EELS: Autonomous snake-like robot with task and motion planning capabilities for ice world exploration.

Ice worlds are at the forefront of astrobiological interest because of the evidence of subsurface oceans. Enceladus in particular is unique among the icy moons because there are known vent systems that are likely connected to a subsurface ocean, through which the ocean water is ejected to space. An existing study has shown that sending small robots into the vents and directly sampling the ocean water is likely possible. To enable such a mission, NASA's Jet Propulsion Laboratory is developing a snake-like robot called Exobiology Extant Life Surveyor (EELS) that can navigate Enceladus' extreme surface and descend an erupting vent to capture unaltered liquid samples and potentially reach the ocean. However, navigating to and through Enceladus' environment is challenging: Because of the limitations of existing orbital reconnaissance, there is substantial uncertainty with respect to its geometry and the physical properties of the surface/vents; communication is limited, which requires highly autonomous robots to execute the mission with limited human supervision. Here, we provide an overview of the EELS project and its development effort to create a risk-aware autonomous robot to navigate these extreme ice terrains/environments. We describe the robot's architecture and the technical challenges to navigate and sense the icy environment safely and effectively. We focus on the challenges related to surface mobility, task and motion planning under uncertainty, and risk quantification. We provide initial results on mobility and risk-aware task and motion planning from field tests and simulated scenarios.

Uso da artéria torácica interna para tratamento cirúrgico de origem anômalo da artéria coronária esquerda: relato de caso / Use of the internal thoracic artery for surgical treatment of anomalous origin of the left coronary artery: case report

A origem anômala da artéria coronária esquerda do tronco pulmonar (Síndrome de Bland-White-Garland ou "Anomalous origin of Coronary Artery" (ALCAPA)) é uma anomalia congênita rara que afeta 1/300.000 nascidos vivos. Em 5% dos casos pode ser acompanhada com outra malformação congênita. Apresenta mortalidade de até 85% no primeiro ano de vida. A sintomatologia se relaciona a isquemia miocárdica e insuficiência cardíaca, sendo a correção cirúrgica o tratamento curativo. As principais técnicas cirurgicas são: reimplante do óstio coronário na aorta, interposição de artéria subclávia esquerda (Cirurgia Meyer), neo-tunelização (cirurgia de Takeuchi) e "bypass" coronário. Apresentamos um caso de paciente avaliado aos 9 meses de idade e 12 kg com quadro clínico de cianose durante as mamadas e dispnéia aos moderados esforços, sem outros antecedentes. Ao exame físico foi identificado sopro sistólico em foco pulmonar e aórtico. Realizou ecocardiograma e angiografia coronária sendo diagnosticado origem anômalo da artéria coronária esquerda. Sendo portanto submetido tratamento cirúrgico através da técnica "bypass" coronário utilizando artéria torácica interna esquerda. O paciente realiza seguimento anual no serviço há 21 anos apresentando evolução favorável. (AU)

Expert Panel Consensus Statement for Proper Evaluation of First Relapse in Multiple Myeloma.

PURPOSE OF REVIEW: A working group of six expert physicians convened to assess the spectrum of multiple myeloma relapse presentations, discussed the features that can define the disease as aggressive and not aggressive, and established whether this information could help in selecting treatment together with the characteristics of disease and of patients and type of prior therapy. RECENT FINDINGS: The working group agreed that relapse should be distinguished between biochemical and clinical according to IMWG. Moreover, the expert panel defined "aggressive disease" as a clinical condition that requires therapy able to induce a rapid and as deep as possible response to release symptoms and to avoid impending danger of new events. According to this definition, relapse was considered aggressive if it presents with at least one of the following features: doubling of M protein rate over 2 months, renal insufficiency, hypercalcemia, extramedullary disease, elevated LDH, high plasma cell proliferative index, presence of plasma cells in peripheral blood, or skeletal-related complications. Moreover, the panel agreed that this classification can be useful to choose therapy in first relapse together with other patient, disease, and prior therapy characteristics. So, this item was included in a new therapeutic algorithm. The treatment choice in MM at relapse is wider than in the past with the availability of many new therapeutic regimens leading to increased diversity of approaches and relevant risk of inappropriate treatment decisions. A practical classification of relapses into aggressive or non-aggressive, included in a decisional algorithm on MM management at first relapse, could help to make the appropriate treatment decisions.

