Neural signatures of cognitive flexibility and reward sensitivity following nicotinic receptor stimulation in dependent smokers : a randomized trial

IMPORTANCE Withdrawal from nicotine is an important contributor to smoking relapse. Understanding how reward-based decision making is affected by abstinence and by pharmacotherapies such as nicotine replacement therapy and varenicline tartrate may aid cessation treatment. OBJECTIVE To independently assess the effects of nicotine dependence and stimulation of the nicotinic acetylcholine receptor on the ability to interpret valence information (reward sensitivity) and subsequently alter behavior as reward contingencies change (cognitive flexibility) in a probabilistic reversal learning task. DESIGN, SETTING, AND PARTICIPANTS Nicotine-dependent smokers and nonsmokers completed a probabilistic reversal learning task during acquisition of functional magnetic resonance imaging (fMRI) in a 2-drug, double-blind placebo-controlled crossover design conducted from January 21, 2009, to September 29, 2011. Smokers were abstinent from cigarette smoking for 12 hours for all sessions. In a fully Latin square fashion, participants in both groups underwent MRI twice while receiving varenicline and twice while receiving a placebo pill, wearing either a nicotine or a placebo patch. Imaging analysis was performed from June 15, 2015, to August 10, 2016. MAIN OUTCOME AND MEASURES A well-established computational model captured effects of smoking status and administration of nicotine and varenicline on probabilistic reversal learning choice behavior. Neural effects of smoking status, nicotine, and varenicline were tested for on MRI contrasts that captured reward sensitivity and cognitive flexibility. RESULTS The study included 24 nicotine-dependent smokers (12 women and 12 men; mean [SD] age, 35.8 [9.9] years) and 20 nonsmokers (10 women and 10 men; mean [SD] age, 30.4 [7.2] years). Computational modeling indicated that abstinent smokers were biased toward response shifting and that their decisions were less sensitive to the available evidence, suggesting increased impulsivity during withdrawal. These behavioral impairments were mitigated with nicotine and varenicline. Similarly, decreased mesocorticolimbic activity associated with cognitive flexibility in abstinent smokers was restored to the level of nonsmokers following stimulation of nicotinic acetylcholine receptors (familywise error-corrected P<.05). Conversely, neural signatures of decreased reward sensitivity in smokers (vs nonsmokers; familywise error-corrected P<.05) in the dorsal striatum and anterior cingulate cortex were not mitigated by nicotine or varenicline. CONCLUSIONS AND RELEVANCE There was a double dissociation between the effects of chronic nicotine dependence on neural representations of reward sensitivity and acute effects of stimulation of nicotinic acetylcholine receptors on behavioral and neural signatures of cognitive flexibility in smokers. These chronic and acute pharmacologic effects were observed in overlapping mesocorticolimbic regions, suggesting that available pharmacotherapies may alleviate deficits in the same circuitry for certain mental computations but not for others

A national survey of 'inactive' physicians in the United States of America: enticements to reentry

<p>Abstract</p> <p>Background</p> <p>Physicians leaving and reentering clinical practice can have significant medical workforce implications. We surveyed inactive physicians younger than typical retirement age to determine their reasons for clinical inactivity and what barriers, real or perceived, there were to reentry into the medical workforce.</p> <p>Methods</p> <p>A random sample of 4975 inactive physicians aged under 65 years was drawn from the Physician Masterfile of the American Medical Association in 2008. Physicians were mailed a survey about activity in medicine and perceived barriers to reentry. Chi-square statistics were used for significance tests of the association between categorical variables and t-tests were used to test differences between means.</p> <p>Results</p> <p>Our adjusted response rate was 36.1%. Respondents were fully retired (37.5%), not currently active in medicine (43.0%) or now active (reentered, 19.4%). Nearly half (49.5%) were in or had practiced primary care. Personal health was the top reason for leaving for fully retired physicians (37.8%) or those not currently active in medicine (37.8%) and the second highest reason for physicians who had reentered (28.8%). For reentered (47.8%) and inactive (51.5%) physicians, the primary reason for returning or considering returning to practice was the availability of part-time work or flexible scheduling. Retired and currently inactive physicians used similar strategies to explore reentry, and 83% of both groups thought it would be difficult; among those who had reentered practice, 35.9% reported it was difficult to reenter. Retraining was uncommon for this group (37.5%).</p> <p>Conclusion</p> <p>Availability of part-time work and flexible scheduling have a strong influence on decisions to leave or reenter clinical practice. Lack of retraining before reentry raises questions about patient safety and the clinical competence of reentered physicians.</p

