Choroidalyzer: An Open-Source, End-to-End Pipeline for Choroidal Analysis in Optical Coherence Tomography.

Purpose: To develop Choroidalyzer, an open-source, end-to-end pipeline for segmenting the choroid region, vessels, and fovea, and deriving choroidal thickness, area, and vascular index. Methods: We used 5600 OCT B-scans (233 subjects, six systemic disease cohorts, three device types, two manufacturers). To generate region and vessel ground-truths, we used state-of-the-art automatic methods following manual correction of inaccurate segmentations, with foveal positions manually annotated. We trained a U-Net deep learning model to detect the region, vessels, and fovea to calculate choroid thickness, area, and vascular index in a fovea-centered region of interest. We analyzed segmentation agreement (AUC, Dice) and choroid metrics agreement (Pearson, Spearman, mean absolute error [MAE]) in internal and external test sets. We compared Choroidalyzer to two manual graders on a small subset of external test images and examined cases of high error. Results: Choroidalyzer took 0.299 seconds per image on a standard laptop and achieved excellent region (Dice: internal 0.9789, external 0.9749), very good vessel segmentation performance (Dice: internal 0.8817, external 0.8703), and excellent fovea location prediction (MAE: internal 3.9 pixels, external 3.4 pixels). For thickness, area, and vascular index, Pearson correlations were 0.9754, 0.9815, and 0.8285 (internal)/0.9831, 0.9779, 0.7948 (external), respectively (all P < 0.0001). Choroidalyzer's agreement with graders was comparable to the intergrader agreement across all metrics. Conclusions: Choroidalyzer is an open-source, end-to-end pipeline that accurately segments the choroid and reliably extracts thickness, area, and vascular index. Especially choroidal vessel segmentation is a difficult and subjective task, and fully automatic methods like Choroidalyzer could provide objectivity and standardization.

Evaluation of an Automated Choroid Segmentation Algorithm in a Longitudinal Kidney Donor and Recipient Cohort.

Purpose: To evaluate the performance of an automated choroid segmentation algorithm in optical coherence tomography (OCT) data using a longitudinal kidney donor and recipient cohort. Methods: We assessed 22 donors and 23 patients requiring renal transplantation over up to 1 year posttransplant. We measured choroidal thickness (CT) and area and compared our automated CT measurements to manual ones at the same locations. We estimated associations between choroidal measurements and markers of renal function (estimated glomerular filtration rate [eGFR], serum creatinine, and urea) using correlation and linear mixed-effects (LME) modeling. Results: There was good agreement between manual and automated CT. Automated measures were more precise because of smaller measurement error over time. External adjudication of major discrepancies was in favor of automated measures. Significant differences were observed in the choroid pre- and posttransplant in both cohorts, and LME modeling revealed significant linear associations observed between choroidal measures and renal function in recipients. Significant associations were mostly stronger with automated CT (eGFR, P < 0.001; creatinine, P = 0.004; urea, P = 0.04) compared to manual CT (eGFR, P = 0.002; creatinine, P = 0.01; urea, P = 0.03). Conclusions: Our automated approach has greater precision than human-performed manual measurements, which may explain stronger associations with renal function compared to manual measurements. To improve detection of meaningful associations with clinical endpoints in longitudinal studies of OCT, reducing measurement error should be a priority, and automated measurements help achieve this. Translational Relevance: We introduce a novel choroid segmentation algorithm that can replace manual grading for studying the choroid in renal disease and other clinical conditions.

An Open-Source Deep Learning Algorithm for Efficient and Fully Automatic Analysis of the Choroid in Optical Coherence Tomography.

