Development of behavioral preferences for the optimal choice following unexpected reward omission is mediated by a reduction of D 2‐like receptor tone in the nucleus accumbens

To survive in a dynamic environment, animals must identify changes in resource availability and rapidly apply adaptive strategies to obtain resources that promote survival. We have utilised a behavioral paradigm to assess differences in foraging strategy when resource (reward) availability unexpectedly changes. When reward magnitude was reduced by 50% (receive one reward pellet instead of two), male and female rats developed a preference for the optimal choice by the second session. However, when an expected reward was omitted (receive no reward pellets instead of one), subjects displayed a robust preference for the optimal choice during the very first session. Previous research shows that, when an expected reward is omitted, dopamine neurons phasically decrease their firing rate, which is hypothesised to decrease dopamine release preferentially affecting D 2‐like receptors. As robust changes in behavioral preference were specific to reward omission, we tested this hypothesis and the functional role of D 1‐ and D 2‐like receptors in the nucleus accumbens in mediating the rapid development of a behavioral preference for the rewarded option during reward omission in male rats. Blockade of both receptor types had no effect on this behavior; however, holding D 2‐like, but not D 1‐like, receptor tone via infusion of dopamine receptor agonists prevented the development of the preference for the rewarded option during reward omission. These results demonstrate that avoiding an outcome that has been tagged with aversive motivational properties is facilitated through decreased dopamine transmission and subsequent functional disruption of D 2‐like, but not D 1‐like, receptor tone in the nucleus accumbens. This study investigates the role of dopamine receptors in the nucleus accumbens in altering behavior in response to the omission of an expected reward. Similarly to controls, multiple doses of a D 1‐like receptor agonist, D 1‐like receptor antagonist, and D 2‐like receptor antagonist do not prevent subjects from developing a robust behavioral preference for the rewarded lever and avoiding the omitted‐reward lever during the first session of reward omission. However, the D 2‐like agonist quinpirole dose‐dependently blocks a behavioral preference for the rewarded lever, suggesting that reductions in D 2‐like receptor tone are necessary for altering behavior away from an aversive option and toward the optimal choice.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/99645/1/ejn12253.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/99645/2/ejn12253-sup-0001-Supplement.pd

Pre-notification letter type and response rate to a postal survey among women who have recently given birth

Background: Surveys are commonly used in health research to assess patient satisfaction with hospital care. Achieving an adequate response rate, in the face of declining trends over time, threatens the quality and reliability of survey results. This paper reports on a postal satisfaction survey conducted with women who had recently given birth, and explores the effect of two strategies on response rates. Methods: A sample of 2048 Australian women who had recently given birth were invited to participate in a postal survey about their recent experiences with maternity care. The study design included two different strategies intended to increase response rates: a randomised controlled trial testing two types of pre-notification letter (with or without the option of opting out of the survey), and a request for consent to link survey data with existing routinely collected health data (omitting the latter data items from the survey reduced survey length and participant burden). Results: The survey had an overall response rate of 46%. Women receiving the pre-notification letter with the option of opting out of the survey were more likely to actively decline to participate than women receiving the letter without this option, although the overall numbers of women were small (27 versus 12). Letter type was not significantly associated with the return of a completed survey. Among women who completed the survey, 97% gave consent to link their survey data with existing health data. Conclusions: Seeking consent for record linkage was highly acceptable to women who completed the survey, and represents an important strategy to add to the arsenal for designing and implementing effective surveys. In addition to aspects of survey design, future research should explore how to more effectively influence personal constructs that contribute to the decision to participate in surveys.NHMR

Spy1 Levels Predict Sensitivity of Refractory Multiple Myeloma to Therapy

Multiple myeloma (MM) is an aggressive hematopoietic malignancy with a poor prognosis that is caused by the abnormal growth of plasma cells in the bone marrow. Cyclin-dependent kinase inhibitors (CKIs) have been explored as a possible treatment for MM, with limited clinical success. We postulate that the cyclin-like protein, Spy1 (SPDYA), which is capable of overriding cell-cycle checkpoints, may play a role in limiting therapeutic effectiveness. To support this hypothesis, we have found that Spy1 is highly expressed in MM patient samples and human cell lines. We aim to explore the role that Spy1 plays in CKI resistance in MM using a variety of in vitro and in vivo techniques. Firstly, we intend to create and optimize an in vitro platform to study MM using patient samples collected from clinicians at Windsor Regional Hospital. Using this culture, and human cell lines, we intend to investigate the methylation status of Spy1 and other MM genes in Spy1 overexpression and knockout conditions to see the effects of epigenetic regulation. Then, we will perform drug and toxicity assays with standard CKIs using our Spy1 overexpression and knock-down lines to observe response to CKIs, expecting lines with higher Spy1 to demonstrate increased therapy resistance. Finally, our cells with manipulated Spy1 levels will be injected into zebrafish to test the effects of CKIs in vivo. Collectively, we aim to explore the role Spy1 may play in resistance to CKI therapy in MM, to improve disease understanding and identify areas treatments may be improved

