"Of Mice and Measures": A Project to Improve How We Advance Duchenne Muscular Dystrophy Therapies to the Clinic

A new line of dystrophic mdx mice on the DBA/2J (D2) background has emerged as a candidate to study the efficacy of therapeutic approaches for Duchenne muscular dystrophy (DMD). These mice harbor genetic polymorphisms that appear to increase the severity of the dystropathology, with disease modifiers that also occur in DMD patients, making them attractive for efficacy studies and drug development. This workshop aimed at collecting and consolidating available data on the pathological features and the natural history of these new D2/mdx mice, for comparison with classic mdx mice and controls, and to identify gaps in information and their potential value. The overall aim is to establish guidance on how to best use the D2/mdx mouse model in preclinical studies

Climate Dynamics: A Network-Based Approach for the Analysis of Global Precipitation

Precipitation is one of the most important meteorological variables for defining the climate dynamics, but the spatial patterns of precipitation have not been fully investigated yet. The complex network theory, which provides a robust tool to investigate the statistical interdependence of many interacting elements, is used here to analyze the spatial dynamics of annual precipitation over seventy years (1941-2010). The precipitation network is built associating a node to a geographical region, which has a temporal distribution of precipitation, and identifying possible links among nodes through the correlation function. The precipitation network reveals significant spatial variability with barely connected regions, as Eastern China and Japan, and highly connected regions, such as the African Sahel, Eastern Australia and, to a lesser extent, Northern Europe. Sahel and Eastern Australia are remarkably dry regions, where low amounts of rainfall are uniformly distributed on continental scales and small-scale extreme events are rare. As a consequence, the precipitation gradient is low, making these regions well connected on a large spatial scale. On the contrary, the Asiatic South-East is often reached by extreme events such as monsoons, tropical cyclones and heat waves, which can all contribute to reduce the correlation to the short-range scale only. Some patterns emerging between mid-latitude and tropical regions suggest a possible impact of the propagation of planetary waves on precipitation at a global scale. Other links can be qualitatively associated to the atmospheric and oceanic circulation. To analyze the sensitivity of the network to the physical closeness of the nodes, short-term connections are broken. The African Sahel, Eastern Australia and Northern Europe regions again appear as the supernodes of the network, confirming furthermore their long-range connection structure. Almost all North-American and Asian nodes vanish, revealing that extreme events can enhance high precipitation gradients, leading to a systematic absence of long-range patterns

Biopsy confirmation of metastatic sites in breast cancer patients:clinical impact and future perspectives

Determination of hormone receptor (estrogen receptor and progesterone receptor) and human epidermal growth factor receptor 2 status in the primary tumor is clinically relevant to define breast cancer subtypes, clinical outcome,and the choice of therapy. Retrospective and prospective studies suggest that there is substantial discordance in receptor status between primary and recurrent breast cancer. Despite this evidence and current recommendations,the acquisition of tissue from metastatic deposits is not routine practice. As a consequence, therapeutic decisions for treatment in the metastatic setting are based on the features of the primary tumor. Reasons for this attitude include the invasiveness of the procedure and the unreliable outcome of biopsy, in particular for biopsies of lesions at complex visceral sites. Improvements in interventional radiology techniques mean that most metastatic sites are now accessible by minimally invasive methods, including surgery. In our opinion, since biopsies are diagnostic and changes in biological features between the primary and secondary tumors can occur, the routine biopsy of metastatic disease needs to be performed. In this review, we discuss the rationale for biopsy of suspected breast cancer metastases, review issues and caveats surrounding discordance of biomarker status between primary and metastatic tumors, and provide insights for deciding when to perform biopsy of suspected metastases and which one (s) to biopsy. We also speculate on the future translational implications for biopsy of suspected metastatic lesions in the context of clinical trials and the establishment of bio-banks of biopsy material taken from metastatic sites. We believe that such bio-banks will be important for exploring mechanisms of metastasis. In the future,advances in targeted therapy will depend on the availability of metastatic tissue

