Studies on the comparative actions of carbamylcholine, physostigmine and neostigmine in different species of domestic animals

In a series of experiments the comparative actions of carbamylcholine, physostigmine and neostigmine were compared in different species. Carbamylcholine was shown to have the following undesirable effects: (i) Respiratory distress due to bronchial secretion and constriction. (ii) Marked drop in blood pressure due to vasocollapse. (iii) Production of uncoordinated contractions of the rumen and inhibition of the reticulum. (iv) Profuse salivation. . (v) Little effect on the large intestine of the horse or sheep. It was more active on the stomach and bladder than the other two drugs tested. Physostigmine and neostigmine had very similar actions characterised by: (i) A slight rise in blood pressure after therapeutic doses. Evidence is produced indicating that this may be due to adrenaline secretion. (ii) Very little effect on the heart rate, salivary secretion or bronchioles. (iii) Little effect on the stomach of the dog or donkey. Increased strength of the contractions of the rumen and reticulum. Marked stimulation of the large intestine in all species. The impression was gained that neostigmine produced purgation in equines and dogs with less signs of colic than did physostigmine.The articles have been scanned in colour with a HP Scanjet 5590; 300dpi. Adobe Acrobat XI Pro was used to OCR the text and also for the merging and conversion to the final presentation PDF-format

Search for Oscillation of the Electron-Capture Decay Probability of 142^{142}Pm

We have searched for time modulation of the electron capture decay probability of $^{142}$Pm in an attempt to confirm a recent claim from a group at the Gesellschaft f\"{u}r Schwerionenforschung (GSI). We produced $^{142}$Pm via the $^{124}$Sn($^{23}$Na, 5n)$^{142}$Pm reaction at the Berkeley 88-Inch Cyclotron with a bombardment time short compared to the reported modulation period. Isotope selection by the Berkeley Gas-filled Separator is followed by implantation and a long period of monitoring the $^{142}$Nd K$_{\alpha}$ x-rays from the daughter. The decay time spectrum of the x-rays is well-described by a simple exponential and the measured half-life of 40.68(53) seconds is consistent with the accepted value. We observed no oscillatory modulation at the proposed frequency at a level 31 times smaller than that reported by Litvinov {\it et al.} (Phys. Lett. B 664 (2008) 162; arXiv:0801.2079 [nucl-ex]). A literature search for previous experiments that might have been sensitive to the reported modulation uncovered another example in $^{142}$Eu electron-capture decay. A reanalysis of the published data shows no oscillatory behavior.Comment: 12 pages (double-spaced), 6 figure

Creating university spin-offs: A science-based design perspective

Academic entrepreneurship by means of university spin-offs commercializes technological breakthroughs, which may otherwise remain unexploited. However, many universities face difficulties in creating spin-offs. This article adopts a science-based design approach to connect scholarly research with the pragmatics of effectively creating university spin-offs. This approach serves to link the practice of university spin-off creation, via design principles, to the scholarly knowledge in this area. As such, science-based design promotes the interplay between emergent and deliberate design processes. This framework is used to develop a set of design principles that are practice based as well as grounded in the existing body of research on university spin-offs. A case-study of spin-off creation at a Dutch university illustrates the interplay between initial processes characterized by emergent design and the subsequent process that was more deliberate in nature. This case study also suggests there are two fundamentally different phases in building capacity for university spin-off creation. First, an infrastructure for spin-off creation (including a collaborative network of investors, managers and advisors) is developed that then enables support activities to individual spin-off ventures. This study concludes that to build and increase capacity for creating spin-offs, universities should do the following: (1) create university-wide awareness of entrepreneurship opportunities, stimulate the development of entrepreneurial ideas, and subsequently screen entrepreneurs and ideas by programs targeted at students and academic staff; (2) support start-up teams in composing and learning the right mix of venturing skills and knowledge by providing access to advice, coaching, and training; (3) help starters in obtaining access to resources and developing their social capital by creating a collaborative network organization of investors, managers, and advisors; (4) set clear and supportive rules and procedures that regulate the university spin-off process, enhance fair treatment of involved parties, and separate spin-off processes from academic research and teaching; and (5) shape a university culture that reinforces academic entrepreneurship by creating norms and exemplars that motivate entrepreneurial behavior. These and other results of this study illustrate how science-based design can connect scholarly research to the pragmatics of actually creating spin-offs in academic institutions

Preservation of Smooth Muscle Cell Integrity and Function: A Target for Limiting Abdominal Aortic Aneurysm Expansion?

