Selective enhancement of neural coding in V1 underlies fine-discrimination learning in tree shrew.

Visual discrimination improves with training, a phenomenon that is thought to reflect plastic changes in the responses of neurons in primary visual cortex (V1). However, the identity of the neurons that undergo change, the nature of the changes, and the consequences of these changes for other visual behaviors remain unclear. We used chronic in vivo 2-photon calcium imaging to monitor the responses of neurons in the V1 of tree shrews learning a Go/No-Go fine orientation discrimination task. We observed increases in neural population measures of discriminability for task-relevant stimuli that correlate with performance and depend on a select subset of neurons with preferred orientations that include the rewarded stimulus and nearby orientations biased away from the non-rewarded stimulus. Learning is accompanied by selective enhancement in the response of these neurons to the rewarded stimulus that further increases their ability to discriminate the task stimuli. These changes persist outside of the trained task and predict observed enhancement and impairment in performance of other discriminations, providing evidence for selective and persistent learning-induced plasticity in the V1, with significant consequences for perception.

Distribution and diversity of intrinsically photosensitive retinal ganglion cells in tree shrew.

Intrinsically photosensitive retinal ganglion cells (ipRGCs) mediate the pupillary light reflex, circadian entrainment, and may contribute to luminance and color perception. The diversity of ipRGCs varies from rodents to primates, suggesting differences in their contributions to retinal output. To further understand the variability in their organization and diversity across species, we used immunohistochemical methods to examine ipRGCs in tree shrew (Tupaia belangeri). Tree shrews share membership in the same clade, or evolutionary branch, as rodents and primates. They are highly visual, diurnal animals with a cone-dominated retina and a geniculo-cortical organization resembling that of primates. We identified cells with morphological similarities to M1 and M2 cells described previously in rodents and primates. M1-like cells typically had somas in the ganglion cell layer, with 23% displaced to the inner nuclear layer (INL). However, unlike M1 cells, they had bistratified dendritic fields ramifying in S1 and S5 that collectively tiled space. M2-like cells had dendritic fields restricted to S5 that were smaller and more densely branching. A novel third type of melanopsin immunopositive cell was identified. These cells had somata exclusively in the INL and monostratified dendritic fields restricted to S1 that tiled space. Surprisingly, these cells immunolabeled for tyrosine hydroxylase, a key component in dopamine synthesis. These cells immunolabeled for an RGC marker, not amacrine cell markers, suggesting that they are dopaminergic ipRGCs. We found no evidence for M4 or M5 ipRGCs, described previously in rodents. These results identify some organizational features of the ipRGC system that are canonical versus species-specific.

Costs and Effectiveness of Treating Homeless Persons with Cocaine Addiction with Alternative Contingency Management Strategies.

BACKGROUND: Between 1990 and 2006 in Birmingham, Alabama USA, 4 separate randomized controlled studies, called "Homeless 1" through "Homeless 4", treated cocaine substance abuse among chronically homeless adults, largely black men, many with non-psychotic mental health problems. The 4 studies had 9 treatment arms that used various counseling methods plus, in some arms, the provision of housing and work therapy usually with a contingent requirement of urine-test verified abstinence from substances. Participants in the abstinent-contingent arms who lapsed on abstinence were removed from housing and sent to an evening public shelter from which they were daily transported to day treatment until they returned to abstinence. AIMS OF THE STUDY: This paper compares the cost effectiveness of the treatment arms. METHODS: Societal cost per participant (in 2014 dollars) for each arm is defined as direct treatment cost plus cost of jail or hospital plus societal expense of public shelter use by lapsed participants. An untreated Base Case is defined as 5 percent abstinence with 95 percent usage of a public shelter. Incremental Cost Effectiveness Ratios (ICERs) for paired arms are defined as the change in cost per participant divided by the change in abstinence. Bootstrapping estimates confidence intervals. RESULTS: Average cost per participant at the end of 6 months of active treatment in 7 arms with comparable data ranged from USD 10,447 to USD 36,194 with corresponding average weeks abstinent ranging from 6.1 to 15.3 out of a possible 26 weeks. In contrast, the Base Case would cost USD 6,123 for 1.3 weeks of abstinence. Compared to the Base Case, the least expensive "DT2" treatment has an ICER of USD 901 (95% CI = USD 571 to USD 1,681) per additional week of abstinence and the most expensive "CMP4" has an ICER of USD 2,147 (95% CI = USD 1,701 to USD 2,848). Additionally, the Homeless 3 study found that the abstinent contingent housing (ACH3) treatment compared to the Non Abstinent Contingent Housing (NAC3), analogous to "Housing First", achieved better abstinence (12.1 v. 10 weeks) at higher average cost (USD 22,512 v. USD 17,541) yielding an ICER for this comparison of (USD 2,367, 95% CI=USD -10,587 to USD 12,467). Similar results are found at 12 months (6 months after active treatment). DISCUSSION: More intensive methods of counseling improved abstinence but 4 of the 7 treatments were inefficient ("dominated"). Bootstrapping shows that results are sensitive to which individuals were randomly assigned to each arm. A limitation of the analysis is that it does not consider the full societal cost of lost wages, crime costs beyond jail expenses and deterioration of neighborhood quality of life. Additionally, populations treated by Housing First programs may differ from the Birmingham Homeless studies in the severity of addiction or co-occuring psychological problems. IMPLICATIONS FOR TREATMENT: The Homeless studies show that abstinent contingent safe housing with counseling can substantially improve abstinence for homeless cocaine abusers. Incremental costs rise sharply with more intensive counseling; modest programs of counseling may be more cost effective in a stepped treatment strategy.

