Automating the analysis of facial emotion expression dynamics: A computational framework and application in psychotic disorders.

Facial emotion expressions play a central role in interpersonal interactions; these displays are used to predict and influence the behavior of others. Despite their importance, quantifying and analyzing the dynamics of brief facial emotion expressions remains an understudied methodological challenge. Here, we present a method that leverages machine learning and network modeling to assess the dynamics of facial expressions. Using video recordings of clinical interviews, we demonstrate the utility of this approach in a sample of 96 people diagnosed with psychotic disorders and 116 never-psychotic adults. Participants diagnosed with schizophrenia tended to move from neutral expressions to uncommon expressions (e.g., fear, surprise), whereas participants diagnosed with other psychoses (e.g., mood disorders with psychosis) moved toward expressions of sadness. This method has broad applications to the study of normal and altered expressions of emotion and can be integrated with telemedicine to improve psychiatric assessment and treatment.

Corneal Opacity in the United States: An American Academy of Ophthalmology IRIS® Registry (Intelligent Research in Sight) Study.

PURPOSE: This study assesses the case frequencies, underlying causes, and vision outcomes in patients with a diagnosis of corneal opacity in the United States. DESIGN: Retrospective cohort study. PARTICIPANTS: Patients in the IRIS® Registry (Intelligent Research in Sight) who received a diagnosis of corneal opacity between January 1, 2013, and November 30, 2020. METHODS: The IRIS Registry contains demographic and clinical data of 79 887 324 patients who sought treatment at eye clinics during the study period. We identified patients with corneal opacity using International Classification of Diseases (ICD), Ninth and Tenth Revisions, codes of 371 (corneal scar) and H17 (corneal opacity), respectively. The analyzed data comprised demographic parameters including age, sex, race, ethnicity, and geographical location. We evaluated clinical data including laterality, cause, disease descriptors, and best-corrected visual acuity (VA) up to 1 year before the onset (± 30 days), at the time of diagnosis, and at 1 year after diagnosis (± 30 days). MAIN OUTCOME MEASURES: Case frequencies, causes, and vision outcomes in patients with a diagnosis of corneal opacity. RESULTS: We identified 5 220 382 patients who received a diagnosis of corneal opacity and scars using H17 (ICD, Tenth Revision) and 371.0 (ICD, Ninth Revision) codes over 7 years. The case frequency of corneal opacity during the study period was 6535 cases per 100 000 patients (6.5%). The mean age of the patients was 63.36 ± 18.14 years, and most were female (57.6%). In the cohort, 38.39% and 30.00% of patients had bilateral and unilateral corneal opacity, respectively. Most of the patients affected by corneal opacity were White (69.13%), followed by Black or African American (6.84%). Corneal dystrophies (64.66%) were the most common cause of corneal opacity in the study cohort. Visual acuity of the patients worsened significantly because of corneal opacity (0.46 ± 0.74 logarithm of the minimum angle of resolution [logMAR]) and did not improve to the baseline (0.37 ± 0.68 logMAR) after management (0.43 ± 0.77 logMAR). The multiple linear regression analysis showed worse vision outcomes in female patients (compared with male patients), and Asian, Black or African American, and American Indian or Alaska Native (compared with White) patients. Additionally, worse vision outcomes were observed in patients with opacity associated with corneal malformation, degenerative disorders, edema, injury, and ulcer compared with those with hereditary corneal dystrophy. CONCLUSIONS: Our study showed that corneal opacity was diagnosed in 6.5% of patients in the IRIS Registry and primarily associated with corneal dystrophies. The final vision outcomes in patients with corneal opacity were significantly worse compared with baseline. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

A chemical probe targeting the PWWP domain alters NSD2 nucleolar localization.

Nuclear receptor-binding SET domain-containing 2 (NSD2) is the primary enzyme responsible for the dimethylation of lysine 36 of histone 3 (H3K36), a mark associated with active gene transcription and intergenic DNA methylation. In addition to a methyltransferase domain, NSD2 harbors two proline-tryptophan-tryptophan-proline (PWWP) domains and five plant homeodomains (PHDs) believed to serve as chromatin reading modules. Here, we report a chemical probe targeting the N-terminal PWWP (PWWP1) domain of NSD2. UNC6934 occupies the canonical H3K36me2-binding pocket of PWWP1, antagonizes PWWP1 interaction with nucleosomal H3K36me2 and selectively engages endogenous NSD2 in cells. UNC6934 induces accumulation of endogenous NSD2 in the nucleolus, phenocopying the localization defects of NSD2 protein isoforms lacking PWWP1 that result from translocations prevalent in multiple myeloma (MM). Mutations of other NSD2 chromatin reader domains also increase NSD2 nucleolar localization and enhance the effect of UNC6934. This chemical probe and the accompanying negative control UNC7145 will be useful tools in defining NSD2 biology.

