How and why do financial incentives contribute to helping people stop smoking? A realist review.

BACKGROUND: Tobacco smoking remains a key cause of preventable illness and death globally. In response, many countries provide extensive services to help people to stop smoking by offering a variety of effective behavioural and pharmacological therapies. However, many people who wish to stop smoking do not have access to or use stop smoking supports, and new modes of support, including the use of financial incentives, are needed to address this issue. A realist review of published international literature was undertaken to understand how, why, for whom, and in which circumstances financial incentives contribute to success in stopping smoking for general population groups and among pregnant women. METHODS: Systematic searches were undertaken from inception to February 2022 of five academic databases: MEDLINE (ovid), Embase.com, CIHAHL, Scopus and PsycINFO. Study selection was inclusive of all study designs. Twenty-two studies were included. Using Pawson and Tilley's iterative realist review approach, data collected were screened, selected, coded, analysed, and synthesised into a set of explanatory theoretical findings. RESULTS: Data were synthesised into six Context-Mechanism-Outcome Configurations and one overarching programme theory after iterative rounds of analysis, team discussion, and expert panel feedback. Our programme theory shows that financial incentives are particularly useful to help people stop smoking if they have a financial need, are pregnant or recently post-partum, have a high threshold for behaviour change, and/or respond well to external rewards. The incentives work through a number of mechanisms including the role their direct monetary value can play in a person's life and through a process of reinforcement where they can help build confidence and self-esteem. CONCLUSION: This is the first realist review to synthesise how, why, and for whom financial incentives work among those attempting to stop smoking, adding to the existing evidence demonstrating their efficacy. The findings will support the implementation of current knowledge into effective programmes which can enhance the impact of stop smoking care. PROSPERO REGISTRATION NUMBER: CRD42022298941.

The role of governance in shaping health system reform: a case study of the design and implementation of new health regions in Ireland, 2018-2023.

BACKGROUND: Effective governance arrangements are central to the successful functioning of health systems. While the significance of governance as a concept is acknowledged within health systems research, its interplay with health system reform initiatives remains underexplored in the literature. This study focuses on the development of new regional health structures in Ireland in the period 2018-2023, one part of a broader health system reform programme aimed at greater universalism, in order to scrutinise how aspects of governance impact on the reform process, from policy design through to implementation. METHODS: This qualitative, multi-method study draws on document analysis of official documents relevant to the reform process, as well as twelve semi-structured interviews with key informants from across the health sector. Interviews were analysed according to thematic analysis methodology. Conceiving governance as comprising five domains (Transparency, Accountability, Participation, Integrity, Capacity) the research uses the TAPIC framework for health governance as a conceptual starting point and as initial, deductive analytic categories for data analysis. RESULTS: The analysis reveals important lessons for policymakers across the five TAPIC domains of governance. These include deficiencies in accountability arrangements, poor transparency within the system and vis-à-vis external stakeholders and the public, and periods during which a lack of clarity in terms of roles and responsibilities for various process and key decisions related to the reform were identified. Inadequate resourcing of implementation capacity, competing policy visions and changing decision-making arrangements, among others, were found to have originated in and continuously reproduced a lack of trust between key institutional actors. The findings highlight how these challenges can be addressed through strengthening governance arrangements and processes. Importantly, the research reveals the interwoven nature of the five TAPIC dimensions of governance and the need to engage with the complexity and relationality of health system reform processes. CONCLUSIONS: Large scale health system reform is a complex process and its governance presents distinct challenges and opportunities for stakeholders. To understand and be able to address these, and to move beyond formulaic prescriptions, critical analysis of the historical context surrounding the policy reform and the institutional relationships at its core are needed.

How do health system factors (funding and performance) impact on access to healthcare for populations experiencing homelessness: a realist evaluation.