Modeling the impacts of temperature and precipitation changes on soil CO2 fluxes from a Switchgrass stand recently converted from cropland.

Switchgrass (Panicum virgatum L.) is a perennial C4 grass native to North America and successfully adapted to diverse environmental conditions. It offers the potential to reduce soil surface carbon dioxide (CO2) fluxes and mitigate climate change. However, information on how these CO2 fluxes respond to changing climate is still lacking. In this study, CO2 fluxes were monitored continuously from 2011 through 2014 using high frequency measurements from Switchgrass land seeded in 2008 on an experimental site that has been previously used for soybean (Glycine max L.) in South Dakota, USA. DAYCENT, a process-based model, was used to simulate CO2 fluxes. An improved methodology CPTE [Combining Parameter estimation (PEST) with "Trial and Error" method] was used to calibrate DAYCENT. The calibrated DAYCENT model was used for simulating future CO2 emissions based on different climate change scenarios. This study showed that: (i) the measured soil CO2 fluxes from Switchgrass land were higher for 2012 which was a drought year, and these fluxes when simulated using DAYCENT for long-term (2015-2070) provided a pattern of polynomial curve; (ii) the simulated CO2 fluxes provided different patterns with temperature and precipitation changes in a long-term, (iii) the future CO2 fluxes from Switchgrass land under different changing climate scenarios were not significantly different, therefore, it can be concluded that Switchgrass grown for longer durations could reduce changes in CO2 fluxes from soil as a result of temperature and precipitation changes to some extent.

Cigarette Smokers are Less Likely to Have Undetectable Viral Loads: Results From Four HIV Clinics.

BACKGROUND: The prevalence of smoking among HIV-infected individuals is 2-3 times that of the general population, increasing the risk of smoking-related morbidity and mortality. We examined characteristics associated with smoking behavior among a large cohort of HIV-infected individuals in care in the United States. METHODS: A convenience sample of 2952 HIV-infected patients in the Centers for AIDS Research (CFAR) Network of Integrated Clinical Systems (CNICS) was assessed during routine clinic visits and was included. Multinomial logistic regression was used to examine the relationship between smoking status, depression/panic symptoms, alcohol/substance use, and demographic and clinical characteristics. RESULTS: Compared with never-smokers, current smokers were more likely to have moderate to severe depression (odds ratio [OR] 1.37), endorse current substance use (OR 14.09), and less likely to report low-risk alcohol use on the Alcohol Use Disorders Identification Test (AUDIT-C) (OR 0.73). Current smokers were less likely to have an undetectable viral load (OR 0.75), and more likely to have current substance abuse (OR 2.81) and moderate to severe depression (OR 1.50), relative to smokers who had quit smoking. CONCLUSIONS: HIV-infected smokers are less likely to have undetectable viral loads and frequently have psychosocial comorbidities including depression and substance abuse that impact antiretroviral therapy adherence and viral load suppression. To be effective, smoking-cessation interventions need to address the complex underlying concurrent risks in this population.

