Performance of the First Short Model 150-mm-Aperture Nb3Sn Quadrupole MQXFS for the High-Luminosity LHC Upgrade

The U.S. LHC Accelerator Research Program (LARP) and CERN combined their efforts in developing Nb Sn magnets for the high-luminosity LHC upgrade. The ultimate goal of this collaboration is to fabricate large aperture Nb Sn quadrupoles for the LHC interaction regions. These magnets will replace the present 70-mm-Aperture NbTi quadrupole triplets for expected increase of the LHC peak luminosity up to 5 × 10 cm s or more. Over the past decade, LARP successfully fabricated and tested short and long models of 90 and 120-mm-Aperture Nb Sn quadrupoles. Recently, the first short model of 150-mm-diameter quadrupole MQXFS was built with coils fabricated both by LARP and CERN. The magnet performance was tested at Fermilab's vertical magnet test facility. This paper reports the test results, including the quench training at 1.9 K, ramp rate and temperature dependence, as well as protection heater studies. 3 3 3 34 -2 -

Role of nucleus accumbens core but not shell in incubation of methamphetamine craving after voluntary abstinence

We recently introduced an animal model to study incubation of drug craving after prolonged voluntary abstinence, mimicking the human condition of relapse after successful contingency management treatment. Here we studied the role of the nucleus accumbens (NAc) in this model. We trained rats to self-administer a palatable solution (sucrose+maltodextrin 1%, 6 h/day, 6 days) and methamphetamine (6 h/day, 12 days). We then evaluated relapse to methamphetamine seeking after 1 and 15 days of voluntary abstinence, achieved via a discrete choice procedure between the palatable solution and methamphetamine (14 days). We used RNAscope in-situ hybridization to quantify the co-labeling of the neuronal activity marker Fos, and dopamine Drd1- and Drd2-expressing medium spiny neurons (MSNs) in NAc core and shell during the incubation tests. Next, we determined the effect of pharmacological inactivation of NAc core and shell by either GABAA and GABAB agonists (muscimol+baclofen, 50+50 ng/side), Drd1-Drd2 antagonist (flupenthixol, 10 µg/side) or the selective Drd1 or Drd2 antagonists (SCH39166 1.0 µg/side or raclopride 1.0 µg/side) during the relapse tests. Incubated methamphetamine seeking after voluntary abstinence was associated with a selective increase of Fos expression in the NAc core, but not shell, and Fos was co-labeled with both Drd1- and Drd2-MSNs. NAc core, but not shell, injections of muscimol+baclofen, flupenthixol, SCH39166, and raclopride reduced methamphetamine seeking after 15 days of abstinence. Together, our results suggest that dopamine transmission through Drd1 and Drd2 in NAc core is critical to the incubation of methamphetamine craving after voluntary abstinence

Identification of Brain Nuclei Implicated in Cocaine-Primed Reinstatement of Conditioned Place Preference: A Behaviour Dissociable from Sensitization

Relapse prevention represents the primary therapeutic challenge in the treatment of drug addiction. As with humans, drug-seeking behaviour can be precipitated in laboratory animals by exposure to a small dose of the drug (prime). The aim of this study was to identify brain nuclei implicated in the cocaine-primed reinstatement of a conditioned place preference (CPP). Thus, a group of mice were conditioned to cocaine, had this place preference extinguished and were then tested for primed reinstatement of the original place preference. There was no correlation between the extent of drug-seeking upon reinstatement and the extent of behavioural sensitization, the extent of original CPP or the extinction profile of mice, suggesting a dissociation of these components of addictive behaviour with a drug-primed reinstatement. Expression of the protein product of the neuronal activity marker c-fos was assessed in a number of brain regions of mice that exhibited reinstatement (R mice) versus those which did not (NR mice). Reinstatement generally conferred greater Fos expression in cortical and limbic structures previously implicated in drug-seeking behaviour, though a number of regions not typically associated with drug-seeking were also activated. In addition, positive correlations were found between neural activation of a number of brain regions and reinstatement behaviour. The most significant result was the activation of the lateral habenula and its positive correlation with reinstatement behaviour. The findings of this study question the relationship between primed reinstatement of a previously extinguished place preference for cocaine and behavioural sensitization. They also implicate activation patterns of discrete brain nuclei as differentiators between reinstating and non-reinstating mice

Role of projections from ventral subiculum to nucleus accumbens shell in context-induced reinstatement of heroin seeking in rats