The reactivity of cyclopropyl cyanide in titan's atmosphere: a possible pre-biotic mechanism.

Cyclopropyl cyanide and other simple nitriles detected in Titan's atmosphere could be precursors leading to the formation of organic macromolecules in the atmosphere of Saturn's largest satellite. Proposing a thermodynamically possible mechanism that explains their formation and supports experimental results represents a difficult challenge. Experiments done in the Atomic and Molecular Physics Laboratory at the University of Trento (AMPL) have studied the ion-molecule reaction between cyclopropyl cyanide and its protonated form, with reaction products being characterized by mass spectrometry. In addition to the expected ion-molecule adduct stabilized by non-covalent long-range interactions, in this work we prove that another distinct species having the same mass to charge ratio (m/z) of 135 is also produced. Moreover, from a previous study of the neutral cyclopropyl cyanide potential energy surface (PES) which shows a partial biradical character it has been possible to characterize the formation through the bimolecular reaction of a new covalent cyclic organic molecule. Calculations have been carried out at the ab initio Møller-Plesset (MP2) level of theory, ensuring the connectivity of the stationary points by using the intrinsic reaction coordinate (IRC) procedure. In order to characterize the reaction transition state, multireference calculations were done using a complete active space involving six electrons and six molecular orbitals [CAS (6 e-, 6 m.o.)]. This study opens the possibility of exploring the formation of new organic molecules by gaseous phase ion-molecule interaction schemes, with such molecules having relevance in interstellar space and in astrobiology (and may be involved in prebiotic molecular evolution).

SETD2 and histone H3 lysine 36 methylation deficiency in advanced systemic mastocytosis.

The molecular basis of advanced systemic mastocytosis (SM) is not fully understood and despite novel therapies the prognosis remains dismal. Exome sequencing of an index-patient with mast cell leukemia (MCL) uncovered biallelic loss-of-function mutations in the SETD2 histone methyltransferase gene. Copy-neutral loss-of-heterozygosity at 3p21.3 (where SETD2 maps) was subsequently found in SM patients and prompted us to undertake an in-depth analysis of SETD2 copy number, mutation status, transcript expression and methylation levels, as well as functional studies in the HMC-1 cell line and in a validation cohort of 57 additional cases with SM, including MCL, aggressive SM and indolent SM. Reduced or no SETD2 protein expression-and consequently, H3K36 trimethylation-was found in all cases and inversely correlated with disease aggressiveness. Proteasome inhibition rescued SETD2 expression and H3K36 trimethylation and resulted in marked accumulation of ubiquitinated SETD2 in SETD2-deficient patients but not in patients with near-normal SETD2 expression. Bortezomib and, to a lesser extent, AZD1775 alone or in combination with midostaurin induced apoptosis and reduced clonogenic growth of HMC-1 cells and of neoplastic mast cells from advanced SM patients. Our findings may have implications for prognostication of SM patients and for the development of improved treatment approaches in advanced SM.

Onabotulinumtoxin A for prophylaxis in chronic migraine: preliminary data from Headache Regional Centre of Aosta Valley.

Chronic migraine (CM) is a complex neurological disorder associated with substantial disability that affects approximately 2 % of general population. Onabotulinumtoxin A is employed for patients suffering from CM refractory to common therapeutic prophylaxis. Since May 2013, we have selected 22 patients referring to our headache centre with a history of CM which meets the diagnostic criteria of ICHD-3 beta (2013). The patients have been treated with onabotulinumtoxin A injection in 31 sites according to the protocol of the PREEMPT study at the total dosage of 155 U/treatment every 3 months. So far, eight patients have been subjected to three treatment sessions, five patients to two treatments and nine patients to one treatment. Three patients dropped for low compliance, but there were no serious adverse events. The frequency of headache days, the intensity of headache and the headache disability have been measured using headache diary, migraine disability assessment (MIDAS) questionnaire and headache impact test (HIT)-6 score. Data concerning the 13 patients who have been submitted to at least two treatment sessions have already shown a decrease of headache days of 20.64 % after the first treatment; MIDAS and HIT-6 scores have been significantly improved with a reduction of the scores, respectively, of 38.45 % for MIDAS and of 6.95 % for HIT-6. These are preliminary results because the observation time, the number of treatment sessions and the number of patients treated are still few.

