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The multidimensional sleep health framework emphasizes that sleep can be characterized across several domains, with implications for developing novel sleep treatments and improved prediction and health screening. However, empirical evidence regarding the domains and representative measures that exist in actigraphy-assessed sleep is lacking. We aimed to establish these domains and representative measures in older adults by examining the factor structure of 28 actigraphy-derived sleep measures from 2,841 older men from the Osteoporotic Fractures in Men Sleep Study and, separately, from 2,719 older women from the Study of Osteoporotic Fractures. Measures included means and standard deviations of actigraphy summary measures and estimates from extended cosine models of the raw actigraphy data. Exploratory factor analyses revealed the same five factors in both sexes: Timing (e.g. mean midpoint from sleep onset to wake-up), Efficiency (e.g. mean sleep efficiency), Duration (e.g. mean minutes from sleep onset to wake-up), Sleepiness/Wakefulness (e.g. mean minutes napping and amplitude of rhythm), and Regularity (e.g. standard deviation of the midpoint). Within each sex, confirmatory factor analyses confirmed the one-factor structure of each factor and the entire five-factor structure (Comparative Fit Index and Tucker-Lewis Index ≥ 0.95; Root Mean Square Error of Approximation 0.08-0.38). Correlation magnitudes among factors ranged from 0.01 to 0.34. These findings demonstrate the validity of conceptualizing actigraphy sleep as multidimensional, provide a framework for selecting sleep health domains and representative measures, and suggest targets for behavioral interventions. Similar analyses should be performed with additional measures of rhythmicity, other age ranges, and more racially/ethnically diverse samples., (© Sleep Research Society 2020. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.)

Background: Insomnia affects almost one in four military service members and veterans. The first-line recommended treatment for insomnia is cognitive-behavioral therapy for insomnia (CBTI). CBTI is typically delivered in-person or online over one-to-four sessions (brief versions) or five-to-eight sessions (standard versions) by a licensed doctoral or masters-level clinician with extensive training in behavioral sleep medicine. Despite its effectiveness, CBTI has limited scalability. Three main factors inhibit access to and delivery of CBTI including restricted availability of clinical expertise; rigid, resource-intensive treatment formats; and limited capacities for just-in-time monitoring and treatment personalization. Digital technologies offer a unique opportunity to overcome these challenges by providing scalable, personalized, resource-sensitive, adaptive, and cost-effective approaches for evidence-based insomnia treatment., Methods: This is a hybrid type 3 implementation-effectiveness randomized trial using a scalable evidence-based digital health software platform, NOCTEM™'s Clinician-Operated Assistive Sleep Technology (COAST™). COAST includes a clinician portal and a patient app, and it utilizes algorithms that facilitate detection of sleep disordered patterns, support clinical decision-making, and personalize sleep interventions. The first aim is to compare three clinician- and system-centered implementation strategies on the reach, adoption, and sustainability of the COAST digital platform by offering (1) COAST only, (2) COAST plus external facilitation (EF: assistance and consultation to providers by NOCTEM's sleep experts), or (3) COAST plus EF and internal facilitation (EF/IF: assistance/consultation to providers by NOCTEM's sleep experts and local champions). The second aim is to quantify improvements in insomnia among patients who receive behavioral sleep care via the COAST platform. We hypothesize that reach, adoption, and sustainability and the magnitude of improvements in insomnia will be superior in the EF and EF/IF groups relative to the COAST-only group., Discussion: Digital health technologies and machine learning-assisted clinical decision support tools have substantial potential for scaling access to insomnia treatment. This can augment the scalability and cost-effectiveness of CBTI without compromising patient outcomes. Engaging providers, stakeholders, patients, and decision-makers is key in identifying strategies to support the deployment of digital health technologies that can promote quality care and result in clinically meaningful sleep improvements, positive systemic change, and enhanced readiness and health among service members., Trial Registration: ClinicalTrials.gov NCT04366284 . Registered on 28 April 2020.

Canine melanomas and mast cell tumours (MCTs) frequently metastasize to lymph nodes, worsening prognosis compared with dogs without metastasis. Sentinel lymph node (SLN) evaluation is more specific than evaluation of the lymph node closest to the tumour, which may not be the draining lymph node. Computed tomography lymphangiography (CTL) allows for SLN identification and one study of canine mammary tumours found that CTL was able to assist in determination of the metastatic status of inguinal SLNs prior to extirpation and histopathology. The objective of the present study was to evaluate CTL for use in determining metastasis to the SLN in dogs with a pre-operative diagnosis of melanoma or MCT in various locations by correlating CTL findings with histopathology. The hypothesis was that CTL would not be able to determine the metastatic status of lymph nodes, based on author experience. Dogs were prospectively enrolled and underwent CTL and subsequent SLN extirpation. Histopathology results for the primary tumour, SLN, and additional extirpated lymph nodes were recorded. Fifteen dogs were enrolled and 21 SLN were evaluated. The SLN enhancement pattern (heterogeneous, homogenous or peripheral) was not associated with metastasis, nor was the attenuation value at 1 minute, 5 minutes, or the change in attenuation value. No correlation was found between CTL findings and metastatic status of SLNs. Based on these results, CTL alone cannot be used to diagnose SLN metastasis. Extirpation of the SLN with histopathology is recommended to diagnose lymph node metastasis in dogs with melanoma and MCT., (© 2020 John Wiley & Sons Ltd.)

Progressive disease is common following anal sacculectomy for apocrine gland anal sac adenocarcinoma (AGASACA); additional therapy may prolong survival. Adherence to medical recommendations influences therapeutic success in humans. The purpose of this study was to assess the adherence to follow-up recommendations in dogs with AGASACA. Medical records of patients that underwent anal sacculectomy for AGASACA, with or without iliosacral lymphadenectomy, between July 2015 and July 2018, were reviewed at eight referral institutions to assess post-operative recommendations and owner adherence to recommendations. One hundred and seventy-four dogs were included, of which 162 underwent unilateral anal sacculectomy, 12 underwent bilateral anal sacculectomy and 39 underwent concurrent iliosacral lymphadenectomy. Seventy-six owners (44%) received recommendations for staging at the time of discharge, histopathology results or at the first follow-up visit. One hundred and forty owners (80%) received recommendations for treatment following the initial surgery. Fifty of seventy-six (66%) owners pursued at least one staging recommendation and 69 of 140 (49%) owners pursued some kind of adjuvant treatment recommendation. Overall, 16 of 76 (21%) were adherent to staging recommendations with 20 adherent for the first year following surgery (26%). Forty-seven of 140 (34%) were adherent to treatment recommendations with 54 (39%) adherent for the first year. Owners that were adherent to restaging recommendations at 1 year following surgery were significantly more likely to pursue treatment for progressive disease (P = .014). Further work is required to assess owner motivation and evaluate strategies to improve adherence, given the potential impact on patient treatment., (© 2020 John Wiley & Sons Ltd.)

Objective: To describe the technique, outcome, and owner satisfaction associated with dorsal offset rhinoplasty (DOR) to treat stenotic nares in brachycephalic dogs., Study Design: Retrospective case series., Animals: Thirty-four client-owned dogs., Methods: Medical records of dogs treated with DOR at a veterinary teaching hospital over a 6-year period were identified. Dorsal offset rhinoplasty was defined as removal of a dorsal wedge of nasal planum from each naris with apposition of the rostral abaxial tissue to the caudal axial tissue, resulting in translocation of the alar cartilage in both median and dorsal planes. Immediate and postoperative complications were recorded. Owners were asked to report any complications with healing of the nares and to score their satisfaction with the appearance of the nares., Results: Thirty-four dogs met the inclusion criteria. Twenty-nine (85%) dogs were examined a median of 402.5 days (range, 23-2042) postoperatively, with no major complications related to the rhinoplasty recorded. Eighteen owners responded a median of 701 days (range, 37-1622) postoperatively. One owner reported that self-trauma led to collapse of one naris. One owner reported collapse of both nares within 4 years; timing and cause were unknown. Sixteen of 17 responding owners reported that they were very satisfied with the outcome of the rhinoplasty. The owner of the dog with the collapsed naris was very unsatisfied. One owner did not provide a satisfaction score., Conclusion: Owners were generally highly satisfied with DOR, and complications were uncommon., Clinical Significance: This report describes an alternate technique to treat stenotic nares., (© 2020 American College of Veterinary Surgeons.)

We have used video imaging and interferometric techniques to investigate the dynamics of spreading of drops of ^{4}He on a solid surface for temperatures ranging from 5.2 K (near the critical point) to 2.2 K (near T_{λ}). After an initial transient, the drops become pancake-shaped with a radius that grows as R(t)≈t^{α}, with α=0.149±0.002. The drops eventually begin to shrink due to evaporation driven by gravitational and curvature effects, which limits their lifetime to about 1000 s. Although helium completely wets the substrate, and the spreading takes place over a pre-existing adsorbed film, a distinct contact line with a contact angle of order one degree is visible throughout this process.