Reviews

The following publications have been reviewed by the mentioned authors;Technology Education for Teachers - reviewed by Bill GoddardUnderstanding Design and Technology Key Stage 2 & 3 - reviewed by Melanie FasciatoElectronics Tasks and Assignments - reviewed by Trevor TaylorOutline Scheme of Work 'Working towards Capability' - reviewed by Bill GoddardCADpius - reviewed by Les PorterTechnology 1 - reviewed by Richard AgerDigital Electronics - reviewed by David FosterAn Introduction to Usability - reviewed by Anne RiggsHow do they do that? - reviewed by Jonty KinsellaD & T Routes: Graphic Products - reviewed by George AsquithD & T Routes: Textiles - reviewed by Jillian MellorD & T Routes: Resistant Materials - reviewed by Chris SnellD & T Routes: Food - reviewed by Margaret JepsonD & T Routes: Control Products - reviewed by Chris WoodD & T Routes: Core Book - reviewed by Jenny JupeD & T Routes: Teacher's Resource - reviewed by Jenny Jup

Novel associations in disorders of sex development: findings from the I-DSD registry

Context: The focus of care in disorders of sex development (DSD) is often directed to issues related to sex and gender development. In addition, the molecular etiology remains unclear in the majority of cases.<p></p> Objective: To report the range of associated conditions identified in the international DSD (I-DSD) Registry.<p></p> Design, Setting, and Patients: Anonymized data were extracted from the I-DSD Registry for diagnosis, karyotype, sex of rearing, genetic investigations, and associated anomalies. If necessary, clarification was sought from the reporting clinician.<p></p> Results: Of 649 accessible cases, associated conditions occurred in 168 (26%); 103 (61%) cases had one condition, 31 (18%) had two conditions, 20 (12%) had three conditions, and 14 (8%) had four or more conditions. Karyotypes with most frequently reported associations included 45,X with 6 of 8 affected cases (75%), 45,X/46,XY with 19 of 42 cases (45%), 46,XY with 112 of 460 cases (24%), and 46,XX with 27 of 121 cases (22%). In the 112 cases of 46,XY DSD, the commonest conditions included small for gestational age in 26 (23%), cardiac anomalies in 22 (20%), and central nervous system disorders in 22 (20%), whereas in the 27 cases of 46,XX DSD, skeletal and renal anomalies were commonest at 12 (44%) and 8 (30%), respectively. Of 170 cases of suspected androgen insensitivity syndrome, 19 (11%) had reported anomalies and 9 of these had confirmed androgen receptor mutations.<p></p> Conclusions: Over a quarter of the cases in the I-DSD Registry have an additional condition. These associations can direct investigators toward novel genetic etiology and also highlight the need for more holistic care of the affected person.<p></p&gt

The Canadian Natural Health Products (NHP) regulations: industry perceptions and compliance factors

BACKGROUND: The use of natural health products, such as vitamins, minerals, and herbs, by Canadians has been increasing with time. As a result of consumer concern about the quality of these products, the Canadian Department of Health created the Natural Health Products (NHP) Regulations. The new Canadian regulations raise questions about whether and how the NHP industry will be able to comply and what impact they will have on market structure. The objectives of this study were to explore who in the interview sample is complying with Canada's new NHP Regulations (i.e., submitted product licensing applications on time); and explore the factors that affect regulatory compliance. METHODS: Twenty key informant interviews were conducted with employees of the NHP industry. The structured interviews focused on the level of satisfaction with the Regulations and perceptions of compliance and non-compliance. Interviews were tape recorded and then transcribed verbatim. Data were independently coded, using qualitative content analysis. Team meetings were held after every three to four interviews to discuss emerging themes. RESULTS: The major finding of this study is that most (17 out of 20) companies interviewed were beginning to comply with the new regulatory regime. The factors that contribute to likelihood of regulatory compliance were: perceptions and knowledge of the regulations and business size. CONCLUSION: The Canadian case can be instructive for other countries seeking to implement regulatory standards for natural health products. An unintended consequence of the Canadian NHP regulations may be the exit of smaller firms, leading to industry consolidation

Unearthing the Infrastructure: Humans and Sensors in Field-Based Scientific Research

Distributed sensing systems for studying scientific phenomena are critical applications of information technologies. By embedding computational intelligence in the environment of study, sensing systems allow researchers to study phenomena at spatial and temporal scales that were previously impossible to achieve. We present an ethnographic study of field research practices among researchers in the Center for Embedded Networked Sensing (CENS), a National Science Foundation Science & Technology Center devoted to developing wireless sensing systems for scientific and social applications. Using the concepts of boundary objects and trading zones, we trace the processes of collaborative research around sensor technology development and adoption within CENS. Over the 10-year lifespan of CENS, sensor technologies, sensor data, field research methods, and statistical expertise each emerged as boundary objects that were understood differently by the science and technology partners. We illustrate how sensing technologies were incompatible with field-based environmental research until researchers “unearthed” their infrastructures, explicitly reintroducing human skill and expertise into the data collection process and developing new collaborative languages that emphasized building dynamic sensing systems that addressed human needs. In collaborating around a dynamic sensing model, the sensing systems became embedded not in the environment of study, but in the practices of the scientists. Status and citation: This is the revised and accepted version, prior to publisher’s copy editing. Please quote the final version: Mayernik, Matthew S., Wallis, Jillian C., & Borgman, Christine L. (In press). Unearthing the infrastructure: Humans and sensors in field-based scientific research. Journal of Computer Supported Cooperative Work. doi: 10.1007/s10606-012-9178-