Existing practices, alternatives

Improvement can be successful if participants\u27 needs are met

Connecting psychophysical performance to neuronal response properties II: Contrast decoding and detection

The purpose of this article is to provide mathematical insights into the results of some Monte Carlo simulations published by Tolhurst and colleagues (Clatworthy, Chirimuuta, Lauritzen, & Tolhurst, 2003; Chirimuuta & Tolhurst, 2005a). In these simulations, the contrast of a visual stimulus was encoded by a model spiking neuron or a set of such neurons. The mean spike count of each neuron was given by a sigmoidal function of contrast, the Naka-Rushton function. The actual number of spikes generated on each trial was determined by a doubly stochastic Poisson process. The spike counts were decoded using a Bayesian decoder to give an estimate of the stimulus contrast. Tolhurst and colleagues used the estimated contrast values to assess the model's performance in a number of ways, and they uncovered several relationships between properties of the neurons and characteristics of performance. Although this work made a substantial contribution to our understanding of the links between physiology and perceptual performance, the Monte Carlo simulations provided little insight into why the obtained patterns of results arose or how general they are. We overcame these problems by deriving equations that predict the model's performance. We derived an approximation of the model's decoding precision using Fisher information. We also analyzed the model's contrast detection performance and discovered a previously unknown theoretical connection between the Naka-Rushton contrast-response function and the Weibull psychometric function. Our equations give many insights into the theoretical relationships between physiology and perceptual performance reported by Tolhurst and colleagues, explaining how they arise and how they generalize across the neuronal parameter space

Assessment of PBTs in the European Union: a critical assessment of the proposed evaluation scheme with reference to plant protection products

n/

Serological survey of <i>Brucella canis</i> in dogs in urban Harare and selected rural communities in Zimbabwe

A cross-sectional study was conducted in order to detect antibodies for Brucella canis (B. canis) in dogs from urban Harare and five selected rural communities in Zimbabwe. Sera from randomly selected dogs were tested for antibodies to B. canis using an enzyme-linked immunosorbent assay. Overall, 17.6% of sera samples tested (57/324, 95% CI: 13.5–21.7) were positive for B. canis antibodies. For rural dogs, seroprevalence varied from 11.7% – 37.9%. Rural dogs recorded a higher seroprevalence (20.7%, 95% CI: 15.0–26.4) compared with Harare urban dogs (12.7%, 95% CI: 6.9–18.5) but the difference was not significant (p = 0.07). Female dogs from both sectors had a higher seroprevalence compared with males, but the differences were not significant (p > 0.05). Five and two of the positive rural dogs had titres of 1:800 and 1:1600, respectively, whilst none of the positive urban dogs had a titre above 1:400. This study showed that brucellosis was present and could be considered a risk to dogs from the studied areas. Further studies are recommended in order to give insight into the epidemiology of brucellosis in dogs and its possible zoonotic consequences in Zimbabwe. Screening for other Brucella spp. (Brucella abortus, Brucella melitensis and Brucella suis) other than B. canis is also recommended

Assessing the reliability of ecotoxicological studies : an overview of current needs and approaches

In general, reliable studies are well designed and well performed, and enough details on study design and performance are reported to assess the study. For hazard and risk assessment in various legal frameworks, many different types of ecotoxicity studies need to be evaluated for reliability. These studies vary in study design, methodology, quality, and level of detail reported (e.g., reviews, peer-reviewed research papers, or industry-sponsored studies documented under Good Laboratory Practice [GLP] guidelines). Regulators have the responsibility to make sound and verifiable decisions and should evaluate each study for reliability in accordance with scientific principles regardless of whether they were conducted in accordance with GLP and/or standardized methods. Thus, a systematic and transparent approach is needed to evaluate studies for reliability. In this paper, 8 different methods for reliability assessment were compared using a number of attributes: categorical versus numerical scoring methods, use of exclusion and critical criteria, weighting of criteria, whether methods are tested with case studies, domain of applicability, bias toward GLP studies, incorporation of standard guidelines in the evaluation method, number of criteria used, type of criteria considered, and availability of guidance material. Finally, some considerations are given on how to choose a suitable method for assessing reliability of ecotoxicity studies. Integr Environ Assess Manag 2017;13:640-651. (c) 2016 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals, Inc. on behalf of Society of Environmental Toxicology & Chemistry (SETAC

Spectroscopic and Theoretical Study of CuI Binding to His111 in the Human Prion Protein Fragment 106-115

