Hungary: Amended Church Law Remains at Variance with OSCE Standards and the European Convention on Human Rights

The statement was submitted by FOREF (Forum for Religious Freedom Europe) at the 2015 OSCE Human Dimension Implementation meeting held this past September in Warsaw, Poland. The statement calls attention to continuing concerns with the state of religious freedom in Hungary. As readers of OPREE will most likely recall, Hungary\u27s anti-liberal government, led by Viktor Orbán, introduced a law on the legal status of churches in 2011 which, among other things, stripped numerous minority religious groups of legal status. In 2014 the European Court of Human Rights found that, in implementing this new law, Hungary had violated the right of religious freedom as protected in the European Convention on Human Rights. Those who observe Hungarian affairs have been waiting since that decision for the government\u27s response. Finally, in September 2015, the Ministry of Justice released a new draft of the law on church status. The statement below from FOREF is one of the first expert analyses of the draft bill to be made public. According to FOREF, the new bill would largely repackage the old law, preserving its most problematic provisions. Should the bill become law, one can expect further legal challenges before the European court in Strasbourg

Physics Case for the ILC Project: Perspective from Beyond the Standard Model

The International Linear Collider (ILC) has recently proven its technical maturity with the publication of a Technical Design Report, and there is a strong interest in Japan to host such a machine. We summarize key aspects of the Beyond the Standard Model physics case for the ILC in this contribution to the US High Energy Physics strategy process. On top of the strong guaranteed physics case in the detailed exploration of the recently discovered Higgs boson, the top quark and electroweak precision measurements, the ILC will offer unique opportunities which are complementary to the LHC program of the next decade. Many of these opportunities have connections to the Cosmic and Intensity Frontiers, which we comment on in detail. We illustrate the general picture with examples of how our world could turn out to be and what the ILC would contribute in these cases, with an emphasis on value-added beyond the LHC. These comprise examples from Supersymmetry including light Higgsinos, a comprehensive bottom-up coverage of NLSP-LSP combinations for slepton, squark, chargino and neutralino NLSP, a stau-coannihilation dark matter scenario and bilinear R-parity violation as explanation for neutrino masses and mixing, as well as generic WIMP searches and Little Higgs models as non-SUSY examples.Comment: 20 pages, 10 figures. Contributed to Snowmass Community Summer Study 201

Quantitative constraints on the gluon distribution function in the proton from collider isolated-photon data

The impact of isolated-photon data from proton-(anti)proton collisions at RHIC, SppbarS, Tevatron and LHC energies, on the parton distribution functions of the proton is studied using a recently developed Bayesian reweighting method. The impact on the gluon density of the 35 existing isolated-gamma measurements is quantified using next-to-leading order (NLO) perturbative QCD calculations complemented with the NNPDF2.1 parton densities. The NLO predictions are found to describe well most of the datasets from 200 GeV up to 7 TeV centre-of-mass energies. The isolated-photon spectra recently measured at the LHC are precise enough to constrain the gluon distribution and lead to a moderate reduction (up to 20%) of its uncertainties around fractional momenta x~0.02. As a particular case, we show that the improved gluon density reduces the PDF uncertainty for the Higgs boson production cross section in the gluon-fusion channel by more than 20% at the LHC. We conclude that present and future isolated-photon measurements constitute an interesting addition to coming global PDF analyses.Comment: 30 pages, 20 figures. Few minor changes to match the published NPB versio

Rapid prototyping of patterned functional nanostructures

Living systems exhibit form and function on multiple length scales, and the prospect of imparting life-like qualities to man-made materials has inspired many recent efforts to devise hierarchical materials assembly strategies. For example, Yang et al. grew surfactant-templated mesoporous silica on hydrophobic patterns prepared by micro-contact printing {micro}CP{sup 3}. Trau et al. formed oriented mesoporous silica patterns, using a micro-molding in capillaries MIMIC technique, and Yang et al. combined MIMIC, polystyrene sphere templating, and surfactant-templating to create oxides with three levels of structural order. Overall, great progress has been made to date in controlling structure on scales ranging from several nanometers to several micrometers. However, materials prepared have been limited to oxides with no specific functionality, whereas for many of the envisioned applications of hierarchical materials in micro-systems, sensors, waveguides, photonics, and electronics, it is necessary to define both form and function on several length scales. In addition, the patterning strategies employed thus far require hours or even days for completion. Such slow processes are inherently difficult to implement in commercial environments. The authors have combined evaporation-induced (silica/surfactant) self-assembly EISA with rapid prototyping techniques like pen lithography, ink-jet printing, and dip-coating on micro-contact printed substrates to form hierarchically organized structures in seconds. In addition, by co-condensation of tetrafunctional silanes (Si(OR){sub 4}) with tri-functional organosilanes ((RO){sub 3}SiR{prime}){sup 12--14} or by inclusion of organic additives, the authors have selectively derivatized the silica framework with functional R{prime} ligands or molecules. The resulting materials exhibit form and function on multiple length scales: on the molecular scale, functional organic moieties are positioned on pore surfaces, on the mesoscale, monosized pores are organized into 1-, 2-, or 3-dimensional networks, providing size-selective accessibility from the gas or liquid phase, and on the macroscale, 2-dimensional arrays and fluidic or photonic systems may be defined