Purpose: To develop an open-source, fully automatic deep learning algorithm, DeepGPET, for choroid region segmentation in optical coherence tomography (OCT) data. Methods: We used a dataset of 715 OCT B-scans (82 subjects, 115 eyes) from three clinical studies related to systemic disease. Ground-truth segmentations were generated using a clinically validated, semiautomatic choroid segmentation method, Gaussian Process Edge Tracing (GPET). We finetuned a U-Net with the MobileNetV3 backbone pretrained on ImageNet. Standard segmentation agreement metrics, as well as derived measures of choroidal thickness and area, were used to evaluate DeepGPET, alongside qualitative evaluation from a clinical ophthalmologist. Results: DeepGPET achieved excellent agreement with GPET on data from three clinical studies (AUC = 0.9994, Dice = 0.9664; Pearson correlation = 0.8908 for choroidal thickness and 0.9082 for choroidal area), while reducing the mean processing time per image on a standard laptop CPU from 34.49 ± 15.09 seconds using GPET to 1.25 ± 0.10 seconds using DeepGPET. Both methods performed similarly according to a clinical ophthalmologist who qualitatively judged a subset of segmentations by GPET and DeepGPET, based on smoothness and accuracy of segmentations. Conclusions: DeepGPET, a fully automatic, open-source algorithm for choroidal segmentation, will enable researchers to efficiently extract choroidal measurements, even for large datasets. As no manual interventions are required, DeepGPET is less subjective than semiautomatic methods and could be deployed in clinical practice without requiring a trained operator. Translational Relevance: DeepGPET addresses the lack of open-source, fully automatic, and clinically relevant choroid segmentation algorithms, and its subsequent public release will facilitate future choroidal research in both ophthalmology and wider systemic health.

Does OSA Increase Risk for Cancer?: A Large Historical Sleep Clinic Cohort Study.

BACKGROUND: The relationship between OSA and cancer is unclear. RESEARCH QUESTION: What is the association between OSA and cancer prevalence and incidence in a large Western Australian sleep clinic cohort (N = 20,289)? STUDY DESIGN AND METHODS: OSA severity was defined by apnea-hypopnea index (AHI) and nocturnal hypoxemia (duration and percentage at oxygen saturation < 90%) measured by in-laboratory polysomnogram. Measures of potential confounding included age, sex, BMI, smoking status, socioeconomic status, and BP. Outcomes were determined from the Western Australian cancer and death registries. Analyses were confined within periods using consistent AHI scoring criteria: January 1, 1989, to July 31, 2002 (American Sleep Disorders Association criteria), and August 1, 2002, to June 30, 2013 (Chicago criteria). We examined associations of AHI and nocturnal hypoxemia with cancer prevalence using logistic regression and cancer incidence using Cox regression analyses. RESULTS: Cancer prevalence at baseline was 329 of 10,561 in the American Sleep Disorders Association period and 633 of 9,728 in the Chicago period. Nocturnal hypoxemia but not AHI was independently associated with prevalent cancer following adjustment for participant age, sex, BMI, smoking status, socioeconomic status, and BP. Of those without prevalent cancer, cancer was diagnosed in 1,950 of 10,232 (American Sleep Disorders Association) and 623 of 9,095 (Chicago) participants over a median follow-up of 11.2 years. Compared with the reference category (no OSA, AHI < 5 events per hour), univariable models estimated higher hazard ratios for cancer incidence for mild (AHI 5-15 events per hour), moderate (AHI 15.1-30 events per hour), and severe (AHI > 30 events per hour) OSA. Multivariable analyses consistently revealed associations between age and, in some cases, sex, BMI, and smoking status, with cancer incidence. After adjusting for confounders, multivariable models showed no independent association between OSA severity and increased cancer incidence. INTERPRETATION: Nocturnal hypoxemia is independently associated with prevalent cancer. OSA severity is associated with incident cancer, although this association seems secondary to other risk factors for cancer development. OSA is not an independent risk factor for cancer incidence.

The changing profile of obstructive sleep apnea: long term trends in characteristics of patients presenting for diagnostic polysomnography.