BACKGROUND: People experiencing long-term homelessness face significant difficulties accessing appropriate healthcare at the right time and place. This study explores how and why healthcare performance management and funding arrangements contribute to healthcare accessibility or the lack thereof using long-term homeless adults as an example of a population experiencing social exclusion. METHODS: A realist evaluation was undertaken. Thirteen realist interviews were conducted after which data were transcribed, coded, and analysed. RESULTS: Fourteen CMOCs were created based on analysis of the data collected. These were then consolidated into four higher-level CMOCs. They show that health systems characterised by fragmentation are designed to meet their own needs above the needs of patients, and they rely on practitioners with a special interest and specialised services to fill the gaps in the system. Key contexts identified in the study include: health system fragmentation; health service fragmentation; bio-medical, one problem at a time model; responsive specialised services; unresponsive mainstream services; national strategy; short health system funding cycles; and short-term goals. CONCLUSION: When health services are fragmented and complex, the needs of socially excluded populations such as those experiencing homelessness are not met. Health systems focus on their own metrics and rely on separate actors such as independent NGOs to fill gaps when certain people are not accommodated in the mainstream health system. As a result, health systems lack a comprehensive understanding of the needs of all population groups and fail to plan adequately, which maintains fragmentation. Policy makers must set policy and plan health services based on a full understanding of needs of all population groups.

Implications for health system reform, workforce recovery and rebuilding in the context of the Great Recession and COVID-19: a case study of workforce trends in Ireland 2008-2021.

BACKGROUND: Workforce is a fundamental health systems building block, with unprecedented measures taken to meet extra demand and facilitate surge capacity during the COVID-19 pandemic, following a prolonged period of austerity. This case study examines trends in Ireland's publicly funded health service workforce, from the global financial crisis, through the Recovery period and into the COVID-19 pandemic, to understand resource allocation across community and acute settings. Specifically, this paper aims to uncover whether skill-mix and staff capacity are aligned with policy intent and the broader reform agenda to achieve universal access to integrated healthcare, in part, by shifting free care into primary and community settings. METHODS: Secondary analysis of anonymised aggregated national human resources data was conducted over a period of almost 14 years, from December 31st 2008 to August 31st 2021. Comparative analysis was conducted, by professional cadre, across three keys periods: 'Recession period' December 31st 2008-December 31st 2014; 'Recovery period' December 31st 2014-December 31st 2019; and the 'COVID-19 period' December 31st 2019-August 31st 2021. RESULTS: During the Recession period there was an overall decrease of 8.1% (n = 9333) between December 31st 2008 and December 31st 2014, while the Recovery period saw the overall staff levels rebound and increase by 15.2% (n = 16,789) between December 31st 2014 and December 31st 2019. These figures continued to grow, at an accelerated rate during the most recent COVID-19 period, increasing by a further 8.9% (n = 10,716) in under 2 years. However, a notable shift occurred in 2013, when the number of staff in acute services surpassed those employed in community services (n = 50,038 and 49,857, respectively). This gap accelerated during the Recovery and COVID-19 phase. By August 2021, there were 13,645 more whole-time equivalents in acute settings compared to community, a complete reverse of the 2008 situation. This was consistent across all cadres. Workforce absence trends indicate short-term spikes resulting from shocks while COVID-19 redeployment disproportionately impacted negatively on primary care and community services. CONCLUSIONS: This paper clearly demonstrates the prioritisation of staff recruitment within acute services-increasing needed capacity, without the same commitment to support government policy to shift care into primary and community settings. Concerted action including the permanent redistribution of personnel is required to ensure progressive and sustainable responses are learned from recent shocks.

'Toothless'-the absence of political priority for oral health: a case study of Ireland 1994-2021.