Rationale and objective: In humans, exposure to contexts previously associated with heroin use can provoke relapse. In rats, exposure to heroin-paired contexts after extinction of drug-reinforced responding in different contexts reinstates heroin seeking. We previously demonstrated that the projections from ventral medial prefrontal cortex (vmPFC) to nucleus accumbens (NAc) shell play a role in this reinstatement. The ventral subiculum (vSub) sends glutamate projections to NAc shell and vmPFC. Here, we determined whether these projections contribute to context-induced reinstatement. Methods: We trained rats to self-administer heroin (0.05–0.1 mg/kg/infusion) for 3 h per day for 12 days; drug infusions were paired with a discrete tone–light cue. Lever pressing in the presence of the discrete cue was subsequently extinguished in a different context. We then tested the rats for reinstatement in the heroin- and extinction-associated contexts under extinction conditions. We combined Fos with the retrograde tracer Fluoro-Gold (FG) to determine projection-specific activation during the context-induced reinstatement tests. We also used anatomical disconnection procedures to determine whether the vSub → NAc shell and vSub → vmPFC projections are functionally involved in this reinstatement. Results: Exposure to the heroin but not the extinction context reinstated lever pressing. Context-induced reinstatement of heroin seeking was associated with increased Fos expression in vSub neurons, including those projecting to NAc shell and vmPFC. Anatomical disconnection of the vSub → NAc shell projection, but not the vSub → vmPFC projection, decreased this reinstatement. Conclusions: Our data indicate that the vSub → NAc shell glutamatergic projection, but not the vSub → vmPFC projection, contributes to context-induced reinstatement of heroin seeking

Coil End Optimization of the Nb3_3Sn Quadrupole for the High Luminosity LHC

As part of the Large Hadron Collider Luminosity upgrade (HiLumi-LHC) program, the US LARP collaboration and CERN are working together to design and build a 150 mm aperture quadrupole magnet that aims at providing a nominal gradient of 140 T/m. The resulting conductor peak field of more than 12 T requires the use of Nb$_{3}$Sn superconducting coils. In this paper the coil design for the quadrupole short model (SQXF) is described, focusing in particular on the optimization of the end-parts. We first describe the magnetic optimization aiming at reducing the peak field enhancement in the ends and minimizing the integrated multipole content. Then we focus on the analysis and tests performed to determine the most suitable shapes of end turns and spacers, minimizing the mechanical stress on the cables. We conclude with a detailed description of the baseline end design for the first series of the short model coils

Sustainability of health information systems: a three-country qualitative study in southern Africa

Abstract Background Health information systems are central to strong health systems. They assist with patient and program management, quality improvement, disease surveillance, and strategic use of information. Many donors have worked to improve health information systems, particularly by supporting the introduction of electronic health information systems (EHIS), which are considered more responsive and more efficient than older, paper-based systems. As many donor-driven programs are increasing their focus on country ownership, sustainability of these investments is a key concern. This analysis explores the potential sustainability of EHIS investments in Malawi, Zambia and Zimbabwe, originally supported by the United States President\u2019s Emergency Plan for AIDS Relief (PEPFAR). Methods Using a framework based on sustainability theories from the health systems literature, this analysis employs a qualitative case study methodology to highlight factors that may increase the likelihood that donor-supported initiatives will continue after the original support is modified or ends. Results Findings highlight commonalities around possible determinants of sustainability. The study found that there is great optimism about the potential for EHIS, but the perceived risks may result in hesitancy to transition completely and parallel use of paper-based systems. Full stakeholder engagement is likely to be crucial for sustainability, as well as integration with other activities within the health system and those funded by development partners. The literature suggests that a sustainable system has clearly-defined goals around which stakeholders can rally, but this has not been achieved in the systems studied. The study also found that technical resource constraints \u2013 affecting system usage, maintenance, upgrades and repairs \u2013 may limit EHIS sustainability even if these other pillars were addressed. Conclusions The sustainability of EHIS faces many challenges, which could be addressed through systems\u2019 technical design, stakeholder coordination, and the building of organizational capacity to maintain and enhance such systems. All of this requires time and attention, but is likely to enhance long-term outcomes

Sustainability of health information systems: a three-country qualitative study in southern Africa.

BackgroundHealth information systems are central to strong health systems. They assist with patient and program management, quality improvement, disease surveillance, and strategic use of information. Many donors have worked to improve health information systems, particularly by supporting the introduction of electronic health information systems (EHIS), which are considered more responsive and more efficient than older, paper-based systems. As many donor-driven programs are increasing their focus on country ownership, sustainability of these investments is a key concern. This analysis explores the potential sustainability of EHIS investments in Malawi, Zambia and Zimbabwe, originally supported by the United States President's Emergency Plan for AIDS Relief (PEPFAR).MethodsUsing a framework based on sustainability theories from the health systems literature, this analysis employs a qualitative case study methodology to highlight factors that may increase the likelihood that donor-supported initiatives will continue after the original support is modified or ends.ResultsFindings highlight commonalities around possible determinants of sustainability. The study found that there is great optimism about the potential for EHIS, but the perceived risks may result in hesitancy to transition completely and parallel use of paper-based systems. Full stakeholder engagement is likely to be crucial for sustainability, as well as integration with other activities within the health system and those funded by development partners. The literature suggests that a sustainable system has clearly-defined goals around which stakeholders can rally, but this has not been achieved in the systems studied. The study also found that technical resource constraints - affecting system usage, maintenance, upgrades and repairs - may limit EHIS sustainability even if these other pillars were addressed.ConclusionsThe sustainability of EHIS faces many challenges, which could be addressed through systems' technical design, stakeholder coordination, and the building of organizational capacity to maintain and enhance such systems. All of this requires time and attention, but is likely to enhance long-term outcomes