Comorbidity effects on cocaine dependence treatment and examination of reciprocal relationships between abstinence and depression.

OBJECTIVE: We examined comorbid disorders' prevalence, their impact on abstinence, and the impact of depressive symptoms on abstinence and of abstinence on depressive symptoms. METHOD: A randomized controlled trial's data on outcomes from treating cocaine dependence were used. It compared abstinence-contingent housing and work to contingency management plus behavioral day treatment. Regardless of original trial arm assignment, groups of participants with no additional Axis I disorders (n = 87) and 1 or more additional Axis I disorders (n = 113) were compared for abstinence. Changes in depression symptoms, measured by the Beck Depression Inventory, were analyzed as a function of 4 cohorts of increased consecutive weeks abstinent. An autoregressive cross-lagged path model examined reciprocal relationships between depression and abstinence. RESULTS: Most prevalent additional disorders were depressive disorders, followed by anxiety disorders. Additional disorders did not significantly affect abstinence. Cohorts with more abstinence were linearly related to lower depression symptoms. The cross-lagged model showed that longer abstinence predicted decreases in depressive symptoms at 6 months. However, depressive symptoms did not predict changes in abstinence. CONCLUSIONS: Our study adds to others that have found an effective treatment targeted at specific problems such as substance abuse, social anxiety disorder, and posttraumatic stress disorder that may have the side benefit of reducing depression. Additionally, we find that depression does not interfere with effective substance abuse treatment for cocaine dependency. This may be the 1st formal analysis comparing the ability of cocaine abstinence to predict future depressive symptoms versus depressive symptoms to predict future cocaine abstinence.

Making housing first happen: organizational leadership in VA's expansion of permanent supportive housing.

BACKGROUND: While most organizational literature has focused on initiatives that transpire inside the hospital walls, the redesign of American health care increasingly asks that health care institutions address matters outside their walls, targeting the health of populations. The US Department of Veterans Affairs (VA)'s national effort to end Veteran homelessness represents an externally focused organizational endeavor. OBJECTIVE: Our aim was to evaluate the role of organizational practices in the implementation of Housing First (HF), an evidence-based homeless intervention for chronically homeless individuals. DESIGN: This was an interview-based comparative case study conducted across eight VA Medical Centers (VAMCs). PARTICIPANTS: Front line staff, mid-level managers, and senior leaders at VA Medical Centers were interviewed between February and December 2012. APPROACH: Using a structured narrative and numeric scoring, we assessed the correlation between successful HF implementation and organizational practices devised according to the organizational transformation model (OTM). KEY RESULTS: Scoring results suggested a strong association between HF implementation and OTM practice. Strong impetus to house Veterans came from national leadership, reinforced by Medical Center directors closely tracking results. More effective Medical Center leaders differentiated themselves by joining front-line staff in the work (at public events and in process improvement exercises), by elevating homeless-knowledgeable persons into senior leadership, and by exerting themselves to resolve logistic challenges. Vertical alignment and horizontal integration advanced at sites that fostered work groups cutting across service lines and hierarchical levels. By contrast, weak alignment from top to bottom typically also hindered cooperation across departments. Staff commitment to ending homelessness was high, though sustainability planning was limited in this baseline year of observation. CONCLUSION: Key organizational practices correlated with more successful implementation of HF for homeless Veterans. Medical Center directors substantively influenced the success of this endeavor through their actions to foster impetus, demonstrate commitment and support alignment and integration.

Protective factors against relapse for practicing nurse anesthetists in recovery from anesthetic opiate dependency.

This qualitative inquiry explored factors that protect recovering anesthetic opioid-dependent nurse anesthetists from relapse after their return to anesthesia practice. Practicing nurse anesthetists in recovery from potent opioids were recruited through online advertising and individually interviewed over the telephone. The interview consisted of open-ended questions that aided description of personal experience of individual factors. Content analysis of the interviews revealed an overarching theme of a commitment to the recovery process, which provided the foundational protective element against relapse. Within this context, two major thematic factors emerged: personal factors and external factors. Personal factors came from within the individual and included such features as removing the obsession to use, self-realization, inner strength, and seeing the future. External factors were external to the individual and described as time away from practice, state regulatory agency involvement, and talking with significant others. Although the Twelve-Step process was not a factor per se, it was credited by all participants as the structure on which their recovery was built. This process provided mechanisms for developing the motivation and learning the tools necessary to maintain their sobriety.