Introduction: We aimed to analyze long-term trends in characteristics of patients undergoing diagnostic polysomnography (PSG) and subsequently diagnosed with obstructive sleep apnea (OSA) to inform delivery of sleep services. Material and Methods: We studied 24,510 consecutive patients undergoing PSG at a tertiary-care sleep service between 1989 and 2013. OSA was defined by an apnea hypopnea index (AHI)≥ 5 events/hour. Changes to hypopnea definition and flow sensing techniques in 2002 created two distinct AHI scoring periods: American Sleep Disorders Association (ASDA) 1989 - July 2002 and American Academy of Sleep Medicine (Chicago) from August 2002. Results: Over 23.5 years there was a steady increase in proportion of females (15% to 45%), small increases in average age and BMI, and a small decline in socioeconomic status in the overall group. AHI varied between scoring periods both overall [ASDA 10.8/h (3.2-29.6), Chicago 24.3/h (11.8-48.1)] and in the large subgroup (80.7%) diagnosed with OSA [ASDA 20.7/h (10.6-44.1), Chicago 27.4/h (14.8-51.5)]. OSA diagnosis rates increased in the Chicago period (ASDA 66%, Chicago 91%). Increases in AHI and proportion diagnosed appeared better explained by changes in scoring methods than key OSA risk factors. Conclusion: Temporal increases in proportion of females and decreases in socioeconomic status of people undergoing PSG may reflect greater community awareness of sleep disorders. Temporal increases in age and obesity are consistent with secular trends. Changes in scoring methods have major impacts on OSA diagnosis and judgement of disease severity, with important implications for contemporary resourcing of sleep services and interpretation of historical OSA data.

Edge Tracing Using Gaussian Process Regression.

We introduce a novel edge tracing algorithm using Gaussian process regression. Our edge-based segmentation algorithm models an edge of interest using Gaussian process regression and iteratively searches the image for edge pixels in a recursive Bayesian scheme. This procedure combines local edge information from the image gradient and global structural information from posterior curves, sampled from the model's posterior predictive distribution, to sequentially build and refine an observation set of edge pixels. This accumulation of pixels converges the distribution to the edge of interest. Hyperparameters can be tuned by the user at initialisation and optimised given the refined observation set. This tunable approach does not require any prior training and is not restricted to any particular type of imaging domain. Due to the model's uncertainty quantification, the algorithm is robust to artefacts and occlusions which degrade the quality and continuity of edges in images. Our approach also has the ability to efficiently trace edges in image sequences by using previous-image edge traces as a priori information for consecutive images. Various applications to medical imaging and satellite imaging are used to validate the technique and comparisons are made with two commonly used edge tracing algorithms.

Sleep-disordered breathing in patients with stroke-induced dysphagia.

This study examined the nature and characteristics of sleep-disordered breathing, including obstructive sleep apnea and central sleep apnea, in patients with post-stroke dysphagia, to determine the demographic, anthropometric and clinical variables that were associated with sleep-disordered breathing. Thirty-nine patients diagnosed with acute stroke (28 males and 11 females with a mean age of 72.3 ± 10.0 years) underwent overnight polysomnography (within 3.9 ± 1.6 days after admission). Sleep-disordered breathing was described by the apnea-hypopnea index and its obstructive and central components by the obstructive apnea-hypopnea index and central apnea-hypopnea index, respectively. Severity of dysphagia was assessed using the Mann Assessment of Swallowing Ability score. Severity of stroke and functional dependence were assessed by the National Institute of Health Stroke Scale and the modified Barthel index, respectively. Most of the cohort (87%) had moderate-to-severe dysphagia (Mann Assessment of Swallowing Ability of 143.2 ± 19.9). Sleep-disordered breathing (apnea-hypopnea index ≥ 5 events/hr) was present in 38 participants (97%) with a mean apnea-hypopnea index of 37.5 ± 24.4 events/hr. Sleep-disordered breathing was predominantly obstructive in nature, with a mean obstructive apnea-hypopnea index and central apnea-hypopnea index of 19.6 ± 15.7 and 11.4 ± 17.6 events/hr, respectively. Multivariate linear regression analyses showed that the apnea-hypopnea index was associated with sex (p = .0001), body mass index (p = .029) and the modified Barthel index (p = .006); the obstructive apnea-hypopnea index was associated with the Mann Assessment of Swallowing Ability (p = .006), sex (p = .004) and body mass index (p = .015) and had a nonlinear relationship with the modified Barthel index (p = .019); and the central apnea-hypopnea index was associated with sex (p = .027) and the modified Barthel index (p = .019). The present study showed that dysphagia severity was associated with obstructive sleep apnea severity and this association was independent of sex, modified Barthel index and body mass index. However, stroke-induced dysphagia was not associated with central sleep apnea or overall sleep-disordered breathing.

The use and effectiveness of adaptive servo ventilation in central sleep apnea: a study of consecutive sleep clinic patients.