Background: In the United States, there are considerable racial inequities in adverse perinatal outcomes. Exposure to racism, sexism, and other forms of oppression may help explain these inequities., Objectives: To describe the application of real-time data collection using ecological momentary assessment (EMA) and smartphone technology to assess exposure to stress, racism, sexism, microaggressions, and other forms of oppression., Methods: The Postpartum Mothers Mobile Study (PMOMS) is an ongoing longitudinal cohort study that began recruitment in December 2017. Participants delivering at a hospital in Pittsburgh, PA are recruited by 29 weeks' gestation. Using smartphones and smart scales, participants complete daily surveys related to psychosocial, behavioural, and contextual factors and weigh themselves weekly for approximately 15 months. We provide a preliminary descriptive analysis of EMA self-reported measures of stress, racism, sexism, and microaggressions; and non-EMA measures of stress and major discrimination., Results: The sample (n = 230) is 63.5% White, 24.8% Black/African American, and 7% Hispanic origin. The most commonly reported item from the Major Discrimination Scale is being unfairly fired (18.1% of the sample). Of those, 31.7% and 17.1% attribute unfair firing to their gender and race, respectively. From the random EMA measures, on average, participants report experiences of racism and sexism at least once daily, in an average 12-hour day over the 4-week period. Black participants indicate about two experiences per day of racism, and White participants indicate more than 1 per day of sexism. Mean stress levels from the EMA measures were similar to the stress measures collected at baseline., Conclusions: The methods applied in PMOMS provide real-time data regarding how participants' daily experiences of stress and discrimination influence their lives. Future work will include understanding if and how these EMA measures may relate to already established measures of racism, sexism, and stress; and ultimately understanding associations with perinatal inequities., (© 2020 John Wiley & Sons Ltd.)

Objective: To describe the clinical features and outcome of functional thyroid tumours in dogs., Materials and Methods: Retrospective multi-institutional study of 70 dogs diagnosed with thyroid mass and concurrent hyperthyroidism. Clinical data regarding presentation, treatment, outcome and functional thyroid status were retrieved., Results: Overall median survival of dogs with functional thyroid tumours was 35.1 months and 1- and 3-year survival rates were 83 and 49%, respectively. Median survival time was 72.6 months for dogs treated with surgical excision and 15.7 months for dogs that did not receive surgery. Of the 50 dogs treated by surgery and for which thyroid status was known following treatment, 64% developed hypothyroidism after surgery. Histopathologically confirmed metastasis was identified in 3% of dogs., Clinical Significance: Dogs with functional thyroid tumours may survive a long time after surgical excision, although post-operative hypothyroidism is common., (© 2020 British Small Animal Veterinary Association.)

Case Description: A 4-year-old spayed female French Bulldog was referred for treatment of a suspected right-sided nasal angiofibroma associated with a 4-month history of unilateral nasal discharge and stertor., Clinical Findings: The dog appeared healthy other than right-sided mucoid debris and decreased airflow through the right naris. The dog was anesthetized, and a large intranasal mass was observed obstructing the right nasal passage and abutting the nasal septum., Treatment and Outcome: A lateral rhinotomy was performed, and rigid endoscopes (0° and 30°) were used to examine the right nasal cavity. The mass filled the anterior aspect of the nasal cavity and involved a portion of the nasal turbinates with some erosion. A coblation unit was used to ablate tumor tissue laterally to remove the tumor in piecemeal fashion. Recovery was routine with only minor epistaxis after surgery, and the dog was discharged the next day. Eight months after surgery, follow-up CT revealed right-sided nasal turbinate and conchal atrophy consistent with prior mass ablation. No macroscopic recurrence was detected, and the owners reported only rare, clear rhinorrhea., Clinical Relevance: Findings suggested that coblation may be an alternative to radiation therapy for vascular tumors with minimal invasion and low metastatic potential.

Objective: To determine long-term outcomes and factors associated with those outcomes in dogs with gastroesophageal intussusception (GEI)., Animals: 36 dogs with GEI evaluated at 16 veterinary hospitals from January 2000 through January 2018., Procedures: Medical records of included dogs were reviewed to collect information regarding signalment, clinical signs, physical examination findings, blood work and diagnostic imaging results, surgical findings, and outcome. Factors were evaluated for associations with various outcomes., Results: Median age of dogs with GEI was 13.2 months, and males (72% [26/36]) and German Shepherd Dogs (33% [12/36]) were most common. Vomiting (67% [24/36]) and regurgitation (33% [12/36]) were the most common clinical signs. Ten of 36 (28%) dogs were euthanized without treatment, and 26 (72%) underwent treatment (25 surgically and 1 endoscopically). Twenty-three of the 26 (88%) treated dogs survived to discharge; median survival time was 995 days. At last follow-up, 15 of the 23 (65%) surviving dogs remained alive and 8 (35%) had died for reasons related to persistent regurgitation (n = 6) or reasons unrelated to GEI (2). Of the 10 dogs for which owners were contacted, 7 had persistent regurgitation, the severity of which was reduced through managed feedings. Dogs with acute (≤ 7 days) clinical signs or a previous diagnosis of megaesophagus were more likely to have persistent regurgitation than were dogs without these factors., Conclusions and Clinical Relevance: Treatment should be considered for dogs with GEI given the high rate of survival to discharge and median survival time. Although persistent regurgitation was common after treatment, a satisfactory outcome was possible with medical management, including managed feedings and medications.

Rationale: Although both type 2 diabetes mellitus (T2DM) and obstructive sleep apnea (OSA) are independently recognized as risk factors for cardiovascular disease, little is known about their interaction. Objectives: We hypothesized that T2DM and OSA act synergistically to increase vascular risk, and that treatment of OSA would improve vascular reactivity in patients with T2DM plus OSA. Methods: Cross-sectional study of 141 adults with T2DM, OSA, T2DM plus OSA, and control subjects, followed by a 3-month, parallel-arm, randomized, placebo-controlled trial comparing active and sham continuous positive airway pressure (CPAP) in 53 adults with T2DM plus OSA. Endothelium-dependent macro- and microvascular reactivity (flow-mediated dilation [FMD] of the brachial artery and acetylcholine-induced dilation of forearm microvasculature, respectively) and cardiovascular magnetic resonance to assess left- and right-ventricular mass/volume. Results: Mean (±SD) FMD was 6.1 (±4.0)%, 7.3 (±3.6)%, 6.8 (±4.5)%, and 4.8 (±2.9)% in control subjects, T2DM only, OSA only, and T2DM plus OSA, respectively. We observed a significant T2DM × OSA interaction on FMD, such that the mean effect of OSA in those with T2DM was 3.1% (95% confidence interval [CI], 0.6 to 5.6) greater than the effect of OSA in those without T2DM. A total of 3 months of CPAP resulted in a mean absolute increase in FMD of 0.3% (95% CI, -1.9 to 2.5; primary endpoint), with a net improvement of 1.1% (95% CI, -1.4 to 3.6) among those with adherence of 4 h/night or greater. A significant T2DM × OSA interaction was found for both left ventricular (LV) and right ventricular end-diastolic volume, such that OSA was associated with a 22.4 ml (95% CI, 3.2 to 41.6) greater LV end-diastolic volume and 23.2 ml (95% CI, 2.6 to 43.8) greater right ventricular end-diastolic volume in those with T2DM compared with the impact of OSA in those without T2DM. We observed a net improvement in LV end-diastolic volume of 8.7 ml (95% CI, -7.0 to 24.4). Conclusions: The combination of T2DM plus OSA is associated with macrovascular endothelial dysfunction beyond that observed with either disease alone. CPAP for 3 months did not significantly improve macrovascular endothelial function in the intent-to-treat analysis; however, cardiovascular magnetic resonance results suggest that there may be a beneficial effect of CPAP on LV diastolic volume.Clinical trial registered with www.clinicaltrials.gov (NCT01629862).

The lateral habenula (LHb) is an epithalamic brain structure critical for processing and adapting to negative action outcomes. However, despite the importance of LHb to behavior and the clear anatomical and molecular diversity of LHb neurons, the neuron types of the habenula remain unknown. Here, we use high-throughput single-cell transcriptional profiling, monosynaptic retrograde tracing, and multiplexed FISH to characterize the cells of the mouse habenula. We find five subtypes of neurons in the medial habenula (MHb) that are organized into anatomical subregions. In the LHb, we describe four neuronal subtypes and show that they differentially target dopaminergic and GABAergic cells in the ventral tegmental area (VTA). These data provide a valuable resource for future study of habenular function and dysfunction and demonstrate neuronal subtype specificity in the LHb-VTA circuit., Competing Interests: MW, KH, DH, MH, GR, BS No competing interests declared, (© 2020, Wallace et al.)