BACKGROUND: Calls are emerging for oral health system reform under the Universal Healthcare (UHC) domain, while internationally there is an absence of political priority for oral health. In the Republic of Ireland there is very limited coverage of oral healthcare for the whole population. 'Smile agus Sláinte' Ireland's oral health policy published in 2019, represents the first change to national policy in over 25 years. METHODS: This research examined the key factors influencing oral health policy, development, and implementation in Ireland during the period 1994-2021. A case study approach was adopted with two strands of data collection: documentary analysis and semi-structured interviews with elite participants. Analysis was guided by Howlett's five stream framework. RESULTS: Ireland shares the international experience of oral health having very low political priority. This has perpetuated unequal access to public dental services for children and special needs populations while austerity measures applied to adult schemes resulted in increased unmet need with no universal coverage for dental care. The only area where there is political interest in oral health is orthodontic care. This low political priority combined with a lack of actor power in national leadership positions in the Department of Health and Health Service Executive has contributed to successive non-implementation of oral health policy recommendations. This is most evident in the failure to publish the Draft National Oral Health Policy in 2009. The research finds a failure to adequately engage with key stakeholders, particularly the dental profession in the development of the 2019 policy. All these weaknesses have been exacerbated by the COVID-19 pandemic. CONCLUSIONS: Ireland's new oral health policy, 'Smile agus Sláinte', presents an opportunity for the provision of much needed public dental services. However, successful reform will require strong political will and collaboration with dental leadership to provide advocacy at national level. Global calls to incorporate oral health into the UHC agenda and an agreed political consensus for UHC in Ireland may provide an opportunity for change. Genuine engagement of all stakeholders to develop an implementation strategy is necessary to harness this potential window of opportunity for oral health system reform.

Auditory and Visual System White Matter Is Differentially Impacted by Normative Aging in Macaques.

Deficits in auditory and visual processing are commonly encountered by older individuals. In addition to the relatively well described age-associated pathologies that reduce sensory processing at the level of the cochlea and eye, multiple changes occur along the ascending auditory and visual pathways that further reduce sensory function in each domain. One fundamental question that remains to be directly addressed is whether the structure and function of the central auditory and visual systems follow similar trajectories across the lifespan or sustain the impacts of brain aging independently. The present study used diffusion magnetic resonance imaging and electrophysiological assessments of auditory and visual system function in adult and aged macaques to better understand how age-related changes in white matter connectivity at multiple levels of each sensory system might impact auditory and visual function. In particular, the fractional anisotropy (FA) of auditory and visual system thalamocortical and interhemispheric corticocortical connections was estimated using probabilistic tractography analyses. Sensory processing and sensory system FA were both reduced in older animals compared with younger adults. Corticocortical FA was significantly reduced only in white matter of the auditory system of aged monkeys, while thalamocortical FA was lower only in visual system white matter of the same animals. Importantly, these structural alterations were significantly associated with sensory function within each domain. Together, these results indicate that age-associated deficits in auditory and visual processing emerge in part from microstructural alterations to specific sensory white matter tracts, and not from general differences in white matter condition across the aging brain.SIGNIFICANCE STATEMENT Age-associated deficits in sensory processing arise from structural and functional alterations to both peripheral sensory organs and central brain regions. It remains unclear whether different sensory systems undergo similar or distinct trajectories in function across the lifespan. To provide novel insights into this question, this study combines electrophysiological assessments of auditory and visual function with diffusion MRI in aged macaques. The results suggest that age-related sensory processing deficits in part result from factors that impact the condition of specific white matter tracts, and not from general decreases in connectivity between sensory brain regions. Such anatomic specificity argues for a framework aimed at understanding vulnerabilities with relatively local influence and brain region specificity.

Rodent mnemonic similarity task performance requires the prefrontal cortex.

Mnemonic similarity task performance, in which a known target stimulus must be distinguished from similar lures, is supported by the hippocampus and perirhinal cortex. Impairments on this task are known to manifest with advancing age. Interestingly, disrupting hippocampal activity leads to mnemonic discrimination impairments when lures are novel, but not when they are familiar. This observation suggests that other brain structures support discrimination abilities as stimuli are learned. The prefrontal cortex (PFC) is critical for retrieval of remote events and executive functions, such as working memory, and is also particularly vulnerable to dysfunction in aging. Importantly, the medial PFC is reciprocally connected to the perirhinal cortex and neuron firing in this region coordinates communication between lateral entorhinal and perirhinal cortices to presumably modulate hippocampal activity. This anatomical organization and function of the medial PFC suggests that it contributes to mnemonic discrimination; however, this notion has not been empirically tested. In the current study, rats were trained on a LEGO object-based mnemonic similarity task adapted for rodents, and surgically implanted with guide cannulae targeting prelimbic and infralimbic regions of the medial PFC. Prior to mnemonic discrimination tests, rats received PFC infusions of the GABAA agonist muscimol. Analyses of expression of the neuronal activity-dependent immediate-early gene Arc in medial PFC and adjacent cortical regions confirmed muscimol infusions led to neuronal inactivation in the infralimbic and prelimbic cortices. Moreover, muscimol infusions in PFC impaired mnemonic discrimination performance relative to the vehicle control across all testing blocks when lures shared 50-90% feature overlap with the target. Thus, in contrast hippocampal infusions, PFC inactivation impaired target-lure discrimination regardless of the novelty or familiarity of the lures. These findings indicate the PFC plays a critical role in mnemonic similarity task performance, but the time course of PFC involvement is dissociable from that of the hippocampus.