Neonicotinoid pesticide limits improvement in buzz pollination by bumblebees

Neonicotinoid pesticides have been linked to global declines of beneficial insects such as bumblebees. Exposure to trace levels of these chemicals causes sub-lethal effects, such as reduced learning and foraging efficiency. Complex behaviours may be particularly vulnerable to the neurotoxic effects of neonicotinoids. Such behaviours may include buzz pollination (sonication), in which pollinators, usually bees, use innate and learned behaviours to generate high-frequency vibrations to release pollen from flowers with specialised anther morphologies. This study assesses the effect of field-realistic, chronic exposure to the widely-used neonicotinoid thiamethoxam on the development of sonication buzz characteristics over time, as well as the collection of pollen from buzz-pollinated flowers. We found that the pollen collection of exposed bees improved less with increasing experience than that of unexposed bees, with exposed bees collecting between 47% and 56% less pollen by the end of 10 trials. We also found evidence of two distinct strategies for maximising pollen collection: (1) extensions to the duration of individual buzzes and (2) extensions of the overall time spent buzzing. We find new complexities in buzz pollination, and conclude that the impacts of field-realistic exposure to a neonicotinoid pesticide may seriously compromise this important ecosystem service

Acute thrombosis of the superior mesenteric artery in a 39-year-old woman with protein-S deficiency: a case report

<p>Abstract</p> <p>Introduction</p> <p>Acute thromboembolic occlusion of the superior mesenteric artery is a condition with an unfavorable prognosis. Treatment of this condition is focused on early diagnosis, surgical or intravascular restoration of blood flow to the ischemic intestine, surgical resection of the necrotic bowel and supportive intensive care. In this report, we describe a case of a 39-year-old woman who developed a small bowel infarct because of an acute thrombotic occlusion of the superior mesenteric artery, also involving the splenic artery.</p> <p>Case presentation</p> <p>A 39-year-old Caucasian woman presented with acute abdominal pain and signs of intestinal occlusion. The patient was given an abdominal computed tomography scan and ultrasonography in association with Doppler ultrasonography, highlighting a thrombosis of the celiac trunk, of the superior mesenteric artery, and of the splenic artery. She immediately underwent an explorative laparotomy, and revascularization was performed by thromboendarterectomy with a Fogarty catheter. In the following postoperative days, she was given a scheduled second and third look, evidencing necrotic jejunal and ileal handles. During all the surgical procedures, we performed intraoperative Doppler ultrasound of the superior mesenteric artery and celiac trunk to control the arterial flow without evidence of a new thrombosis.</p> <p>Conclusion</p> <p>Acute mesenteric ischemia is a rare abdominal emergency that is characterized by a high mortality rate. Generally, acute mesenteric ischemia is due to an impaired blood supply to the intestine caused by thromboembolic phenomena. These phenomena may be associated with a variety of congenital prothrombotic disorders. A prompt diagnosis is a prerequisite for successful treatment. The treatment of choice remains laparotomy and thromboendarterectomy, although some prefer an endovascular approach. A second-look laparotomy could be required to evaluate viable intestinal handles. Some authors support a laparoscopic second-look. The possibility of evaluating the arteriotomy, during a repeated laparotomy with a Doppler ultrasound, is crucial to show a new thrombosis. Although the prognosis of acute mesenteric ischemia due to an acute arterial mesenteric thrombosis remains poor, a prompt diagnosis, aggressive surgical treatment and supportive intensive care unit could improve the outcome for patients with this condition.</p

Effects of external irradiation of the neck region on intima media thickness of the common carotid artery