Reducing Road Traffic Accidents and Mortalities in Mwanza, Tanzania: Proposal

We will implement a multi-disciplinary approach to help resolve the high instances of motor vehicle accidents and mortalities in Mwanza, Tanzania. We intend to reduce RTAs, injuries, morbidities, and mortalities, and increase road safety awareness through: Education services through various advertising strategies; Training services to medical personnel, healthcare professionals, and local citizens; and GPS intervention to implement smart phones with GPS to dala dalas and taxi drivers

A new taeniolabidoid multituberculate (Mammalia) from the middle Puercan of the Nacimiento Formation, New Mexico, and a revision of taeniolabidoid systematics and phylogeny

Multituberculates were amongst the most abundant and taxonomically diverse mammals of the late Mesozoic and the Paleocene, reaching their zenith in diversity and body size in the Paleocene. Taeniolabidoidea, the topic of this paper, includes the largest known multituberculates, which possess highly complex cheek teeth adapted for herbivory. A new specimen from the early Paleocene (middle Puercan; biochron Pu2) of the Nacimiento Formation, New Mexico represents a new large-bodied taeniolabidoid genus and species, Kimbetopsalis simmonsae. A phylogenetic analysis to examine the relationships within Taeniolabidoidea that includes new information from Kimbetopsalis gen. et sp. nov. and gen. nov. and from new specimens of Catopsalis fissidens, first described here, and data from all other described North American and Asian taeniolabidoids. This analysis indicates that Catopsalis is nonmonophyletic and justifies our transfer of the basal-most taeniolabidoid ‘Catopsalis’ joyneri to a new genus, Valenopsalis. Kimbetopsalis and Taeniolabis form a clade (Taeniolabididae), as do the Asian Lambdopsalis, Sphenopsalis, and possibly also Prionessus (Lambdopsalidae). Taeniolabidoids underwent a modest taxonomic radiation during the early Paleocene of North America and underwent a dramatic increase in body size, with Taeniolabis taoensis possibly exceeding 100 kg. Taeniolabidoids appear to have gone extinct in North America by the late Paleocene but the appearance of lambdopsalids in the late Paleocene of Asia suggests that they dispersed from North America in the early to middle Paleocene

Exploring the benefits of doll play through neuroscience

It has long been hypothesized that pretend play is beneficial to social and cognitive development. However, there is little evidence regarding the neural regions that are active while children engage in pretend play. We examined the activation of prefrontal and posterior superior temporal sulcus (pSTS) regions using near-infrared spectroscopy while 42 4- to 8-year-old children freely played with dolls or tablet games with a social partner or by themselves. Social play activated right prefrontal regions more than solo play. Children engaged the pSTS during solo doll play but not during solo tablet play, suggesting they were rehearsing social cognitive skills more with dolls. These findings suggest social play utilizes multiple neural regions and highlight how doll play can achieve similar patterns of activation, even when children play by themselves. Doll play may provide a unique opportunity for children to practice social interactions important for developing social-emotional skills, such as empathy

Redefining the performing arts archive

This paper investigates representations of performance and the role of the archive. Notions of record and archive are critically investigated, raising questions about applying traditional archival definitions to the performing arts. Defining the nature of performances is at the root of all difficulties regarding their representation. Performances are live events, so for many people the idea of recording them for posterity is inappropriate. The challenge of creating and curating representations of an ephemeral art form are explored and performance-specific concepts of record and archive are posited. An open model of archives, encouraging multiple representations and allowing for creative reuse and reinterpretation to keep the spirit of the performance alive, is envisaged as the future of the performing arts archive

Terrestrial carbon isotope stratigraphy and mammal turnover during post-PETM hyperthermals in the Bighorn Basin, Wyoming, USA