Acute vagus nerve stimulation enhances reversal learning in rats.

Cognitive flexibility is a prefrontal cortex-dependent neurocognitive process that enables behavioral adaptation in response to changes in environmental contingencies. Electrical vagus nerve stimulation (VNS) enhances several forms of learning and neuroplasticity, but its effects on cognitive flexibility have not been evaluated. In the current study, a within-subjects design was used to assess the effects of VNS on performance in a novel visual discrimination reversal learning task conducted in touchscreen operant chambers. The task design enabled simultaneous assessment of acute VNS both on reversal learning and on recall of a well-learned discrimination problem. Acute VNS delivered in conjunction with stimuli presentation during reversal learning reliably enhanced learning of new reward contingencies. Enhancement was not observed, however, if VNS was delivered during the session but was not coincident with presentation of to-be-learned stimuli. In addition, whereas VNS delivered at 30 HZ enhanced performance, the same enhancement was not observed using 10 or 50 Hz. Together, these data show that acute VNS facilitates reversal learning and indicate that the timing and frequency of the VNS are critical for these enhancing effects. In separate rats, administration of the norepinephrine reuptake inhibitor atomoxetine also enhanced reversal learning in the same task, consistent with a noradrenergic mechanism through which VNS enhances cognitive flexibility.

Auditory Processing Deficits Are Selectively Associated with Medial Temporal Lobe Mnemonic Function and White Matter Integrity in Aging Macaques.

Deficits in auditory function and cognition are hallmarks of normative aging. Recent evidence suggests that hearing-impaired individuals have greater risks of developing cognitive impairment and dementia compared to people with intact auditory function, although the neurobiological bases underlying these associations are poorly understood. Here, a colony of aging macaques completed a battery of behavioral tests designed to probe frontal and temporal lobe-dependent cognition. Auditory brainstem responses (ABRs) and visual evoked potentials were measured to assess auditory and visual system function. Structural and diffusion magnetic resonance imaging were then performed to evaluate the microstructural condition of multiple white matter tracts associated with cognition. Animals showing higher cognitive function had significantly better auditory processing capacities, and these associations were selectively observed with tasks that primarily depend on temporal lobe brain structures. Tractography analyses revealed that the fractional anisotropy (FA) of the fimbria-fornix and hippocampal commissure were associated with temporal lobe-dependent visual discrimination performance and auditory sensory function. Conversely, FA of frontal cortex-associated white matter was not associated with auditory processing. Visual sensory function was not associated with frontal or temporal lobe FA, nor with behavior. This study demonstrates significant and selective relationships between ABRs, white matter connectivity, and higher-order cognitive ability.

The Value of Interracial Contact for Reducing Anti-Black Bias Among Non-Black Physicians: A Cognitive Habits and Growth Evaluation (CHANGE) Study Report.