<p>Abstract</p> <p>Background</p> <p>Several studies have shown that common carotid intima-media thickness (IMT) is increased after radiotherapy (RT) to the head and neck. However, further studies are needed to define the exact mechanism of radiation-induced injury in large vessels, investigate the relationship between radiation dose and large vessel injury and evaluate the rate of progress of atherosclerosis in irradiated vessels.</p> <p>Objectives</p> <p>To investigate whether external irradiation to the carotid area has any effect on IMT of the common carotid artery in a group of patients who received RT vs control group matched for age, gender and race.</p> <p>Methods</p> <p>We studied 19 patients (10 male; 47.8 ± 17.4 years) during a 5-month period (January 2009-July 2009); they had completed RT with a mean of 2.9 years before (range: 1 month-6 years) The mean radiation dose to the neck in the irradiated patients was 41.2 ± 15.6 Gy (range: 25-70 Gy). Common carotid IMT was measured with echo-color Doppler. Nineteen healthy adult patients (10 male; 47.8 ± 17.6) were recruited as a control group.</p> <p>Results</p> <p>IMT was not significantly higher in patients when compared to the control group (0.59 ± 0.16 vs 0.56 ± 0.16 mm, p = 0.4). There was no significant difference between the two groups in relation to the absence (p = 0.7) or presence (p = 0.6) of vascular risk factors. Although the difference did not reach statistical significance (p = 0.1), the irradiated young patients (age ≤ 52 years) had IMT measurements higher (0.54 ± 0.08 mm) than the non-irradiated young patients (0.49 ± 0.14 mm). The mean carotid IMT increased with increasing doses of radiation to the neck (p = 0.04).</p> <p>Conclusion</p> <p>This study shows that increased IMT of the common carotid artery after RT is radiation-dose-related. Therefore it is important to monitor IMT, which can be used as an imaging biomarker for early diagnosis of cerebrovascular disease in patients who have had radiotherapy for treatment of cancer of the head and neck and who are at increased risk for accelerated atherosclerosis in carotid arteries.</p