The use of adaptive servo ventilation to treat central sleep apnea in the clinical setting is incompletely understood and could be under-utilized. We reviewed our experience of adaptive servo ventilation use in patients with central sleep apnea. This study shows the effectiveness of adaptive servo ventilation in treating patients with central sleep apnea, irrespective of a predisposing factor, as assessed during a 4-week treatment trial. Results show that adaptive servo ventilation was effective and superior to continuous positive airway pressure in controlling central sleep apnea and improving symptoms. Only a small proportion of these patients had comorbid heart failure. Early treatment with adaptive servo ventilation may improve long-term adherence to therapy. These findings highlight the utility of adaptive servo ventilation in the management of central sleep apnea.

Factors determining satisfaction among facility-based maternity clients in Nepal.

BACKGROUND: With an increasing number of institutional deliveries, the Nepalese health system faces a challenge to ensure a quality of service provision. This paper aims to identify the determinants of client satisfaction with maternity care in Nepal using data from a nationally representative health facility survey. METHODS: A total of 447 exit interviews, with women who had either recently delivered or who had experienced obstetric complications, were conducted across 13 districts in Nepal (87% in hospitals, 8% in Primary Health Care Centres (PHCCs), and 5% in Sub/Health Posts(S/HPs). Client satisfaction was measured using an eight item scale that covered accessibility, interpersonal communication, physical environment, technical aspect of care and decision making. A client satisfaction index was computed using ordinal principal component analysis. A multivariate probit model was used to assess the net effect of explanatory variables on client satisfaction. RESULTS: Longer waiting times and overcrowding increased the likelihood of dissatisfaction. Having an opportunity to ask questions was positively associated with client satisfaction. Respondents from hill districts and rural areas were more likely to be satisfied in comparison to respondents from mountain, terai and urban areas. Socio-demographic factors (age, parity, caste/ethnicity, education, and ecological zone) and supply side factors (the time taken to reach a facility, type of facility, payment for services, and unknown heath worker or anyone entering the delivery room) were not statistically associated with satisfaction. CONCLUSIONS: The findings suggest client satisfaction with the quality of maternity services in Nepal could be improved by reducing waiting times and overcrowding, and giving the mothers adequate time to ask questions. If clients are more satisfied they are more likely to use the facility again/recommend to a friend.

Treating Chronic Hypoventilation With Automatic Adjustable Versus Fixed EPAP Intelligent Volume-Assured Positive Airway Pressure Support (iVAPS): A Randomized Controlled Trial.

Objectives: New noninvasive ventilation (NIV) modes can automatically adjust pressure support settings to deliver effective ventilation in response to varying ventilation demands. It is recommended that fixed expiratory positive airway pressure (FixedEPAP) is determined by attended laboratory polysomnographic (PSG) titration. This study investigated whether automatically determined EPAP (AutoEPAP) was noninferior to FixedEPAP for the control of obstructive sleep apnea (OSA) during intelligent volume-assured pressure support (iVAPS) treatment of chronic hypoventilation. Methods: In this randomized, double-blind, crossover study, patients with chronic hypoventilation and OSA used iVAPS with AutoEPAP or FixedEPAP over two separate nights of attended PSG. PSG recordings were scored by an independent scorer using American Academy of Sleep Medicine 2012 criteria. Results: Twenty-five adults (14 male) with chronic hypoventilation secondary to obesity hypoventilation syndrome (n = 11), chronic obstructive pulmonary disease (n = 9), or neuromuscular disease (n = 5), all of whom were on established home NIV therapy, were included (age 57 ± 7 years, NIV for ≥3 months, apnea-hypopnea index [AHI] >5/hour). AutoEPAP was noninferior to FixedEPAP for the primary outcome measure (median [interquartile range] AHI 2.70 [1.70-6.05]/hour vs. 2.40 [0.25-5.95]/hour; p = .86). There were no significant between-mode differences in PSG sleep breathing and sleep quality, or self-reported sleep quality, device comfort, and patient preference. Mean EPAP with the Auto and Fixed modes was 10.8 ± 2.0 and 11.8 ± 3.9 cmH2O, respectively (p = .15). Conclusions: In patients with chronic hypoventilation using iVAPS, the AutoEPAP algorithm was noninferior to FixedEPAP over a single night's therapy.