Early application of percutaneous vertebroplasty reduces pain without affecting peripheral blood stem cell (PBSC) collection and transplant in newly diagnosed multiple myeloma (MM) patients.

Vertebral fractures occur in over 60% of newly diagnosed multiple myeloma (MM) patients and can cause pain, disability and poor quality of life. Antimyeloma therapy can lead to symptoms improvement, but these effects can take time to be perceived. Application of radiotherapy prior to peripheral blood stem cells (PBSC) mobilisation can impair stem cell collection. Percutaneous vertebroplasty has been proposed as a suitable option to rapidly relieve bone pain from vertebral fractures in MM patients, but, little is known about the effects of this procedure on subsequent PBSC mobilisation, collection and transplant. Eighteen patients (10M/8F, median age 64.5 years) with untreated MM and painful vertebral lesions underwent vertebroplasty prior to proceed to the planned transplant program at our Institution. Forty-one procedures were performed at C2-L5 levels, eight patients were treated at ≥2 levels. Ninety-five per cent of the cases obtained a complete or optimal pain control. All the patients successfully mobilised PBSC (median CD34+ cells = 10.8 × 10(6) /kg) and underwent autologous PBSC transplant; both polymorphonucleates and platelets recovery averaged 11 days. Our data seem to suggest that percutaneous vertebroplasty is useful in newly diagnosed MM patients with painful vertebral fractures as it allows rapid and durable achievement of pain control, without interfering with further treatment.

Efficacy and tolerability of bendamustine, bortezomib and dexamethasone in patients with relapsed-refractory multiple myeloma: a phase II study.

Bendamustine demonstrated synergistic efficacy with bortezomib against multiple myeloma (MM) cells in vitro and seems an effective treatment for relapsed-refractory MM (rrMM). This phase II study evaluated bendamustine plus bortezomib and dexamethasone (BVD) administered over six 28-day cycles and then every 56 days for six further cycles in patients with rrMM treated with 4 prior therapies and not refractory to bortezomib. The primary study end point was the overall response rate after four cycles. In total, 75 patients were enrolled, of median age 68 years. All patients had received targeted agents, 83% had 1-2 prior therapies and 33% were refractory to the last treatment. The response ratepartial response (PR) was 71.5% (16% complete response, 18.5% very good PR, 37% partial remission). At 12 months of follow-up, median time-to-progression (TTP) was 16.5 months and 1-year overall survival was 78%. According to Cox regression analysis, only prior therapy with bortezomib plus lenalidomide significantly reduced TTP (9 vs 17 months; hazard ratio=4.5; P=0.005). The main severe side effects were thrombocytopenia (30.5%), neutropenia (18.5%), infections (12%), neuropathy (8%) and gastrointestinal and cardiovascular events (both 6.5%). The BVD regimen is feasible, effective and well-tolerated in difficult-to-treat patients with rrMM.

MR-defecography in obstructed defecation syndrome (ODS): technique, diagnostic criteria and grading.