Ductility of wide-beam RC frames as lateral resisting system

[EN] Some Mediterranean seismic codes consider wide-beam reinforced concrete moment resisting frames (WBF) as horizontal load carrying systems that cannot guarantee high ductility performances. Conversely, Eurocode 8 allows High Ductility Class (DCH) design for such structural systems. Code prescriptions related to WBF are systematically investigated. In particular, lesson learnt for previous earthquakes, historical reasons, and experimental and numerical studies underpinning specific prescriptions on wide beams in worldwide seismic codes are discussed. Local and global ductility of WBF are then analytically investigated through (1) a parametric study on chord rotations of wide beams with respect to that of deep beams, and (2) a spectral-based comparison of WBF with conventional reinforced concrete moment resisting frames (i.e. with deep beams). Results show that the set of prescriptions given by modern seismic codes provides sufficient ductility to WBF designed in DCH. In fact, global capacity of WBF relies more on the lateral stiffness of the frames and on the overstrength of columns rather than on the local ductility of wide beams, which is systematically lower with respect to that of deep beams.Gómez-Martínez, F.; Alonso Durá, A.; De Luca, F.; Verderame, GM. (2016). Ductility of wide-beam RC frames as lateral resisting system. Bulletin of Earthquake Engineering. 14(6):1545-1569. doi:10.1007/s10518-016-9891-xS15451569146ACI (1989) Building code requirements for reinforced concrete (ACI 318-89). ACI Committee 318, American Concrete Institute, Farmington Hills, Michigan, USAACI (2008) Building code requirements for structural concrete (ACI 318-08) and commentary (318-08). ACI Committee 318, American Concrete Institute, Farmington Hills, Michigan, USAACI-ASCE (1991) Recommendations for design of beam-column connections in monolithic reinforced concrete structures (ACI 352R-91). Joint ACI-ASCE Committee 352, American Concrete Institute, Farmington Hills, Michigan, USAACI-ASCE (2002) Recommendations for design of beam-column connections in monolithic reinforced concrete structures (ACI 352R-02). Joint ACI-ASCE Committee 352, American Concrete Institute, Farmington Hills, Michigan, USAArslan MH, Korkmaz HH (2007) What is to be learned from damage and failure of reinforced concrete structures during recent earthquakes in Turkey? Eng Fail Anal 14(1):1–22ASCE (2007) Seismic Rehabilitation of Existing Buildings, ASCE/SEI 41-06. American Society of Civil Engineers, RestonASCE (2010) Minimum Design Loads for Building and Other Structures, ASCE/SEI 7-10. American Society of Civil Engineers, RestonBenavent-Climent A (2007) Seismic behavior of RC side beam-column connections under dynamic loading. J Earthquake Eng 11:493–511Benavent-Climent A, Zahran R (2010) An energy-based procedure for the assessment of seismic capacity of existing frames: application to RC wide beam systems in Spain. Soil Dyn Earthq Eng 30:354–367Benavent-Climent A, Cahís X, Zahran R (2009) Exterior wide beam-column connections in existing RC frames subjected to lateral earthquake loads. Eng Struct 31:1414–1424Benavent-Climent A, Cahís X, Vico JM (2010) Interior wide beam-column connections in existing RC frames subjected to lateral earthquake loading. Bull Earthq Eng 8:401–420BHRC (2004) Iranian Code of Practice for Seismic Resistant Design of Buildings. Standard Nº 2800, 3rd edn. Building and Housing Research Center, TehranBorzi B, Elnashai AS (2000) Refined force reduction factors for seismic design. Eng Struct 22:1244–1260Borzi B, Pinho R, Crowley H (2008) Simplified pushover-based vulnerability analysis for large-scale assessment of RC buildings. Eng Struct 30:804–820BSI (2004) Eurocode 2: Design of concrete structures: Part 1-1: General rules and rules for buildings. British Standards Institutions, LondonCalvi GM (1999) A displacement-based approach for vulnerability evaluation of classes of buildings. J Earthquake Eng 3(3):411–438CDSC (1994) Seismic construction code, NCSR-94. Committee for the Development of Seismic Codes, Spanish Ministry of Construction, Madrid, Spain (in Spanish)CDSC (2002) Seismic construction code, NCSE-02. Committee for the Development of Seismic Codes, Spanish Ministry of