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Surgery around the ankle is increasingly embedded in outpatient treatment concepts. Unfortunately, the classic "ankle block" as a concept of regional anesthesia is inappropriate for surgery around the ankle because the injection sites are too distal to block this specific region.The "high ankle block" avoids this disadvantage by dislocating the injection points 15 cm proximal to the malleoli. Three of five peripheral nerves necessary to perform the block can be reached by a circumferential subcutaneous wall. The Posterior Tibial Nerve and the Deep Peroneal Nerve are addressed by an ultrasound guided approach.The efficacy of the technique is highlighted by a case series (3 cases) in which the new blockade was used as a stand-alone procedure, i.e. without additional general anesthesia.The "high ankle block" may serve as an ultrasound guided expansion to the classic techniques, extending the operative spectrum to the ankle region.

SummaryThe coronavirus disease 2019 (COVID-19) pandemic disrupted daily life and changes to routines were made in accordance with public health regulations. In 2020, nonpharmaceutical interventions were put in place to reduce exposure to and spread of the disease. The goal of this work was to quantify the effect of school closure during the first year of COVID-19 pandemic in Switzerland. This allowed us to determine the usefulness of school closures as a pandemic countermeasure for emerging coronaviruses in the absence of pharmaceutical interventions. The use of multivariate endemic-epidemic modelling enabled us to analyse disease spread between age groups which we believe is a necessary inclusion in any model seeking to achieve our goal. Sophisticated time-varying contact matrices encapsulating four different contact settings were included in our complex statistical modelling approach to reflect the amount of school closure in place on a given day. Using the model, we projected case counts under various transmission scenarios (driven by implemented social distancing policies). We compared these counterfactual scenarios against the true levels of social distancing policies implemented, where schools closed in the spring and reopened in the autumn. We found that if schools had been kept open, the vast majority of additional cases would be expected among primary school-aged children with a small fraction of cases percolating into other age groups following the contact matrix structure. Under this scenario where schools were kept open, the cases were highly concentrated among the youngest age group. In the scenario where schools had remained closed, most reduction would also be expected in the lowest age group with less effects seen in other groups.

Motherhood induces a drastic, sometimes long-lasting, change in internal state and behavior in many female animals. How a change in reproductive state or the discrete event of mating modulates specific female behaviors is still incompletely understood. Using calcium imaging of the whole brain of Drosophila females, we find that mating does not induce a global change in brain activity. Instead, mating modulates the pheromone response of dopaminergic neurons innervating the fly’s learning and memory center, the mushroom body (MB). Using the mating-induced increased attraction to the odor of important nutrients, polyamines, we show that disruption of the female fly’s ability to smell, for instance the pheromone cVA, during mating leads to a reduction in polyamine preference for days later indicating that the odor environment at mating lastingly influences female perception and choice behavior. Moreover, dopaminergic neurons including innervation of the β’1 compartment are sufficient to induce the lasting behavioral increase in polyamine preference. We further show that MB output neurons (MBON) of the β’1 compartment are activated by pheromone odor and their activity during mating bidirectionally modulates preference behavior in mated and virgin females. Their activity is not required, however, for the expression of polyamine attraction. Instead, inhibition of another type of MBON innervating the β’2 compartment enables expression of high odor attraction. In addition, the response of a lateral horn (LH) neuron, AD1b2, which output is required for the expression of polyamine attraction, shows a modulated polyamine response after mating. Taken together, our data in the fly suggests that mating-related sensory experience regulates female odor perception and expression of choice behavior through a dopamine-gated learning circuit.

Background & Aims: Obeticholic acid (OCA) is an agonist of the nuclear bile acid receptor farnesoid X receptor, which regulates hepatic bile acid metabolism. We tested whether OCA treatment would influence hepatic transport of conjugated bile acids in patients with primary biliary cholangitis (PBC) who responded inadequately to treatment with ursodeoxycholic acid (UDCA). Methods: Eight UDCA-treated patients with PBC with alkaline phosphatase ≥1.5 times the upper limit of normal range participated in a double-blind, placebo-controlled study. While continuing on UDCA, the patients were randomised to two 3-month crossover treatment periods with placebo and OCA, in random order, separated by a 1-month washout period without study treatment. After each of the two treatment periods, we determined rate constants for transport of conjugated bile acids between blood, hepatocytes, biliary canaliculi, and bile ducts by positron emission tomography of the liver using the conjugated bile acid tracer [N-methyl- 11C]cholylsarcosine ( 11C-CSar). The hepatic blood perfusion was measured using infusion of indocyanine green and Fick's principle. Results: Compared with placebo, OCA increased hepatic blood perfusion by a median of 11% (p = 0.045), the unidirectional uptake clearance of 11C-CSar from blood into hepatocytes by a median of 11% (p = 0.01), and the rate constant for secretion of 11C-CSar from hepatocytes into biliary canaliculi by a median of 73% (p = 0.03). This resulted in an OCA-induced decrease in the hepatocyte residence time of 11C-CSar by a median of 30% (p = 0.01), from group median 11 min to 8 min. Conclusions: This study of UDCA-treated patients with PBC showed that, compared with placebo, OCA increased the hepatic transport of the conjugated bile acid tracer 11C-CSar, and thus endogenous conjugated bile acids, from hepatocytes into biliary canaliculi. As a result, OCA reduced the time hepatocytes are exposed to potentially cytotoxic bile acids. Lay summary: Primary biliary cholangitis is a chronic liver disease in which the small bile ducts are progressively destroyed. We tested whether the treatment with obeticholic acid (OCA) would improve liver excretion of bile acids compared with placebo in 8 patients with primary biliary cholangitis. A special scanning technique (PET scan) showed that OCA increased the transport of bile acids from blood to bile. OCA thereby reduced the time that potentially toxic bile acids reside in the liver by approximately one-third.

Motherhood induces a drastic, sometimes long-lasting, change in internal state and behavior in many female animals. How a change in reproductive state or the discrete event of mating modulates specific female behaviors is still incompletely understood. Using calcium imaging of the whole brain of

Quantum mechanics describes seemingly paradoxical relations between the outcomes of measurements that cannot be performed jointly. In Hilbert space, the outcomes of such incompatible measurements are represented by non-orthogonal states. In this paper, we investigate how the relation between outcomes represented by non-orthogonal quantum states differs from the relations suggested by a joint assignment of measurement outcomes that do not depend on the actual measurement context. The analysis is based on a well-known scenario where three statements about the impossibilities of certain outcomes would seem to make a specific fourth outcome impossible as well, yet quantum theory allows the observation of that outcome with a non-vanishing probability. We show that the Hilbert space formalism modifies the relation between the four measurement outcomes by defining a lower bound of the fourth probability that increases as the total probability of the first three outcomes drops to zero. Quantum theory thus makes the violation of non-contextual consistency between the measurement outcomes not only possible, but actually requires it as a necessary consequence of the Hilbert space inner products that describe the contextual relation between the outcomes of different measurements., Comment: 10 pages, 1 figure, improved introduction and notation