Objective: To evaluate the occlusion of an intra-abdominal vessel as a model of an extrahepatic portosystemic shunt by thin film banding in a controlled setting and to document histologically the perivascular region's response to thin film banding after 8 weeks., Study Design: Experimental study., Animals: Six purpose-bred healthy domestic short hair cats., Methods: Thin film bands were placed around the external iliac vein, with a sham procedure on the contralateral vessel. Closure rates were monitored via computed tomographic angiography (CTA) every 2 weeks for a total of 8 weeks. After 8 weeks, the vessels were resected, if possible, and submitted for histopathologic evaluation., Results: All cats tolerated the procedure without surgical complications. Eight weeks after surgery, closure was evaluated as complete in one cat, marked in two cats, moderate in one cat, and mild in two cats according to CTA. Histological examination (in three cats) was consistent with chronic, multifocal, granulomatous inflammation with moderate fibrosis and collagen degeneration., Conclusion: Venous occlusion was inconsistent and often incomplete 8 weeks after thin film banding of the external iliac vein despite the presence of moderate to abundant perivascular fibrous tissue., Clinical Significance: Vascular occlusion by thin film banding in cats is mainly incomplete after 2 months. This study supports the theory that high level of residual shunting may be expected in some cats after thin film banding., (© 2019 The American College of Veterinary Surgeons.)

Childhood trauma may sensitize the brain, increasing vulnerability to maladaptive stress responses following adulthood trauma exposure. Previous work has identified the cingulum as a white matter pathway that may be sensitized to adulthood trauma by childhood maltreatment. In this pilot study of young adult male military veterans (N = 28), we examined a priori regions of interest (ROIs) connected by the cingulum, including regions involved in cognitive processes and stress responses. Our goal was to examine the interaction between childhood maltreatment and combat exposure on stress-related activity within cingulum-associated ROIs. As such we utilized a mild cognitive stress task, a performance-titrated multi-source interference task (MSIT). We found that childhood maltreatment moderated the effect of combat exposure on stress-related, interference-evoked activity within the dorsal anterior cingulate cortex (dACC, activation), subgenual ACC (sgACC, deactivation) and posterior midcingulate cortex (pMCC, deactivation). Greater combat exposure was associated with greater interference-evoked activation within the dACC, and less sgACC and pMCC deactivation among individuals with more severe childhood maltreatment. Our findings suggest that child maltreatment sensitizes these anterior and mid-cingulate regions to later life trauma. These findings may have implications for cognitive control, autonomic regulation/stress reactivity, and responses to noxious/aversive stimuli, which may contribute to increased psychiatric vulnerability., Competing Interests: The authors declare no competing financial interests. Anne Germain, Ph.D., has no conflict of interest related to this work. She serves as CEO and holds equity in Rehat, LLC. She has also served as a consultant for Jazz Pharmaceuticals, Inc., (© 2020 Society for Military Psychology, Division 19 of the American Psychological Association.)

Background: Lower urinary tract transitional cell carcinoma (TCC) is an important but rarely described disease of cats., Objectives: To report the clinical characteristics, treatments, and outcomes in a cohort of cats with lower urinary tract TCC and to test identified variables for prognostic relevance., Animals: One-hundred eighteen client-owned cats with lower urinary tract carcinoma., Methods: Medical records were retrospectively reviewed to obtain information regarding clinical characteristics, treatments, and outcomes. Recorded variables were analyzed statistically., Results: Median age of affected cats was 15 years (range, 5.0-20.8 years) and median duration of clinical signs was 30 days (range, 0-730 days). The trigone was the most common tumor location (32/118; 27.1%) as assessed by ultrasound examination, cystoscopy, or both. Treatment was carried out in 73 of 118 (61.9%) cats. Metastatic disease was documented in 25 of 118 (21.2%) cats. Median progression-free survival and survival time for all cats were 113 days (95% confidence interval [CI], 69-153) and 155 days (95% CI, 110-222), respectively. Survival increased significantly (P < .001) when comparing cats across the ordered treatment groups: no treatment, treatment without partial cystectomy, and treatment with partial cystectomy. Partial cystectomy (hazard ratio [HR], 0.31; 95% CI, 0.17-0.87) and treatment with nonsteroidal anti-inflammatory drugs (HR, 0.55; 95% CI, 0.33-0.93) were significantly associated with longer survival times., Conclusions and Clinical Importance: The results support treatment using partial cystectomy and NSAIDs in cats with TCC., (© 2019 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

The objective of this study was to determine risk factors for vomiting and inappetence and evaluate long-term outcome after surgical treatment of pancreatic β-cell tumors in dogs. Records of 33 dogs that underwent surgery for such tumors were retrospectively evaluated. Inappetence and vomiting occurred in 27.3% and 24.2% of dogs, respectively. Risk factors for postoperative vomiting were longer duration of clinical signs before surgery, higher preoperative total protein concentration, and lack of liver metastasis. No significant risk factors for inappetence or survival were identified. Median survival time was 723 days. Dogs with a longer duration of clinical signs before surgery may have had greater pancreatic involvement or more pronounced systemic perturbations. Higher preoperative total protein concentration may reflect preoperative dehydration or inflammation. Significance of lack of liver metastasis is unknown. The long survival time indicates a good overall prognosis with surgical treatment, justifying surgical intervention in patients with advanced disease., (Copyright and/or publishing rights held by the Canadian Veterinary Medical Association.)

Background: Sleep characteristics related to duration, timing, continuity, and sleepiness are associated with mortality in older adults, but rarely considered in health recommendations. We applied machine learning to: (i) establish the predictive ability of a multidimensional self-reported sleep domain for all-cause and cardiovascular mortality in older adults relative to other established risk factors and (ii) to identify which sleep characteristics are most predictive., Methods: The analytic sample includes N = 8,668 older adults (54% female) aged 65-99 years with self-reported sleep characterization and longitudinal follow-up (≤15.5 years), aggregated from three epidemiological cohorts. We used variable importance (VIMP) metrics from a random survival forest to rank the predictive abilities of 47 measures and domains to which they belong. VIMPs > 0 indicate predictive variables/domains., Results: Multidimensional sleep was a significant predictor of all-cause (VIMP [99.9% confidence interval {CI}] = 0.94 [0.60, 1.29]) and cardiovascular (1.98 [1.31, 2.64]) mortality. For all-cause mortality, it ranked below that of the sociodemographic (3.94 [3.02, 4.87]), physical health (3.79 [3.01, 4.57]), and medication (1.33 [0.94, 1.73]) domains but above that of the health behaviors domain (0.22 [0.06, 0.38]). The domains were ranked similarly for cardiovascular mortality. The most predictive individual sleep characteristics across outcomes were time in bed, hours spent napping, and wake-up time., Conclusion: Multidimensional sleep is an important predictor of mortality that should be considered among other more routinely used predictors. Future research should develop tools for measuring multidimensional sleep-especially those incorporating time in bed, napping, and timing-and test mechanistic pathways through which these characteristics relate to mortality., (© The Author(s) 2019. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: To describe clinical characteristics and surgical outcomes for kittens with phimosis and to develop a system to classify phimosis on the basis of gross pathological lesions., Animals: 8 kittens with phimosis., Procedures: Medical record databases of 2 veterinary teaching hospitals were searched to identify records of cats ≤ 20 weeks old (ie, kittens) with phimosis that underwent surgical intervention between 2009 and 2017. For each kitten, information extracted from the record included signalment, history, clinical signs, physical examination findings, treatments, and details regarding the surgical procedure performed, postoperative complications, and outcome., Results: The most common clinical signs were stranguria (n = 6), marked preputial swelling (5), and a small (6) or inevident (2) preputial orifice. Six kittens had type 1 phimosis (generalized preputial swelling owing to urine pooling without penile-preputial adhesions) and underwent circumferential preputioplasty. Two kittens had type 2 phimosis (focal preputial swelling and urine pooling in the presence of penile-preputial adhesions) and underwent preputial urethrostomy. No postoperative complications were recorded for kittens that underwent preputial urethrostomy. All 6 kittens that underwent circumferential preputioplasty had some exposure of the tip of the penis immediately after surgery, which typically resolved over time. At the time of last follow-up (mean, 1.4 years after surgery), all 8 patients were able to urinate and had no signs of phimosis recurrence., Conclusions and Clinical Relevance: Results suggested that circumferential preputioplasty and preputial urethrostomy could be used to successfully manage kittens with type 1 and type 2 phimosis, respectively.

Objective: To characterize abdominal lymphatic drainage in cats after thoracic duct ligation (TDL) and cisterna chyli ablation (CCA)., Animals: 7 purpose-bred research cats., Procedures: Baseline CT lymphangiography was performed. A popliteal lymph node was injected with iohexol, and images were acquired at 5-minute intervals for 15 minutes. Cats underwent TDL and CCA; methylene blue was used to aid in identifying lymphatic vessels. The CT lymphangiography was repeated immediately after and 30 days after surgery. All cats were euthanized and necropsied., Results: Results of baseline CT lymphangiography were unremarkable for all 7 cats. Only 5 cats completed the study. Leakage of contrast medium at the level of the cisterna chyli was seen on CT lymphangiography images obtained from all cats immediately after surgery. Evaluation of 30-day postoperative CT lymphangiography images revealed small branches entering the caudal vena cava in 2 cats, leakage of contrast medium into the caudal vena cava with no visible branches in 1 cat, and no contrast medium in the caudal vena cava in 2 cats. Contrast medium did not flow beyond the level of the cisterna chyli in any cat. Gross examination during necropsy revealed that all cats had small lymphatic vessels that appeared to connect to local vasculature identified in the region of the cisterna chyli., Conclusions and Clinical Relevance: Abdominal lymphaticovenous anastomoses formed after TDL and CCA in cats. This would support use of these procedures for treatment of cats with idiopathic chylothorax, although additional studies with clinically affected cats are warranted.