Although scholars have long studied circumstances that shape prejudice, inquiry into factors associated with long-term prejudice reduction has been more limited. Using a 6-year longitudinal study of non-Black physicians in training (N = 3,134), we examined the effect of three medical-school factors-interracial contact, medical-school environment, and diversity training-on explicit and implicit racial bias measured during medical residency. When accounting for all three factors, previous contact, and baseline bias, we found that quality of contact continued to predict lower explicit and implicit bias, although the effects were very small. Racial climate, modeling of bias, and hours of diversity training in medical school were not consistently related to less explicit or implicit bias during residency. These results highlight the benefits of interracial contact during an impactful experience such as medical school. Ultimately, professional institutions can play a role in reducing anti-Black bias by encouraging more frequent, and especially more favorable, interracial contact.

Targeted hippocampal GABA neuron ablation by Stable Substance P-saporin causes hippocampal sclerosis and chronic epilepsy in rats.

Cryptogenic temporal lobe epilepsy develops in the absence of identified brain injuries, infections, or structural malformations, and in these cases, an unidentified pre-existing abnormality may initiate febrile seizures, hippocampal sclerosis, and epilepsy. Although a role for GABAergic dysfunction in epilepsy is intuitively obvious, no causal relationship has been established. In this study, hippocampal GABA neurons were targeted for selective elimination to determine whether a focal hippocampal GABAergic defect in an otherwise normal brain can initiate cryptogenic temporal lobe epilepsy with hippocampal sclerosis. We used Stable Substance P-saporin conjugate (SSP-saporin) to target rat hippocampal GABA neurons, which selectively and constitutively express the neurokinin-1 receptors that internalize this neurotoxin. Bilateral and longitudinally extensive intrahippocampal microinjections of SSP-saporin caused no obvious behavioral effects for several days. However, starting ~4 days postinjection, rats exhibited episodes of immobilization, abnormal flurries of "wet-dog" shakes, and brief focal motor seizures characterized by facial automatisms and forepaw clonus. These clinically subtle behaviors stopped after ~4 days. Convulsive status epilepticus did not develop, and no deaths occurred. Months later, chronically implanted rats exhibited spontaneous focal motor seizures and extreme hippocampal sclerosis. These data suggest that hippocampal GABAergic dysfunction is epileptogenic and can produce the defining features of cryptogenic temporal lobe epilepsy.

Visual Object Discrimination Impairment as an Early Predictor of Mild Cognitive Impairment and Alzheimer's Disease.

OBJECTIVE: Detection of cognitive impairment suggestive of risk for Alzheimer's disease (AD) progression is crucial to the prevention of incipient dementia. This study was performed to determine if performance on a novel object discrimination task improved identification of earlier deficits in older adults at risk for AD. METHOD: In total, 135 participants from the 1Florida Alzheimer's Disease Research Center [cognitively normal (CN), Pre-mild cognitive impairment (PreMCI), amnestic mild cognitive impairment (aMCI), and dementia] completed a test of object discrimination and traditional memory measures in the context of a larger neuropsychological and clinical evaluation. RESULTS: The Object Recognition and Discrimination Task (ORDT) revealed significant differences between the PreMCI, aMCI, and dementia groups versus CN individuals. Moreover, relative risk of being classified as PreMCI rather than CN increased as an inverse function of ORDT score. DISCUSSION: Overall, the obtained results suggest that a novel object discrimination task improves the detection of very early AD-related cognitive impairment, increasing the window for therapeutic intervention. (JINS, 2019, 25, 688-698).

Content validity of the developmental care scale for neonates with CHD.

PurposeNeuroprotective developmental care is paramount for neonates with CHD. Although several developmental care scales exist, either they have not been psychometrically tested or were not designed for the needs of neonates with CHD. The purpose of this study is to describe item development and content validity testing of the developmental care scale for neonates with CHD, which measures five domains of the developmental care provided by bedside nurses to neonates in the cardiac ICU: sleep, pain and stress management, activities of daily living, family-centred care, and environment. METHODS: For this cross-sectional study, items were developed based on clinical expertise and the core measures for developmental care. In this study, seven experts provided content validity ratings of items for total scale and subscale fit and relevance. A content validity index was used to determine item retention. Item modifications and additions were based on expert feedback. RESULTS: Expert ratings provided evidence of content validity on 24 of 53 items within the five domains of developmental care. A total of 24 items were deleted, and five items with low content validity ratings were retained, because of conceptual importance, and revised. An additional 11 items were added based on expert qualitative feedback. CONCLUSIONS: This study provided evidence of content validity of the developmental care scale for neonates with CHD by researchers and bedside nurses caring for these neonates. Further psychometric testing is warranted to provide evidence of internal consistency reliability, construct validity, and to identify variables that influence quality of the developmental care.

