Pharmacological activation of mGlu5 receptors with the positive allosteric modulator, VU0360172 modulates thalamic GABAergic transmission

Previous studies have shown that injection of the mGlu5 receptor positive allosteric modulator (PAM) VU0360172 into either the thalamus or somatosensory cortex markedly reduces the frequency of spike-and-wave discharges (SWDs) in the WAG/Rij model of absence epilepsy. Here we have investigated the effects of VU0360172 on GABA transport in the thalamus and somatosensory cortex, as possible modes of action underlying the suppression of SWDs. Systemic VU0360172 injections increase GABA uptake in thalamic synaptosomes from epileptic WAG/Rij rats. Consistent with this observation, VU0360172 could also enhance thalamic GAT-1 protein expression, depending on the dosing regimen. This increase in GAT-1 expression was also observed in the thalamus from non-epileptic rats (presymptomatic WAG/Rij and Wistar) and appeared to occur selectively in neurons. The tonic GABAA receptor current present in ventrobasal thalamocortical neurons was significantly reduced by VU0360172 consistent with changes in GAT-1 and GABA uptake. The in vivo effects of VU0360172 (reduction in tonic GABA current and increase in GAT-1 expression) could be reproduced in vitro by treating thalamic slices with VU0360172 for at least 1 hour and appeared to be dependent on the activation of PLC. Thus, the effects of VU0360172 do not require an intact thalamocortical circuit. In the somatosensory cortex, VU0360172 reduced GABA uptake but did not cause significant changes in GAT-1 protein levels. These findings reveal a novel mechanism of regulation mediated by mGlu5 receptors, which could underlie the powerful anti-absence effect of mGlu5 receptor enhancers in animal models

The COVID-19 pandemic’s effects on voter turnout

The COVID-19 pandemic has increased the risk of participating in public events, among them elections. We assess whether the voter turnout in the 2020 local government elections in Italy was affected by the COVID-19 pandemic. We do so by exploiting the variation among municipalities in the intensity of the COVID-19 outbreak as measured by the mortality rate among the elderly. We find that a 1 percentage point increase in the elderly mortality rate decreased the voter turnout by 0.5 percentage points, with no gender differences in the behavioural response. The effect was especially strong in densely populated municipalities. We do not detect statistically significant heterogeneous effects between the North and the South or among different levels of autonomy from the central government

Fiscal rules and budget forecast errors of Italian municipalities

We study the impact of the domestic stability pact on the accuracy of budget forecasts of Italian municipalities. Identification of the causal effect exploits a quasi-natural experiment generated by the removal in 2001 of the fiscal restraints on budget decisions for municipalities with fewer than 5000 inhabitants and by stricter budgetary restrictions and severe penalties for noncompliers in 2002. We find that relaxing fiscal rules had a sizeable impact on budget forecast errors, especially in 2002. In fact, revenue (expenditure) forecast errors for municipalities with fewer than 5000 inhabitants became 26% (22%) larger than in the past

Fiscal rules and budget forecast errors of Italian municipalities

We study the impact of the domestic stability pact on the budget forecast errors of Italian municipalities. The identification of the causal effect exploits a quasi-natural experiment generated by the removal in 2001 of the fiscal restraints on budget decisions for municipalities with less than 5,000 inhabitants and by stricter budgetary restrictions and severe penalties for noncompliers in 2002. We find that relaxing fiscal rules had a sizeable impact on budget forecast errors, especially in 2002. Revenue (expenditure) forecast errors for municipalities below 5,000 inhabitants became indeed 26% (22%) larger than in the past

The COVID-19 pandemic’s effects on voter turnout

The COVID-19 pandemic has increased the risk of participating in public events, among them elections. We assess whether the voter turnout in the 2020 local government elections in Italy was affected by the COVID-19 pandemic. We do so by exploiting the variation among municipalities in the intensity of the COVID-19 outbreak as measured by the mortality rate among the elderly. We find that a 1 percentage point increase in the elderly mortality rate decreased the voter turnout by 0.5 percentage points, with no gender differences in the behavioural response. The effect was especially strong in densely populated municipalities. We do not detect statistically significant differences in voter turnout among different levels of autonomy from the central government

Use of Stirling cryocoolers in small-scale LNG plants: opportunities and critical issues

Nowadays an increasing numbers of small-scale LNG projects are arising in the world beside very big plants in the Asia Pacific area. In Europe a new regulatory framework is preparing the ground for the design and construction of many distributed LNG plants, with an increasing interest on micro-scale plants with production below 40TPD. In a LNG storage tank, because of the inevitably heat incomes from the ambient part of boil-off gas is generated. Especially in small-scale plants and in storage facilities, boil-off phenomena are very important and several methods are currently adopted to minimize the boil-off and re-liquefy the vaporized natural gas. Among the different technologies to carry out this process, Stirling engines used as cryocoolers prove to have a very interesting potential because they are able to achieve temperatures well below the liquefaction of the natural gas thus assuring the continuous re-liquefaction of the boil-off or the subcooling of the natural gas. In this work, the authors first analyse the most critical aspects related to the thermodynamic and operation of the LNG plants and storage that give rise to the boiloff phenomena and then evaluate the potential for the adoption of Stirling cycle cryocoolers. In particular, two small-scale LNG storage tanks with capacity of 1’500 m3 and 10’000 m3 have been considered. Despite the BOG from loading and unloading of the tanks has not been taken into account, the analysis has proved that StirLNG-4 and StirLNG-16 cryocoolers respectively are able to manage the generated BOG. Hence, the analysis has shown that commercially available Stirling cycle cryocoolers could be used to re-liquify the BOG generated in small-scale LNG plants thus enlarging the potential market of these machines

