PMF the front end electronic for the ALFA detector

International audienceThe PMF (Photo Multiplier Front end) is the front end electronics designed for the ATLAS luminometer ALFA (Absolute Luminosity For ATLAS) made of 20 staggered U-V scintillating fiber layers inserted in Roman Pots (eight in total). Each of these plans is made of 64 fibers. The PMF consists of a 64 channels photomultiplier (MAPMT) and a very compact stack of three different PCBs (3x3 cm2), mounted directly on the back and in the shadow of the MAPMT: a board which brings the high voltage to the MAPMT, an intermediate board used to send the signals to connectors located on the edge and, finally, a board with the readout chip MAROC (Multi Anode Read Out Chip), directly bonded on the PCB, on one side and a FPGA on the other. The 64 inputs MAROC ASIC allows correcting for the gain spread of MAPMT channels thanks to a 6 bits variable gain preamplifier. For each channel the signal is shaped (fast shaper, 15ns) and discriminated to produce a trigger output. A multiplexed charge output is also produced both in analog and digital thanks to a Wilkinson ADC. The main requirements are the following: 100 % trigger efficiency for a signal greater than 1/3 of a photoelectron, a charge measurement up to 30 photoelectrons with a linearity of 2 % or better and a cross talk of 1 % or less. The performances of the second version of MAROC were checked successfully during the year 2007 at LAL-Orsay. A nice dispersion of the trigger output (± 5 fC) was, in particular, observed. A sample of PMFs was produced during autumn 2007 as a prototype. Laboratory tests were performed both at LAL and CERN respectively on the third PCB (the one with MAROC) and on a full PMF equipped with a MAPMT illuminated by a LED. They were carried out using dedicated test board and acquisition software and have allowed the approval of the design and the green light for the final production and integration with the detector. Beam tests of a complete Roman Pot, equipped with 23 PMFs, will take place during summer 2008 for two periods and will conclude the test phase and mark the beginning of the final production

Growth and welfare in mixed health system financing with physician dual practice in a developing economy: a case of Indonesia

Based on Indonesia’s hybrid BPJS Kesehatan health system, we analyze for welfare-optimal government financing strategy in an economy with a mixed health system using an endogenous growth framework with physician dual practice. We find the model solution to produce two vastly different regimes in terms of policy implications: a “high” public-sector congestion regime as in the benchmark case of Indonesia, and a “low” public-sector congestion, high capacity regime. In the former, welfare-optimal health financing strategy appears to be promoting private health service. In contrast, in the low-congestion, high capacity regime, a welfare-optimal strategy is to do the opposite of increasing government physician wage at the expense of private health subsidy. These results highlight the importance of developing a benchmarking system that measures the actual degree of congestion faced by the public health service in a developing economy, as it ultimately would influence the optimal health financing strategy to be pursued

Improving biomass production and saccharification in Brachypodium distachyon through overexpression of a sucrose-phosphate synthase from sugarcane

The substitution of fossil by renewable energy sources is a major strategy in reducing CO2 emission and mitigating climate change. In the transport sector, which is still mainly dependent on liquid fuels, the production of second generation ethanol from lignocellulosic feedstock is a promising strategy to substitute fossil fuels. The main prerequisites on designated crops for increased biomass production are high biomass yield and optimized saccharification for subsequent use in fermentation processes. We tried to address these traits by the overexpression of a sucrose-phosphate synthase gene (SoSPS) from sugarcane (Saccharum officinarum) in the model grass Brachypodium distachyon. The resulting transgenic B. distachyon lines not only revealed increased plant height at early growth stages but also higher biomass yield from fully senesced plants, which was increased up to 52 % compared to wild-type. Additionally, we determined higher sucrose content in senesced leaf biomass from the transgenic lines, which correlated with improved biomass saccharification after conventional thermo-chemical pretreatment and enzymatic hydrolysis. Combining increased biomass production and saccharification efficiency in the generated B. distachyon SoSPS overexpression lines, we obtained a maximum of 74 % increase in glucose release per plant compared to wild-type. Therefore, we consider SoSPS overexpression as a promising approach in molecular breeding of energy crops for optimizing yields of biomass and its utilization in second generation biofuel production

Comparing generic drug markets in Europe and the United States: prices, volumes, and spending

Our study indicates that there are opportunities for cost savings in generic drug markets in Europe and the United States. Regulators should make it easier for generic drugs to reach the market. Regulators and payers should apply measures to stimulate price competition among generic drugmakers and to increase generic drug use. To meaningfully evaluate policy options, it is important to analyze historical context and understand why similar initiatives failed previously. Context: Rising drug prices are putting pressure on health care budgets. Policymakers are assessing how they can save money through generic drugs. Methods: We compared generic drug prices and market shares in 13 European countries, using data from 2013, to assess the amount of variation that exists between countries. To place these results in context, we reviewed evidence from recent studies on the prices and use of generics in Europe and the United States. We also surveyed peer‐reviewed studies, gray literature, and books published since 2000 to (1) outline existing generic drug policies in European countries and the United States; (2) identify ways to increase generic drug use and to promote price competition among generic drug companies; and (3) explore barriers to implementing reform of generic drug policies, using a historical example from the United States as a case study. Findings: The prices and market shares of generics vary widely across Europe. For example, prices charged by manufacturers in Switzerland are, on average, more than 2.5 times those in Germany and more than 6 times those in the United Kingdom, based on the results of a commonly used price index. The proportion of prescriptions filled with generics ranges from 17% in Switzerland to 83% in the United Kingdom. By comparison, the United States has historically had low generic drug prices and high rates of generic drug use (84% in 2013), but has in recent years experienced sharp price increases for some off‐patent products. There are policy solutions to address issues in Europe and the United States, such as streamlining the generic drug approval process and requiring generic prescribing and substitution where such policies are not yet in place. The history of substitution laws in the United States provides insights into the economic, political, and cultural issues influencing the adoption of generic drug policies. Conclusions: Governments should apply coherent supply‐ and demand‐side policies in generic drug markets. An immediate priority is to convince more physicians, pharmacists, and patients that generic drugs are bioequivalent to branded products. Special‐interest groups continue to obstruct reform in Europe and the United States

