The Influence of Orthopedic Surgery on Circulating Metabolite Levels, and their Associations with the Incidence of Postoperative Delirium

The mechanisms underlying the occurrence of postoperative delirium development are unclear and measurement of plasma metabolites may improve understanding of its causes. Participants (n = 54) matched for age and gender were sampled from an observational cohort study investigating postoperative delirium. Participants were ≥65 years without a diagnosis of dementia and presented for primary elective hip or knee arthroplasty. Plasma samples collected pre-and postoperatively were grouped as either control (n = 26, aged: 75.8 ± 5.2) or delirium (n = 28, aged: 76.2 ± 5.7). Widespread changes in plasma metabolite levels occurred following surgery. The only metabolites significantly differing between corresponding control and delirium samples were ornithine and spermine. In delirium cases, ornithine was 17.6% higher preoperatively, and spermine was 12.0% higher postoperatively. Changes were not associated with various perioperative factors. In binary logistic regression modeling, these two metabolites did not confer a significantly increased risk of delirium. These findings support the hypothesis that disturbed polyamine metabolism is an underlying factor in delirium that warrants further investigation

Behavioral Modernity and the Cultural Transmission of Structured Information: The Semantic Axelrod Model

Cultural transmission models are coming to the fore in explaining increases in the Paleolithic toolkit richness and diversity. During the later Paleolithic, technologies increase not only in terms of diversity but also in their complexity and interdependence. As Mesoudi and O'Brien (2008) have shown, selection broadly favors social learning of information that is hierarchical and structured, and multiple studies have demonstrated that teaching within a social learning environment can increase fitness. We believe that teaching also provides the scaffolding for transmission of more complex cultural traits. Here, we introduce an extension of the Axelrod (1997} model of cultural differentiation in which traits have prerequisite relationships, and where social learning is dependent upon the ordering of those prerequisites. We examine the resulting structure of cultural repertoires as learning environments range from largely unstructured imitation, to structured teaching of necessary prerequisites, and we find that in combination with individual learning and innovation, high probabilities of teaching prerequisites leads to richer cultural repertoires. Our results point to ways in which we can build more comprehensive explanations of the archaeological record of the Paleolithic as well as other cases of technological change.Comment: 24 pages, 7 figures. Submitted to "Learning Strategies and Cultural Evolution during the Paleolithic", edited by Kenichi Aoki and Alex Mesoudi, and presented at the 79th Annual Meeting of the Society for American Archaeology, Austin TX. Revised 5/14/1

Quantum Computing

Quantum mechanics---the theory describing the fundamental workings of nature---is famously counterintuitive: it predicts that a particle can be in two places at the same time, and that two remote particles can be inextricably and instantaneously linked. These predictions have been the topic of intense metaphysical debate ever since the theory's inception early last century. However, supreme predictive power combined with direct experimental observation of some of these unusual phenomena leave little doubt as to its fundamental correctness. In fact, without quantum mechanics we could not explain the workings of a laser, nor indeed how a fridge magnet operates. Over the last several decades quantum information science has emerged to seek answers to the question: can we gain some advantage by storing, transmitting and processing information encoded in systems that exhibit these unique quantum properties? Today it is understood that the answer is yes. Many research groups around the world are working towards one of the most ambitious goals humankind has ever embarked upon: a quantum computer that promises to exponentially improve computational power for particular tasks. A number of physical systems, spanning much of modern physics, are being developed for this task---ranging from single particles of light to superconducting circuits---and it is not yet clear which, if any, will ultimately prove successful. Here we describe the latest developments for each of the leading approaches and explain what the major challenges are for the future.Comment: 26 pages, 7 figures, 291 references. Early draft of Nature 464, 45-53 (4 March 2010). Published version is more up-to-date and has several corrections, but is half the length with far fewer reference

Acid Glycohydrolases in Rat Spermatocytes, Spermatids and Spermatozoa: Enzyme Activities, Biosynthesis and Immunolocalization

