rule (Brancaccio and Fontana, 2013, 2015). These lines of research challenge the simplistic argument that the scope of monetary policy consists in the stabilization of inflation, real GDP, or nominal income around a “natural equilibrium” level. Rather, they suggest that central banks actually follow a more complex purpose, which is the political regulation of the financial system with particular reference to the relations between creditors and debtors and the related solvency of economic units

Current cosmological bounds on neutrino masses and relativistic relics

We combine the most recent observations of large-scale structure (2dF and SDSS galaxy surveys) and cosmic microwave anisotropies (WMAP and ACBAR) to put constraints on flat cosmological models where the number of massive neutrinos and of massless relativistic relics are both left arbitrary. We discuss the impact of each dataset and of various priors on our bounds. For the standard case of three thermalized neutrinos, we find an upper bound on the total neutrino mass sum m_nu < 1.0 (resp. 0.6) eV (at 2sigma), using only CMB and LSS data (resp. including priors from supernovae data and the HST Key Project), a bound that is quite insensitive to the splitting of the total mass between the three species. When the total number of neutrinos or relativistic relics N_eff is left free, the upper bound on sum m_nu (at 2sigma, including all priors) ranges from 1.0 to 1.5 eV depending on the mass splitting. We provide an explanation of the parameter degeneracy that allows larger values of the masses when N_eff increases. Finally, we show that the limit on the total neutrino mass is not significantly modified in the presence of primordial gravitational waves, because current data provide a clear distinction between the corresponding effects.Comment: 13 pages, 6 figure

Pembrolizumab as Consolidation Strategy in Patients with Multiple Myeloma: Results of the GEM-Pembresid Clinical Trial

PD1 expression in CD4+ and CD8+ T cells is increased after treatment in multiple myeloma patients with persistent disease. The GEM-Pembresid trial analyzed the efficacy and safety of pembrolizumab as consolidation in patients achieving at least very good partial response but with persistent measurable disease after first- or second-line treatment. Moreover, the characteristics of the immune system were investigated to identify potential biomarkers of response to pembrolizumab. One out of the 17 evaluable patients showed a decrease in the amount of M-protein, although a potential late effect of high-dose melphalan could not be ruled out. Fourteen adverse events were considered related to pembrolizumab, two of which (G3 diarrhea and G2 pneumonitis) prompted treatment discontinuation and all resolving without sequelae. Interestingly, pembrolizumab induced a decrease in the percentage of NK cells at cycle 3, due to the reduction of the circulating and adaptive subsets (0.615 vs. 0.43, p = 0.007; 1.12 vs. 0.86, p = 0.02). In the early progressors, a significantly lower expression of PD1 in CD8+ effector memory T cells (MFI 1327 vs. 926, p = 0.03) was observed. In conclusion, pembrolizumab used as consolidation monotherapy shows an acceptable toxicity profile but did not improve responses in this MM patient population. The trial was registered at clinicaltrials.gov with identifier NCT02636010 and with EUDRACT number 2015-003359-23.This study was funded by Fundación Ramón Areces (FRA 16/003). T.P. is supported by a grant from the AECC (INVES18043PAIN). This study received financial support from Merck Sharp & Dohme of Spain, a subsidiary of Merck & Co., Inc., Whitehouse Station, New Jersey, USA

Results of an early access treatment protocol of daratumumab monotherapy in spanish patients with relapsed or refractory multiple myeloma

Daratumumab is a human CD38-targeted monoclonal antibody approved as monotherapy for heavily pretreated relapsed and refractory multiple myeloma. We report findings for the Spanish cohort of an open-label treatment protocol that provided early access to daratumumab monotherapy and collected safety and patient-reported outcomes data for patients with relapsed or refractory multiple myeloma. At 15 centers across Spain, intravenous daratumumab (16mg/kg) was administered to 73 patients who had ≥3 prior lines of therapy, including a proteasome inhibitor and an immunomodulatory drug, or who were double refractory to both. The median duration of daratumumab treatment was 3.3 (range: 0.03–13.17) months, with a median number of 12 (range: 1–25) infusions. Grade 3/4 treatment-emergent adverse events were reported in 74% of patients and included lymphopenia (28.8%), thrombocytopenia (27.4%), neutropenia (21.9%), leukopenia (19.2%), and anemia (15.1%). Common (>5%) serious treatmentemergent adverse events included respiratory tract infection (9.6%), general physical health deterioration (6.8%), and back pain (5.5%). Infusion-related reactions occurred in 45% of patients. The median change from baseline in all domains of the EQ-5D-5L and EORTC QLQ-C30 was mostly 0. A total of 18 (24.7%) patients achieved a partial response or better, with 10 (13.7%) patients achieving a very good partial response or better. Median progression-free survival was 3.98 months. The results of this early access treatment protocol are consistent with previously reported trials of daratumumab monotherapy and confirm its safety and antitumoral efficacy in Spanish patients with heavily treated relapsed or refractory multiple myeloma