BACKGROUND: The aim of this study was to evaluate the use of a magnetic resonance (MR)-based classification system of obstructive defecation syndrome (ODS) to guide physicians in patient management. METHODS: The medical records and imaging series of 105 consecutive patients (90 female, 15 male, aged 21-78 years, mean age 46.1 ± 5.1 years) referred to our center between April 2011 and January 2012 for symptoms of ODS were retrospectively examined. After history taking and a complete clinical examination, patients underwent MR imaging according to a standard protocol using a 0.35 T permanent field, horizontally oriented open-configuration magnet. Static and dynamic MR-defecography was performed using recognized parameters and well-established diagnostic criteria. RESULTS: Sixty-seven out of 105 (64 %) patients found the prone position more comfortable for the evacuation of rectal contrast while 10/105 (9.5 %) were unable to empty their rectum despite repeated attempts. Increased hiatus size, anterior rectocele and focal or extensive defects of the levator ani muscle were the most frequent abnormalities (67.6, 60.0 and 51.4 %, respectively). An MR-based classification was developed based on the combinations of abnormalities found: Grade 1 = functional abnormality, including paradoxical contraction of the puborectalis muscle, without anatomical defect affecting the musculo-fascial structures; Grade 2 = functional defect associated with a minor anatomical defect such as rectocele ≤ 2 cm in size and/or first-degree intussusception; Grade 3 = severe defects confined to the posterior anatomical compartment, including >2 cm rectocele, second- or higher-degree intussusception, full-thickness external rectal prolapse, poor mesorectal posterior fixation, rectal descent >5 cm, levator ani muscle rupture, ballooning of the levator hiatus and focal detachment of the endopelvic fascia; Grade 4 = combined defects of two or three pelvic floor compartments, including cystocele, hysterocele, enlarged urogenital hiatus, fascial tears enterocele or peritoneocele; Grade 5 = changes after failed surgical repair abscess/sinus tracts, rectal pockets, anastomotic strictures, small uncompliant rectum, kinking and/or lateral shift of supra-anastomotic portion and pudendal nerve entrapment. CONCLUSIONS: According to our classification, Grades 1 and 2 may be amenable to conservative therapy; Grade 3 may require surgical intervention by a coloproctologist; Grade 4 would need a combined urogynecological and coloproctological approach; and Grade 5 may require an even more complex multidisciplinary approach. Validation studies are needed to assess whether this MR-based classification system leads to a better management of patients with ODS.

Update on the role of autologous hematopoietic stem cell transplantation in multiple myeloma.

Autologous stem cell transplantation is considered the standard of care for multiple myeloma patients aged < 65 years with no relevant comorbidities. The addition of drugs acting both on bone marrow microenvironment and on neoplastic plasma cells has significantly increased the proportion of patients achieving a complete remission after induction therapy, and these results are mantained after high-dose melphalan, leading to a prolonged disease control. Studies are being carried out in order to evaluate whether short term consolidation or long-term maintenance therapy can result into disease eradication at the molecular level thus increasing also patients survival. The efficacy of these new drugs has raised the issue of deferring the transplant after achiving a second response upon relapse. Another controversial point is the optimal treatment strategy for high-risk patients, that do not benefit from autologous stem cell transplantation and for whom the efficacy of new drugs is still matter of debate.

Lipid profiles of oil from trout (Oncorhynchus mykiss) heads, spines and viscera: trout by-products as a possible source of omega-3 lipids?

Lipid profiles of fish oil extracted from trout heads, spines and viscera using supercritical carbon dioxide and Randall extraction with hexane were measured. The amount of unsaturated fatty acids (as a percentage of total fatty acids) was within the range of 72.6-75.3% in all the substrates. A significant presence of the most important omega-3 fatty acids was detected. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) content in oil from spines, heads and viscera resulted to be 8.7% and 7.3%, 7.9% and 6.3%, and 6.4% and 6.0%, respectively. A low (≈3%), but worth noting, presence of lipids with omega-1 polyunsaturated fatty chains was observed in all the oils. Finally, significant differences were noticed in the relative amounts of triacylglycerides (TAG), diacylglycerides (DAG) and free fatty acids (FFA). Whereas oil from heads and spines was essentially composed of TAG (≈98%), in viscera oil the molar distribution ratio became TAG:DAG:FFA=87:8:5.

Infrared spectroscopy of copper-resveratrol complexes: a joint experimental and theoretical study.