Making data platforms smarter with MOSES

The rise of data platforms has enabled the collection and processing of huge volumes of data, but has opened to the risk of losing their control. Collecting proper metadata about raw data and transformations can significantly reduce this risk. In this paper we propose MOSES, a technology-agnostic, extensible, and customizable framework for metadata handling in big data platforms. The framework hinges on a metadata repository that stores information about the objects in the big data platform and the processes that transform them. MOSES provides a wide range of functionalities to different types of users of the platform. Differently from previous high-level proposals, MOSES is fully implemented and it was not conceived for a specific technology. Besides discussing the rationale and the features of MOSES, in this paper we describe its implementation and we test it on a real case study. The ultimate goal is to take a significant step forward towards proving that metadata handling in big data platforms is feasible and beneficial

Closed Medial Malleolar Multifragment Fracture With a Posterior Tibialis Tendon Rupture: A Case Report and Review of the Literature

Ankle fractures represent an excitingfield of traumatology because of the wide variety of clinical pre-sentations, injury mechanisms, and treatment options. Rupture of the posterior tibialis tendon (PTT) withankle fracture can occur during trauma that involves pronation and external rotation of the foot or, lesscommonly, secondary to direct trauma to the ankle. This tendon injury is uncommon and probably mis-diagnosed in many cases, because of the difficult clinical examination secondary to the pain and swelling. Theidentification and early treatment of PTT tears is essential for good functional outcomes to prevent the mainmid- to long-term complication of disabling acquiredflatfoot due to tendon failure. In the present report, weprovide a review of the published data regarding ankle fractures associated with PTT rupture and describe ourexperience with a case of a multifragment medial malleolus fracture and complete rupture of the PTT diag-nosed intraoperatively and surgically treated in a 34-year-old male, with 2.5 years of follow-up

Consensus for management of sacral fractures: from the diagnosis to the treatment, with a focus on the role of decompression in sacral fractures

Abstract Background There is no evidence in the current literature about the best treatment option in sacral fracture with or without neurological impairment. Materials and methods The Italian Pelvic Trauma Association (A.I.P.) decided to organize a consensus to define the best treatment for traumatic and insufficiency fractures according to neurological impairment. Results Consensus has been reached for the following statements: When complete neurological examination cannot be performed, pelvic X-rays, CT scan, hip and pelvis MRI, lumbosacral MRI, and lower extremities evoked potentials are useful. Lower extremities EMG should not be used in an acute setting; a patient with cauda equina syndrome associated with a sacral fracture represents an absolute indication for sacral reduction and the correct timing for reduction is “as early as possible”. An isolated and incomplete radicular neurological deficit of the lower limbs does not represent an indication for laminectomy after reduction in the case of a displaced sacral fracture in a high-energy trauma, while a worsening and progressive radicular neurological deficit represents an indication. In the case of a displaced sacral fracture and neurological deficit with imaging showing no evidence of nerve root compression, a laminectomy after reduction is not indicated. In a patient who was not initially investigated from a neurological point of view, if a clinical investigation conducted after 72 h identifies a neurological deficit in the presence of a displaced sacral fracture with nerve compression on MRI, a laminectomy after reduction may be indicated. In the case of an indication to perform a sacral decompression, a first attempt with closed reduction through external manoeuvres is not mandatory. Transcondylar traction does not represent a valid method for performing a closed decompression. Following a sacral decompression, a sacral fixation (e.g. sacroiliac screw, triangular osteosynthesis, lumbopelvic fixation) should be performed. An isolated and complete radicular neurological deficit of the lower limbs represents an indication for laminectomy after reduction in the case of a displaced sacral fracture in a low-energy trauma associated with imaging suggestive of root compression. An isolated and incomplete radicular neurological deficit of the lower limbs does not represent an absolute indication. A worsening and progressive radicular neurological deficit of the lower limbs represents an indication for laminectomy after reduction in the case of a displaced sacral fracture in a low-energy trauma associated with imaging suggestive of root compression. In the case of a displaced sacral fracture and neurological deficit in a low-energy trauma, sacral decompression followed by surgical fixation is indicated. Conclusions This consensus collects expert opinion about this topic and may guide the surgeon in choosing the best treatment for these patients. Level of Evidence: IV. Trial registration: not applicable (consensus paper)