Paleogene hyperthermals, including the Paleocene–Eocene Thermal Maximum (PETM) and several other smaller events, represent global perturbations to Earth’s climate system and are characterized by warmer temperatures, changes in floral and faunal communities, and hydrologic changes. These events are identified in the geologic record globally by negative carbon isotope excursions (CIEs), resulting from the input of isotopically light carbon into Earth’s atmosphere. Much about the causes and effects of hyperthermals remains uncertain, including whether all hyperthermals were caused by the same underlying processes, how biotic effects scale with the magnitude of hyperthermals, and why CIEs are larger in paleosol carbonates relative to marine records. Resolving these questions is crucial for a full understanding of the causes of hyperthermals and their application to future climate scenarios. The primary purpose of this study was to identify early Eocene hyperthermals in the Fifteenmile Creek area of the south-central Bighorn Basin, Wyoming, USA. This area preserves a sequence of fluvial floodplain sedimentary rocks containing paleosol carbonates and an extensive record of fossil mammals. Previous analysis of faunal assemblages in this area revealed two pulses of mammal turnover and changes in diversity interpreted to correlate with the ETM2 and H2 hyperthermals that follow the PETM. This was, however, based on long-distance correlation of the fossil record in this area with chemostratigraphic records from elsewhere in the basin. We present new carbon isotope stratigraphies using micrite δ13C values from paleosol carbonate nodules preserved in and between richly fossiliferous mammal localities at Fifteenmile Creek to identify the stratigraphic positions of ETM2 and H2. Carbon isotope results show that the ETM2 and H2 hyperthermals, and possibly the subsequent I1 hyperthermal, are recorded at Fifteenmile Creek. ETM2 and H2 overlap with the two previously recognized pulses of mammal turnover. The CIEs for these hyperthermals are also somewhat smaller in magnitude than in more northerly Bighorn Basin records. We suggest that basin-wide differences in soil moisture and/or vegetation could contribute to variable CIE amplitudes in this and other terrestrial records

Selective-cold output through a distinct subset of lamina I spinoparabrachial neurons

Spinal projection neurons are a major pathway through which somatic stimuli are conveyed to the brain. However, the manner in which this information is coded is poorly understood. Here, we report the identification of a modality-selective spinoparabrachial (SPB) neuron subtype with unique properties. Specifically, we find that cold-selective SPB neurons are differentiated by selective afferent input, reduced sensitivity to substance P, distinct physiological properties, small soma size, and low basal drive. In addition, optogenetic experiments reveal that cold-selective SPB neurons do not receive input from Nos1 inhibitory interneurons and, compared with other SPB neurons, show significantly smaller inhibitory postsynaptic currents upon activation of Pdyn inhibitory interneurons. Together, these data suggest that cold output from the spinal cord to the parabrachial nucleus is mediated by a specific cell type with distinct properties

The prevalence and causes of vision loss in Indigenous Australians: the National Indigenous Eye Health Survey

Aim: To determine the prevalence and causes of vision loss in Indigenous Australians. Design, setting and participants: A national, stratified, random cluster sample was drawn from 30 communities across Australia that each included about 300 Indigenous people of all ages. A sample of non-Indigenous adults aged 40 years was also tested at several remote sites for comparison. Participants were examined using a standardised protocol that included a questionnaire (self-administered or completed with the help of field staff), visual acuity (VA) testing on presentation and after correction, visual field testing, trachoma grading, and fundus and lens photography. The data were collected in 2008. Main outcome measures: VA; prevalence of low vision and blindness; causes of vision loss; rates of vision loss in Indigenous compared with non-Indigenous adults. Results: 1694Indigenouschildrenand1189Indigenousadultswereexamined, representing recruitment rates of 84% for children aged 5–15 years and 72% for adults aged 40 years. Rates of low vision (VA \u3c 6/12 to 6/60) were 1.5% (95% CI, 0.9%–2.1%) in children and 9.4% (95% CI, 7.8%–11.1%) in adults. Rates of blindness (VA \u3c 6/60) were 0.2% (95% CI, 0.04%–0.5%) in children and 1.9% (95% CI, 1.1%–2.6%) in adults. The principal cause of low vision in both adults and children was refractive error. The principal causes of blindness in adults were cataract, refractive error and optic atrophy. Relative risks (RRs) of vision loss and blindness in Indigenous adults compared with adults in the mainstream Australian population were 2.8 and 6.2, respectively. By contrast, RRs of vision loss and blindness in Indigenous children compared with mainstream children were 0.2 and 0.6, respectively. Conclusion: Many causes of vision loss in our sample were readily avoidable. Better allocation of services and resources is required to give all Australians equal access to eye health services