Infrared multiple-photon dissociation spectroscopy has been used to record vibrational spectra of charged copper-resveratrol complexes in the 3500-3700 cm(-1) and 1100-1900 cm(-1) regions. Minimum energy structures have been determined by density functional theory calculations using plane waves and pseudopotentials. In particular, the copper(I)-resveratrol complex presents a tetra-coordinated metal bound with two carbon atoms of the alkenyl moiety and two closest carbons of the adjoining resorcinol ring. For these geometries vibrational spectra have been calculated by using linear response theory. The good agreement between experimental and calculated IR spectra for the selected species confirms the overall reliability of the proposed geometries.

Idiosyncratic control of the center of mass in expert climbers.

Here, we studied posture and movement coordination adopted by expert climbers. The investigation of such expertise might be of particular interest to gain understanding about the mechanisms underlying the biomechanical control of vertical quadrupedal locomotion. A novel custom setup was developed to analyze the motion of the center-of-mass (COM) and complementary information about the dynamic distribution of vertical reaction forces under the feet during climbing in nine elite climbers (EC) and nine control subjects. Two adaptive features were found in EC. First, unexpectedly they tended to maintain larger COM distances from the wall relative to controls, during both the static and dynamic phases of vertical motion (by ∼5 cm in both cases). Second, while the control subjects tended to restrain the lateral motion of the COM, all EC demonstrated systematic COM oscillations (∼1.3 times larger) associated with a significant alternating dynamic redistribution of the body weight between the limbs during the double support phase. The latter phenomenon likely reflects an adopted basic climbing strategy in experts. Furthermore, a convergence of the optimal solution towards a more diagonal climbing strategy in EC may shed light on the origin of the diagonal gait in primates and early hominids habituated to quadrupedal vertical locomotion.

Energy cost and efficiency of ski mountaineering. A laboratory study.

AIM: The purpose of this study is to estimate the energy cost of ski mountaineering at different speeds under laboratory conditions. METHODS: By using roller skis on a motorized treadmill we have estimated the energy cost and biomechanics parameters of ski mountaineering as a function of climbing speed at the gradient of 21%. RESULTS: The metabolic energy spent for unit mass and distance, C, shows a broad minimum of about 10.6±0.2 J kg-1m-1 at roughly 3.5 km h-1. In addition we find a size-dependent effect: tall subjects spend less metabolic energy for unit mass and distance than small subjects at the same speed. CONCLUSION: The value of C measured in laboratory agrees with that obtained in the field at the preferred speed. This shows that skiers self select a speed that minimizes their metabolic cost. The dependence of C on the subject's size is explained by a simple model of the skier's dynamics. In addition we have calculated the ratio between mechanical work and metabolic energy, which may give some hints on the efficiency as a function of the speed. It turns out that efficiency increases with the speed up to a maximum located at around 4.5 km/h.

The use of biochemical markers of bone remodeling in multiple myeloma: a report of the International Myeloma Working Group.

Lytic bone disease is a frequent complication of multiple myeloma (MM). Lytic lesions rarely heal and X-rays are of limited value in monitoring bone destruction during anti-myeloma or anti-resorptive treatment. Biochemical markers of bone resorption (amino- and carboxy-terminal cross-linking telopeptide of type I collagen (NTX and CTX, respectively) or CTX generated by matrix metalloproteinases (ICTP)) and bone formation provide information on bone dynamics and reflect disease activity in bone. These markers have been investigated as tools for evaluating the extent of bone disease, risk of skeletal morbidity and response to anti-resorptive treatment in MM. Urinary NTX, serum CTX and serum ICTP are elevated in myeloma patients with osteolytic lesions and correlate with advanced disease stage. Furthermore, urinary NTX and serum ICTP correlate with risk for skeletal complications, disease progression and overall survival. Bone markers have also been used for the early diagnosis of bone lesions. This International Myeloma Working Group report summarizes the existing data for the role of bone markers in assessing the extent of MM bone disease and in monitoring bone turnover during anti-myeloma therapies and provides information on novel markers that may be of particular interest in the near future.

Eosinophilic esophagitis: an Italian experience.

