A Rydberg Quantum Simulator

Following Feynman and as elaborated on by Lloyd, a universal quantum simulator (QS) is a controlled quantum device which reproduces the dynamics of any other many particle quantum system with short range interactions. This dynamics can refer to both coherent Hamiltonian and dissipative open system evolution. We investigate how laser excited Rydberg atoms in large spacing optical or magnetic lattices can provide an efficient implementation of a universal QS for spin models involving (high order) n-body interactions. This includes the simulation of Hamiltonians of exotic spin models involving n-particle constraints such as the Kitaev toric code, color code, and lattice gauge theories with spin liquid phases. In addition, it provides the ingredients for dissipative preparation of entangled states based on engineering n-particle reservoir couplings. The key basic building blocks of our architecture are efficient and high-fidelity n-qubit entangling gates via auxiliary Rydberg atoms, including a possible dissipative time step via optical pumping. This allows to mimic the time evolution of the system by a sequence of fast, parallel and high-fidelity n-particle coherent and dissipative Rydberg gates.Comment: 8 pages, 4 figure

To respond or not to respond - a personal perspective of intestinal tolerance

For many years, the intestine was one of the poor relations of the immunology world, being a realm inhabited mostly by specialists and those interested in unusual phenomena. However, this has changed dramatically in recent years with the realization of how important the microbiota is in shaping immune function throughout the body, and almost every major immunology institution now includes the intestine as an area of interest. One of the most important aspects of the intestinal immune system is how it discriminates carefully between harmless and harmful antigens, in particular, its ability to generate active tolerance to materials such as commensal bacteria and food proteins. This phenomenon has been recognized for more than 100 years, and it is essential for preventing inflammatory disease in the intestine, but its basis remains enigmatic. Here, I discuss the progress that has been made in understanding oral tolerance during my 40 years in the field and highlight the topics that will be the focus of future research

Physiological and molecular responses to an acute bout of reduced-exertion high-intensity interval training (REHIT)

PurposeWe have previously shown that 6 weeks of reduced-exertion high-intensity interval training (REHIT) improves V˙O2V˙O2 max in sedentary men and women and insulin sensitivity in men. Here, we present two studies examining the acute physiological and molecular responses to REHIT.MethodsIn Study 1, five men and six women (age: 26 ± 7 year, BMI: 23 ± 3 kg m−2, V˙O2V˙O2 max: 51 ± 11 ml kg−1 min−1) performed a single 10-min REHIT cycling session (60 W and two 20-s ‘all-out’ sprints), with vastus lateralis biopsies taken before and 0, 30, and 180 min post-exercise for analysis of glycogen content, phosphorylation of AMPK, p38 MAPK and ACC, and gene expression of PGC1α and GLUT4. In Study 2, eight men (21 ± 2 year; 25 ± 4 kg·m−2; 39 ± 10 ml kg−1 min−1) performed three trials (REHIT, 30-min cycling at 50 % of V˙O2V˙O2 max, and a resting control condition) in a randomised cross-over design. Expired air, venous blood samples, and subjective measures of appetite and fatigue were collected before and 0, 15, 30, and 90 min post-exercise.ResultsAcutely, REHIT was associated with a decrease in muscle glycogen, increased ACC phosphorylation, and activation of PGC1α. When compared to aerobic exercise, changes in V˙O2V˙O2 , RER, plasma volume, and plasma lactate and ghrelin were significantly more pronounced with REHIT, whereas plasma glucose, NEFAs, PYY, and measures of appetite were unaffected.ConclusionsCollectively, these data demonstrate that REHIT is associated with a pronounced disturbance of physiological homeostasis and associated activation of signalling pathways, which together may help explain previously observed adaptations once considered exclusive to aerobic exercise

Early discontinuation of endocrine therapy for breast cancer: Who is at risk in clinical practice?