Construction, Madrid, Spain (in Spanish)CEN (2004) Eurocode 8: design of structures for earthquake resistance—part 1: general rules, seismic actions and rules for buildings. European Standard EN 1998-1:2003—Comité Européen de Normalisation, Brussels, BelgiumCEN (2005) Eurocode 8: design of structures for earthquake resistance—part 3: assessment and retrofitting of buildings. European Standard EN 1998-1:2005—Comité Européen de Normalisation, Brussels, BelgiumCheung PC, Paulay T, Park R (1991) Mechanisms of slab contributions in beam-column subassemblages. ACI Spec Publ 123Cosenza E, Manfredi G, Polese M, Verderame GM (2005) A multilevel approach to the capacity assessment of existing RC buildings. J Earthquake Eng 9(1):1–22Crowley H, Pinho R (2010) Revisiting Eurocode 8 formulae for periods of vibration and their employment in linear seismic analysis. Earthquake Eng Struct Dynam 39:223–235CS.LL.PP (2009) Instructions for the application of the technique code for the Constructions. Official Gazette of the Italian Republic, 47, Regular Supplement no. 27 (in Italian)De Luca F, Vamvatsikos D, Iervolino I (2013) Near-optimal piecewise linear fits of static pushover capacity curves for equivalent SDOF analysis. Earthquake Eng Struct Dynam 42(4):523–543De Luca F, Verderame GM, Gómez-Martínez F, Pérez-García A (2014) The structural role played by masonry infills on RC building performances after the 2011 Lorca, Spain, earthquake. Bull Earthq Eng 12(5):1999–2026Decanini LD, Mollaioli F (2000) Analisi di vulnerabilità sismica di edifici in cemento armato pre-normativa. In: Cosenza E (ed) Comportamento sismico di edifici in cemento armato progettati per carichi verticali. CNR—Gruppo Nazionale per la Difesa dei Terremoti, Rome (in Italian)Dolšek M, Fajfar P (2004) IN2—a simple alternative for IDA. In: Proceedings of the 13th World conference on Earthquake Engineering. August 1–6, Vancouver, Canada. Paper 3353Domínguez D, López-Almansa F, Benavent-Climent A (2014) Comportamiento para el terremoto de Lorca de 11-05-2011, de edificios de vigas planas proyectados sin tener en cuenta la acción sísmica. Informes de la Construcción 66(533):e008 (in Spanish)Domínguez D, López-Almansa F, Benavent-Climent A (2016) Would RC wide-beam buildings in Spain have survived Lorca earthquake (11-05-2011)? Eng Struct 108:134–154Dönmez C (2013) Seismic Performance of Wide-Beam Infill-Joist Block RC Frames in Turkey. J Perform Constr Facil 29(1):04014026Fadwa I, Ali TA, Nazih E, Sara M (2014) Reinforced concrete wide and conventional beam-column connections subjected to lateral load. Eng Struct 76:34–48Fardis MN (2009) Seismic design, assessment and retrofitting of concrete, Buildings edn. Springer, LondonGentry TR, Wight JK (1992) Reinforced concrete wide beam-column connections under earthquake-type loading. Report no. UMCEE 92-12. Department of Civil and Environmental Engineering, University of Michigan, Ann Arbor, Michigan, USAGómez-Martínez F (2015) FAST simplified vulnerability approach for seismic assessment of infilled RC MRF buildings and its application to the 2011 Lorca (Spain) earthquake. Ph.D. Thesis, Polytechnic University of Valencia, SpainGómez-Martínez F, Pérez García A, De Luca F, Verderame GM (2015a) Comportamiento de los edificios de HA con tabiquería durante el sismo de Lorca de 2011: aplicación del método FAST. Informes de la Construcción 67(537):e065 (in Spanish)Gómez-Martínez F, Pérez-García A, Alonso Durá A, Martínez Boquera A, Verderame GM (2015b) Eficacia de la norma NCSE-02 a la luz de los daños e intervenciones tras el sismo de Lorca de 2011. In: Proceedings of Congreso Internacional sobre Intervención en Obras Arquitectónicas tras Sismo: L’Aquila (2009), Lorca (2011) y Emilia Romagna (2012), May 13–14, Murcia, Spain (in Spanish)Gómez-Martínez F, Verderame GM, De Luca F, Pérez-García A, Alonso-Durá, A (2015c). High ductility seismic performances of wide-beam RC frames. In; XVI Convegno ANIDIS. September 13–17, L'Aquila, ItalyHawkins NM, Mitchell D (1979) Progressive collapse of flat plate structures. ACI J 76(7):775–808Iervolino I, Manfredi G, Polese M, Verderame GM, Fabbrocino G (2007) Seismic risk of RC building classes. Eng Struct 29(5):813–820Inel M, Ozmen HB, Akyol E (2013) Observations on the building damages after 19 May 2011 