Methadone maintenance for HIV positive and HIV negative patients in Kyiv: acceptability and treatment response.

BACKGROUND: With up to 40% of opioid injectors infected with HIV, Ukraine has one of the most concentrated HIV epidemics in the world, mainly due to unsterile injection practices and a historical absence of effective prevention services. Harm reduction programs, including syringe exchange and a small buprenorphine treatment program, were introduced in 2004 and methadone maintenance was allowed in 2007. Despite an initial expansion, by 2009, only 3221 injectors were receiving methadone treatment. A growing body of research on methadone maintenance has found high retention rates with reduction in opioid use and HIV risk behaviors. We report on the acceptability and initial outcome of methadone treatment as a function of HIV status, an issue that has not yet been reported for injectors in Ukraine. METHODS: Longitudinal observational study of a 12-week course of methadone treatment in 25 HIV+ and 25 HIV- opioid addicted individuals recruited from a harm reduction program and the city AIDS Center. Drug use and HIV risk were assessed at baseline and weeks 4, 8, 12 and 20; all patients were offered continued methadone maintenance in the Kyiv city program at the end of 12 weeks. RESULTS: Fifty-four individuals were asked if they were interested in the study and 50, demographically similar to other samples of opioid addicted Ukrainians, agreed to participate. Two died of non-study related causes; the other 48 completed assessments at weeks 4, 8 and 12, and 47 completed followups at week 20. Significant reductions were seen in use of heroin (p<0.0001), other opiates/analgesics (p<0.0001), and HIV risk behaviors (drug, sex, total; all p<0.0001). All 48 patients chose to continue methadone after the 12-weeks of study medication ended. Unlike most opioid treatment studies, sexual risk was somewhat higher than injecting risk at study intake. CONCLUSIONS: Methadone maintenance was well accepted by HIV+ and HIV- opioid dependent individuals and has the potential for significant public health impact if made more widely available with sustained access and support.

VA's expansion of supportive housing: successes and challenges on the path toward Housing First.

OBJECTIVES: The U.S. Department of Veterans Affairs (VA) is transitioning to a Housing First approach to placement of veterans in permanent supportive housing through the use of rental vouchers, an ambitious organizational transformation. This qualitative study examined the experiences of eight VA facilities undertaking this endeavor in 2012. METHODS: A multidisciplinary team interviewed facility leadership, midlevel managers, and frontline staff (N=95 individuals) at eight VA facilities representing four U.S. regions. The team used a semistructured interview protocol and the constant comparative method to explore how individuals throughout the organizations experienced and responded to the challenges of transitioning to a Housing First approach. RESULTS: Frontline staff faced challenges in rapidly housing homeless veterans because of difficult rental markets, the need to coordinate with local public housing authorities, and a lack of available funds for move-in costs. Staff sought to balance their time spent on housing activities with intensive case management of highly vulnerable veterans. Finding low-demand sheltering options (that is, no expectations regarding sobriety or treatment participation, as in the Housing First model) for veterans waiting for housing presented a significant challenge to implementation of Housing First. Facility leadership supported Housing First implementation through resource allocation, performance monitoring, and reliance on midlevel managers to understand and meet the challenges of implementation. CONCLUSIONS: The findings highlight the considerable practical challenges and innovative solutions arising from a large-scale effort to implement Housing First, with particular attention to the experiences of individuals at all levels within an organization.

A qualitative study on factors impacting HIV care adherence among postpartum HIV-infected women in the rural southeastern USA.