Purpose: Despite evidence supporting at least five years of endocrine therapy for early breast cancer, many women discontinue therapy early. We investigated the impact of initial therapy type and specific comorbidities on discontinuation of endocrine therapy in clinical practice. Methods We identified women in a population-based cohort with a diagnosis of early breast cancer and an incident dispensing of anastrozole, letrozole or tamoxifen from 2003-2008 (N = 1531). Pharmacy and health service data were used to determine therapy duration, treatment for pre-existing and post-initiation comorbidities (anxiety, depression, hot flashes, musculoskeletal pain, osteoporosis, vaginal atrophy), demographic and other clinical characteristics. Time to discontinuation of initial, and any, endocrine therapy was calculated. Cox regression determined the association of different characteristics on early discontinuation. Results Initial endocrine therapy continued for a median of 2.2 years and any endocrine therapy for 4.8 years. Cumulative probability of discontinuing any therapy was 17% after one year and 58% by five years. Initial tamoxifen, pre-existing musculoskeletal pain and newly-treated anxiety predicted shorter initial therapy but not discontinuation of any therapy. Early discontinuation of any therapy was associated with newly-treated hot flashes (HR = 2.1, 95%CI = 1.3-3.3), not undergoing chemotherapy (HR = 1.4, 95%CI = 1.1-1.8) and not undergoing mastectomy (HR = 1.5, 95%CI = 1.2-1.8). Conclusions Less than half of women completed five years of endocrine therapy. Women at greatest risk of stopping any therapy early were those with newly-treated hot flashes, no initial chemotherapy, or no initial mastectomy. This suboptimal use means that the reductions in recurrence demonstrated in clinical trials may not be realised in practice

Effect of Reimbursement Reductions on Bone Mineral Density Testing for Female Medicare Beneficiaries

Abstract Background: We examined whether the recent reimbursement reductions on the bone mineral density (BMD) test affected BMD testing in female Medicare beneficiaries with or without supplemental private health insurance. Methods: Retrospectively analyzing hospital administrative and clinical data on female Medicare beneficiaries (n=1320), we reviewed whether participants received BMD testing before (January 2004?December 2006) or after (January 2007?December 2009) reimbursement reductions for BMD testing. After adjusting for demographics and clinical characteristics, we performed Cox proportional hazard regression analyses of the BMD test including data from all study participants; we then performed separate regression analyses using data with or without supplemental private health insurance. Results: In those without supplemental private health insurance (n=421), less frequent BMD testing occurred after reimbursement reductions for BMD testing (hazard ratio [HR] 0.67, 95% confidence intervals [CI] 0.34-0.98; p=0.03). By contrast, in the overall participants (n=1320) and those with supplemental private health insurance (n=899), the number of BMD tests did not change significantly after reimbursement reductions for BMD testing. Conclusions: We found a significant association between reimbursement reductions and decrease in BMD tests in female Medicare beneficiaries without supplemental private health insurance.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98463/1/jwh%2E2012%2E3517.pd

Understanding the interplay between social and spatial behaviour

According to personality psychology, personality traits determine many aspects of human behaviour. However, validating this insight in large groups has been challenging so far, due to the scarcity of multi-channel data. Here, we focus on the relationship between mobility and social behaviour by analysing trajectories and mobile phone interactions of ∼1000 individuals from two high-resolution longitudinal datasets. We identify a connection between the way in which individuals explore new resources and exploit known assets in the social and spatial spheres. We show that different individuals balance the exploration-exploitation trade-off in different ways and we explain part of the variability in the data by the big five personality traits. We point out that, in both realms, extraversion correlates with the attitude towards exploration and routine diversity, while neuroticism and openness account for the tendency to evolve routine over long time-scales. We find no evidence for the existence of classes of individuals across the spatio-social domains. Our results bridge the fields of human geography, sociology and personality psychology and can help improve current models of mobility and tie formation

P2Y2 and P2Y6 receptor activation elicits intracellular calcium responses in human adipose-derived mesenchymal stromal cells