Simav (Turkey) earthquake. Bull Earthq Eng 11(1):255–283Kurose Y, Guimaraes GN, Zuhua L, Kreger ME, Jirsa JO (1991) Evaluation of slab-beam-column connections subjected to bidirectional loading. ACI Spec Publ 123:39–67LaFave JM, Wight JK (1997) Behavior of reinforced exterior wide beam-column-slab connections subjected to lateral earthquake loading. Report no. UMCEE 97-01. Department of Civil and Environmental Engineering, University of Michigan, Ann Arbor, Michigan, USALaFave JM, Wight JK (1999) Reinforced concrete exterior wide beam-column-slab connections subjected to lateral earthquake loading. ACI Struct J 96(4):577–586LaFave JM, Wight JK (2001) Reinforced concrete wide-beam construction vs. conventional construction: resistance to lateral earthquake loads. Earthq Spectra 17(3):479–505Li B, Kulkarni SA (2010) Seismic behavior of reinforced concrete exterior wide beam-column joints. J Struct Eng (ASCE) 136(1):26–36López-Almansa F, Domínguez D, Benavent-Climent A (2013) Vulnerability analysis of RC buildings with wide beams located in moderate seismicity regions. Eng Struct 46:687–702Masi A, Santarsiero G, Nigro D (2013a) Cyclic tests on external RC beam-column joints: role of seismic design level and axial load value on the ultimate capacity. J Earthquake Eng 17(1):110–136Masi A, Santarsiero G, Mossucca A, Nigro D (2013b) Seismic behaviour of RC beam-column subassemblages with flat beam. In: Proceedings of XV Convegno della Associazione Nazionale Italiana di Ingegneria Sismica, ANIDIS. Padova, ItalyMazzolani FM, Piluso V (1997) Plastic design of seismic resistant steel frames. Earthquake Eng Struct Dynam 26:167–191MEPP (2000a) Greek earthquake resistant design code, EAK 2000. Ministry of Environment, Planning and Public Works, AthensMEPP (2000b) Greek code for the design and construction of concrete works, EKOS 2000. Ministry of Environment, Planning and Public Works, Athens (in Greek)Miranda E, Bertero VV (1994) Evaluation of strength reduction factors for earthquake-resistant design. Earthq Spectra 10(2):357–379MPWS (2007) Specifications for buildings to be built in seismic areas. Turkish Standards Institution, Ministry of Public Works and Settlement, Ankara (in Turkish)Mwafy AM, Elnashai AS (2002) Calibration of force reduction factors of RC buildings. J Earthquake Eng 6(2):239–273NZS (2004) Structural design actions. Part 5: earthquake actions, NZS 1170.5. New Zealand Standards, WellingtonNZS (2006) Concrete structures standard: part 1—the design of concrete structures, NZS 3101 part 1. New Zealand Standards, WellingtonPan A, Moehle JP (1989) Lateral displacement ductility of reinforced concrete flat plates. ACI Struct J 86(3):250–258Panagiotakos TB, Fardis MN (2001) Deformations of reinforced concrete members at yielding and ultimate. ACI Struct J 98(2):135–148 [and Appendix 1 (69 pp)]Paulay T, Priestley MJN (1992) Seismic design of concrete and masonry structures. Wiley, New York, USAQuintero-Febres CG, Wight JK (1997) Investigation on the seismic behavior of RC interior wide beam-column connections. Report no. UMCEE 97-15. Department of Civil and Environmental Engineering, University of Michigan, Ann Arbor, Michigan, USAQuintero-Febres CG, Wight JK (2001) Experimental study of Reinforced concrete interior wide beam-column connections subjected to lateral loading. ACI Struct J 98(4):572–582Serna-Ros P, Fernández-Prada MA, Miguel-Sosa P, Debb OAR (2001) Influence of stirrup distribution and support width on the shear strength of reinforced concrete wide beams. Mag Concr Res 54(00):1–11Shuraim AB (2012) Transverse stirrup configurations in RC wide shallow beams supported on narrow columns. J Struct Eng 138(3):416–424Siah WL, Stehle JS, Mendis P, Goldsworthy H (2003) Interior wide beam connections subjected to lateral earthquake loading. Eng Struct 25:281–291Tore E, Demiral T (2014) A parametric study of code-based performance limits for wide beams. e-GFOS 5(8):1–11Vamvatsikos D, Cornell CA (2002) Incremental Dynamic Analysis. Earthquake Eng Struct Dynam 31:491–514Vidic T, Fajfar P, Fischinger M (1994) Consistent inelastic design spectra: strength and displacement. Earthquake Eng Struct Dynam 23:507–521Vielma JC, Barbat AH, Oller S (2010) Seismic safety of low ductility structures used in Spain. Bull Earthq Eng 8:135–15