Clinical teaching self-efficacy positively predicts professional fulfillment and negatively predicts burnout amongst Thai physicians: a cross-sectional survey.

BACKGROUND: Clinician teachers (physicians who teach in clinical settings) experience considerable psychological challenges in providing both educational training and patient care. This study aimed to determine the prevalence of physician burnout and professional fulfillment, and to identify internal and external factors associated with mental health outcomes among Thai clinician teachers working in non-university teaching hospitals. METHOD: A one-time online questionnaire was completed by physicians at 37 governmental, non-university teaching hospitals in Thailand, with 227 respondents being assessed in the main analyses. Four outcomes were evaluated including burnout, professional fulfillment, quality of life, and intentions to quit. RESULTS: The observed prevalence of professional fulfillment was 20%, and burnout was 30.7%. Hierarchical regression analysis showed a significant internal, psychological predictor (clinical teaching self-efficacy) and external, structural predictors (multiple roles at work, teaching support), controlling for the background variables of gender, years of teaching experience, family roles, and active chronic disease, with clinical teaching self-efficacy positively predicting professional fulfillment (b = 0.29, p ≤.001) and negatively predicting burnout (b = - 0.21, p =.003). CONCLUSIONS: Results highlight the importance of faculty development initiatives to enhance clinical teaching self-efficacy and promote mental health among Thai physicians.

Harnessing imaging tools to guide immunotherapy trials: summary from the National Cancer Institute Cancer Imaging Steering Committee workshop.

As the immuno-oncology field continues the rapid growth witnessed over the past decade, optimising patient outcomes requires an evolution in the current response-assessment guidelines for phase 2 and 3 immunotherapy clinical trials and clinical care. Additionally, investigational tools-including image analysis of standard-of-care scans (such as CT, magnetic resonance, and PET) with analytics, such as radiomics, functional magnetic resonance agents, and novel molecular-imaging PET agents-offer promising advancements for assessment of immunotherapy. To document current challenges and opportunities and identify next steps in immunotherapy diagnostic imaging, the National Cancer Institute Clinical Imaging Steering Committee convened a meeting with diverse representation among imaging experts and oncologists to generate a comprehensive review of the state of the field.

Homoeologous evolution of the allotetraploid genome of Poa annua L.

BACKGROUND: Poa annua (annual bluegrass) is an allotetraploid turfgrass, an agronomically significant weed, and one of the most widely dispersed plant species on earth. Here, we report the chromosome-scale genome assemblies of P. annua's diploid progenitors, P. infirma and P. supina, and use multi-omic analyses spanning all three species to better understand P. annua's evolutionary novelty. RESULTS: We find that the diploids diverged from their common ancestor 5.5 - 6.3 million years ago and hybridized to form P. annua ≤ 50,000 years ago. The diploid genomes are similar in chromosome structure and most notably distinguished by the divergent evolutionary histories of their transposable elements, leading to a 1.7 × difference in genome size. In allotetraploid P. annua, we find biased movement of retrotransposons from the larger (A) subgenome to the smaller (B) subgenome. We show that P. annua's B subgenome is preferentially accumulating genes and that its genes are more highly expressed. Whole-genome resequencing of several additional P. annua accessions revealed large-scale chromosomal rearrangements characterized by extensive TE-downsizing and evidence to support the Genome Balance Hypothesis. CONCLUSIONS: The divergent evolutions of the diploid progenitors played a central role in conferring onto P. annua its remarkable phenotypic plasticity. We find that plant genes (guided by selection and drift) and transposable elements (mostly guided by host immunity) each respond to polyploidy in unique ways and that P. annua uses whole-genome duplication to purge highly parasitized heterochromatic sequences. The findings and genomic resources presented here will enable the development of homoeolog-specific markers for accelerated weed science and turfgrass breeding.

Effectiveness of Microinvasive Glaucoma Surgery in the United States: Intelligent Research in Sight Registry Analysis 2013-2019.

