The effect of developmental vitamin D deficiency in male and female Sprague-Dawley rats on decision-making using a rodent gambling task

Developmental vitamin D (DVD) deficiency is a plausible risk factor for schizophrenia that has been associated with behavioural alterations including disruptions in latent inhibition and response inhibition. The rodent gambling task (rGT) assesses risk-based decision-making, which is a key cognitive deficit observed in schizophrenia patients. The primary aim of this study was to examine risk-based decision-making in DVD-deficient and control rats on the rGT. We also evaluated the performance of female Sprague–Dawley rats on the rGT for the first time. Adult male and female Sprague–Dawley rats from control and vitamin D deficient dams were trained to perform the rGT in standard operant chambers and their performance and choice-preferences were assessed. Female rats were significantly faster to reach rGT training criteria compared with male rats and DVD-deficient rats were faster to reach training criteria than control animals. After reaching stable performance on the rGT DVD-deficient and control rats showed a significant preference for the optimal choice-option in the rGT, but there were no significant effects of sex or diet on these responses. DVD deficiency did not alter the decision-making processes on the rGT because no significant changes in choice-preferences were evident. This is the first study to demonstrate that once established, the performance of females is comparable to male Sprague–Dawley rats on the rGT

Path Integrals in Polar Field Variables in QFT

We show how to transform a $d$-dimensional Euclidean path integral in terms of two (Cartesian) fields to a path integral in terms of polar field variables. First we present a conjecture that states how this transformation should be done. Then we show that this conjecture is correct in the case of two toy models. Finally the conjecture will be proven for a general QFT model with two fields

Enhancing Communication about Paediatric Medicines: Lessons from a Qualitative Study of Parents' Experiences of Their Child's Suspected Adverse Drug Reaction

Background: There is little research on parents’ experiences of suspected adverse drug reactions in their children and hence little evidence to guide clinicians when communicating with families about problems associated with medicines. Objective: To identify any unmet information and communication needs described by parents whose child had a suspected adverse drug reaction. Methods: Semi-structured qualitative interviews with parents of 44 children who had a suspected adverse drug reaction identified on hospital admission, during in-patient treatment or reported by parents using the Yellow Card Scheme (the UK system for collecting spontaneous reports of adverse drug reactions). Interviews were conducted face-to-face or by telephone; most interviews were audiorecorded and transcribed. Analysis was informed by the principles of the constant comparative method. Results: Many parents described being dissatisfied with how clinicians communicated about adverse drug reactions and unclear about the implications for their child’s future use of medicines. A few parents felt that clinicians had abandoned their child and reported refusing the use of further medicines because they feared a repeated adverse drug reaction. The accounts of parents of children with cancer were different. They emphasised their confidence in clinicians’ management of adverse drug reactions and described how clinicians prospectively explained the risks associated with medicines. Parents linked symptoms to medicines in ways that resembled the established reasoning that clinicians use to evaluate the possibility that a medicine has caused an adverse drug reaction. Conclusion: Clinicians’ communication about adverse drug reactions was poor from the perspective of parents, indicating that improvements are needed. The accounts of parents of children with cancer indicate that prospective explanation about adverse drug reactions at the time of prescription can be effective. Convergence between parents and clinicians in their reasoning for linking children’s symptoms to medicines could be a starting point for improved communication

Pole structure of the Hamiltonian ζ\zeta-function for a singular potential

We study the pole structure of the $\zeta$-function associated to the Hamiltonian $H$ of a quantum mechanical particle living in the half-line $\mathbf{R}^+$, subject to the singular potential $g x^{-2}+x^2$. We show that $H$ admits nontrivial self-adjoint extensions (SAE) in a given range of values of the parameter $g$. The $\zeta$-functions of these operators present poles which depend on $g$ and, in general, do not coincide with half an integer (they can even be irrational). The corresponding residues depend on the SAE considered.Comment: 12 pages, 1 figure, RevTeX. References added. Version to appear in Jour. Phys. A: Math. Ge

Evolution of surface gravity waves over a submarine canyon

The effects of a submarine canyon on the propagation of ocean surface waves are examined with a three-dimensional coupled-mode model for wave propagation over steep topography. Whereas the classical geometrical optics approximation predicts an abrupt transition from complete transmission at small incidence angles to no transmission at large angles, the full model predicts a more gradual transition with partial reflection/transmission that is sensitive to the canyon geometry and controlled by evanescent modes for small incidence angles and relatively short waves. Model results for large incidence angles are compared with data from directional wave buoys deployed around the rim and over Scripps Canyon, near San Diego, California, during the Nearshore Canyon Experiment (NCEX). Wave heights are observed to decay across the canyon by about a factor 5 over a distance shorter than a wavelength. Yet, a spectral refraction model predicts an even larger reduction by about a factor 10, because low frequency components cannot cross the canyon in the geometrical optics approximation. The coupled-mode model yields accurate results over and behind the canyon. These results show that although most of the wave energy is refractively trapped on the offshore rim of the canyon, a small fraction of the wave energy 'tunnels' across the canyon. Simplifications of the model that reduce it to the standard and modified mild slope equations also yield good results, indicating that evanescent modes and high order bottom slope effects are of minor importance for the energy transformation of waves propagating across depth contours at large oblique angles