Objective: To compare surgical models for teaching enterotomies to students., Study Design: Prospective, randomized study., Sample Population: Second-year veterinary students (n = 59) and faculty surgeons/surgery residents (n = 19)., Methods: Participants performed an enterotomy on each of 3 models (equine cadaver intestine, SurgiReal small intestine simulator, and SynDaver canine bowel) and completed a survey comparing them to either an enterotomy on an anesthetized pig (students) or intestinal surgery experience (faculty/residents). Surveys results were compiled and analyzed., Results: Both student and faculty/resident groups rated cadaver intestine as more similar to live intestine compared with the synthetic models for incision, tissue handling, mucosal eversion, needle passage, knot tying, and best preparing for live intestine. Students rated SynDaver as more similar to live intestine than SurgiReal for incision and ranked SurgiReal as more similar to live intestine than SynDaver for mucosal eversion. There was no difference between the ranks assigned to SurgiReal and SynDaver for faculty/residents. Faculty/residents responded most often that cadaver intestine would be the model they recommend for training students., Conclusion: Cadaver intestine was the model most similar to live intestine for all variables tested. SurgiReal and SynDaver models were comparable to each other but did not simulate live intestine as well as cadaver intestine., Clinical Significance: Cadaver intestine more closely approximated live intestine compared with either synthetic model. SurgiReal and SynDaver may be adequate alternatives if cadaver intestine is unavailable., (© 2019 The American College of Veterinary Surgeons.)

Background: Sleep timing and evening chronotype have been implicated in alcohol use problems but research has yet to study them in relation to theory-driven laboratory-based measures of alcohol use disorder risk. The current study examined (i) whether chronotype, sleep timing, and/or sleep duration are associated with alcohol response (subjective stimulation, sedation, and behavioral disinhibition) and (ii) if sex and race moderate these associations., Methods: Adult drinkers (N = 144; 46 female participants) completed 2 counterbalanced beverage administration sessions (alcohol and nonalcohol) during which they rated stimulation/sedation and completed a cued go/no-go task. They reported bed and waketimes over 10 days., Results: Later sleep timing was associated with greater increases in alcohol stimulation, but among male and White participants only. Later sleep timing (among male participants) and greater eveningness (examined among White male participants only) were associated with greater overall stimulation on average in the alcohol session relative to the nonalcohol session, irrespective of alcohol consumption. More variable sleep duration was associated with greater increases in sedation., Conclusions: These findings offer preliminary, but novel evidence that sleep characteristics may relate to the relative stimulating and sedating effects of alcohol, thereby influencing the risk for alcohol problems., (© 2019 by the Research Society on Alcoholism.)

Background: A novel injectable expanding foam based on hydrophobically modified chitosan (HM-CS) was developed to improve hemostasis during surgeries. HM-CS is an amphiphilic derivative of the natural biopolymer chitosan (CS); HM-CS has been shown to improve the natural hemostatic characteristics of CS, but its internal safety has not been systematically evaluated. The goal of this study was to compare the long-term in vivo safety of HM-CS relative to a commonly used fibrin sealant (FS), TISSEEL (Baxter)., Methods: Sixty-four Sprague-Dawley rats (275-325 g obtained from Charles River Laboratories) were randomly assigned to control (n = 16) or experimental (n = 48) groups. Samples of the test materials (HM-CS [n = 16], CS [n = 16], and FS [n = 16]) applied to a nonlethal liver excision (0.4 ± 0.3 g of the medial lobe) in rats were left inside the abdomen to degrade. Animals were observed daily for signs of morbidity and mortality. Surviving animals were sacrificed at 1 and 6 wk; the explanted injury sites were microscopically assessed., Results: All animals (64/64) survived both the 1- and 6-wk time points without signs of morbidity. Histological examination showed a comparable pattern of degradation for the various test materials. FS remnants and significant adhesions to neighboring tissues were observed at 6 wk. Residual CS and HM-CS were observed at the 6 wk with fatty deposits at the site of injury. Minimal adhesions were observed for CS and HM-CS., Conclusions: The internal safety observed in the HM-CS test group after abdominal implantation indicates that injectable HM-CS expanding foam may be an appropriate internal use hemostatic candidate., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: There are significant racial disparities in pregnancy and postpartum health outcomes, including postpartum weight retention and cardiometabolic risk. These racial disparities are a result of a complex interplay between contextual, environmental, behavioral, and psychosocial factors., Objective: This protocol provides a description of the development and infrastructure for the Postpartum Mothers Mobile Study (PMOMS), designed to better capture women's daily experiences and exposures from late pregnancy through 1 year postpartum. The primary aims of PMOMS are to understand the contextual, psychosocial, and behavioral factors contributing to racial disparities in postpartum weight and cardiometabolic health, with a focus on the daily experiences of stress and racism, as well as contextual forms of stress (eg, neighborhood stress and structural racism)., Methods: PMOMS is a longitudinal observation study that is ancillary to an existing randomized control trial, GDM 2 (Comparison of Two Screening Strategies for Gestational Diabetes). PMOMS uses an efficient and cost-effective approach for recruitment by leveraging the infrastructure of GDM 2 , facilitating enrollment of participants while consolidating staff support from both studies. The primary data collection method is ecological momentary assessment (EMA) and through smart technology (ie, smartphones and scales). The development of the study includes: (1) the pilot phase and development of the smartphone app; (2) feedback and further development of the app including selection of key measures; and (3) implementation, recruitment, and retention., Results: PMOMS aims to recruit 350 participants during pregnancy, to be followed through the first year after delivery. Recruitment and data collection started in December 2017 and are expected to continue through September 2020. Initial results are expected in December 2020. As of early May 2019, PMOMS recruited a total of 305 participants. Key strengths and features of PMOMS have included data collection via smartphone technology to reduce the burden of multiple on-site visits, low attrition rate because of participation in an ongoing trial in which women are already motivated and enrolled, high EMA survey completion and the use of EMA as a unique data collection method to understand daily experiences, and shorter than expected timeframe for enrollment because of the infrastructure of the GDM 2 trial., Conclusions: This protocol outlines the development of the PMOMS, one of the first published studies to use an ongoing EMA and mobile technology protocol during pregnancy and throughout 1 year postpartum to understand the health of childbearing populations and enduring racial disparities in postpartum weight and cardiometabolic health. Our findings will contribute to the improvement of data collection methods, particularly the role of EMA in capturing multiple exposures and knowledge in real time. Furthermore, the results of the study will inform future studies investigating weight and cardiometabolic health during pregnancy and the postpartum period, including how social determinants produce population disparities in these outcomes., International Registered Report Identifier (irrid): DERR1-10.2196/13569., (©Dara D Mendez, Sarah A Sanders, Hassan A Karimi, Pedram Gharani, Stephen L Rathbun, Tiffany L Gary-Webb, Meredith L Wallace, John J Gianakas, Lora E Burke, Esa M Davis. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 26.06.2019.)

Objective: To evaluate long-term outcomes and identify factors associated with death or the need for revision surgery in dogs with permanent tracheostomies (PTs)., Design: Retrospective cohort study., Animals: 69 client-owned dogs that received a PT between January 2002 and June 2016 at 1 of 4 veterinary teaching hospitals., Procedures: Medical records were reviewed, and data extracted included signalment, history, clinical signs, radiographic and laryngeal examination findings, presence of esophageal abnormalities, date and reason for receiving a PT, postoperative complications, cause of death, and survival time. Dogs surviving < 2 weeks after receiving a PT were excluded., Results: Major complications occurred in 42 of 69 (61%) dogs, with aspiration pneumonia (13 [19%]), skinfold occlusion (13 [19%]), and stoma stenosis (12 [17%]) being most common. Revision surgery was performed in 24 of 69 (35%) dogs, most commonly because of stoma stenosis or skinfold occlusion (9/24 [38%] each). Brachycephalic dogs were more likely (OR, 3.5; 95% confidence interval, 1.2 to 10.2) to require revision surgery than were nonbrachycephalic dogs. The overall median survival time was 1,825 days, and dogs that received corticosteroids before receiving a PT, had tracheal collapse, or were older had shorter survival times., Conclusions and Clinical Relevance: Results of the present study indicated that creation of a PT was a viable treatment option for obstructive upper airway diseases in dogs and that long-term survival after receiving a PT was possible; however, a PT may not reduce the risk of aspiration pneumonia in dogs.