PURPOSE: To evaluate the effectiveness of microinvasive glaucoma surgery (MIGS) with and without concurrent phacoemulsification. DESIGN: Multicenter, retrospective cohort study. PARTICIPANTS: Patients in the Intelligent Research in Sight (IRIS®) Registry who underwent Xen gel stent (ab interno) implantation, endoscopic cyclophotocoagulation (ECP), or goniotomy or canaloplasty from 2013 through 2019. METHODS: Kaplan-Meier survival analysis was used to assess reoperation rates. We defined reoperation as any subsequent glaucoma surgery occurring 1 month to 3 years after the initial procedure. Multivariable Cox proportional hazard models were used to determine factors predictive of reoperation. MAIN OUTCOME MEASURES: Reoperation rate, mean intraocular pressure (IOP) and visual acuity (VA), postoperative complications, predictors of reoperation, and reoperation procedure type. RESULTS: A total of 79 363 eyes from 57 561 patients were included, with 15 118 eyes (19%) receiving stand-alone MIGS and 64 245 eyes (81%) receiving MIGS concurrent with phacoemulsification. Overall, patients who underwent MIGS concurrently with phacoemulsification showed lower reoperation rates compared with stand-alone MIGS, most pronounced in ECP and goniotomy or canaloplasty. At postoperative year 2, the cumulative reoperation rate for stand-alone procedures was 15% for ECP, 24% for Xen implantation, and 24% for goniotomy or canaloplasty compared with 3% for ECP, 19% for Xen implantation, and 6% for goniotomy or canaloplasty concurrent with phacoemulsification (P < 0.001 for each stand-alone MIGS vs. MIGS with phacoemulsification). Black race, older age, moderate and severe glaucoma, higher baseline IOP, and glaucoma subtype were associated with higher reoperation risk. Although IOP decreased in all groups, stand-alone MIGS showed a more substantial decrease in mean IOP. Complication rates from MIGS were low overall: 1% for ECP, 1% for Xen implantation, and 2% for goniotomy or canaloplasty. CONCLUSIONS: In current United States clinical practice, MIGS has substantially lower reoperation rates when performed with phacoemulsification, especially for ECP and goniotomy or canaloplasty. Approximately one-sixth of patients undergoing stand-alone ECP and one-quarter of patients undergoing stand-alone Xen implantation or goniotomy or canaloplasty require reoperation by 2 years. Black race, diagnosis coding of moderate to severe glaucoma, and higher baseline IOP were associated with higher risk of reoperation after MIGS procedures. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Open-Globe Injury Repairs in the American Academy of Ophthalmology IRIS® Registry 2014 - 2018: Incidence, Risk Factors, and Visual Outcomes.

PURPOSE: To estimate incidence and evaluate demographic risk factors and visual acuity (VA) outcomes of open-globe injuries requiring surgical repair in the IRIS® Registry (Intelligent Research in Sight). DESIGN: Retrospective cohort study. PARTICIPANTS: Patients with open-globe injury repairs (OGRs) were identified by Current Procedural Terminology codes (65275, 65280, 65285, 65286, 65235, 65260, and 65265) from 2014 through 2018 in the IRIS Registry. METHODS: Logistic regression models adjusting for age, sex, race, ethnicity, United States region, concurrent and subsequent surgeries, and baseline VA. MAIN OUTCOME MEASURES: Outcomes included annual and 5-year incidence rates per 100 000 people and factors associated with OGR, VA better than 20/40, and VA of 20/200 or worse at final follow-up (3-12 months after OGR). RESULTS: Thirteen thousand seven hundred sixty-six OGRs were identified; 5-year cumulative incidence was 28.0 per 100 000 patients. Open-globe repair was associated with age 21 to 40 years compared with younger than 21 years (odds ratio [OR], 1.6; 95% confidence interval [CI], 1.5-1.7]), male sex (OR, 2.8; 95% CI, 2.7-2.9), Black versus White race (OR, 1.3; 95% CI, 1.2-1.4), Hispanic versus non-Hispanic ethnicity (OR, 1.7; 95% CI, 1.6-1.8), and South (OR, 1.4; 95% CI, 1.3-1.5) and West (OR, 1.3; 95% CI, 1.2-1.4) versus Midwest regions and associated inversely with Asian versus White race (OR, 0.6; 95% CI, 0.6-0.7). Visual acuity outcomes, analyzed in a subset of 2966 patients with VA data available, showed vision impairment (VA < 20/40) at final follow-up was associated with VA of 20/200 or worse at presentation (20/200 better than 20/40; OR, 11.1; 95% CI, 8.0-15.7), older age (e.g., > 80 years vs. < 21 years; OR, 5.8; 95% CI, 3.2-10.7), and Black versus White race (OR, 1.8; 95% CI, 1.3-2.6). Risk factors were similar for VA of 20/200 or worse after OGR. Among the 1063 patients undergoing OGR with VA of 20/200 or worse at presentation, VA did not improve to better than 20/200 at follow-up in 35% of patients (1063/2996). CONCLUSIONS: Our findings bring to light racial disparities in risk of OGR and poor visual outcomes that warrant further exploration. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Dissociation of basolateral and central amygdala effective connectivity predicts the stability of emotion-related impulsivity in adolescents and emerging adults with borderline personality symptoms: a resting-state fMRI study.