Declines in HIV care and treatment adherence among HIV-infected women from pregnancy to the postpartum period have significant implications for the clinical outcomes and overall well-being of HIV-infected women, especially due to immunosuppression during the postpartum period. While the overall increased risk for mortality associated with HIV care discontinuation is well established, the reasons for HIV care nonadherence among HIV-infected postpartum women are largely unknown. Eighteen HIV-infected women were recruited from four clinics in Alabama to participate in focus groups or individual interviews to discuss barriers and facilitators impacting postpartum HIV care adherence. Sessions were audio-recorded, transcribed, and coded; content analysis was used to analyze the verbatim transcripts. Mixed methods analysis procedures were used to triangulate data from three sources (focus group transcripts, individual rankings of barriers and facilitators according to the Nominal Group Technique, and individual questionnaires of sociodemographic and adherence data). The majority of participants were African-American (83.3%), single (66.7%), with more than half of the participants living on less than $1000 a month (55.6%). Barriers to retention in HIV care included access to and cost of transportation and fitting HIV care into work and childcare schedules. Facilitators to HIV care adherence included wanting to stay healthy for their own well-being as well as for the care of their children, receiving family support, and appointment reminders. The current study highlights contextual factors contributing to poor HIV care adherence among HIV-infected postpartum women. Intervention studies need to be cognizant of the specific needs of HIV-infected postpartum women to improve long-term clinical outcomes among this population, who have children.

Learning fast accurate movements requires intact frontostriatal circuits.

The basal ganglia are known to play a crucial role in movement execution, but their importance for motor skill learning remains unclear. Obstacles to our understanding include the lack of a universally accepted definition of motor skill learning (definition confound), and difficulties in distinguishing learning deficits from execution impairments (performance confound). We studied how healthy subjects and subjects with a basal ganglia disorder learn fast accurate reaching movements. We addressed the definition and performance confounds by: (1) focusing on an operationally defined core element of motor skill learning (speed-accuracy learning), and (2) using normal variation in initial performance to separate movement execution impairment from motor learning abnormalities. We measured motor skill learning as performance improvement in a reaching task with a speed-accuracy trade-off. We compared the performance of subjects with Huntington's disease (HD), a neurodegenerative basal ganglia disorder, to that of premanifest carriers of the HD mutation and of control subjects. The initial movements of HD subjects were less skilled (slower and/or less accurate) than those of control subjects. To factor out these differences in initial execution, we modeled the relationship between learning and baseline performance in control subjects. Subjects with HD exhibited a clear learning impairment that was not explained by differences in initial performance. These results support a role for the basal ganglia in both movement execution and motor skill learning.

Substance use among HIV-infected patients engaged in primary care in the United States: findings from the Centers for AIDS Research Network of Integrated Clinical Systems cohort.

OBJECTIVES: The purpose of this study was to better understand substance use behaviors and deleterious health consequences among individuals with HIV. METHODS: We examined a multicenter cohort of HIV-infected patients (n = 3,413) receiving care in 4 US cities (Seattle, Birmingham, San Diego, Boston) between December 2005 and April 2010 in the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS). We used generalized estimating equations to model specific substance use outcomes. RESULTS: Overall, 24% of patients reported recent use of marijuana; 9% reported amphetamine use, 9% reported crack-cocaine use, 2% reported opiate use, 3.8% reported injection drug use, and 10.3% reported polydrug use. In adjusted multivariable models, those who reported unprotected anal sex had higher odds of marijuana, amphetamine, injection drug, and polydrug use. An increased number of distinct vaginal sexual partners was associated with polydrug and crack-cocaine use. Nonadherence to antiretroviral therapy was associated with the use of all substances other than marijuana. CONCLUSIONS: The co-occurrence of substance use, unprotected intercourse, and medication nonadherence could attenuate the public health benefits of test, treat, and link to care strategies. Prevention programs are needed that address these coprevalent conditions.

Boosting workplace stair utilization: a study of incremental reinforcement.

PURPOSE: This study was designed to determine whether engagement in stair taking can be increased in a worksite setting through the provision of an employer-sponsored, behavior-based incentive system in which employees (members) accumulate points that can be redeemed for merchandise. METHODS/DESIGN: ChipRewards implemented stair utilization in one employer as a part of a larger health incentive engagement program. Using an AB (baseline-intervention) design, members (N = 216) were observed for 6 months (6.17.10 to 12.14.10 or 129 weekdays after excluding 52 weekend days) before the intervention (baseline) and after 6 months (1.1.11 to 6.30.11 with the same number of weekdays) of implementation. RESULTS: Members were 84% female, 51% Caucasian, 48% African American, 3% Hispanic, and 45 years average age. The number of total stair transactions for all members for all days monitored increased from 5,070 to 38,900, and the average number of stair transactions per day rose from 39 to 301, representing over a 600% increase. The overall cost of incentives for stair utilization was $3,739.30 or $17.55 per member on average. CONCLUSION/IMPLICATIONS: This study supports that stair usage in the workplace is a viable way to increase physical activity. This study adds to existing research that attempted to increase stair utilization through promotion only by adding a behavioral reinforcement strategy. Finally, this study demonstrates that a physical activity among employees at the worksite can be increased with minimal relative cost.