BACKGROUND: Eosinophilic esophagitis is an esophageal disorder characterized by esophageal and/or upper gastrointestinal tract symptoms, and by dense esophageal eosinophilia associated with a normal gastric and duodenal mucosa. Prevalently reported in children, eosinophilic esophagitis has recently been reported with increased frequency also in adults. AIMS: The purpose of this study was to report our experience with eosinophilic esophagitis in Italy, since there are only very few series of such patients in our country. PATIENTS AND METHODS: We retrospectively reviewed the histological data of consecutive patients with a diagnosis of esophagitis or reflux disease in the period September 2004-September 2008. Eosinophils were counted where they appeared most numerous in the biopsy, with a cutoff > 15 eosinophils in more than one high-power field as diagnostic of eosinophilic esophagitis. Patients were excluded if gastric or duodenal biopsies showed a prominent eosinophilic infiltrate. RESULTS: Twenty two patients (14 adults, 8 children, age range 2-59 years) were identified according to the above criteria. The average eosinophil count was 86/ high-power field (range 31-150), associated with other pathologic features (eosinophilic microabscesses eosinophil degranulation, basal zone hyperplasia, papillary elongation). The main clinical complaints were dysphagia, food impaction, and heartburn, and endoscopic findings consisted of mucosal thickening and inelasticity, longitudinal shearing, rings, and white specks, without difference between adults and children for both clinical and endoscopic variables. CONCLUSIONS: Eosinophilic esophagitis is not rare in Italy, and displays clinical, endoscopic, and pathologic features similar to those described in other countries.

Eosinophilic esophagitis: an Italian experience

Background: eosinophilic esophagitis is an esophageal disorder characterized by esophageal and/or upper gastrointestinal tract symptoms, and by dense esophageal eosinophilia associated with a normal gastric and duodenal mucosa. Prevalently reported in children, eosinophilic esophagitis has recently been reported with increased frequency also in adults. Aims: the purpose of this study was to report our experience with eosinophilic esophagitis in Italy, since there are only very few series of such patients in our country. Patients and methods: we retrospectively reviewed the histological data of consecutive patients with a diagnosis of esophagitis or reflux disease in the period September 2004-September 2008. Eosinophils were counted where they appeared most numerous in the biopsy, with a cutoff > 15 eosinophils in more than one high-power field as diagnostic of eosinophilic esophagitis. Patients were excluded if gastric or duodenal biopsies showed a prominent eosinophilic infiltrate. Results: twenty two patients (14 adults, 8 children, age range 2-59 years) were identified according to the above criteria. The average eosinophil count was 86/ high-power field (range 31- 150), associated with other pathologic features (eosinophilic microabscesses eosinophil degranulation, basal zone hyperplasia, papillary elongation). The main clinical complaints were dysphagia, food impaction, and heartburn, and endoscopic findings consisted of mucosal thickening and inelasticity, longitudinal shearing, rings, and white specks, without difference between adults and children for both clinical and endoscopic variables. Conclusions: eosinophilic esophagitis is not rare in Italy, and displays clinical, endoscopic, and pathologic features similar to those described in other countries(AU)

Guided-ion-beam and ab initio study of the Li+, K+, and Rb+ association reactions with gas-phase butanone and cyclohexanone in their ground electronic states.

The association reactions between Li(+), K(+), and Rb(+) (M) and butanone and cyclohexanone molecules under single collision conditions have been studied using a radiofrequency-guided ion-beam apparatus, characterizing the adducts by mass spectrometry. The excitation function for the [M-(molecule)](+) adducts (in arbitrary units) has been obtained at low collision energies in the 0.10 eV up to a few eV range in the center of mass frame. The measured relative cross sections decrease when collision energy increases, showing the expected energy dependence for adduct formation. The energetics and structure of the different adducts have been calculated ab initio at the MP2(full) level, showing that the M(+)-molecule interaction takes place through the carbonyl oxygen atom, as an example of a nontypical covalent chemical bond. The cross-section energy dependence and the role of radiative cooling rates allowing the stabilization of the collision complexes are also discussed.