Attenuated Activity across Multiple Cell Types and Reduced Monosynaptic Connectivity in the Aged Perirhinal Cortex.

The perirhinal cortex (PER), which is critical for associative memory and stimulus discrimination, has been described as a wall of inhibition between the neocortex and hippocampus. With advanced age, rats show deficits on PER-dependent behavioral tasks and fewer PER principal neurons are activated by stimuli, but the role of PER interneurons in these altered circuit properties in old age has not been characterized. In the present study, PER neurons were recorded while rats traversed a circular track bidirectionally in which the track was either empty or contained eight novel objects evenly spaced around the track. Putative interneurons were discriminated from principal cells based on the autocorrelogram, waveform parameters, and firing rate. While object modulation of interneuron firing was observed in both young and aged rats, PER interneurons recorded from old animals had lower firing rates compared with those from young animals. This difference could not be accounted for by differences in running speed, as the firing rates of PER interneurons did not show significant velocity modulation. Finally, in the aged rats, relative to young rats, there was a significant reduction in detected excitatory and inhibitory monosynaptic connections. Together these data suggest that with advanced age there may be reduced afferent drive from excitatory cells onto interneurons that may compromise the wall of inhibition between the hippocampus and cortex. This circuit dysfunction could erode the function of temporal lobe networks and ultimately contribute to cognitive aging.SIGNIFICANCE STATEMENT We report that lower firing rates observed in aged perirhinal cortical principal cells are associated with weaker interneuron activity and reduced monosynaptic coupling between excitatory and inhibitory cells. This is likely to affect feedforward inhibition from the perirhinal to the entorhinal cortex that gates the flow of information to the hippocampus. This is significant because cognitive dysfunction in normative and pathological aging has been linked to hyperexcitability in the aged CA3 subregion of the hippocampus in rats, monkeys, and humans. The reduced inhibition in the perirhinal cortex reported here could contribute to this circuit imbalance, and may be a key point to consider for therapeutic interventions aimed at restoring network function to optimize cognition.

Correction to: Medical School Factors Associated with Changes in Implicit and Explicit Bias Against Gay and Lesbian People among 3492 Graduating Medical Students.

Due to a tagging error, two authors were incorrectly listed in indexing systems. Brook W. Cunningham should be B.A. Cunningham and Mark W. Yeazel should be M.W. Yeazel for indexing purposes.

Association of Clinical Specialty With Symptoms of Burnout and Career Choice Regret Among US Resident Physicians.