Routine depression screening in an HIV clinic cohort identifies patients with complex psychiatric co-morbidities who show significant response to treatment.

This study described characteristics, psychiatric diagnoses and response to treatment among patients in an outpatient HIV clinic who screened positive for depression. Depressed (25 %) were less likely to have private insurance, less likely to have suppressed HIV viral loads, had more anxiety symptoms, and were more likely to report current substance abuse than not depressed. Among depressed, 81.2 % met diagnostic criteria for a depressive disorder; 78 % for an anxiety disorder; 61 % for a substance use disorder; and 30 % for co-morbid anxiety, depression, and substance use disorders. Depressed received significantly more treatment for depression and less HIV primary care than not depressed patients. PHQ-9 total depression scores decreased by 0.63 from baseline to 6-month follow-up for every additional attended depression treatment visit. HIV clinics can routinely screen and treat depressive symptoms, but should consider accurate psychiatric diagnosis as well as co-occurring mental disorders.

Effects of therapeutic goal management (TGM) on treatment attendance and drug abstinence among men with co-occurring substance use and axis I mental disorders who are homeless: results of the Birmingham EARTH program.

PURPOSE: This study describes the implementation and impact of Therapeutic Goal Management (TGM) in a Substance Abuse and Mental Health Services Administration (SAMHSA)-sponsored demonstration project entitled Enhanced Addiction Recovery through Housing (EARTH). PARTICIPANTS: The sample included 28 male participants followed at six months who completed some treatment. Forty-three percent were Caucasian, and 57% were African American. The average age of participants was 42 years. DESIGN: The relationships between TGM goal achievement, treatment attendance, and drug abstinence outcomes were studied among EARTH program participants who were homeless and met criteria for co-occurring substance use and severe DSM-IV Axis I mental disorders. RESULTS: The results revealed an overall drug abstinence rate of 72.4% over six months and significant positive relationships between TGM goal achievement and drug abstinence (r=0.693) and TGM goal achievement and treatment attendance (r=0.843). CONCLUSIONS: This research demonstrated the relationship and potential positive impact of systematically setting, monitoring, and reinforcing personalized goals in multiple life areas on drug abstinence and treatment attendance outcomes among persons who are homeless with co-occurring substance use and other Axis I disorders in a integrated community service delivery program.

Opioid abuse among nurse anesthetists and anesthesiologists.

Abuse and dependency on potent opioids have long been recognized as problems among nurse anesthetists and anesthesiologists. Research has provided insight into the incidence of abuse, risk factors associated with this type of dependency, identification of an impaired provider, treatment for abuse and dependency, and prevention strategies. Although several factors influence the development of abuse and dependency, access to potent opioids likely has a large role. This access also makes returning to practice while in recovery extremely difficult because the temptation for relapse continually surrounds a recovering anesthesia provider. There is research supporting successful reentry of anesthesia providers into the practice of anesthesia; however, research also reveals high relapse rates among anesthesia providers who return to the practice of anesthesia. This article reviews the literature regarding opioid abuse and dependency among nurse anesthetists and anesthesiologists and offers implications for future research.

Trajectories of drug use and mortality outcomes among adults followed over 18 years.

