Congenital Toxoplasmosis in Austria: Prenatal Screening for Prevention is Cost-Saving

Background: Primary infection of Toxoplasma gondii during pregnancy can be transmitted to the unborn child and may have serious consequences, including retinochoroiditis, hydrocephaly, cerebral calcifications, encephalitis, splenomegaly, hearing loss, blindness, and death. Austria, a country with moderate seroprevalence, instituted mandatory prenatal screening for toxoplasma infection to minimize the effects of congenital transmission. This work compares the societal costs of congenital toxoplasmosis under the Austrian national prenatal screening program with the societal costs that would have occurred in a No-Screening scenario. Methodology/Principal Findings: We retrospectively investigated data from the Austrian Toxoplasmosis Register for birth cohorts from 1992 to 2008, including pediatric long-term follow-up until May 2013. We constructed a decision-analytic model to compare lifetime societal costs of prenatal screening with lifetime societal costs estimated in a No-Screening scenario. We included costs of treatment, lifetime care, accommodation of injuries, loss of life, and lost earnings that would have occurred in a No-Screening scenario and compared them with the actual costs of screening, treatment, lifetime care, accommodation, loss of life, and lost earnings. We replicated that analysis excluding loss of life and lost earnings to estimate the budgetary impact alone. Our model calculated total lifetime costs of €103 per birth under prenatal screening as carried out in Austria, saving €323 per birth compared with No-Screening. Without screening and treatment, lifetime societal costs for all affected children would have been €35 million per year; the implementation costs of the Austrian program are less than €2 million per year. Calculating only the budgetary impact, the national program was still cost-saving by more than €15 million per year and saved €258 million in 17 years. Conclusions/Significance: Cost savings under a national program of prenatal screening for toxoplasma infection and treatment are outstanding. Our results are of relevance for health care providers by supplying economic data based on a unique national dataset including long-term follow-up of affected infants

Disrupting the CH1 Domain Structure in the Acetyltransferases CBP and p300 Results in Lean Mice with Increased Metabolic Control

SummaryOpposing activities of acetyltransferases and deacetylases help regulate energy balance. Mice heterozygous for the acetyltransferase CREB binding protein (CBP) are lean and insulin sensitized, but how CBP regulates energy homeostasis is unclear. In one model, the main CBP interaction with the glucagon-responsive factor CREB is not limiting for liver gluconeogenesis, whereas a second model posits that Ser436 in the CH1 (TAZ1) domain of CBP is required for insulin and the antidiabetic drug metformin to inhibit CREB-mediated liver gluconeogenesis. Here we show that conditional knockout of CBP in liver does not decrease fasting blood glucose or gluconeogenic gene expression, consistent with the first model. However, mice in which the CBP CH1 domain structure is disrupted by deleting residues 342–393 (ΔCH1) are lean and insulin sensitized, as are p300ΔCH1 mutants. CBPΔCH1/ΔCH1 mice remain metformin responsive. An intact CH1 domain is thus necessary for normal energy storage, but not for the blood glucose-lowering actions of insulin and metformin

Extended Gravity Theories and the Einstein-Hilbert Action

I discuss the relation between arbitrarily high-order theories of gravity and scalar-tensor gravity at the level of the field equations and the action. I show that $(2n+4)$-order gravity is dynamically equivalent to Brans-Dicke gravity with an interaction potential for the Brans-Dicke field and $n$ further scalar fields. This scalar-tensor action is then conformally equivalent to the Einstein-Hilbert action with $n+1$ scalar fields. This clarifies the nature and extent of the conformal equivalence between extended gravity theories and general relativity with many scalar fields.Comment: 12 pages, Plain Latex, SUSSEX-AST-93/7-

The No-Triangle Hypothesis for N=8 Supergravity

We study the perturbative expansion of N=8 supergravity in four dimensions from the viewpoint of the ``no-triangle'' hypothesis, which states that one-loop graviton amplitudes in N=8 supergravity only contain scalar box integral functions. Our computations constitute a direct proof at six-points and support the no-triangle conjecture for seven-point amplitudes and beyond.Comment: 43page

MHV-Vertices for Gravity Amplitudes

We obtain a CSW-style formalism for calculating graviton scattering amplitudes and prove its validity through the use of a special type of BCFW-like parameter shift. The procedure is illustrated with explicit examples.Comment: 21 pages, minor typos corrected, proof added in section

Negative screening of Fabry disease in patients with conduction disorders requiring a pacemaker.