US Cosmic Visions: New Ideas in Dark Matter 2017: Community Report

This white paper summarizes the workshop "U.S. Cosmic Visions: New Ideas in Dark Matter" held at University of Maryland on March 23-25, 2017.Comment: 102 pages + reference

MEtop - a generator for single top production via FCNC interactions

We present a generator for single top quark production via flavour-changing neutral currents. The MEtop event generator allows for Next-to-Leading-Order direct top production $pp \to t$ and Leading-Order production of several other single top processes. A few packages with definite sets of dimension six operators are available. We discuss how to improve the bounds on the effective operators and how well new physics can be probed with each set of independent dimension six operators.Comment: 26 pages, 22 figure

The cold-induced lipokine 12,13-diHOME promotes fatty acid transport into brown adipose tissue

Brown adipose tissue (BAT) and beige adipose tissue combust fuels for heat production in adult humans, and so constitute an appealing target for the treatment of metabolic disorders such as obesity, diabetes and hyperlipidemia1,2. Cold exposure can enhance energy expenditure by activating BAT, and it has been shown to improve nutrient metabolism3–5. These therapies, however, are time consuming and uncomfortable, demonstrating the need for pharmacological interventions. Recently, lipids have been identified that are released from tissues and act locally or systemically to promote insulin sensitivity and glucose tolerance; as a class, these lipids are referred to as ‘lipokines’6–8. Because BAT is a specialized metabolic tissue that takes up and burns lipids and is linked to systemic metabolic homeostasis, we hypothesized that there might be thermogenic lipokines that activate BAT in response to cold. Here we show that the lipid 12,13-dihydroxy-9Z-octadecenoic acid (12,13-diHOME) is a stimulator of BAT activity, and that its levels are negatively correlated with body-mass index and insulin sensitivity. Using a global lipidomic analysis, we found that 12,13-diHOME was increased in the circulation of humans and mice exposed to cold. Furthermore, we found that the enzymes that produce 12,13-diHOME were uniquely induced in BAT by cold stimulation. The injection of 12,13-diHOME acutely activated BAT fuel uptake and enhanced cold tolerance, which resulted in decreased levels of serum triglycerides. Mechanistically, 12,13-diHOME increased fatty acid (FA) uptake into brown adipocytes by promoting the translocation of the FA transporters FATP1 and CD36 to the cell membrane. These data suggest that 12,13-diHOME, or a functional analog, could be developed as a treatment for metabolic disorders

Relevance of genetic testing in the gene-targeted trial era: the Rostock Parkinsons disease study.

Estimates of the spectrum and frequency of pathogenic variants in Parkinsons disease (PD) in different populations are currently limited and biased. Furthermore, although therapeutic modification of several genetic targets has reached the clinical trial stage, a major obstacle in conducting these trials is that PD patients are largely unaware of their genetic status and, therefore, cannot be recruited. Expanding the number of investigated PD-related genes and including genes related to disorders with overlapping clinical features in large, well-phenotyped PD patient groups is a prerequisite for capturing the full variant spectrum underlying PD and for stratifying and prioritizing patients for gene-targeted clinical trials. The Rostock Parkinsons disease (ROPAD) study is an observational clinical study aiming to determine the frequency and spectrum of genetic variants contributing to PD in a large international cohort. We investigated variants in 50 genes with either an established relevance for PD or possible phenotypic overlap in a group of 12 580 PD patients from 16 countries [62.3% male; 92.0% White; 27.0% positive family history (FH+), median age at onset (AAO) 59 years] using a next-generation sequencing panel. Altogether, in 1864 (14.8%) ROPAD participants (58.1% male; 91.0% White, 35.5% FH+, median AAO 55 years), a PD-relevant genetic test (PDGT) was positive based on GBA1 risk variants (10.4%) or pathogenic/likely pathogenic variants in LRRK2 (2.9%), PRKN (0.9%), SNCA (0.2%) or PINK1 (0.1%) or a combination of two genetic findings in two genes (∼0.2%). Of note, the adjusted positive PDGT fraction, i.e. the fraction of positive PDGTs per country weighted by the fraction of the population of the world that they represent, was 14.5%. Positive PDGTs were identified in 19.9% of patients with an AAO ≤ 50 years, in 19.5% of patients with FH+ and in 26.9% with an AAO ≤ 50 years and FH+. In comparison to the idiopathic PD group (6846 patients with benign variants), the positive PDGT group had a significantly lower AAO (4 years, P = 9 × 10-34). The probability of a positive PDGT decreased by 3% with every additional AAO year (P = 1 × 10-35). Female patients were 22% more likely to have a positive PDGT (P = 3 × 10-4), and for individuals with FH+ this likelihood was 55% higher (P = 1 × 10-14). About 0.8% of the ROPAD participants had positive genetic testing findings in parkinsonism-, dystonia/dyskinesia- or dementia-related genes. In the emerging era of gene-targeted PD clinical trials, our finding that ∼15% of patients harbour potentially actionable genetic variants offers an important prospect to affected individuals and their families and underlines the need for genetic testing in PD patients. Thus, the insights from the ROPAD study allow for data-driven, differential genetic counselling across the spectrum of different AAOs and family histories and promote a possible policy change in the application of genetic testing as a routine part of patient evaluation and care in PD