BACKGROUND: Borderline personality disorder (BPD) is associated with altered activity in the prefrontal cortex (PFC) and amygdala, yet no studies have examined fronto-limbic circuitry in borderline adolescents and emerging adults. Here, we examined the contribution of fronto-limbic effective connectivity (EC) to the longitudinal stability of emotion-related impulsivity, a key feature of BPD, in symptomatic adolescents and young adults. METHODS: We compared resting-state EC in 82 adolescents and emerging adults with and without clinically significant borderline symptoms (n BPD = 40, ages 13-30). Group-specific directed networks were estimated amongst fronto-limbic nodes including PFC, ventral striatum (VS), central amygdala (CeN), and basolateral amygdala (BLA). We examined the association of directed centrality metrics with initial levels and rates of change in emotion-related impulsivity symptoms over a one-year follow-up using latent growth curve models (LGCMs). RESULTS: In controls, ventromedial prefrontal cortex (vmPFC) and dorsal ACC had a directed influence on CeN and VS, respectively. In the BPD group, bilateral BLA had a directed influence on CeN, whereas in the healthy group CeN influenced BLA. LGCMs indicated that emotion-related impulsivity was stable across a one-year follow-up in the BPD group. Further, higher EC of R CeN to other regions in controls was associated with stronger within-person decreases in emotion-related impulsivity. CONCLUSIONS: Functional inputs from BLA and vmPFC appear to play competing roles in influencing CeN activity. In borderline adolescents and young adults, BLA may predominate over CeN activity, while in controls the ability of CeN to influence BLA activity predicted more rapid reductions in emotion-related impulsivity.

The effect of repeated testing on judgement bias in domestic dogs (Canis familiaris).

Judgement bias paradigms are increasingly being used as a measure of affective state in dogs. Approach to an ambiguous stimulus is commonly used as a measure of affect, however, this may also be influenced by learning. This study directly measured the impact of learning on a commonly used judgement bias paradigm in the absence of an affective state manipulation. Dogs (N = 15) were tested on a judgement bias task across five sessions. The dogs' latency to approach a bowl placed in one of three ambiguous locations between non-baited (negative) and baited (positive) locations was measured. Results show that session number had a significant effect on the dogs' latencies to reach the ambiguous bowl locations, with post-hoc tests revealing that dogs were significantly slower to approach the locations as the number of sessions increased. Session number also had a significant effect on the number of times the dogs did not approach the bowl within 30 s of being released, with the number of no approaches generally increasing across sessions. When dog identity was included as a fixed effect, a significant effect on latency to approach was found, suggesting that some dogs were consistently faster than others across sessions. To assess whether the paradigm produced repeatable results, Intraclass Correlation Coefficients were used. A low degree of reliability was found between latencies to approach each bowl position across sessions. This study demonstrates that dogs learned that the ambiguous locations were not rewarded with repeated exposures, and that this impacted their responses. We conclude that this judgement bias paradigm may require further consideration if applied across multiple exposures and that repeated results should be interpreted with caution as they are likely impacted by learning.

Transscleral vs endoscopic cyclophotocoagulation: safety and efficacy when combined with phacoemulsification.