Background: Cognitive behavioral therapy (CBT) is the gold standard treatment for adult anxiety disorders but is often not readily available in a scalable manner in many clinical settings., Objective: This study examines the feasibility, acceptability, and effectiveness of a coach-facilitated digital cognitive behavioral program for anxious adults in primary care., Methods: In an open trial, patients who screened positive for anxiety (General Anxiety Disorder-7 [GAD7] score ≥5) were offered the digital cognitive behavioral program (active group, n=593). Primary outcomes included anxiety, quality of life (QoL), and ambulatory medical use over 6 months. Intent-to-treat (ITT) and modified intent-to-treat (mITT) analyses were completed. Subsequently, we compared the outcomes of participants with those of a matched control group receiving primary care as usual (CAU; n=316)., Results: More than half of the patients downloaded the cognitive behavioral mobile app program and about 60% of these were considered engaged, which was defined as completion of ≥3 techniques. The active group demonstrated medium size effects on reducing anxiety symptoms (effect size d=0.44; P<.001) and improving mental health QoL (d=0.49; P<.001) and showed significantly improved physical health QoL (d=0.39; P=.002) and a decreased likelihood of high utilization of outpatient medical care (odds ratio=0.49; P<.001). The active group did not significantly outperform the CAU group in anxiety reduction or QoL improvement (d=0.20; P=.07). However, intent-to-treat analysis showed that the active group had a significantly lower likelihood of high utilization of outpatient medical care than the enhanced CAU group (P<.0001; odds ratio=0.09)., Conclusions: A coach-facilitated digital cognitive behavioral program prescribed in primary care is feasible and acceptable. Primary care patients prescribed a digital cognitive behavioral program for anxiety experienced significant improvements in anxiety symptoms, QoL, and reduced medical utilization. This effect was observed even among patients with chronic medical conditions and behavioral health comorbidities. Although the primary outcomes in the active group did not improve significantly more than the CAU group, health care utilization declined, and some secondary outcomes improved in participants who engaged in the program compared to the CAU group., Trial Registration: ClinicalTrials.gov NCT03186872; https://clinicaltrials.gov/ct2/show/NCT03186872., (©Megan Oser, Meredith L Wallace, Francis Solano, Eva Maria Szigethy. Originally published in JMIR Mental Health (http://mental.jmir.org), 04.04.2019.)

Food cue-reactivity tasks are used to induce and evaluate food cravings. Extant research has implicated the role of tasting foods in heightening cue-elicited food craving. The present study was the first to evaluate a taste manipulation during a food cue-reactivity task to optimize cue-elicited craving and predict food intake. Participants with overweight/obesity (N = 35; M age = 33.46 years [SD = 13.27]; M BMI = 32.91 kg/m 2 [SD = 5.34]) engaged in one laboratory session and were randomized to a 'No Taste' or 'Taste' condition. All participants reported baseline food craving and observed two types of high-calorie food cues during a cue-reactivity task: photographic and real foods. The Taste group tasted real food cues and the No Taste group did not. Cue-elicited craving was assessed after the presentation of each food cue. Calorie intake of palatable foods was subsequently measured during a bogus taste test. Results indicated that cue-elicited craving to high-calorie foods was greater for the No Taste relative to the Taste group and that calorie intake was greater for the Taste relative to the No Taste group; both effects were nonsignificant, but of medium-size. Cue-elicited craving was significantly greater following exposure to high-calorie real food cues compared to photographic food cues. Results provide initial evidence that presenting high-calorie real (vs. photographic) food cues and forgoing taste manipulation during a food cue-reactivity task may optimize cue-elicited craving, and that taste manipulation could increase subsequent food intake. Future research should be conducted to replicate findings in larger samples with greater power to detect significant effects., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Two hip quality phenotypes-a hip-extended score assigned by a board certified radiologist and the PennHIP distraction index-were analyzed to estimate genetic parameters and to calculate estimated breeding values used for selecting replacement breeders. Radiographs obtained at 12-18 months of age were available on 5,201 German Shepherd Dogs, 4,987 Labrador Retrievers and 2,308 Golden Retrievers. Obtained by fitting a two-trait model using Bayesian techniques, estimates of heritability for the hip-extended score were 0.76, 0.72, and 0.41 in German Shepherd Dogs, Labrador Retrievers, and Golden Retrievers, respectively, while estimated heritabilities for distraction index were 0.60, 0.66 and 0.59, respectively. Genetic correlations between the two hip quality measures were -0.28 in German Shepherd Dogs, -0.21 in Labrador Retrievers, and -0.29 in Golden Retrievers. Genetic selection for improved hip quality based upon the hip extended score phenotype began in 1980. Among first generation puppies, 34% of 273 German Shepherd Dogs, 55% of 323 Labrador Retrievers, and 43% of 51 Golden Retrievers had an Excellent hip extended score. After 8 generations of selection, mostly based on estimated breeding values derived from the hip extended score, over 93% of 695 German Shepherd Dogs, 94% of 528 Labrador Retrievers, and 87% of 116 Golden Retrievers received an Excellent hip extended score. With respect to PennHIP distraction index values among these same dogs, median values were at or above 0.30 for all 3 breeds meaning that half or more of dogs possessing the Excellent hip-extended-score phenotype remained susceptible to developing the osteoarthritis of canine hip dysplasia. Genetic improvement of the hip-extended-view phenotype to its desired biological endpoint left a surprising proportion of dogs expressing sufficient joint laxity to place them in an osteoarthritis at-risk state as they age. Only by directly applying selection pressure to reduce distraction index was marked reduction in joint laxity noted., Competing Interests: Most of the data collection for this publication occurred while PennHIP was a not-for-profit service wholly owned and operated by the University of Pennsylvania. In December, 2013 PennHIP was acquired by Antech Imaging Services of Fountain Valley, CA, United States of America. Antech Imaging Services is a segment of VCAAntech, which was purchased in 2018 by Mars, Inc. Since 2013 PennHIP has been a for-profit diagnostic service available world-wide. Dr. Gail K. Smith is currently an employee of Antech Imaging Services, where he is the Director of AIS PennHIP. The Seeing Eye, Inc. is a not-for-profit charity with a focused mission to provide healthy, well-trained dogs to serve as guides for blind people. In pursuit of this mission, The Seeing Eye has, occasionally, funded targeted research in areas of canine health. One such project was to develop an improved, alternative method for assessing hip quality in young dogs. Funding for much of this targeted research support was channeled through Morris Animal Foundation, who provides oversight and an established peer-review process for awarding research grants. Some of the funds dispensed by Morris Animal Foundation for developing the distraction index method originated with The Seeing Eye, Inc. During some of the years when this funding support was provided by The Seeing Eye, Drs. Eldin A. Leighton and Dolores Holle were employed by The Seeing Eye and participated in the decision-making process that led to this funding support. After the PennHIP program was established as a service provided by the University of Pennsylvania and later by AIS, The Seeing Eye was a consumer of the service, obtaining PennHIP scores on thousands of dogs under contract with the University of Pennsylvania and later with AIS. The Seeing Eye holds no patents or income producing interest in PennHIP. Our disclosure of these relationships is intended to provide transparency to our readers. Furthermore, these relationships do not alter our adherence to PLOS ONE policies on sharing data and materials.

Comparing the neural outcomes of two randomized experimental groups is a primary aim of many functional neuroimaging studies. However, between-group effects can be obscured by heterogeneity in neural responses. Optimal Combined Moderator (OCM) approaches have previously been used to clarify heterogeneity in clinical outcomes following treatment randomization. We show that OCMs can also be used to clarify heterogeneity in the effect of a randomized experimental condition on neural responses. In 78 healthy adults aged 18-30 from the Effects of Dose-Dependent Sleep Disruption on Fear and Reward (SFeRe) study, we used demographic, clinical, genetic, and polysomnographic characteristics to develop OCMs for the effect of a randomized sleep restriction (SR) versus normal sleep (NS) condition on blood-oxygen-level dependent responses in the right amygdala (RAmyg) and subgenual anterior cingulate cortex (sgACC) during fear conditioning (FC) and extinction (FE) paradigms. The OCM for the RAmyg during FE was strongest [r (95% CI) = 0.52 (0.42, 0.68)], withstood cross-validation, and divided the sample into two subgroups with opposing experimental effects. Among N = 48 participants ("SR < NS"), those with SR exhibited less RAmyg activation during FE than those with NS [d (95%CI) = -1.10 (-1.86, -0.77)]. Among the remaining N = 30 participants ("SR > NS"), those with SR exhibited greater RAmyg activation during FE following SR than those with NS [d (95%CI) = 0.87 (0.37,1.78)]. SR > NS participants were more likely to be female, white, l/l genotype carriers, and have a psychiatric history. They had less sleep (overall and in REM), lower REM density, and lower spindle activity (12-16 Hz). Applying OCMs to randomized studies with neural outcomes can clarify neural heterogeneity and jumpstart mechanistic research; with further validation they also offer promise for personalized brain-based treatments and interventions., (Copyright © 2018. Published by Elsevier Inc.)