Impact of prior therapies and subsequent transplantation on outcomes in adult patients with relapsed or refractory B-cell acute lymphoblastic leukemia treated with brexucabtagene autoleucel in ZUMA-3

Background Brexucabtagene autoleucel (brexu-cel) is an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy approved in the USA for adults with relapsed or refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL) and in the European Union for patients ≥26 years with R/R B-ALL. After 2 years of follow-up in ZUMA-3, the overall complete remission (CR) rate (CR+CR with incomplete hematological recovery (CRi)) was 73%, and the median overall survival (OS) was 25.4 months in 78 Phase 1 and 2 patients with R/R B-ALL who received the pivotal dose of brexu-cel. Outcomes by prior therapies and subsequent allogeneic stem cell transplantation (alloSCT) are reported. Methods Eligible adults had R/R B-ALL and received one infusion of brexu-cel (1×106 CAR T cells/kg) following conditioning chemotherapy. The primary endpoint was the CR/CRi rate per central review. Post hoc subgroup analyses were exploratory with descriptive statistics provided. Results Phase 1 and 2 patients (N=78) were included with median follow-up of 29.7 months (range, 20.7-58.3). High CR/CRi rates were observed across all prior therapy subgroups examined: 1 prior line of therapy (87%, n=15) and ≥2 prior lines (70%, n=63); prior blinatumomab (63%, n=38) and no prior blinatumomab (83%, n=40); prior inotuzumab (59%, n=17) and no prior inotuzumab (77%, n=61); and prior alloSCT (76%, n=29) and no prior alloSCT (71%, n=49). The frequency of Grade ≥3 cytokine release syndrome, neurological events, and treatment-related Grade 5 adverse events were largely similar among prior therapy subgroups. Median duration of remission (DOR) in responders with (n=14) and without (n=43) subsequent alloSCT was 44.2 (95% CI, 8.1 to not estimable (NE)) and 18.6 months (95% CI, 9.4 to NE); median OS was 47.0 months (95% CI, 10.2 to NE) and not reached (95% CI, 23.2 to NE), respectively. Median DOR and OS were not reached in responders without prior or subsequent alloSCT (n=22). Conclusions In ZUMA-3, adults with R/R B-ALL benefited from brexu-cel, regardless of prior therapies and subsequent alloSCT status, though survival appeared better in patients without certain prior therapies and in earlier lines of therapy. Additional studies are needed to determine the impact prior therapies and subsequent alloSCT have on outcomes of patients who receive brexu-cel

Evaluation of individual and ensemble probabilistic forecasts of COVID-19 mortality in the United States

Short-term probabilistic forecasts of the trajectory of the COVID-19 pandemic in the United States have served as a visible and important communication channel between the scientific modeling community and both the general public and decision-makers. Forecasting models provide specific, quantitative, and evaluable predictions that inform short-term decisions such as healthcare staffing needs, school closures, and allocation of medical supplies. Starting in April 2020, the US COVID-19 Forecast Hub (https://covid19forecasthub.org/) collected, disseminated, and synthesized tens of millions of specific predictions from more than 90 different academic, industry, and independent research groups. A multimodel ensemble forecast that combined predictions from dozens of groups every week provided the most consistently accurate probabilistic forecasts of incident deaths due to COVID-19 at the state and national level from April 2020 through October 2021. The performance of 27 individual models that submitted complete forecasts of COVID-19 deaths consistently throughout this year showed high variability in forecast skill across time, geospatial units, and forecast horizons. Two-thirds of the models evaluated showed better accuracy than a naïve baseline model. Forecast accuracy degraded as models made predictions further into the future, with probabilistic error at a 20-wk horizon three to five times larger than when predicting at a 1-wk horizon. This project underscores the role that collaboration and active coordination between governmental public-health agencies, academic modeling teams, and industry partners can play in developing modern modeling capabilities to support local, state, and federal response to outbreaks