Management of chronic hepatitis B in childhood: ESPGHAN clinical practice guidelines: Consensus of an expert panel on behalf of the European Society of Pediatric Gastroenterology, Hepatology and Nutrition

More than 360 million persons worldwide (6% of the world population) are chronically infected by the hepatitis B Virus (HBV). Although the incidence of HBV infection has dramatically declined since the implementation of universal immunization programs in several countries and blood-donor screening, a significant number of children are still infected each year, often developing chronic infection and requiring appropriate followup [1]. Despite a rather benign course of chronic hepatitis B (CHB) during childhood and adolescence, 3-5% and 0.01-0.03% of chronic carriers develop cirrhosis or hepatocellular carcinoma (HCC), respectively, before adulthood [2,3]. Such a risk for HCC rises to 9-24% when considering the whole lifetime, with an incidence of cirrhosis of 2-3% per year [4,5]. Worldwide universal vaccination remains the goal for eliminating HBV infection and its complications. Treatment of CHB in childhood has been hampered by the chronic delay in licensing new drugs for pediatric use. Safe and effective antiviral therapies are available in adults, but few are labeled for the use in children, and an accurate selection of whom to treat and the identification of the right timing for treatment are needed to optimize response and reduce the risk of antiviral resistance. Although several guidelines on the management of adult patients with CHB have been published by major international societies, the clinical approach to infected children is still evolving, and is mostly based on consensus of expert opinion [6-9]

SPARC: a matricellular regulator of tumorigenesis

Although many clinical studies have found a correlation of SPARC expression with malignant progression and patient survival, the mechanisms for SPARC function in tumorigenesis and metastasis remain elusive. The activity of SPARC is context- and cell-type-dependent, which is highlighted by the fact that SPARC has shown seemingly contradictory effects on tumor progression in both clinical correlative studies and in animal models. The capacity of SPARC to dictate tumorigenic phenotype has been attributed to its effects on the bioavailability and signaling of integrins and growth factors/chemokines. These molecular pathways contribute to many physiological events affecting malignant progression, including extracellular matrix remodeling, angiogenesis, immune modulation and metastasis. Given that SPARC is credited with such varied activities, this review presents a comprehensive account of the divergent effects of SPARC in human cancers and mouse models, as well as a description of the potential mechanisms by which SPARC mediates these effects. We aim to provide insight into how a matricellular protein such as SPARC might generate paradoxical, yet relevant, tumor outcomes in order to unify an apparently incongruent collection of scientific literature

Genetic background of congenital chloride diarrhea in high-incidence populations: Finland, Poland, and Saudi Arabia and Kuwait.

Congenital chloride diarrhea (CLD) is an inherited intestinal disorder caused by mutations in the down-regulated in adenoma gene. In Finland, the disease is prevalent because of a founder effect, and all but one of the CLD-associated chromosomes carry the same mutation, V317del. In Poland, another area with a high incidence of CLD, as many as seven different mutations have been detected so far. A third known cluster of CLD, around the Persian Gulf, has not been genetically studied. We studied the allelic diversity of CLD in Poland, in Saudi Arabia and Kuwait, and in three isolated families from North America and Hong Kong. Altogether, eight novel mutations were identified, making a total of 19 known CLD gene mutations. The Polish major mutation I675-676ins was found in 47% of the Polish CLD-associated chromosomes. Haplotype analysis and clustering of the I675-676ins mutation supported a founder effect and common ancestral origin. As in Finland, a major founder effect was observed in Arab patients: 94% of the CLD-associated chromosomes carried a nonsense mutation, G187X, which occurred in either a conserved ancestral haplotype or its derivative. Our data confirm that the same locus is mutated in all cases of CLD studied so far. In Poland, a relatively common founder mutation is likely to highlight a set of rare mutations that would very rarely produce homozygosity alone. This suggests that mutations in the CLD locus are not rare events. Although the disease is thought to be rare, undiagnosed patients may not be uncommon

PMF: the front end electronic of the ALFA detector

The front end electronic (PMF) of the future ATLAS luminometer is described here. It is composed of a MAPMT and a compact stack of three PCBs, which deliver high voltage, route and read out of the output signals. The third board contains an FPGA and MAROC, a 64-channel ASIC, which can correct the non-uniformity of the MAPMT channels gain, thanks to a variable gain preamplifier. Its main role is to shape and discriminate the input signals at 1/3 photo-electron and produce 64 trigger outputs. Laboratory tests performed on prototype and pre-series PMFs have showed performances in good agreement with the requirements and have fulfilled the approval criteria for the final production of all elements