Yes(1) Abdominal aortic aneurysm (AAA) is a silent, progressive disease with significant mortality from rupture. Whilst screening programmes are now able to detect this pathology early in its development, no therapeutic intervention has yet been identified to halt or retard aortic expansion. The inability to obtain aortic tissue from humans at early stages has created a necessity for laboratory models, yet it is essential to create a timeline of events from EARLY to END stage AAA progression. (2) We used a previously validated ex vivo porcine bioreactor model pre-treated with protease enzyme to create "aneurysm" tissue. Mechanical properties, histological changes in the intact vessel wall, and phenotype/function of vascular smooth muscle cells (SMC) cultured from the same vessels were investigated. (3) The principal finding was significant hyperproliferation of SMC from EARLY stage vessels, but without obvious histological or SMC aberrancies. END stage tissue exhibited histological loss of α-smooth muscle actin and elastin; mechanical impairment; and, in SMC, multiple indications of senescence. (4) Aortic SMC may offer a therapeutic target for intervention, although detailed studies incorporating intervening time points between EARLY and END stage are required. Such investigations may reveal mechanisms of SMC dysfunction in AAA development and hence a therapeutic window during which SMC differentiation could be preserved or reinstated.This research was funded in part by The Leeds Teaching Hospitals Charitable Foundation (R11/8002). E.R.C. was supported by a PhD studentship from the Engineering and Physical Sciences Research Council (EPSRC; EP/F500513/1). R.J.H. was the recipient of an Intercalated Batchelor of Science Degree in Science award from the Royal College of Surgeons of England. M.A.B.(FS/18/12/33270 and FS/12/54/29671), K.I.B. (FS/12/26/29395), and K.J.G. (FS/11/91/29090) were supported by BHF Clinical Research Training Fellowships

Vapour-liquid coexistence in many-body dissipative particle dynamics

Many-body dissipative particle dynamics is constructed to exhibit vapour-liquid coexistence, with a sharp interface, and a vapour phase of vanishingly small density. In this form, the model is an unusual example of a soft-sphere liquid with a potential energy built out of local-density dependent one-particle self energies. The application to fluid mechanics problems involving free surfaces is illustrated by simulation of a pendant drop.Comment: 8 pages, 6 figures, revtex

The Timing, the Treatment, the Question: Comparison of Epidemiologic Approaches to Minimize Immortal Time Bias in Real-World Data Using a Surgical Oncology Example

Background: Studies evaluating the effects of cancer treatments are prone to immortal time bias that, if unaddressed, can lead to treatments appearing more beneficial than they are. Methods: To demonstrate the impact of immortal time bias, we compared results across several analytic approaches (dichotomous exposure, dichotomous exposure excluding immortal time, time-varying exposure, landmark analysis, clone-censor-weight method), using surgical resection among women with metastatic breast cancer as an example. All adult women diagnosed with incident metastatic breast cancer from 2013–2016 in the National Cancer Database were included. To quantify immortal time bias, we also conducted a simulation study where the “true” relationship between surgical resection and mortality was known. Results: 24,329 women (median age 61, IQR 51–71) were included, and 24% underwent surgical resection. The largest association between resection and mortality was observed when using a dichotomized exposure [HR, 0.54; 95% confidence interval (CI), 0.51–0.57], followed by dichotomous with exclusion of immortal time (HR, 0.62; 95% CI, 0.59–0.65). Results from the time-varying exposure, landmark, and clone-censor-weight method analyses were closer to the null (HR, 0.67–0.84). Results from the plasmode simulation found that the time-varying exposure, landmark, and clone-censor-weight method models all produced unbiased HRs (bias -0.003 to 0.016). Both standard dichotomous exposure (HR, 0.84; bias, -0.177) and dichotomous with exclusion of immortal time (HR, 0.93; bias, -0.074) produced meaningfully biased estimates. Conclusions: Researchers should use time-varying exposures with a treatment assessment window or the clone-censor-weight method when immortal time is present. Impact: Using methods that appropriately account for immortal time will improve evidence and decision-making from research using real-world data

Self-Consistent Quasi-Particle RPA for the Description of Superfluid Fermi Systems

Self-Consistent Quasi-Particle RPA (SCQRPA) is for the first time applied to a more level pairing case. Various filling situations and values for the coupling constant are considered. Very encouraging results in comparison with the exact solution of the model are obtained. The nature of the low lying mode in SCQRPA is identified. The strong reduction of the number fluctuation in SCQRPA vs BCS is pointed out. The transition from superfluidity to the normal fluid case is carefully investigated.Comment: 23 pages, 18 figures and 1 table, submitted to Phys. Rev.