PURPOSE: To compare the effectiveness and safety of phacoemulsification combined with endoscopic cyclophotocoagulation (phaco/ECP), phacoemulsification combined with MicroPulse transscleral cyclophotocoagulation (phaco/MP-TSCPC), and phacoemulsification alone (phaco) in the treatment of coexisting cataract and glaucoma. METHODS: Retrospective cohort study of consecutive cases at Massachusetts Eye & Ear. The main outcome measures were the cumulative probabilities of failure between the phaco/ECP group, phaco/MP-TSCPC group, and the phaco alone group with failure defined as reaching NLP vision at any point postoperatively, undergoing additional glaucoma surgery, or the inability to maintain ≥ 20% IOP reduction from baseline with IOP between 5-18 mmHg while maintaining ≤ baseline medications. Additional outcome measures included changes in average IOP, number of glaucoma medications, and complication rates. RESULTS: Sixty-four eyes from 64 patients (25 phaco/ECP, 20 phaco/MPTSCPC, 19 phaco alone) were included in this study. The groups did not differ in age (mean 71.04 ± 6.7 years) or length of follow-up time. Baseline IOPs were significantly different between groups (15.78 ± 4.7 mmHg phaco/ECP, 18.37 ± 4.6 mmHg phaco/MP-TSCPC, 14.30 ± 4.2 mmHg phaco alone, p = 0.02). Primary open-angle glaucoma was the most common type of glaucoma in the phaco alone (42%) and phaco/ECP (48%) groups while mixed-mechanism glaucoma was the most common type in the phaco/MP-TSCPC group (40%). Surgical failure was less likely in eyes in the phaco/MP-TSCPC (3.40 times, p = 0.005) and phaco/ECP (1.40 times, p = 0.044) groups compared to phaco alone based on the Kaplan-Meier survival criteria. These differences maintained statistical significance when differences in preoperative IOP were taken into account using the Cox PH model (p = 0.011 and p = 0.004, respectively). Additionally, surgical failure was 1.98 times less likely following phaco/MP-TSCPC compared to phaco/ECP (p = 0.038). This difference only approached significance once differences in preoperative IOP were accounted for (p = 0.052). There was no significant difference in IOP reduction at 1 year between groups. Mean IOP reductions at 1 year were 3.07 ± 5.3 mmHg from a baseline of 15.78 ± 4.7 in the phaco/ECP group, 6.0 ± 4.3 mmHg from a baseline of 18.37 ± 4.6 in the phaco/MP-TSCPC group and 1.0 ± 1.6 from a baseline of 14.30 ± 4.2 mmHg in the phaco alone group. There were no differences in complication rates among the three groups. CONCLUSIONS: Both Phaco/MP-TSCPC and phaco/ECP appear to provide superior efficacy for IOP control when compared to phaco alone. All three procedures had similar safety profiles.

Comparative Transcriptome Profiling Unfolds a Complex Defense and Secondary Metabolite Networks Imparting Corynespora cassiicola Resistance in Soybean (Glycine max (L.) Merrill).

Target spot is caused by Corynespora cassiicola, which heavily affects soybean production areas that are hot and humid. Resistant soybean genotypes have been identified; however, the molecular mechanisms governing resistance to infection are unknown. Comparative transcriptomic profiling using two known resistant genotypes and two susceptible genotypes was performed under infected and control conditions to understand the regulatory network operating between soybean and C. cassiicola. RNA-Seq analysis identified a total of 2571 differentially expressed genes (DEGs) which were shared by all four genotypes. These DEGs are related to secondary metabolites, immune response, defense response, phenylpropanoid, and flavonoid/isoflavonoid pathways in all four genotypes after C. cassiicola infection. In the two resistant genotypes, additional upregulated DEGs were identified affiliated with the defense network: flavonoids, jasmonic acid, salicylic acid, and brassinosteroids. Further analysis led to the identification of differentially expressed transcription factors, immune receptors, and defense genes with a leucine-rich repeat domain, dirigent proteins, and cysteine (C)-rich receptor-like kinases. These results will provide insight into molecular mechanisms of soybean resistance to C. cassiicola infection and valuable resources to potentially pyramid quantitative resistance loci for improving soybean germplasm.

Adjustable Suture Technique Is Associated with Fewer Strabismus Reoperations in the Intelligent Research in Sight Registry.