Objective: To report outcomes and risk factors for mortality in dogs that underwent surgical management of lung lobe torsion., Study Design: Retrospective case series from 5 veterinary teaching hospitals (2005-2017)., Animals: Fifty dogs with 52 instances of lung lobe torsion., Methods: Data collected from medical records included signalment, clinical findings, results of clinicopathologic testing and diagnostic imaging, surgical treatment, lung lobe affected, intraoperative and postoperative complications, histopathologic and microbiologic findings, and outcome. Follow-up was obtained from medical records and telephone contact with primary care veterinarians., Results: Fifty-two instances of lung lobe torsion were identified in 50 dogs, with a median follow-up of 453 days (range, 0-3075). Forty-six (92%) dogs survived to discharge. Dogs with concurrent torsion of the right cranial and middle lung lobes were less likely to survive (2/4) than those with torsion of the left cranial lung lobe (22/22). No other risk factors for mortality prior to hospital discharge were identified. Overall median survival time after hospital discharge was 1369 days. Four dogs had >1 episode of lung lobe torsion., Conclusion: The percentage of dogs surviving to discharge after surgical treatment of lung lobe torsion was higher than previously reported. The short- and long-term prognosis was excellent with surgical treatment of lung lobe torsion., Clinical Significance: Surgery should be recommended when lung lobe torsion is suspected because of the high survival to discharge rate and excellent long-term prognosis., (© 2018 The American College of Veterinary Surgeons.)

The purpose of this study was to evaluate owner perception of outcome following permanent tracheostomy (PT) in dogs. Medical records of dogs who received PT from 2002 to 2016 were reviewed. A questionnaire was given to owners verbally or by e-mail to ascertain their perception of their dog's outcome after PT. Median time to questionnaire administration from PT surgery was 608 days (64-3,708). Owner satisfaction after PT was high (89.7%), with the majority stating they would have the procedure performed again (79.5%). Owners reported an improvement in their dog's personality (30.8%) and increased activity (41%). Median survival time was 1,825 days (64-2,663), with 6 of 39 dogs (15.4%) alive at study end. Of the 33 dogs who died, 11 (33.3%) died from underlying respiratory conditions suspected to be related to the PT. The overall complication rate was 82.1%, with mucus secretion being the most common. Revision surgery was required in 30.8% of dogs (most commonly due to skin occlusion), and aspiration pneumonia occurred in 17.9% of dogs. Overall, owner satisfaction after PT in dogs is high despite intensive postoperative management, and long survival times can be achieved.

Objective: To determine the ability of a polyacrylic acid-silicone radiolucent self-retaining gradual occlusion device (PAS-OD) to attenuate congenital extrahepatic portosystemic shunts (EHPSS) in dogs., Study Design: Prospective clinical trial., Animals: Six client-owned dogs with single, congenital EHPSS., Methods: Serum bile acids (SBA), abdominal ultrasonography, and computed tomographic angiography (CTA) were performed preoperatively and at 4 and 8 weeks postoperatively. Each dog was treated for EHPSS by placement of a PAS-OD., Results: PAS-OD were placed without complication an average of 4.3 seconds (range, 3-7) after isolation of the shunt. Median surgical time was 38.5 minutes (range, 28-84) including concurrent procedures. All dogs recovered from surgery without complications. SBA were normal in 5 of 6 dogs at 4 and 8 weeks after surgery. The shunt was completely attenuated in 2 of 6 dogs at 4 weeks and in 4 of 6 dogs at 8 weeks, without evidence of acquired shunt formation in any dog. The size and velocity of the portal vasculature were improved in 5 of 6 dogs according to 8-week postoperative CTA and ultrasonography results, respectively. The remaining dog had a persistently decreased portal vasculature size but a normal velocity according to 8-week postoperative CTA and ultrasound results, respectively., Conclusion: The PAS-OD led to complete attenuation in 4 of 6 dogs and partial attenuation with mild residual flow of 2 EHPSS over an 8-week period in dogs., Clinical Significance: The PAS-OD is a new option for gradual occlusion of congenital EHPSS over 8 weeks., (© 2018 The American College of Veterinary Surgeons.)

Medical records of 17 client-owned dogs diagnosed with os clitoris on physical examination or diagnostic imaging were reviewed to describe the clinical signs and surgical management of this condition. All dogs were phenotypically female. The most common presenting complaints included an enlarged clitoris ( n = 10), urinary tract infection ( n = 5), and licking of the vulva ( n = 3). Other frequently reported clinical signs included vaginal discharge and/or lower urinary tract signs such as pollakiuria. Ten dogs were surgically managed with os clitorectomy. Concurrent related procedures included gonadohysterectomy ( n = 7), and episioplasty ( n = 3). Clitorectomy in the surgically managed dogs created a more normal female anatomy and resolved clinical signs associated with the exposed clitoris.

Study Objectives: Sleep is multidimensional, with domains including duration, timing, continuity, regularity, rhythmicity, quality, and sleepiness/alertness. Individual sleep characteristics representing these domains are known to predict health outcomes. However, most studies consider sleep characteristics in isolation, resulting in an incomplete understanding of which sleep characteristics are the strongest predictors of health outcomes. We applied three multivariable approaches to robustly determine which sleep characteristics increase mortality risk in the osteoporotic fractures in men sleep study., Methods: In total, 2,887 men (mean 76.3 years) completed relevant assessments and were followed for up to 11 years. One actigraphy or self-reported sleep characteristic was selected to represent each of seven sleep domains. Multivariable Cox models, survival trees, and random survival forests were applied to determine which sleep characteristics increase mortality risk., Results: Rhythmicity (actigraphy pseudo-F statistic) and continuity (actigraphy minutes awake after sleep onset) were the most robust sleep predictors across models. In a multivariable Cox model, lower rhythmicity (hazard ratio, HR [95%CI] =1.12 [1.04, 1.22]) and lower continuity (1.16 [1.08, 1.24]) were the strongest sleep predictors. In the random survival forest, rhythmicity and continuity were the most important individual sleep characteristics (ranked as the sixth and eighth most important among 43 possible sleep and non-sleep predictors); moreover, the predictive importance of all sleep information considered simultaneously followed only age, cognition, and cardiovascular disease., Conclusions: Research within a multidimensional sleep health framework can jumpstart future research on causal pathways linking sleep and health, new interventions that target specific sleep health profiles, and improved sleep screening for adverse health outcomes., (© Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.)

Postoperative seizures occur in 5-12% of dogs following surgical attenuation of congenital extrahepatic portosystemic shunts (CEPSS) and are often refractory to treatment. Because pugs are predisposed to necrotizing meningoencephalitis, they may be at higher risk of developing neurologic complications after CEPSS attenuation. We hypothesized that pugs have a higher prevalence of postoperative neurologic complications and that pugs who died due to neurologic complications would have evidence of encephalitis at necropsy. Records were searched for pugs that had undergone surgical correction of a single extrahepatic CEPSS. Fourteen pugs met the inclusion criteria and were compared with a control group of 30 dogs of varying breeds who also underwent surgical attenuation for a single CEPSS. Four of 14 pugs (28.6%) died or were euthanized within 1 mo after surgery for neurologic complications, compared with only 1 of 30 dogs in the control group (P < .029). No evidence of necrotizing meningoencephalitis was seen on necropsy. Pugs may be at an increased risk of developing fatal neurologic complications following surgical attenuation for CEPSS. Further studies are indicated to investigate reasons for this increased risk, as well as to determine any factors that may indicate which pugs are at higher risk.

In sleep research, applying finite mixture models to sleep characteristics captured 8 through multiple data types, including self-reported sleep diary, a wrist monitor capturing movement (actigraphy), and brain waves (polysomnography), may suggest new phenotypes that reflect underlying disease mechanisms. However, a direct mixture model application is challenging because there are many sleep variables from which to choose, and sleep variables are often highly skewed even in homogenous samples. Moreover, previous sleep research findings indicate that some of the most clinically interesting solutions will be those that incorporate all three data types. Thus, we present two novel skewed variable selection algorithms based on the multivariate skew normal (MSN) distribution: one that selects the best set of variables ignoring data type and another that embraces the exploratory nature of clustering and suggests multiple statistically plausible sets of variables that each incorporate all data types. Through a simulation study we empirically compare our approach with other asymmetric and normal dimension reduction strategies for clustering. Finally, we demonstrate our methods using a sample of older adults with and without insomnia. The proposed MSN-based variable selection algorithm appears to be suitable for both MSN and multivariate normal cluster distributions, especially with moderate to large sample sizes.