Mammalian sperm acrosome contains several glycohydrolases thought to aid in the dispersion and digestion of vestments surrounding the egg. In this study, we have used multiple approaches to examine the origin of acrosome-associated glycohdyrdolases. Mixed spermatogenic cells, prepared from rat testis, were separated by unit gravity sedimentation. The purified germ cells (spermatocytes [SP], round spermatids [RS], and elongated/condensed spermatids [E/CS]) contained several glycohydrolase activities. Metabolic labeling in the cell culture, immunoprecipitation, and autoradiographic approaches revealed that β-D-galactosidase was synthesized in SP and RS in 88/90 kDa forms which undergo processing in a cell-specific manner. Immunohistochemical approaches demonstrated that the enzyme was localized in Golgi membranes/vesicles, and lysosome-like structures in SP and RS, and forming/formed acrosome of E/CS

Cladribine with cyclophosphamide and prednisone in the management of low-grade lymphoproliferative malignancies

The feasibility of combining cladribine with cyclophosphamide and prednisone in the management of indolent lymphoid malignancies was determined. Nineteen patients [nine chronic lymphocytic leukaemia (CLL), seven non-Hodgkin's lymphoma (NHL) and three macroglobulinaemia (M))] received cladribine 0.1 mg kg−1 per day as a subcutaneous bolus injection on days 1–3 (up to 5 injections) with intravenous cyclophosphamide 500 mg m−2 on day 1 and oral prednisone 40 mg m−2 on days 1–5 at 4-weekly intervals up to a maximum of six courses. A total of 80 courses were given. Overall response rate was 88%, with four patients achieving a complete clinical and haematological response and 12 achieving a partial response. Neutropenia WHO grade 4 in two patients and WHO grade 3 infection in one patient were the limiting toxicities on treatment. During the follow-up, WHO grade ≥3 haematological complications occurred in five patients and WHO grade ≥3 non-haematological complications in five patients. There were no treatment-related deaths. This study demonstrates the feasibility of the cladribine/cyclophosphamide/prednisone (CCP) combination that appears highly active and safe in the management of indolent lymphoid malignancies. © 1999 Cancer Research Campaig

Phase-locked indistinguishable photons with synthesized waveforms from a solid-state source

Resonance fluorescence in the Heitler regime provides access to single photons with coherence well beyond the Fourier transform limit of the transition, and holds the promise to circumvent environment-induced dephasing common to all solid-state systems. Here we demonstrate that the coherently generated single photons from a single self-assembled InAs quantum dot display mutual coherence with the excitation laser on a timescale exceeding 3 seconds. Exploiting this degree of mutual coherence we synthesize near-arbitrary coherent photon waveforms by shaping the excitation laser field. In contrast to post-emission filtering, our technique avoids both photon loss and degradation of the single photon nature for all synthesized waveforms. By engineering pulsed waveforms of single photons, we further demonstrate that separate photons generated coherently by the same laser field are fundamentally indistinguishable, lending themselves to creation of distant entanglement through quantum interference.Comment: Additional data and analysis in PDF format is available for download at the publications section of our website: http://www.amop.phy.cam.ac.uk/amop-ma

mTORC1 in the Paneth cell niche couples intestinal stem cell function to calorie intake

How adult tissue stem and niche cells respond to the nutritional state of an organism is not well understood. Here we find that Paneth cells, a key constituent of the mammalian intestinal stem-cell (ISC) niche, augment stem-cell function in response to calorie restriction. Calorie restriction acts by reducing mechanistic target of rapamycin complex 1 (mTORC1) signalling in Paneth cells, and the ISC-enhancing effects of calorie restriction can be mimicked by rapamycin. Calorie intake regulates mTORC1 in Paneth cells, but not ISCs, and forced activation of mTORC1 in Paneth cells during calorie restriction abolishes the ISC-augmenting effects of the niche. Finally, increased expression of bone stromal antigen 1 (Bst1) in Paneth cells—an ectoenzyme that produces the paracrine factor cyclic ADP ribose—mediates the effects of calorie restriction and rapamycin on ISC function. Our findings establish that mTORC1 non-cell-autonomously regulates stem-cell self-renewal, and highlight a significant role of the mammalian intestinal niche in coupling stem-cell function to organismal physiology.National Institutes of Health (U.S.) (CA103866)National Institutes of Health (U.S.) (CA129105)David H. Koch Institute for Integrative Cancer Research at MIT (Initiator Award)Ellison Medical FoundationNational Cancer Institute (U.S.) (NCI (T32CA09216) fellowship support)Academy of FinlandFoundations’ Postdoc PoolNational Institutes of Health (U.S.) (NIH (1F32AG032833-01A1))Jane Coffin Childs Memorial Fund for Medical Researc