Adipose tissue contains self-renewing multipotent cells termed mesenchymal stromal cells. In situ, these cells serve to expand adipose tissue by adipogenesis, but their multipotency has gained interest for use in tissue regeneration. Little is known regarding the repertoire of receptors expressed by adipose-derived mesenchymal stromal cells (AD-MSCs). The purpose of this study was to undertake a comprehensive analysis of purinergic receptor expression. Mesenchymal stromal cells were isolated from human subcutaneous adipose tissue and confirmed by flow cytometry. The expression profile of purinergic receptors was determined by quantitative real-time PCR and immunocytochemistry. The molecular basis for adenine and uracil nucleotide-evoked intracellular calcium responses was determined using Fura-2 measurements. All the known subtypes of P2X and P2Y receptors, excluding P2X2, P2X3 and P2Y12 receptors, were detected at the mRNA and protein level. ATP, ADP and UTP elicited concentration-dependent calcium responses in mesenchymal cells (N = 7–9 donors), with a potency ranking ADP (EC50 1.3 ± 1.0 μM) > ATP (EC50 2.2 ± 1.1 μM) = UTP (3.2 ± 2.8 μM). Cells were unresponsive to UDP (< 30 μM) and UDP-glucose (< 30 μM). ATP responses were attenuated by selective P2Y2 receptor antagonism (AR-C118925XX; IC50 1.1 ± 0.8 μM, 73.0 ± 8.5% max inhibition; N = 7 donors), and UTP responses were abolished. ADP responses were attenuated by the selective P2Y6 receptor antagonist, MRS2587 (IC50 437 ± 133nM, 81.0 ± 8.4% max inhibition; N = 6 donors). These data demonstrate that adenine and uracil nucleotides elicit intracellular calcium responses in human AD-MSCs with a predominant role for P2Y2 and P2Y6 receptor activation. This study furthers understanding about how human adipose-derived mesenchymal stromal cells can respond to external signalling cues

A basal lithostrotian titanosaur (Dinosauria: Sauropoda) with a complete skull: Implications for the evolution and paleobiology of titanosauria

We describe Sarmientosaurus musacchioi gen. et sp. nov., a titanosaurian sauropod dinosaur from the Upper Cretaceous (Cenomanian - Turonian) Lower Member of the Bajo Barreal Formation of southern Chubut Province in central Patagonia, Argentina. The holotypic and only known specimen consists of an articulated, virtually complete skull and part of the cranial and middle cervical series. Sarmientosaurus exhibits the following distinctive features that we interpret as autapomorphies: (1) maximum diameter of orbit nearly 40% rostrocaudal length of cranium; (2) complex maxilla - lacrimal articulation, in which the lacrimal clasps the ascending ramus of the maxilla; (3) medial edge of caudal sector of maxillary ascending ramus bordering bony nasal aperture with low but distinct ridge; (4) ´tongue-like´ ventral process of quadratojugal that overlaps quadrate caudally; (5) separate foramina for all three branches of the trigeminal nerve; (6) absence of median venous canal connecting infundibular region to ventral part of brainstem; (7) subvertical premaxillary, procumbent maxillary, and recumbent dentary teeth; (8) cervical vertebrae with ´strut-like´ centroprezygapophyseal laminae; (9) extremely elongate and slender ossified tendon positioned ventrolateral to cervical vertebrae and ribs. The cranial endocast of Sarmientosaurus preserves some of the most complete information obtained to date regarding the brain and sensory systems of sauropods. Phylogenetic analysis recovers the new taxon as a basal member of Lithostrotia, as the most plesiomorphic titanosaurian to be preserved with a complete skull. Sarmientosaurus provides a wealth of new cranial evidence that reaffirms the close relationship of titanosaurs to Brachiosauridae. Moreover, the presence of the relatively derived lithostrotian Tapuiasaurus in Aptian deposits indicates that the new Patagonian genus represents a ´ghost lineage´ with a comparatively plesiomorphic craniodental form, the evolutionary history of which is missing for at least 13 million years of the Cretaceous. The skull anatomy of Sarmientosaurus suggests that multiple titanosaurian species with dissimilar cranial structures coexisted in the early Late Cretaceous of southern South America. Furthermore, the new taxon possesses a number of distinctive morphologies - such as the ossified cervical tendon, extremely pneumatized cervical vertebrae, and a habitually downward- facing snout - that have rarely, if ever, been documented in other titanosaurs, thus broadening our understanding of the anatomical diversity of this remarkable sauropod clade. The latter two features were convergently acquired by at least one penecontemporaneous diplodocoid, and may represent mutual specializations for consuming low-growing vegetation.Fil: Martínez, Rubén Darío. Universidad Nacional de la Patagonia; ArgentinaFil: Lamanna, Matthew C.. Carnegie Museum Of Natural History; Estados UnidosFil: Novas, Fernando Emilio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Museo Argentino de Ciencias Naturales "bernardino Rivadavia"; ArgentinaFil: Ridgely, Ryan C.. Ohio University College Of Osteopathic Medicine; Estados UnidosFil: Casal, Gabriel. Universidad Nacional de la Patagonia; ArgentinaFil: Martínez, Javier E.. Hospital Regional de Comodoro Rivadavia; ArgentinaFil: Vita, Javier R.. Resonancia Magnética Borelli; ArgentinaFil: Witmer, Lawrence M.. Ohio University College Of Osteopathic Medicine; Estados Unido