PURPOSE: To compare the reoperation rates after strabismus surgery with and without the adjustable suture technique. DESIGN: Retrospective cohort study. PARTICIPANTS: Patients 18 years of age or older in the Intelligent Research in Sight (IRIS®) Registry who underwent strabismus surgery between January 1, 2013, and December 31, 2018. METHODS: Data were collected from the electronic health records of practices participating in the IRIS Registry. The primary exposure of interest was use of the adjustable suture technique, identified by Current Procedural Terminology coding. MAIN OUTCOME MEASURES: The primary outcome was repeat strabismus surgery within 1 year of initial strabismus surgery. Odds ratios (ORs) were derived from a multivariable logistic regression model evaluating the association between the use of adjustable sutures and reoperation rate, adjusting for patient demographics and surgical factors. RESULTS: A total of 34 872 patients who underwent strabismus surgery during the study interval were identified: 72% underwent horizontal muscle surgery, 17% underwent vertical muscle surgery, and 11% underwent combined horizontal and vertical muscle surgery. Adjustable sutures were used in 18% of patients. The overall reoperation rate within 1 year of strabismus surgery was 7.7%. The 1-year reoperation rate was 6.0% for patients treated with adjustable sutures and 8.1% for patients treated without adjustable sutures (P < 0.001). The multivariable regression model revealed a statistically significant 30% decrease in the odds of reoperation within 1 year of surgery when adjustable sutures were used (OR, 0.70; 95% confidence interval [CI], 0.62-0.78), a 40% increase in those with a history of prior strabismus surgery (OR, 1.40; 95% CI, 1.28-1.53), and a 9% increase per decade of age at surgery (OR, 1.09; 95% CI, 1.06-1.11). CONCLUSIONS: In adults cared for in practices participating in the IRIS Registry, the adjustable suture technique was associated with a significantly lower reoperation rate within 1 year of undergoing horizontal or combined horizontal and vertical strabismus surgery. Adjustable suture use in vertical strabismus surgery alone did not reduce the 1-year reoperation rate significantly. A history of prior strabismus surgery was associated with increased odds of reoperation.

Neurotrophic Keratopathy in the United States: An Intelligent Research in Sight Registry Analysis.

PURPOSE: To describe the characteristics of neurotrophic keratopathy (NK) in the United States. DESIGN: Retrospective database study. PARTICIPANTS: Thirty-one thousand nine hundred fifteen eyes of 27 483 patients with a diagnosis of NK. METHODS: Retrospective analysis of visits associated with a diagnosis of NK between 2013 and 2018 using the American Academy of Ophthalmology Intelligent Research in Sight (IRIS®) Registry. MAIN OUTCOME MEASURES: Demographic information, prevalence, visual acuity (VA), concomitant diagnosis and procedure codes, and risk factors impacting VA most closely after NK onset date. RESULTS: Mean ± standard deviation (SD) age at initial diagnosis of NK was 68.0 ± 16.0 years, and 58.91% of patients were women (P < 0.0001). Presentation was unilateral in 58.14%, bilateral in 16.13%, and unspecified in 25.73%. Average 6-year prevalence of NK in the IRIS Registry was 21.34 cases per 100 000 patients. Mean ± SD VA was 0.60 ± 0.79 logMAR before diagnosis and 0.88 ± 0.94 logMAR after diagnosis (P < 0.0001). Most common concomitant diagnoses included herpetic keratitis (33.70%), diabetes (31.59%), and corneal dystrophy (14.28%). Common procedures for NK management included the use of amniotic membrane (29.90%), punctal plugs (29.65%), and bandage contact lenses (22.67%). Age, male sex, Black race, Hispanic or Latino ethnicity, unilateral involvement, concomitant diagnoses of diabetes, corneal transplantation, and herpetic keratitis were associated significantly with worse VA. CONCLUSIONS: Based on the IRIS Registry, the prevalence of NK is 21.34 cases per 100 000 patients. Visual acuity was significantly worse after NK diagnosis compared with other time points. Neurotrophic keratopathy was associated most commonly with herpetic keratitis and diabetes. Worse VA in patients with NK was associated with several demographic characteristics, history of diabetes, corneal transplantation, and herpetic keratitis.

Prognostic value of interim FDG-PET in diffuse large cell lymphoma: results from the CALGB 50303 Clinical Trial.