A Regulatory Mechanism Involving TBP-1/Tat-Binding Protein 1 and Akt/PKB in the Control of Cell Proliferation

TBP-1 /Tat-Binding Protein 1 (also named Rpt-5, S6a or PSMC3) is a multifunctional protein, originally identified as a regulator of HIV-1-Tat mediated transcription. It is an AAA-ATPase component of the 19S regulative subunit of the proteasome and, as other members of this protein family, fulfils different cellular functions including proteolysis and transcriptional regulation. We and others reported that over expression of TBP-1 diminishes cell proliferation in different cellular contexts with mechanisms yet to be defined. Accordingly, we demonstrated that TBP-1 binds to and stabilizes the p14ARF oncosuppressor increasing its anti-oncogenic functions. However, TBP-1 restrains cell proliferation also in the absence of ARF, raising the question of what are the molecular pathways involved. Herein we demonstrate that stable knock-down of TBP-1 in human immortalized fibroblasts increases cell proliferation, migration and resistance to apoptosis induced by serum deprivation. We observe that TBP-1 silencing causes activation of the Akt/PKB kinase and that in turn TBP-1, itself, is a downstream target of Akt/PKB. Moreover, MDM2, a known Akt target, plays a major role in this regulation. Altogether, our data suggest the existence of a negative feedback loop involving Akt/PKB that might act as a sensor to modulate TBP-1 levels in proliferating cells

Aszites, Pfortaderthrombose und hepatische Enzephalopathie bei Leberzirrhose: Aktuelle Therapieempfehlungen

Treatment of Ascites, Portal Vein Thrombosis and Hepatic Encephalopathy in Patients with Cirrhosis of the Liver Background: Ascites, portal vein thrombosis and hepatic encephalopathy are important complications of cirrhosis of the liver. Guidelines for the treatment of ascites have recently been published. Method: This manuscript summarizes up-to-date recommendations on the basis of the DGVS S3 guideline and of other guidelines as well as of the authors' experience. Results and Conclusions: TIPS (transjugular intrahepatic porto-systemic shunt) is the preferred treatment for refractory or recidivant ascites unless there are contraindications. The therapy of hepatorenal syndrome type 1 with albumin and the vasoconstrictor Terlipressin has been proven effective. Treatment of portal vein thrombosis comprises a strategy of anticoagulation, TIPS and liver transplantation. The most important therapeutic strategy for hepatic encephalopathy is the search for as well as the treatment of trigger events. Rifaximin is being increasingly used for the treatment and prophylaxis of hepatic encephalopathy

Floral sonication is an innate behaviour in bumblebees that can be fine-tuned with experience in manipulating flowers

Bumblebees demonstrate an extensive capacity for learning complex motor skills to maximise exploitation of floral rewards. This ability is well studied in nectar collection but its role in pollen foraging is less well understood. Floral sonication is used by bees to extract pollen from some plant species with anthers which must be vibrated (buzzed) to release pollen. Pollen removal is determined by sonication characteristics including frequency and amplitude, and thus the ability to optimise sonication should allow bees to maximise the pollen collection. We investigated the ability of the buff-tailed bumblebee (Bombus terrestris) to modify the frequency and amplitude of their buzzes with increasing experience manipulating flowers of the buzz-pollinated plantSolanum rostratum. We analysed flight and feeding vibrations generated by na&iuml;ve workers across feeding bouts. Feeding buzzes were of a higher frequency and a lower amplitude than flight buzzes. Both flight and feeding buzzes had reduced amplitudes with increasing number of foraging trips. However, the frequency of their feeding buzzes was reduced significantly more than their flight buzzes as bumblebee workers gained experience manipulating flowers. These results suggest that bumblebees are able to modify the characteristics of their buzzes with experience manipulating buzz-pollinated flowers. We discuss our findings in the context of bumblebee learning, and the current understanding of the optimal sonication characteristics for releasing pollen in buzz-pollinated species. Our results present a tantalising insight into the potential role of learning in floral sonication, paving the way for future research in this area