Limbic white matter pathways link emotion, cognition, and behavior and are potentially malleable to the influences of traumatic events throughout development. However, the impact of interactions between childhood and later life trauma on limbic white matter pathways has yet to be examined. Here, we examined whether childhood maltreatment moderated the effect of combat exposure on diffusion tensor imaging measures within a sample of military veterans (N = 28). We examined five limbic tracts of interest: two components of the cingulum (cingulum, cingulate gyrus, and cingulum hippocampus [CGH]), the uncinate fasciculus, the fornix/stria terminalis, and the anterior limb of the internal capsule. Using effect sizes, clinically meaningful moderator effects were found only within the CGH. Greater combat exposure was associated with decreased CGH fractional anisotropy (overall structural integrity) and increased CGH radial diffusivity (perpendicular water diffusivity) among individuals with more severe childhood maltreatment. Our findings provide preliminary evidence of the moderating effect of childhood maltreatment on the relationship between combat exposure and CGH structural integrity. These differences in CGH structural integrity could have maladaptive implications for emotion and memory, as well as provide a potential mechanism by which childhood maltreatment induces vulnerability to later life trauma exposure.

Background: The past decade of research has seen considerable interest in computer-based approaches designed to directly target cognitive mechanisms of anxiety, such as attention bias modification (ABM)., Methods: By pooling patient-level datasets from randomized controlled trials of ABM that utilized a dot-probe training procedure, we assessed the impact of training "dose" on relevant outcomes among a pooled sample of 693 socially anxious adults., Results: A paradoxical effect of the number of training trials administered was observed for both posttraining social anxiety symptoms and behavioral attentional bias (AB) toward threat (the target mechanism of ABM). Studies administering a large (>1,280) number of training trials showed no benefit of ABM over control conditions, while those administering fewer training trials showed significant benefit for ABM in reducing social anxiety (P = .02). These moderating effects of dose were not better explained by other examined variables and previously identified moderators, including patient age, training setting (laboratory vs. home), or type of anxiety assessment (clinician vs. self-report)., Conclusions: Findings inform the optimal dosing for future dot-probe style ABM applications in both research and clinical settings, and suggest several novel avenues for further research., (© 2017 Wiley Periodicals, Inc.)

Resistive-pulse sensing is a label-free method for characterizing individual particles as they pass through ion-conducting channels or pores. During a resistive pulse experiment, the ionic current through a conducting channel is monitored as particles suspended in the solution translocate through the channel. The amplitude of the current decrease during a translocation, or 'pulse', depends not only on the ratio of the particle and channel sizes, but also on the particle position, which is difficult to resolve with the resistive pulse signal alone. We present experiments of simultaneous electrical and optical detection of particles passing through microfluidic channels to resolve the positional dependencies of the resistive pulses. Particles were tracked simultaneously in the two signals to create a mapping of the particle position to resistive pulse amplitude at the same instant in time. The hybrid approach will improve the accuracy of object characterization and will pave the way for observing dynamic changes of the objects such as deformation or change in orientation. This combined approach of optical detection and resistive pulse sensing will join with other attempts at hybridizing high-throughput detection techniques such as imaging flow cytometry.

It is firmly established that many mammalian neurons release various combinations of amino acids, their derivatives, and other small molecules from presynaptic terminals in order to signal to their postsynaptic targets. Here we discuss recent findings about four types of multi-transmitter neurons-those that release GABA and acetylcholine (Ach); dopamine (DA) and GABA or glutamate; and glutamate and GABA. The mechanisms of co-release in each class differ and highlight the complex and dynamic nature of neurotransmitter release. Furthermore, identifying the neurotransmitter signature of each neuron and the post-synaptic targets of each neurotransmitter remain challenging. The existence of multi-transmitter neurons complicates the interpretation of connectomic wiring diagrams and poses interesting challenges for our understanding of circuit function in the brain., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Angelman syndrome (AS) is a neurodevelopmental disorder caused by loss of the maternally inherited allele of UBE3A Ube3a STOP/p+ mice recapitulate major features of AS in humans and allow conditional reinstatement of maternal Ube3a with the expression of Cre recombinase. We have recently shown that AS model mice exhibit reduced inhibitory drive onto layer (L)2/3 pyramidal neurons of visual cortex, which contributes to a synaptic excitatory/inhibitory imbalance. However, it remains unclear how this loss of inhibitory drive affects neural circuits in vivo. Here we examined visual cortical response properties in individual neurons to explore the consequences of Ube3a loss on intact cortical circuits and processing. Using in vivo patch-clamp electrophysiology, we measured the visually evoked responses to square-wave drifting gratings in L2/3 regular-spiking (RS) neurons in control mice, Ube3a -deficient mice, and mice in which Ube3a was conditionally reinstated in GABAergic neurons. We found that Ube3a -deficient mice exhibited enhanced pyramidal neuron excitability in vivo as well as weaker orientation tuning. These observations are the first to show alterations in cortical computation in an AS model, and they suggest a basis for cortical dysfunction in AS. NEW & NOTEWORTHY Angelman syndrome (AS) is a severe neurodevelopmental disorder caused by the loss of the gene UBE3A Using electrophysiological recording in vivo, we describe visual cortical dysfunctions in a mouse model of AS. Aberrant cellular properties in AS model mice could be improved by reinstating Ube3a in inhibitory neurons. These findings suggest that inhibitory neurons play a substantial role in the pathogenesis of AS., (Copyright © 2017 the American Physiological Society.)