As part of a randomized, prospective clinical trial in large cell lymphoma, we conducted serial fluorodeoxyglucose positron emission tomography (FDG-PET) at baseline, after 2 cycles of chemotherapy (interim PET [i-PET]), and at end of treatment (EoT) to identify biomarkers of response that are predictive of remission and survival. Scans were interpreted in a core laboratory by 2 imaging experts, using the visual Deauville 5-point scale (5-PS), and by calculating percent change in FDG uptake (change in standardized uptake value [ΔSUV]). Visual scores of 1 through 3 and ΔSUV ≥66% were prospectively defined as negative. Of 524 patients enrolled in the parent trial, 169 agreed to enroll in the PET substudy and 158 were eligible for final analysis. In this selected population, all had FDG-avid disease at baseline; by 5-PS, 55 (35%) remained positive on i-PET and 28 (18%) on EoT PET. Median ΔSUV on i-PET was 86.2%. With a median follow-up of 5 years, ΔSUV, as continuous variable, was associated with progression-free survival (PFS) (hazard ratio [HR] = 0.99; 95% confidence interval [CI], 0.97-1.00; P = .02) and overall survival (OS) (HR, 0.98; 95% CI, 0.97-0.99; P = .03). ΔSUV ≥66% was predictive of OS (HR, 0.31; 95% CI, 0.11-0.85; P = .02) but not PFS (HR, 0.47; 95% CI, 0.19-1.13; P = .09). Visual 5-PS on i-PET did not predict outcome. ΔSUV, but not visual analysis, on i-PET predicted OS in DLBCL, although the low number of events limited the statistical analysis. These data may help guide future clinical trials using PET response-adapted therapy. This trial was registered at www.clinicaltrials.gov as #NCT00118209.

Outcomes of a combination of augmented MicroPulse and limited Continuous Wave Cyclophotocoagulation in patients with refractory glaucoma.

PURPOSE: To assess the safety and effectiveness of augmented MicroPulse (MP-TSCPC) with limited Continuous Wave Transscleral Cyclophotocoagulation (CW-TSCPC) in patients with refractory glaucoma. METHODS: Thirty-eight eyes of 38 patients underwent combined MP-TSCPC and CW-TSCPC at Massachusetts Eye and Ear. Kaplan-Meier survival curves and Wilcoxon paired sign rank tests were performed to evaluate intraocular pressure (IOP), glaucoma medication burden, best corrected visual acuity (BCVA), and adverse events. RESULTS: With success defined as IOP reduction ≥ 30% and IOP between 5 and 18 mmHg, the cumulative probability of success at 1 year and 1.5 years were 0.81 (95% confidence interval (CI), 0.68-0.96) and 0.65 (95% CI, 0.50-0.86), respectively. With success defined as IOP reduction ≥ 50% and IOP between 5 and 18 mmHg, the success probability at 1 year and 1.5 years were 0.72 (95% CI, 0.57-0.89) and 0.56 (95% CI, 0.40-0.78), respectively. IOP and medication burden reductions were significant at all follow-up visits compared to baseline. Average IOP decreased from 27.9 mmHg at baseline to 11.4 mmHg at 1 year (p < 0.001) and 10.0 mmHg at 1.5 years (p < 0.001). Average medication burden decreased from 3.8 to 1.7 at 1.5 years (p = 0.001). No significant differences in visual acuity were observed at any time point. No long-term sight-threatening complications due to the combined procedure were observed, and most of the complications observed were mild and transient. CONCLUSION: In patients with refractory glaucoma, the combination of augmented MP-TSCPC with limited CW-TSCPC provides a significant IOP-lowering effect and decrease in medication burden without increased risk of postoperative complications.

Detection of subgenome bias using an anchored syntenic approach in Eleusine coracana (finger millet).

BACKGROUND: Finger millet (Eleusine coracana 2n = 4x = 36) is a hardy, nutraceutical, climate change tolerant, orphan crop that is consumed throughout eastern Africa and India. Its genome has been sequenced multiple times, but A and B subgenomes could not be separated because no published genome for E. indica existed. The classification of A and B subgenomes is important for understanding the evolution of this crop and provide a means to improve current and future breeding programs. RESULTS: We produced subgenome calls for 704 syntenic blocks and inferred A or B subgenomic identity for 59,377 genes 81% of the annotated genes. Phylogenetic analysis of a super matrix containing 455 genes shows high support for A and B divergence within the Eleusine genus. Synonymous substitution rates between A and B genes support A and B calls. The repetitive content on highly supported B contigs is higher than that on similar A contigs. Analysis of syntenic singletons showed evidence of biased fractionation showed a pattern of A genome dominance, with 61% A, 37% B and 1% unassigned, and was further supported by the pattern of loss observed among cyto-nuclear interacting genes. CONCLUSION: The evidence of individual gene calls within each syntenic block, provides a powerful tool for inference for subgenome classification. Our results show the utility of a draft genome in resolving A and B subgenomes calls, primarily it allows for the proper polarization of A and B syntenic blocks. There have been multiple calls for the use of phylogenetic inference in subgenome classification, our use of synteny is a practical application in a system that has only one parental genome available.