Cutting cardiovascular risk in barbershops

http://dx.doi.org/10.1016/j.jomh.2009.07.00

Dust Devil Tracks

Dust devils that leave dark- or light-toned tracks are common on Mars and they can also be found on the Earth’s surface. Dust devil tracks (hereinafter DDTs) are ephemeral surface features with mostly sub-annual lifetimes. Regarding their size, DDT widths can range between ∼1 m and ∼1 km, depending on the diameter of dust devil that created the track, and DDT lengths range from a few tens of meters to several kilometers, limited by the duration and horizontal ground speed of dust devils. DDTs can be classified into three main types based on their morphology and albedo in contrast to their surroundings; all are found on both planets: (a) dark continuous DDTs, (b) dark cycloidal DDTs, and (c) bright DDTs. Dark continuous DDTs are the most common type on Mars. They are characterized by their relatively homogenous and continuous low albedo surface tracks. Based on terrestrial and martian in situ studies, these DDTs most likely form when surficial dust layers are removed to expose larger-grained substrate material (coarse sands of ≥500 μm in diameter). The exposure of larger-grained materials changes the photometric properties of the surface; hence leading to lower albedo tracks because grain size is photometrically inversely proportional to the surface reflectance. However, although not observed so far, compositional differences (i.e., color differences) might also lead to albedo contrasts when dust is removed to expose substrate materials with mineralogical differences. For dark continuous DDTs, albedo drop measurements are around 2.5 % in the wavelength range of 550–850 nm on Mars and around 0.5 % in the wavelength range from 300–1100 nm on Earth. The removal of an equivalent layer thickness around 1 μm is sufficient for the formation of visible dark continuous DDTs on Mars and Earth. The next type of DDTs, dark cycloidal DDTs, are characterized by their low albedo pattern of overlapping scallops. Terrestrial in situ studies imply that they are formed when sand-sized material that is eroded from the outer vortex area of a dust devil is redeposited in annular patterns in the central vortex region. This type of DDT can also be found in on Mars in orbital image data, and although in situ studies are lacking, terrestrial analog studies, laboratory work, and numerical modeling suggest they have the same formation mechanism as those on Earth. Finally, bright DDTs are characterized by their continuous track pattern and high albedo compared to their undisturbed surroundings. They are found on both planets, but to date they have only been analyzed in situ on Earth. Here, the destruction of aggregates of dust, silt and sand by dust devils leads to smooth surfaces in contrast to the undisturbed rough surfaces surrounding the track. The resulting change in photometric properties occurs because the smoother surfaces have a higher reflectance compared to the surrounding rough surface, leading to bright DDTs. On Mars, the destruction of surficial dust-aggregates may also lead to bright DDTs. However, higher reflective surfaces may be produced by other formation mechanisms, such as dust compaction by passing dust devils, as this may also cause changes in photometric properties. On Mars, DDTs in general are found at all elevations and on a global scale, except on the permanent polar caps. DDT maximum areal densities occur during spring and summer in both hemispheres produced by an increase in dust devil activity caused by maximum insolation. Regionally, dust devil densities vary spatially likely controlled by changes in dust cover thicknesses and substrate materials. This variability makes it difficult to infer dust devil activity from DDT frequencies. Furthermore, only a fraction of dust devils leave tracks. However, DDTs can be used as proxies for dust devil lifetimes and wind directions and speeds, and they can also be used to predict lander or rover solar panel clearing events. Overall, the high DDT frequency in many areas on Mars leads to drastic albedo changes that affect large-scale weather patterns

Functional diversity of chemokines and chemokine receptors in response to viral infection of the central nervous system.

Encounters with neurotropic viruses result in varied outcomes ranging from encephalitis, paralytic poliomyelitis or other serious consequences to relatively benign infection. One of the principal factors that control the outcome of infection is the localized tissue response and subsequent immune response directed against the invading toxic agent. It is the role of the immune system to contain and control the spread of virus infection in the central nervous system (CNS), and paradoxically, this response may also be pathologic. Chemokines are potent proinflammatory molecules whose expression within virally infected tissues is often associated with protection and/or pathology which correlates with migration and accumulation of immune cells. Indeed, studies with a neurotropic murine coronavirus, mouse hepatitis virus (MHV), have provided important insight into the functional roles of chemokines and chemokine receptors in participating in various aspects of host defense as well as disease development within the CNS. This chapter will highlight recent discoveries that have provided insight into the diverse biologic roles of chemokines and their receptors in coordinating immune responses following viral infection of the CNS