Importance: Burnout among physicians is common and has been associated with medical errors and lapses in professionalism. It is unknown whether rates for symptoms of burnout among resident physicians vary by clinical specialty and if individual factors measured during medical school relate to the risk of burnout and career choice regret during residency. Objective: To explore factors associated with symptoms of burnout and career choice regret during residency. Design, Setting, and Participants: Prospective cohort study of 4732 US resident physicians. First-year medical students were enrolled between October 2010 and January 2011 and completed the baseline questionnaire. Participants were invited to respond to 2 questionnaires; one during year 4 of medical school (January-March 2014) and the other during the second year of residency (spring of 2016). The last follow-up was on July 31, 2016. Exposures: Clinical specialty, demographic characteristics, educational debt, US Medical Licensing Examination Step 1 score, and reported levels of anxiety, empathy, and social support during medical school. Main Outcomes and Measures: Prevalence during second year of residency of reported symptoms of burnout measured by 2 single-item measures (adapted from the Maslach Burnout Inventory) and an additional item that evaluated career choice regret (defined as whether, if able to revisit career choice, the resident would choose to become a physician again). Results: Among 4696 resident physicians, 3588 (76.4%) completed the questionnaire during the second year of residency (median age, 29 [interquartile range, 28.0-31.0] years in 2016; 1822 [50.9%] were women). Symptoms of burnout were reported by 1615 of 3574 resident physicians (45.2%; 95% CI, 43.6% to 46.8%). Career choice regret was reported by 502 of 3571 resident physicians (14.1%; 95% CI, 12.9% to 15.2%). In a multivariable analysis, training in urology, neurology, emergency medicine, and general surgery were associated with higher relative risks (RRs) of reported symptoms of burnout (range of RRs, 1.24 to 1.48) relative to training in internal medicine. Characteristics associated with higher risk of reported symptoms of burnout included female sex (RR, 1.17 [95% CI, 1.07 to 1.28]; risk difference [RD], 7.2% [95% CI, 3.1% to 11.3%]) and higher reported levels of anxiety during medical school (RR, 1.08 per 1-point increase [95% CI, 1.06 to 1.11]; RD, 1.8% per 1-point increase [95% CI, 1.6% to 2.0%]). A higher reported level of empathy during medical school was associated with a lower risk of reported symptoms of burnout during residency (RR, 0.99 per 1-point increase [95% CI, 0.99 to 0.99]; RD, -0.5% per 1-point increase [95% CI, -0.6% to -0.3%]). Reported symptoms of burnout (RR, 3.20 [95% CI, 2.58 to 3.82]; RD, 15.0% [95% CI, 12.8% to 17.3%]) and clinical specialty (range of RRs, 1.66 to 2.60) were both significantly associated with career choice regret. Conclusions and Relevance: Among US resident physicians, symptoms of burnout and career choice regret were prevalent, but varied substantially by clinical specialty. Further research is needed to better understand these differences and to address these issues.

Movement Enhances the Nonlinearity of Hippocampal Theta.

The nonlinear, metastable dynamics of the brain are essential for large-scale integration of smaller components and for the rapid organization of neurons in support of behavior. Therefore, understanding the nonlinearity of the brain is paramount for understanding the relationship between brain dynamics and behavior. Explicit quantitative descriptions of the properties and consequences of nonlinear neural networks, however, are rare. Because the local field potential (LFP) reflects the total activity across a population of neurons, nonlinearites of the nervous system should be quantifiable by examining oscillatory structure. We used high-order spectral analysis of LFP recorded from the dorsal and intermediate regions of the rat hippocampus to show that the nonlinear character of the hippocampal theta rhythm is directly related to movement speed of the animal. In the time domain, nonlinearity is expressed as the development of skewness and asymmetry in the theta shape. In the spectral domain, nonlinear dynamics manifest as the development of a chain of harmonics statistically phase coupled to the theta oscillation. This evolution was modulated across hippocampal regions, being stronger in the dorsal CA1 relative to more intermediate areas. The intensity and timing of the spiking activity of pyramidal cells and interneurons was strongly correlated to theta nonlinearity. Because theta is known to propagate from dorsal to ventral regions of the hippocampus, these data suggest that the nonlinear character of theta decreases as it travels and supports a hypothesis that activity dissipates along the longitudinal axis of the hippocampus. SIGNIFICANCE STATEMENT: We describe the first explicit quantification regarding how behavior enhances the nonlinearity of the nervous system. Our findings demonstrate uniquely how theta changes with increasing speed due to the altered underlying neuronal dynamics and open new directions of research on the relationship between single-neuron activity and propagation of theta through the hippocampus. This work is significant because it will encourage others to consider the nonlinear nature of the nervous system and higher-order spectral analyses when examining oscillatory interactions.

Rodent age-related impairments in discriminating perceptually similar objects parallel those observed in humans.