Study design and methods of the BoTULS trial: a randomised controlled trial to evaluate the clinical effect and cost effectiveness of treating upper limb spasticity due to stroke with botulinum toxin type A

Background Following a stroke, 55–75% of patients experience upper limb problems in the longer term. Upper limb spasticity may cause pain, deformity and reduced function, affecting mood and independence. Botulinum toxin is used increasingly to treat focal spasticity, but its impact on upper limb function after stroke is unclear. The aim of this study is to evaluate the clinical and cost effectiveness of botulinum toxin type A plus an upper limb therapy programme in the treatment of post stroke upper limb spasticity. Methods Trial design : A multi-centre open label parallel group randomised controlled trial and economic evaluation. Participants : Adults with upper limb spasticity at the shoulder, elbow, wrist or hand and reduced upper limb function due to stroke more than 1 month previously. Interventions : Botulinum toxin type A plus upper limb therapy (intervention group) or upper limb therapy alone (control group). Outcomes : Outcome assessments are undertaken at 1, 3 and 12 months. The primary outcome is upper limb function one month after study entry measured by the Action Research Arm Test (ARAT). Secondary outcomes include: spasticity (Modified Ashworth Scale); grip strength; dexterity (Nine Hole Peg Test); disability (Barthel Activities of Daily Living Index); quality of life (Stroke Impact Scale, Euroqol EQ-5D) and attainment of patient-selected goals (Canadian Occupational Performance Measure). Health and social services resource use, adverse events, use of other antispasticity treatments and patient views on the treatment will be compared. Participants are clinically reassessed at 3, 6 and 9 months to determine the need for repeat botulinum toxin type A and/or therapy. Randomisation : A web based central independent randomisation service. Blinding : Outcome assessments are undertaken by an assessor who is blinded to the randomisation group. Sample size : 332 participants provide 80% power to detect a 15% difference in treatment successes between intervention and control groups. Treatment success is defined as improvement of 3 points for those with a baseline ARAT of 0–3 and 6 points for those with ARAT of 4–56

FAK-inhibition opens the door to checkpoint immunotherapy in Pancreatic Cancer

Immunotherapy has had remarkable success in the treatment of some cancer types. However, pancreatic cancer has remained largely refractory to immunotherapy, including immune checkpoint inhibitors. Recently, Jiang and colleagues identified a key role for FAK in regulating the composition of the fibrotic and immuno-suppressive pancreatic tumour niche, and showed that FAK inhibitors can be used in combination with immune checkpoint blockade and gemcitabine chemotherapy to significantly delay pancreatic tumour progression. This study further supports the use of FAK inhibitors in combination with immunotherapy