Manipulation of drugs to achieve the required dose is intrinsic to paediatric practice but is not supported by guidelines or evidence

Background: A lack of age-appropriate formulations can make it difficult to administer medicines to children. A manipulation of the dosage form may be required to achieve the required dose. This study aimed to describe medicines that are manipulated to achieve the required dose in paediatric practice.Method: A structured, undisguised observational study and postal survey. The observational study investigated drug manipulations occurring in clinical practice across three sites. The questionnaire, administered to a sample of paediatric nurses throughout the UK, surveyed manipulations conducted and nurses' experiences and views.Results: The observational study identified 310 manipulations, of which 62% involved tablets, 21% were intravenous drugs and 10% were sachets. Of the 54 observed manipulations 40 involved tablets with 65% of the tablets being cut and 30% dispersed to obtain a smaller dose. 188 manipulations were reported by questionnaire respondents, of these 46% involved tablets, 12% were intravenous drugs, and 12% were nebuliser solutions. Manipulations were predominantly, but not exclusively, identified in specialist clinical areas with more highly dependent patients. Questionnaire respondents were concerned about the accuracy of the dose achieved following manipulations and the lack of practice guidance.Conclusion: Manipulations to achieve the required dose occur throughout paediatric in-patient settings. The impact of manipulations on the efficacy of the drugs, the accuracy of the dose and any adverse effects on patients is not known. There is a need to develop evidence-based guidance for manipulations of medicines in children

Exact expression for the diffusion propagator in a family of time-dependent anharmonic potentials

We have obtained the exact expression of the diffusion propagator in the time-dependent anharmonic potential $V(x,t)={1/2}a(t)x^2+b\ln x$. The underlying Euclidean metric of the problem allows us to obtain analytical solutions for a whole family of the elastic parameter a(t), exploiting the relation between the path integral representation of the short time propagator and the modified Bessel functions. We have also analyzed the conditions for the appearance of a non-zero flow of particles through the infinite barrier located at the origin (b<0).Comment: RevTex, 19 pgs. Accepted in Physical Review

Selective inhibition of protein secretion by abrogating receptor–coat interactions during ER export

Protein secretion is an essential process that drives cell growth, movement, and commu-nication. Protein traffic within the secretory pathway occurs via transport intermediatesthat bud from one compartment and fuse with a downstream compartment to delivertheir contents. Here, we explore the possibility that protein secretion can be selectivelyinhibited by perturbing protein–protein interactions that drive capture into transportvesicles. Human proprotein convertase subtilisin/kexin type 9 (PCSK9) is a determi-nant of cholesterol metabolism whose secretion is mediated by a specific cargo adaptorprotein, SEC24A. We map a series of protein–protein interactions between PCSK9, itsendoplasmic reticulum (ER) export receptor SURF4, and SEC24A that mediate secre-tion of PCSK9. We show that the interaction between SURF4 and SEC24A can beinhibited by 4-phenylbutyrate (4-PBA), a small molecule that occludes a cargo-bindingdomain of SEC24. This inhibition reduces secretion of PCSK9 and additional SURF4clients that we identify by mass spectrometry, leaving other secreted cargoes unaffected.We propose that selective small-molecule inhibition of cargo recognition by SEC24 is apotential therapeutic intervention for atherosclerosis and other diseases that are modu-lated by secreted proteins

Selective inhibition of protein secretion by abrogating receptor–coat interactions during ER export

Protein secretion is an essential process that drives cell growth, movement, and commu-nication. Protein traffic within the secretory pathway occurs via transport intermediatesthat bud from one compartment and fuse with a downstream compartment to delivertheir contents. Here, we explore the possibility that protein secretion can be selectivelyinhibited by perturbing protein–protein interactions that drive capture into transportvesicles. Human proprotein convertase subtilisin/kexin type 9 (PCSK9) is a determi-nant of cholesterol metabolism whose secretion is mediated by a specific cargo adaptorprotein, SEC24A. We map a series of protein–protein interactions between PCSK9, itsendoplasmic reticulum (ER) export receptor SURF4, and SEC24A that mediate secre-tion of PCSK9. We show that the interaction between SURF4 and SEC24A can beinhibited by 4-phenylbutyrate (4-PBA), a small molecule that occludes a cargo-bindingdomain of SEC24. This inhibition reduces secretion of PCSK9 and additional SURF4clients that we identify by mass spectrometry, leaving other secreted cargoes unaffected.We propose that selective small-molecule inhibition of cargo recognition by SEC24 is apotential therapeutic intervention for atherosclerosis and other diseases that are modu-lated by secreted proteins

America\u27s Waters: A New Era of Sustainability: Report of the Long\u27s Peak Working Group on National Water Policy

12 p. ; 28 cmhttps://scholar.law.colorado.edu/books_reports_studies/1070/thumbnail.jp