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Women's Satisfaction of Maternity Care in Nepal and Its Correlation with Intended Future Utilization.

The impact of rapid increase in institutional birth rate in Nepal on women's satisfaction and planned future utilization of services is less well known. This study aimed to measure women's satisfaction with maternity care and its correlation with intended future utilisation. Data came from a nationally representative facility-based survey conducted across 13 districts in Nepal and included client exit interviews with 447 women who had either recently delivered or had experienced complications. An eight-item quality of care instrument was used to measure client satisfaction. Multivariate probit model was used to assess the attribution of different elements of client satisfaction with intended future utilization of services. Respondents were most likely to suggest maintaining clean/hygienic health facilities (42%), increased bed provision (26%), free services (24%), more helpful behaviour by health workers (18%), and better privacy (9%). Satisfaction with the information received showed a strong correlation with the politeness of staff, involvement in decision making, and overall satisfaction with the care received. Satisfaction with waiting time (p = 0.035), information received (p = 0.02), and overall care in the maternity care (<0.001) showed strong associations with willingness to return to facility. The findings suggest improving physical environment and interpersonal communication skills of service providers and reducing waiting time for improving client satisfaction and intention to return to the health facility.

Study of a Novel APAP Algorithm for the Treatment of Obstructive Sleep Apnea in Women.

STUDY OBJECTIVES: To assess the efficacy of a novel female-specific autotitrating continuous positive airway pressure (CPAP) algorithm (AutoSet for her, AfH) in premenopausal women relative to a standard autotitrating algorithm (AutoSet, S9) (ResMed Ltd., Bella Vista, New South Wales, Australia). DESIGN: Prospective randomised crossover noninferiority trial. SETTING: Tertiary hospital sleep clinic and university research sleep laboratory. PARTICIPANTS: 20 female patients with obstructive sleep apnea (OSA) established on long-term CPAP treatment. INTERVENTIONS: Treatment with 1 night each of AfH and AutoSet while monitored with overnight laboratory-based polysomnography (PSG); order randomly allocated. MEASUREMENTS AND RESULTS: The primary outcome variables were the apnea-hypopnea index (AHI) and 3% oxygen desaturation index (ODI 3%) determined from PSG. Treatment efficacy on the AfH night was noninferior to the AutoSet night as assessed by median (IQR) AHI (1.2 [0.60-1.85]/h versus 1.15 [0.40-2.85]/h, respectively, P = 0.51) and 3% ODI (0.85 [0.25-1.5]/h versus 0.5 [0.25-2.55]/h, respectively, P = 0.83). Other PSG measures were similar, except for the percentage of the night spent in flow limitation, which was lower on the AfH (0.14%) than the AutoSet night (0.19%, P = 0.007). The device-downloaded 95th centile pressure on the AfH night was also lower than on the AutoSet night (10.6 ± 1.7 versus 11.6 ± 2.6 cmH2O, respectively; mean difference [95% confidence interval]: -1.1 [-2.13 to -0.01] cm H2O). CONCLUSION: Among premenopausal women a novel female-specific autotitrating algorithm (AfH) is as effective as the standard AutoSet algorithm in controlling obstructive sleep apnea (OSA). The new algorithm may reduce flow limitation more than the standard algorithm and achieve control of OSA at a lower (95th centile) pressure.

Phytophthora infestans RXLR effector PexRD2 interacts with host MAPKKK ε to suppress plant immune signaling.

Mitogen-activated protein kinase cascades are key players in plant immune signaling pathways, transducing the perception of invading pathogens into effective defense responses. Plant pathogenic oomycetes, such as the Irish potato famine pathogen Phytophthora infestans, deliver RXLR effector proteins to plant cells to modulate host immune signaling and promote colonization. Our understanding of the molecular mechanisms by which these effectors act in plant cells is limited. Here, we report that the P. infestans RXLR effector PexRD2 interacts with the kinase domain of MAPKKKε, a positive regulator of cell death associated with plant immunity. Expression of PexRD2 or silencing MAPKKKε in Nicotiana benthamiana enhances susceptibility to P. infestans. We show that PexRD2 perturbs signaling pathways triggered by or dependent on MAPKKKε. By contrast, homologs of PexRD2 from P. infestans had reduced or no interaction with MAPKKKε and did not promote disease susceptibility. Structure-led mutagenesis identified PexRD2 variants that do not interact with MAPKKKε and fail to support enhanced pathogen growth or perturb MAPKKKε signaling pathways. Our findings provide evidence that P. infestans RXLR effector PexRD2 has evolved to interact with a specific host MAPKKK to perturb plant immunity-related signaling.