The ability to accurately remember distinct episodes is supported by high-level sensory discrimination. Performance on mnemonic similarity tasks, which test high-level discrimination, declines with advancing age in humans and these deficits have been linked to altered activity in hippocampal CA3 and dentate gyrus. Lesion studies in animal models, however, point to the perirhinal cortex as a brain region critical for sensory discriminations that serve memory. Reconciliation of the contributions of different regions within the cortical-hippocampal circuit requires the development of a discrimination paradigm comparable to the human mnemonic similarity task that can be used in rodents. In the present experiments, young and aged rats were cross-characterized on a spatial water maze task and two variants of an object discrimination task: one in which rats incrementally learned which object of a pair was rewarded and different pairs varied in their similarity (Experiment 1), and a second in which rats were tested on their ability to discriminate a learned target object from multiple lure objects with an increasing degree of feature overlap (Experiment 2). In Experiment 1, aged rats required more training than young to correctly discriminate between similar objects. Comparably, in Experiment 2, aged rats were impaired in discriminating a target object from lures when the pair shared more features. Discrimination deficits across experiments were correlated within individual aged rats, though, for the cohort tested, aged rats were not impaired overall in spatial learning and memory. This could suggest discrimination deficits emerging with age precede declines in spatial or episodic memory, an observation that has been made in humans. Findings of robust impairments in object discrimination abilities in the aged rats parallel results from human studies, supporting use of the developed tasks for mechanistic investigation of cortical-hippocampal circuit dysfunction in aging and disease.

Medial prefrontal-perirhinal cortical communication is necessary for flexible response selection.

The ability to use information from the physical world to update behavioral strategies is critical for survival across species. The prefrontal cortex (PFC) supports behavioral flexibility; however, exactly how this brain structure interacts with sensory association cortical areas to facilitate the adaptation of response selection remains unknown. Given the role of the perirhinal cortex (PER) in higher-order perception and associative memory, the current study evaluated whether PFC-PER circuits are critical for the ability to perform biconditional object discriminations when the rule for selecting the rewarded object shifted depending on the animal's spatial location in a 2-arm maze. Following acquisition to criterion performance on an object-place paired association task, pharmacological blockade of communication between the PFC and PER significantly disrupted performance. Specifically, the PFC-PER disconnection caused rats to regress to a response bias of selecting an object on a particular side regardless of its identity. Importantly, the PFC-PER disconnection did not interfere with the capacity to perform object-only or location-only discriminations, which do not require the animal to update a response rule across trials. These findings are consistent with a critical role for PFC-PER circuits in rule shifting and the effective updating of a response rule across spatial locations.

Medical School Factors Associated with Changes in Implicit and Explicit Bias Against Gay and Lesbian People among 3492 Graduating Medical Students.

BACKGROUND: Implicit and explicit bias among providers can influence the quality of healthcare. Efforts to address sexual orientation bias in new physicians are hampered by a lack of knowledge of school factors that influence bias among students. OBJECTIVE: To determine whether medical school curriculum, role modeling, diversity climate, and contact with sexual minorities predict bias among graduating students against gay and lesbian people. DESIGN: Prospective cohort study. PARTICIPANTS: A sample of 4732 first-year medical students was recruited from a stratified random sample of 49 US medical schools in the fall of 2010 (81% response; 55% of eligible), of which 94.5% (4473) identified as heterosexual. Seventy-eight percent of baseline respondents (3492) completed a follow-up survey in their final semester (spring 2014). MAIN MEASURES: Medical school predictors included formal curriculum, role modeling, diversity climate, and contact with sexual minorities. Outcomes were year 4 implicit and explicit bias against gay men and lesbian women, adjusted for bias at year 1. KEY RESULTS: In multivariate models, lower explicit bias against gay men and lesbian women was associated with more favorable contact with LGBT faculty, residents, students, and patients, and perceived skill and preparedness for providing care to LGBT patients. Greater explicit bias against lesbian women was associated with discrimination reported by sexual minority students (b = 1.43 [0.16, 2.71]; p = 0.03). Lower implicit sexual orientation bias was associated with more frequent contact with LGBT faculty, residents, students, and patients (b = -0.04 [-0.07, -0.01); p = 0.008). Greater implicit bias was associated with more faculty role modeling of discriminatory behavior (b = 0.34 [0.11, 0.57); p = 0.004). CONCLUSIONS: Medical schools may reduce bias against sexual minority patients by reducing negative role modeling, improving the diversity climate, and improving student preparedness to care for this population.