Identification of Fabry disease (FD) in cardiac patients has been restricted so far to patients with left ventricular hypertrophy. Conduction problems are frequent in FD and could precede other manifestations, offering a possible earlier diagnosis. We studied the prevalence of FD in 188 patients < 70 years with conduction problems requiring pacemaker implantation. Although classical manifestations of FD were not rare, no patient with FD was identified. Screening efforts should not be conducted in this population.post-print523 K

Identification of PKD1L1 Gene Variants in Children with the Biliary Atresia Splenic Malformation Syndrome

Biliary atresia (BA) is the most common cause of end‐stage liver disease in children and the primary indication for pediatric liver transplantation, yet underlying etiologies remain unknown. Approximately 10% of infants affected by BA exhibit various laterality defects (heterotaxy) including splenic abnormalities and complex cardiac malformations — a distinctive subgroup commonly referred to as the biliary atresia splenic malformation (BASM) syndrome. We hypothesized that genetic factors linking laterality features with the etiopathogenesis of BA in BASM patients could be identified through whole exome sequencing (WES) of an affected cohort. DNA specimens from 67 BASM subjects, including 58 patient‐parent trios, from the NIDDK‐supported Childhood Liver Disease Research Network (ChiLDReN) underwent WES. Candidate gene variants derived from a pre‐specified set of 2,016 genes associated with ciliary dysgenesis and/or dysfunction or cholestasis were prioritized according to pathogenicity, population frequency, and mode of inheritance. Five BASM subjects harbored rare and potentially deleterious bi‐allelic variants in polycystin 1‐like 1, PKD1L1, a gene associated with ciliary calcium signaling and embryonic laterality determination in fish, mice and humans. Heterozygous PKD1L1 variants were found in 3 additional subjects. Immunohistochemical analysis of liver from the one BASM subject available revealed decreased PKD1L1 expression in bile duct epithelium when compared to normal livers and livers affected by other non‐cholestatic diseases. Conclusion WES identified bi‐allelic and heterozygous PKD1L1 variants of interest in 8 BASM subjects from the ChiLDReN dataset. The dual roles for PKD1L1 in laterality determination and ciliary function suggest that PKD1L1 is a new, biologically plausible, cholangiocyte‐expressed candidate gene for the BASM syndrome

Observations of Energetic-particle Population Enhancements along Intermittent Structures near the Sun from the Parker Solar Probe

Observations at 1 au have confirmed that enhancements in measured energetic-particle (EP) fluxes are statistically associated with "rough" magnetic fields, i.e., fields with atypically large spatial derivatives or increments, as measured by the Partial Variance of Increments (PVI) method. One way to interpret this observation is as an association of the EPs with trapping or channeling within magnetic flux tubes, possibly near their boundaries. However, it remains unclear whether this association is a transport or local effect; i.e., the particles might have been energized at a distant location, perhaps by shocks or reconnection, or they might experience local energization or re-acceleration. The Parker Solar Probe (PSP), even in its first two orbits, offers a unique opportunity to study this statistical correlation closer to the corona. As a first step, we analyze the separate correlation properties of the EPs measured by the Integrated Science Investigation of the Sun (IS⊙IS) instruments during the first solar encounter. The distribution of time intervals between a specific type of event, i.e., the waiting time, can indicate the nature of the underlying process. We find that the IS⊙IS observations show a power-law distribution of waiting times, indicating a correlated (non-Poisson) distribution. Analysis of low-energy (~15 – 200 keV/nuc) IS⊙IS data suggests that the results are consistent with the 1 au studies, although we find hints of some unexpected behavior. A more complete understanding of these statistical distributions will provide valuable insights into the origin and propagation of solar EPs, a picture that should become clear with future PSP orbits

Magnetofluid dynamics of magnetized cosmic plasma: firehose and gyrothermal instabilities

Both global dynamics and turbulence in magnetized weakly collisional cosmic plasmas are described by general magnetofluid equations that contain pressure anisotropies and heat fluxes that must be calculated from microscopic plasma kinetic theory. It is shown that even without a detailed calculation of the pressure anisotropy or the heat fluxes, one finds the macroscale dynamics to be generically unstable to microscale Alfvenically polarized fluctuations. Two instabilities are considered in detail: the parallel firehose instability (including the finite-Larmor-radius effects that determine the fastest growing mode) and the gyrothermal instability (GTI). The latter is a new result - it is shown that a parallel ion heat flux destabilizes Alfvenically polarized fluctuations even in the absence of the negative pressure anisotropy required for the firehose. The main conclusion is that both pressure anisotropies and heat fluxes trigger plasma microinstabilities and, therefore, their values will likely be set by the nonlinear evolution of these instabilities. Ideas for understanding this nonlinear evolution are discussed. It is argued that cosmic plasmas will generically be "three-scale systems," comprising global dynamics, mesoscale turbulence and microscale plasma fluctuations. The astrophysical example of cool cores of galaxy clusters is considered and it is noted that observations point to turbulence in clusters being in a marginal state with respect to plasma microinstabilities and so it is the plasma microphysics that is likely to set the heating and conduction properties of the intracluster medium. In particular, a lower bound on the scale of temperature fluctuations implied by the GTI is derived.Comment: 10 pages, MNRAS tex style, 1 figur