Evaluation and resolution of many challenges of neural spike sorting: a new sorter.

We evaluate existing spike sorters and present a new one that resolves many sorting challenges. The new sorter, called "full binary pursuit" or FBP, comprises multiple steps. First, it thresholds and clusters to identify the waveforms of all unique neurons in the recording. Second, it uses greedy binary pursuit to optimally assign all the spike events in the original voltages to separable neurons. Third, it resolves spike events that are described more accurately as the superposition of spikes from two other neurons. Fourth, it resolves situations where the recorded neurons drift in amplitude or across electrode contacts during a long recording session. Comparison with other sorters on ground-truth data sets reveals many of the failure modes of spike sorting. We examine overall spike sorter performance in ground-truth data sets and suggest postsorting analyses that can improve the veracity of neural analyses by minimizing the intrusion of failure modes into analysis and interpretation of neural data. Our analysis reveals the tradeoff between the number of channels a sorter can process, speed of sorting, and some of the failure modes of spike sorting. FBP works best on data from 32 channels or fewer. It trades speed and number of channels for avoidance of specific failure modes that would be challenges for some use cases. We conclude that all spike sorting algorithms studied have advantages and shortcomings, and the appropriate use of a spike sorter requires a detailed assessment of the data being sorted and the experimental goals for analyses.NEW & NOTEWORTHY Electrophysiological recordings from multiple neurons across multiple channels pose great difficulty for spike sorting of single neurons. We propose methods that improve the ability to determine the number of individual neurons present in a recording and resolve near-simultaneous spike events from single neurons. We use ground-truth data sets to demonstrate the pros and cons of several current sorting algorithms and suggest strategies for determining the accuracy of spike sorting when ground-truth data are not available.

The Hospital Frailty Risk Score-outcomes in specialised services.

BACKGROUND: Frailty is increasingly used to risk stratify older people, but across specialised services there is no standardised approach. The aim of this study was to assess if the Hospital Frailty Risk Score (HFRS) could describe outcomes for older people within English specialised services. DESIGN: A retrospective cohort study was performed using the Secondary Uses Service (SUS) electronic database for people aged 75 or older admitted between April 2017 and March 2018. METHODS: Based on HFRS, the populations were risk stratified into mild, moderate and severe frailty risk. The relationships with length of stay, readmission rate, mortality and some selected condition specific treatment complications were quantified using descriptive statistics. RESULTS: Very few individuals (<2%) could not be risk stratified for frailty risk. Frailty was differentially distributed across the specialties; around one-third had mild frailty; another third had moderate frailty and one-quarter severe frailty. Increasing frailty risk was associated with increased length of stay for the index admission, more days in hospital in the year following intervention and increased risk of dying in hospital. Severe frailty was a powerful discriminator of the risk of death; between 25 and 40% of those with severe frailty risk died at 30 months across all specialties. CONCLUSIONS: This study demonstrates the first application of the HFRS to a national dataset to describe service outcomes and mortality for older people undergoing a range of specialised interventions. This information could be used to identify those that might benefit from holistic assessment, aid prognostication, commissioning and service planning.

Disentangling cognitive processes in externalizing psychopathology using drift diffusion modeling: Antagonism, but not disinhibition, is associated with poor cognitive control.

Although externalizing psychopathology has been linked to deficits in cognitive control, the cognitive processes underlying this association are unclear. Here, we provide a theoretical account of how research on cognitive processes can help to integrate and distinguish personality and psychopathology. We then apply this account to connect the two major subcomponents of externalizing, Antagonism and Disinhibition, with specific control processes using a battery of inhibitory control tasks and corresponding computational modeling. Participants (final N = 104) completed the flanker, go/no-go, and recent probes tasks, as well as normal and maladaptive personality inventories and measures of psychological distress. We fit participants' task behavior using a hierarchical drift diffusion model (DDM) to decompose their responses into specific cognitive processes. Using multilevel structural equation models, we found that Antagonism was associated with faster RTs on the flanker task and lower accuracy on flanker and go/no-go tasks. These results were complemented by DDM parameter associations: Antagonism was linked to decreased threshold and drift rate parameter estimates in the flanker task and a decreased drift rate on no-go trials. Altogether, our findings indicate that Antagonism is associated with specific impairments in fast (sub-second) inhibitory control processes involved in withholding prepared/prepotent responses and filtering distracting information. Disinhibition and momentary distress, however, were not associated with task performance.