BACKGROUND: For adults in general population community settings, data regarding long-term course and outcomes of illicit drug use are sparse, limiting the formulation of evidence-based recommendations for drug use screening of adults in primary care. OBJECTIVE: To describe trajectories of three illicit drugs (cocaine, opioids, amphetamines) among adults in community settings, and to assess their relation to all-cause mortality. DESIGN: Longitudinal cohort, 1987/88-2005/06. SETTING: Community-based recruitment from four cities (Birmingham, Chicago, Oakland, Minneapolis). PARTICIPANTS: Healthy adults, balanced for race (black and white) and gender were assessed for drug use from 1987/88-2005/06, and for mortality through 12/31/2008 (n = 4301) MEASUREMENTS: Use of cocaine, amphetamines, and opioids (last 30 days) was queried in the following years: 1987/88, 1990/91, 1992/93, 1995/96, 2000/01, 2005/06. Survey-based assessment of demographics and psychosocial characteristics. Mortality over 18 years. RESULTS: Trajectory analysis identified four groups: Nonusers (n = 3691, 85.8%), Early Occasional Users (n = 340, 7.9%), Persistent Occasional Users (n = 160, 3.7%), and Early Frequent/Later Occasional Users (n = 110, 2.6%). Trajectories conformed to expected patterns regarding demographics, other substance use, family background and education. Adjusting for demographics, baseline health status, health behaviors (alcohol, tobacco), and psychosocial characteristics, Early Frequent/Later Occasional Users had greater all-cause mortality (Hazard Ratio, HR = 4.94, 95% CI = 1.58-15.51, p = 0.006). LIMITATIONS: Study is restricted to three common drugs, and trajectory analyses represent statistical approximations rather than identifiable "types". Causal inferences are tentative. CONCLUSIONS: Four trajectories describe illicit drug use from young adulthood to middle age. Two trajectories, representing over one third of adult users, continued use into middle age. These persons were more likely to continue harmful risk behaviors such as smoking, and more likely to die.

Patient reported outcomes in routine care: advancing data capture for HIV cohort research.

INTRODUCTION: Computerized collection of standardized measures of patient reported outcomes (PROs) provides a novel paradigm for data capture at the point of clinical care. Comparisons between data from PROs and Electronic Health Records (EHR) are lacking. We compare EHR and PRO for capture of depression and substance abuse and their relationship to adherence to antiretroviral therapy (ART). METHODS: This retrospective study includes HIV-positive patients at an HIV clinic who completed an initial PRO assessment April 2008-July 2009. The questionnaire includes measures of depression (PHQ-9) and substance abuse (ASSIST). Self-reported ART adherence was modeled using separate logistic regression analyses (EHR vs PRO). RESULTS: The study included 782 participants. EHR vs PRO diagnosis of current substance abuse was 13% (n = 99) vs 6% (n = 45) (P < .0001), and current depression was 41% (n = 317) vs 12% (n = 97) (P < .0001). In the EHR model, neither substance abuse (OR = 1.25; 95% CI = 0.70-2.21) nor depression (OR = 0.93; 95% CI = 0.62-1.40) was significantly associated with poor ART adherence. Conversely, in the PRO model, current substance abuse (OR = 2.78; 95% CI = 1.33-5.81) and current depression (OR = 1.93; 95% CI = 1.12-3.33) were associated with poor ART adherence. DISCUSSIONS: The explanatory characteristics of the PRO model correlated best with factors known to be associated with poor ART adherence (substance abuse; depression). The computerized capture of PROs as a part of routine clinical care may prove to be a complementary and potentially transformative health informatics technology for research and patient care.

Anesthetic state modulates excitability but not spectral tuning or neural discrimination in single auditory midbrain neurons.

The majority of sensory physiology experiments have used anesthesia to facilitate the recording of neural activity. Current techniques allow researchers to study sensory function in the context of varying behavioral states. To reconcile results across multiple behavioral and anesthetic states, it is important to consider how and to what extent anesthesia plays a role in shaping neural response properties. The role of anesthesia has been the subject of much debate, but the extent to which sensory coding properties are altered by anesthesia has yet to be fully defined. In this study we asked how urethane, an anesthetic commonly used for avian and mammalian sensory physiology, affects the coding of complex communication vocalizations (songs) and simple artificial stimuli in the songbird auditory midbrain. We measured spontaneous and song-driven spike rates, spectrotemporal receptive fields, and neural discriminability from responses to songs in single auditory midbrain neurons. In the same neurons, we recorded responses to pure tone stimuli ranging in frequency and intensity. Finally, we assessed the effect of urethane on population-level representations of birdsong. Results showed that intrinsic neural excitability is significantly depressed by urethane but that spectral tuning, single neuron discriminability, and population representations of song do not differ significantly between unanesthetized and anesthetized animals.