Effect of evening postexercise cold water immersion on subsequent sleep.

PURPOSE: This study investigated the effect of cold water immersion after evening exercise on subsequent sleep quality and quantity in trained cyclists. METHODS: In the evenings (~1900 h) on three separate occasions, male cyclists (n = 11) underwent either no exercise (control, CON), exercise only (EX), or exercise followed by cold water immersion (CWI). EX comprised cycling for 15 min at 75% peak power, then a 15-min maximal time trial. After each condition, a full laboratory-based sleep study (polysomnography) was performed. Core and skin temperature, heart rate, salivary melatonin, ratings of perceived fatigue, and recovery were measured in each trial. RESULTS: No differences were observed between conditions for any whole night sleep measures, including total sleep time, sleep efficiency, sleep onset latency, rapid eye movement onset latency, wake after sleep onset, or proportion of the night spent in different sleep stages. Core temperature in EX and CWI trials was higher than CON, until it decreased below that of EX and CON until bedtime in CWI. After bedtime, core temperature was similar for all conditions throughout the night, except for a 90-min period where it was lower for CWI than EX and CON (3.5-4.5 h postexercise). Heart rates for EX and CWI were both significantly higher than CON postexercise until bedtime, whereas skin temperature after CWI was significantly lower than EX and CON, remaining lower than EX until 3 h postexercise. Melatonin levels and recovery ratings were similar between conditions. Fatigue ratings were significantly elevated after exercise in both CWI and EX conditions, with EX still being elevated compared with CON at bedtime. CONCLUSION: Whole night sleep architecture is not affected by evening exercise alone or when followed by CWI.

Effectiveness of suspension seats in maintaining performance following military high-speed boat transits.

OBJECTIVE: The aim of this study was to investigate whether suspension seats (SS) fitted to rigid inflatable boats (RIB) could help maritime boarding teams maintain running performance during the high-risk posttransit phase. BACKGROUND: High-speed RIB transits have been reported to cause reductions in the running performance of boarding teams posttransit. METHOD: In this experiment, two pairs of teams completed a 3-hr transit in either calm or rough seas (calm, 5 vs. 5; rough, 6 vs. 6) in an RIB fitted with either fixed (FS) or Suspension seats (SS). Exhaustive shuttle run distance was measured pre- and immediately posttransit. Transit heart rate and perceived exertion (RPE) were measured and deck and seat pan acceleration recorded; the latter were reported as impacts count and peak magnitude. RESULTS: Distance run was reduced for the FS teams following both transits (calm,-250 m,-20%, p < .07; rough, -398 m, -26%, p < .05), whereas it was unchanged for the SS teams. All transit heart rates and RPE indicated light exertion levels. Seat pan impacts were similarly reduced during the calm transit (FS, -42%; SS, -30%); however, during the rough transit, the SS was more than twice as effective (FS, -32%; SS, -71%). Peak impact magnitudes were reduced by the SS (calm, -38%; rough, -57%) and amplified by the FS (calm, +3%; rough, +28%). CONCLUSION: Suspension seats effectively maintained posttransit running performance by reducing magnitude of the vertical shocks imposed on the passengers. APPLICATION: High-speed RIB transits followed immediately by high-intensity activity are intrinsic to contemporary maritime operations; suspension seats can maintain post-transit physical performance, thereby enhancing safety and operational effectiveness.

A comparison of attitudes toward opioid agonist treatment among short-term buprenorphine patients.