The basal ganglia (BG) integrate inputs from diverse sensorimotor, limbic, and associative regions to guide action-selection and goal-directed behaviors. The entopeduncular nucleus (EP) is a major BG output nucleus and has been suggested to channel signals from distinct BG nuclei to target regions involved in diverse functions. Here we use single-cell transcriptional and molecular analyses to demonstrate that the EP contains at least three classes of projection neurons-glutamate/GABA co-releasing somatostatin neurons, glutamatergic parvalbumin neurons, and GABAergic parvalbumin neurons. These classes comprise functionally and anatomically distinct output pathways that differentially affect EP target regions, such as the lateral habenula (LHb) and thalamus. Furthermore, LHb- and thalamic-projecting EP neurons are differentially innervated by subclasses of striatal and pallidal neurons. Therefore, we identify previously unknown subdivisions within the EP and reveal the existence of cascading, molecularly distinct projections through striatum and globus pallidus to EP targets within epithalamus and thalamus., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Do day-to-day emotions, social interactions, and sleep play a role in determining which anxious youth respond to supportive child-centered therapy (CCT) versus cognitive behavioral therapy (CBT)? We explored whether measures of day-to-day functioning (captured through ecological momentary assessment, sleep diary, and actigraphy), along with clinical and demographic measures, were predictors or moderators of treatment outcome in 114 anxious youth randomized to CCT or CBT. We statistically combined individual moderators into a single, optimal composite moderator to characterize subgroups for which CCT or CBT may be preferable. The strongest predictors of better outcome included: (a) experiencing higher positive affect when with one's mother and (b) fewer self-reported problems with sleep duration. The composite moderator indicated that youth for whom CBT was indicated had: (a) more day-to-day sleep problems related to sleep quality, efficiency, and waking, (b) day-to-day negative events related to interpersonal concerns, (c) more DSM-IV anxiety diagnoses, and (d) college-educated parents. These findings illustrate the value of both day-to-day functioning characteristics and more traditional sociodemographic and clinical characteristics in identifying optimal anxiety treatment assignment. Future studies will need to enhance the practicality of real-time measures for use in clinical decision making and evaluate additional anxiety treatments., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Individuals diagnosed with bipolar 1 disorder (BP1), bipolar 2 disorder (BP2), or major depressive disorder (MDD) experience varying levels of depressive and (hypo)manic symptoms. Clarifying symptom heterogeneity is meaningful, as even subthreshold symptoms may impact quality of life and treatment outcome. The MOODS Lifetime self-report instrument was designed to capture the full range of depressive and (hypo)manic characteristics., Methods: This study applied clustering methods to 347 currently depressed adults with MDD, BP2, or BP1 to reveal naturally occurring MOODS subgroups. Subgroups were then compared on baseline clinical and demographic characteristics and as well as depressive and (hypo)manic symptoms over twenty weeks of treatment., Results: Four subgroups were identified: (1) high depressive and (hypo)manic symptoms (N=77, 22%), (2) moderate depressive and (hypo)manic symptoms (N=115, 33%), (3) low depressive and moderate (hypo)manic symptoms (N=82, 24%), and (4) low depressive and (hypo)manic symptoms (N=73, 21%). Individuals in the low depressive/moderate (hypo)manic subgroup had poorer quality of life and greater depressive symptoms over the course of treatment. Individuals in the high and moderate severity subgroups had greater substance use, longer duration of illness, and greater (hypo)manic symptoms throughout treatment. Treatment outcomes were primarily driven by individuals diagnosed with MDD., Limitations: The sample was drawn from three randomized clinical trials. Validation is required for this exploratory study., Conclusions: After validation, these subgroups may inform classification and personalized treatment beyond categorical diagnosis., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Personalizing treatment for late-life depression requires identifying and integrating information from multiple factors that influence treatment efficacy (moderators). We performed exploratory moderator analyses using data from a multi-site, randomized, placebo-controlled, double-blind trial of aripiprazole augmentation. Patients (n = 159) aged ≥60 years had major depressive disorder that failed to remit with venlafaxine monotherapy. We examined effect sizes of 39 potential moderators of aripiprazole (vs. placebo) augmentation efficacy using the outcome of percentage reduction in depressive symptom after 12 weeks. We then incorporated information from the individually relevant variables in combined moderators. A larger aripiprazole treatment effect was related to: white race, better physical function, better performance on Trail-Making, attention, immediate, and delayed memory tests, greater psychomotor agitation and suicidality symptoms, and a history of adequate antidepressant pharmacotherapy. A smaller aripiprazole treatment effect was observed in patients with: more pain and more work/activity impairment and libido symptoms. Combining information from race and Trail-Making test performance (base combined moderator (Mb*)) produced a larger effect size (Spearman effect size = 0.29 (95% confidence interval (CI): 0.15, 0.42)) than any individual moderator. Adding other individually relevant moderators in the full combined moderator (Mf*) further improved effect size (Spearman effect size = 0.39 (95% CI: 0.25, 0.52)) and identified a sub-group benefiting more from placebo plus continuation venlafaxine monotherapy than adjunctive aripiprazole. Combining moderators can help clinicians personalize depression treatment. We found the majority of our patients benefited from adjunctive aripiprazole, but a smaller subgroup that is identifiable using clinical measures appeared to benefit more from continuation venlafaxine plus placebo., Competing Interests: SFS, MLW, BSD, MAB, MAD, SJA, FEL have no conflicts of interest to declare. Dr. Lenze reports current grants from NIH (NIA, NCCIH, NIMH, OBSSR), grants from FDA, grants from McKnight Brain Research Foundation, grants from Taylor Family Institute for Innovative Psychiatric Research, grants from Barnes Jewish Foundation, grants from Takeda, grants from Lundbeck, and past grants from Roche, Sidney R. Baer Foundation, that did not influence the submitted work. Dr. Reynolds III, MD reports grants from National Institute of Health (NIH), grants from Center for Medicare and Medicaid Services (CMS), grants from Patient Centered Outcomes Research Institute (PCORI), grants from John A. Hartford Foundation, grants from American Foundation for Suicide Prevention, grants from Commonwealth of Pennsylvania, grants from Clinical and Translational Science Institute (CTSI), grants from National Palliative Care Research Center (NPCRC), during the conduct of the study; personal fees from American Association for Geriatric Psychiatry, personal fees from UPMC Endowment in Geriatric Psychiatry, an speakers honorarium from Medscape/WebMD did not influence the submitted work; in addition, Dr. Reynolds III, MD has a patent Psychometric analysis of the Pittsburgh Sleep Quality Index (PSQI) with royalties paid to Dr. Daniel Buysse. Bristol Meyers Squibb, Forrest Labs, Lily, Pfizer provide pharmaceutical supplies for NIH-sponsored work (these pharmaceutical companies play no role in the design, analysis, or reporting of my data in peer reviewed journals). Dr. Blumberger reports other from Tonika Magventure, grants from Canadian Institutes of Health Research, grants from National Institute of Health, other from Brain Research and Development Services, grants from Brain Canada, did not influence the submitted work. Dr. Mulsant reports grants from National Institute of Mental Health (NIMH, USA), non-financial support from Pfizer, non-financial support from Bristol-Myers-Squibb, during the conduct of the study; grants from Brain Canada, grants from Canadian Institutes of Health Research, grants from US National Institute of Health, grants from Centre for Addiction and Mental Health Foundation, non-financial support from Eli Lilly, non-financial support from General Electric, did not influence the submitted work. Dr. Karp reports receipt of medication supplies for investigator initiated studies from Pfizer and Invidior that did not influence the submitted work., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: The first generation of South African (SA) children perinatally infected with HIV is entering adulthood, and there is now a pressing need for systematised transfer of these patients from paediatric to adult care., Objectives: Previous research has investigated the HIV healthcare transition in North America and Europe, yet none has been conducted in SA. Our study is the first to describe the perspectives of healthcare providers overseeing the transition in resource-limited settings., Methods: We approached healthcare providers working in government paediatric HIV clinics and hospitals in the Western Cape Province, SA. Seven physicians and counsellors in adolescent/paediatric care, representing five clinics, were interviewed, and 43 completed a written survey. Interviews addressed the current state of the transition, barriers and facilitators, and model components. Interviews were assessed for major themes using framework analysis, while logistic regression was applied to survey responses to identify associations with measured covariates., Results: Analysis of interview transcripts revealed several overarching perspectives that were corroborated by survey responses. One barrier identified was the healthcare providers' difficulty in letting go of their relationships with the adolescent patients. Since healthcare providers regarded their patients as particularly vulnerable, they felt a strong and protective attachment towards them. A second barrier identified was a lack of structure and effective communication between adult and paediatric providers; accordingly, healthcare providers feared that they were transferring their adolescents unprepared, to a judgemental, depersonalised and overburdened environment. All interviewees and a majority of survey respondents (&gt;80%) agreed that the formation of adolescent support groups in adult care clinics as well as a later transition age would improve the transition process., Conclusion: This study highlights the need for a systematic healthcare transition for HIV-positive adolescents cared for in the Western Cape, while acknowledging the limitations of the current healthcare infrastructure. Several feasible recommendations have been identified, including forming support groups and greater involvement of adolescent healthcare providers to facilitate the transition.

Objective: The goal of this study was to explore the association of timing of and frequency of meals with markers of cardiometabolic risk in patients with bipolar disorder in out-patient maintenance treatment., Methods: We used Pittsburgh Sleep Diary and actigraphy measures for individuals with bipolar I disorder. Linear and logistic regression analyses were used to determine whether dinnertime, instability of dinnertime, and/or interval between meals were associated with metabolic syndrome and its components., Results: Later dinnertime was associated with greater waist circumference (β = 0.25, P = 0.02) after adjusting for age, sex, dinner-to-bed interval, and sleep duration. Longer breakfast-to-lunch intervals were also associated with greater waist circumferences (β =-.35, P = .002) after adjusting for age, sex, and sleep duration. Neither instability of dinnertime nor number of meals per day was associated with the metabolic syndrome or its components., Conclusion: Weight gain is often perceived as inevitable side-effect of medications. While patients often need to be on medication to function, a more careful lifestyle assessment with attention to social rhythms and timing of activities may be critical not only for mood stability, but also to reduce cardiovascular risk., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

OBJECTIVE To evaluate the closure rate and completeness of closure for a silicone-polyacrylic acid gradual venous occlusion device placed around an intra-abdominal vein to simulate gradual occlusion of an extrahepatic portosystemic shunt. ANIMALS 3 purpose-bred cats and 2 purpose-bred dogs. PROCEDURES The device was surgically placed around an external (cats) or internal (dogs) iliac vein. Computed tomographic angiography was performed at the time of surgery and 2, 4, and 6 weeks after surgery. Ultrasonographic examinations of blood flow through the vein within the device were performed at the time of surgery and at weekly intervals thereafter. Dogs were euthanized 6 weeks after surgery, and the external iliac veins were harvested for histologic examination. RESULTS The prototype gradual venous occlusion device was successfully placed in all animals, and all animals recovered without complications following the placement procedure. The vessel was completely occluded in 2 cats by 6 weeks after surgery, as determined on the basis of results of CT and ultrasonography; there was incomplete occlusion with a luminal diameter of 1.5 mm in the other cat by 6 weeks after surgery. The vessel was completely occluded in both dogs by 6 weeks after surgery. Histologic examination of the external iliac veins obtained from the dogs revealed minimal inflammation of the vessel wall and no thrombus formation. CONCLUSIONS AND CLINICAL RELEVANCE The prototype device induced gradual attenuation of an intra-abdominal vessel over a 6-week period. This device may provide another option for gradual occlusion of extrahepatic portosystemic shunts.

Loss of maternal UBE3A causes Angelman syndrome (AS), a neurodevelopmental disorder associated with severe epilepsy. We previously implicated GABAergic deficits onto layer (L) 2/3 pyramidal neurons in the pathogenesis of neocortical hyperexcitability, and perhaps epilepsy, in AS model mice. Here we investigate consequences of selective Ube3a loss from either GABAergic or glutamatergic neurons, focusing on the development of hyperexcitability within L2/3 neocortex and in broader circuit and behavioral contexts. We find that GABAergic Ube3a loss causes AS-like increases in neocortical EEG delta power, enhances seizure susceptibility, and leads to presynaptic accumulation of clathrin-coated vesicles (CCVs)-all without decreasing GABAergic inhibition onto L2/3 pyramidal neurons. Conversely, glutamatergic Ube3a loss fails to yield EEG abnormalities, seizures, or associated CCV phenotypes, despite impairing tonic inhibition onto L2/3 pyramidal neurons. These results substantiate GABAergic Ube3a loss as the principal cause of circuit hyperexcitability in AS mice, lending insight into ictogenic mechanisms in AS., (Copyright © 2016 Elsevier Inc. All rights reserved.)