The ability of the cellular prion protein (PrPC) to bind copper in vivo points to a physiological role for PrPC in copper transport. Six copper binding sites have been identified in the nonstructured N-terminal region of human PrPC. Among these sites, the His111 site is unique in that it contains a MKHM motif that would confer interesting CuI and CuII binding properties. We have evaluated CuI coordination to the PrP(106-115) fragment of the human PrP protein, using NMR and X-ray absorption spectroscopies and electronic structure calculations. We find that Met109 and Met112 play an important role in anchoring this metal ion. CuI coordination to His111 is pH-dependent: at pH >8, 2N1O1S species are formed with one Met ligand; in the range of pH 5-8, both methionine (Met) residues bind to CuI, forming a 1N1O2S species, where N is from His111 and O is from a backbone carbonyl or a water molecule; at pH <5, only the two Met residues remain coordinated. Thus, even upon drastic changes in the chemical environment, such as those occurring during endocytosis of PrPC (decreased pH and a reducing potential), the two Met residues in the MKHM motif enable PrPC to maintain the bound CuI ions, consistent with a copper transport function for this protein. We also find that the physiologically relevant CuI-1N1O2S species activates dioxygen via an inner-sphere mechanism, likely involving the formation of a copper(II) superoxide complex. In this process, the Met residues are partially oxidized to sulfoxide; this ability to scavenge superoxide may play a role in the proposed antioxidant properties of PrPC. This study provides further insight into the CuI coordination properties of His111 in human PrPC and the molecular mechanism of oxygen activation by this site.Fil: Arcos López, Trinidad. Instituto Politécnico Nacional. Centro de Investigación y de Estudios Avanzado; MéxicoFil: Qayyum, Munzarin. University of Stanford; Estados UnidosFil: Rivillas Acevedo, Lina. Instituto Politécnico Nacional. Centro de Investigación y de Estudios Avanzado; MéxicoFil: Miotto, Marco César. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Investigaciones para el Descubrimiento de Fármacos de Rosario. Universidad Nacional de Rosario. Instituto de Investigaciones para el Descubrimiento de Fármacos de Rosario; Argentina. Max Planck Laboratory for Structural Biology; ArgentinaFil: Grande Aztatzi, Rafael. Instituto Politécnico Nacional. Centro de Investigación y de Estudios Avanzado; MéxicoFil: Fernandez, Claudio Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Investigaciones para el Descubrimiento de Fármacos de Rosario. Universidad Nacional de Rosario. Instituto de Investigaciones para el Descubrimiento de Fármacos de Rosario; Argentina. Max Planck Laboratory for Structural Biology; ArgentinaFil: Hedman, Britt. University of Stanford; Estados UnidosFil: Hodgson, Keith O.. University of Stanford; Estados UnidosFil: Vela, Alberto. Instituto Politécnico Nacional. Centro de Investigación y de Estudios Avanzado; MéxicoFil: Solomon, Edward I.. University of Stanford; Estados UnidosFil: Quintanar, Liliana. Instituto Politécnico Nacional. Centro de Investigación y de Estudios Avanzado; Méxic

Preliminary needs assessment of mobile technology use for healthcare among homeless veterans

Background. Homeless veterans have complex healthcare needs, but experience many barriers to treatment engagement. While information technologies (IT), especially mobile phones, are used to engage patients in care, little is known about homeless veterans\u27 IT use. This study examines homeless veterans\u27 access to and use of IT, attitudes toward health-related IT use, and barriers to IT in the context of homelessness. Methods. Qualitative interviews were conducted with 30 homeless veterans in different housing programs in Boston, MA, ranging from emergency shelters to supportive transitional housing that allow stays of up to 2 years. Interviews were conducted in person, audio recorded and then transcribed. Three researchers coded transcripts. Inductive thematic analysis was used. Results. Most participants (90%) had a mobile phone and were receptive to IT use for health-related communications. A common difficulty communicating with providers was the lack of a stable mailing address. Some participants were using mobile phones to stay in touch with providers. Participants felt mobile-phone calls or text messages could be used to remind patients of appointments, prescription refills, medication taking, and returning for laboratory results. Mobile phone text messaging was seen as convenient, and helped participants stay organized because necessary information was saved in text messages. Some reported concerns about the costs associated with mobile phone use (calls and texting), the potential to be annoyed by too many text messages, and not knowing how to use text messaging. Conclusion. Homeless veterans use IT and welcome its use for health-related purposes. Technology-assisted outreach among this population may lead to improved engagement in care

SGLT2 Inhibitors for Type 2 Diabetes Mellitus Treatment

SGLT2 inhibitors are plausible second-line drugs that provide powerful additional A1c-lowering effects while inducing weight loss without hypoglycemia

Structure of the Reduced Copper Active Site in Pre-Processed Galactose Oxidase: Ligand Tuning for One-Electron O2 Activation in Cofactor Biogenesis

Galactose oxidase (GO) is a copper-dependent enzyme that accomplishes 2e- substrate oxidation by pairing a single copper with an unusual cysteinylated tyrosine (Cys-Tyr) redox cofactor. Previous studies have demonstrated that the post-translational biogenesis of Cys-Tyr is copper- and O2-dependent, resulting in a self-processing enzyme system. To investigate the mechanism of cofactor biogenesis in GO, the active-site structure of Cu(I)-loaded GO was determined using X-ray absorption near edge structure (XANES) and extended X-ray absorption fine structure (EXAFS) spectroscopy, and density-functional theory (DFT) calculations were performed on this model. Our results show that the active-site tyrosine lowers the Cu potential to enable the thermodynamically unfavorable 1e- reduction of O2, and the resulting Cu(II)-O2¿- is activated toward H atom abstraction from cysteine. The final step of biogenesis is a concerted reaction involving coordinated Tyr ring deprotonation where Cu(II) coordination enables formation of the Cys-Tyr cross-link. These spectroscopic and computational results highlight the role of the Cu(I) in enabling O2 activation by 1e- and the role of the resulting Cu(II) in enabling substrate activation for biogenesis