BACKGROUND: Obtaining data on attitudes toward buprenorphine and methadone of opioid-dependent individuals in the United States may help fashion approaches to increase treatment entry and improve patient outcomes. OBJECTIVES: This secondary analysis study compared attitudes toward methadone and buprenorphine of opioid-dependent adults entering short-term buprenorphine treatment (BT) with opioid-dependent adults who are either entering methadone maintenance treatment or not entering treatment. METHODS: The 417 participants included 132 individuals entering short-term BT, 191 individuals entering methadone maintenance, and 94 individuals not seeking treatment. Participants were administered an Attitudes toward Methadone scale and its companion Attitudes toward Buprenorphine scale. Demographic characteristics for the three groups were compared using χ(2) tests of independence and one-way analysis of variance. A repeated-measures multivariate analysis of variance with planned contrasts was used to compare mean attitude scores among the groups. RESULTS: Participants entering BT had significantly more positive attitudes toward buprenorphine than toward methadone (p < .001) and more positive attitudes toward BT than methadone-treatment (MT) participants and out-of-treatment (OT) participants (p < .001). In addition, BT participants had less positive attitudes toward methadone than participants entering MT (p < .001). CONCLUSIONS: Participants had a clear preference for a particular medication. Offering a choice of medications to OT individuals might enhance their likelihood of entering treatment. Treatment programs should offer a choice of medications when possible to new patients, and future comparative effectiveness research should incorporate patient preferences into clinical trials. SCIENTIFIC SIGNIFICANCE: These data contribute to our understanding of why people seek or do not seek effective pharmacotherapy for opioid addiction.

Structures of Phytophthora RXLR effector proteins: a conserved but adaptable fold underpins functional diversity.

Phytopathogens deliver effector proteins inside host plant cells to promote infection. These proteins can also be sensed by the plant immune system, leading to restriction of pathogen growth. Effector genes can display signatures of positive selection and rapid evolution, presumably a consequence of their co-evolutionary arms race with plants. The molecular mechanisms underlying how effectors evolve to gain new virulence functions and/or evade the plant immune system are poorly understood. Here, we report the crystal structures of the effector domains from two oomycete RXLR proteins, Phytophthora capsici AVR3a11 and Phytophthora infestans PexRD2. Despite sharing <20% sequence identity in their effector domains, they display a conserved core α-helical fold. Bioinformatic analyses suggest that the core fold occurs in ∼44% of annotated Phytophthora RXLR effectors, both as a single domain and in tandem repeats of up to 11 units. Functionally important and polymorphic residues map to the surface of the structures, and PexRD2, but not AVR3a11, oligomerizes in planta. We conclude that the core α-helical fold enables functional adaptation of these fast evolving effectors through (i) insertion/deletions in loop regions between α-helices, (ii) extensions to the N and C termini, (iii) amino acid replacements in surface residues, (iv) tandem domain duplications, and (v) oligomerization. We hypothesize that the molecular stability provided by this core fold, combined with considerable potential for plasticity, underlies the evolution of effectors that maintain their virulence activities while evading recognition by the plant immune system.

Transitioning opioid-dependent patients from detoxification to long-term treatment: efficacy of intensive role induction.

Despite findings that opioid detoxification serves little more than a palliative function, few patients who enter detoxification subsequently transition to long-term treatment. The current study evaluated intensive role induction (IRI), a strategy adapted from a single-session intervention previously shown to facilitate engagement of substance-dependent patients in drug-free treatment. IRI was delivered either alone or combined with case management (IRI+CM) to determine the capacity of each condition to enhance transition and engagement in long-term treatment of detoxification patients. Study participants were 240 individuals admitted to a 30-day buprenorphine detoxification delivered at a publicly funded outpatient drug treatment clinic. Following clinic intake, participants were randomly assigned to IRI, IRI+CM, or standard clinic treatment (ST). Outcomes were assessed in terms of adherence and satisfaction with the detoxification program, detoxification completion, and transition and retention in treatment following detoxification. Participants who received IRI and IRI+CM attended more counseling sessions during detoxification than those who received ST (both ps<.001). IRI, but not IRI+CM participants, were more likely to complete detoxification (p=.017), rated their counselors more favorably (p=.01), and were retained in long-term treatment for more days following detoxification (p=.005), than ST participants. The current study demonstrated that an easily administered psychosocial intervention can be effective for enhancing patient involvement in detoxification and for enabling their engagement in long-term treatment following detoxification.