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Functional impairment is common in patients with major depressive disorder (MDD). The Functioning Assessment Short Test (FAST) provides a detailed clinician-rated assessment of functioning across multiple aspects of daily life. This study aimed to establish clinically relevant response thresholds for the FAST in patients with MDD receiving antidepressant treatment. Data were derived from three 8-week clinical trials of antidepressant therapy in patients with MDD that included assessment of functioning using the FAST as a pre-specified endpoint. The minimal clinically important difference (MCID) and threshold for response in terms of change in FAST total score were determined using anchor-based methods. After 8 weeks of antidepressant treatment, the mean reduction in FAST total score in patients considered clinically minimally improved (Clinical Global Impression–Improvement [CGI-I] score of 3) was 7–9 points (~20 % reduction). The threshold for functional response (reduction in FAST total score from baseline in patients with a CGI-I score of ≤2 at week 8) was 16–19 points (~50 % reduction). The threshold for functional response was higher in patients with MDD and comorbid generalized anxiety disorder than in those with MDD alone (mean reduction in FAST total score at 8 weeks: 26 points [63 %]). Short-term studies. These results provide further validation of the FAST for assessing functioning in patients with MDD. In patients with MDD, the suggested MCID for FAST total score is 7–9 points and the proposed threshold for response is a reduction from baseline of approximately 50 %. • Patients with major depressive disorder (MDD) experience functional impairments that impact all aspects of their daily life • The Functioning Assessment Short Test (FAST) provides a detailed assessment of functional impairments in patients with MDD • In patients with MDD, the minimal clinically important difference in FAST total score after 8 weeks therapy was 7–9 points • A reduction in FAST total score of approximately 50 % after 8 weeks of antidepressant treatment was indicative of response • The threshold for functional response was higher in patients with comorbid anxiety than in those with MDD alone [ABSTRACT FROM AUTHOR]

OBJECTIVE The use of umbilical artery catheters (UACs) for parenteral nutrition (PN) administration is controversial, and limited data exist on the safety of administration through this route. The objective of this research is to evaluate neonates who received PN through a UAC and assess catheter-related complications and PN composition. METHODS This retrospective study evaluated all neonates who received PN through their UAC while admitted in the neonatal intensive care unit between January 2019 and December 2022. Neonates were evaluated for development of catheter-related complications such as infiltration, extravasation, thrombus formation, infection, or hypertension. RESULTS The administration of PN through UAC was identified in 31 neonates. Among the 31 neonates, 17 (55%) were classified as preterm, and 15 (48%) were classified as low birth weight. No patient experienced a UAC-related complication. Death occurred among 7 (23%) neonates. Two deaths occurred while the neonates were receiving PN via the UAC, but neither death was attributed to UAC complications. In 19 (61%) of the 31 neonates, osmolarity of PN exceeded 900 mOsm/L. CONCLUSIONS Results of this study suggest that UACs may serve as a safe route for PN administration in neonates. The absence of catheter-related complications and the absence of adverse events support the safety of this approach. Further research with a larger sample size and rigorous study design is warranted to validate these findings and establish guidelines for the use of UACs in PN administration. [ABSTRACT FROM AUTHOR]

Background: The multinational, open-label COMPLETE study (NCT03835715) investigated the effectiveness of vortioxetine in alleviating emotional blunting in patients with major depressive disorder (MDD) experiencing inadequate response and emotional blunting while being treated with a selective serotonin reuptake inhibitor (SSRI) or serotonin–noradrenaline reuptake inhibitor (SNRI). This paper presents results for the subgroup of patients enrolled in Spain. Methods: Patients with MDD (n = 67) experiencing partial response and emotional blunting during monotherapy with an SSRI or SNRI were switched to vortioxetine (10– 20 mg/day) for 8 weeks. The primary study outcome was emotional blunting, assessed by the Oxford Depression Questionnaire (ODQ). Results: After 8 weeks of vortioxetine, the mean (SE) change in ODQ total score from baseline was − 26.0 (2.9) (P < 0.001). Respective changes in Montgomery–Åsberg Depression Rating Scale (MADRS), Motivation and Energy Inventory, Digit Symbol Substitution Test, and Sheehan Disability Scale (SDS) total scores were − 14.9 (0.8), +34.2 (4.5), +6.3 (1.6), and ‒9.0 (1.3) (all P < 0.001 vs baseline). At week 8, 70.4% of patients no longer reported emotional blunting and 53.7% had achieved remission from their depressive symptoms (defined as a MADRS total score ≤ 10). Mediation analysis showed 77.1% of the change in SDS total score to be a direct effect of the improvement in ODQ total score after switching to vortioxetine. Adverse events were reported by 35 patients (52.2%), most commonly nausea (14 patients, 20.9%). At week 8, 33/54 patients (61.1%) were receiving vortioxetine 20 mg/day. Conclusion: In this study investigating the effectiveness of vortioxetine in Spanish patients with MDD who experienced inadequate response and emotional blunting on SSRI/SNRI monotherapy, significant improvements in emotional blunting, core depressive symptoms (including anhedonia), sleep duration, motivation and energy, cognitive performance, and overall patient functioning were observed during the 8 weeks of treatment. Two-thirds of patients no longer reported emotional blunting and over half were in remission from their depressive symptoms at week 8. [ABSTRACT FROM AUTHOR]

Purpose: Patients with advanced keratoconus (KCN) are less likely to benefit from corneal cross-linking and may require a partial or full thickness keratoplasty. This study aimed to determine whether racial disparities exist in the clinical presentation and initial treatment recommendations for patients evaluated for KCN. Methods: A single-center retrospective review was conducted on all patients who presented to the cornea department for initial evaluation of KCN between 2018 and 2020. Patients who had undergone prior corneal procedures or surgeries were excluded. Baseline sociodemographic and clinical information was collected and stratified according to black versus non-black race. Generalized estimating equations were used to examine the association between black race and presenting corrected distance visual acuity (CDVA), presence of corneal scarring, keratometry values, Belin ABCD score, and treatment recommendations. Multivariate models were adjusted for patient demographics. Results: A total of 128 patients (251 eyes) were included in this study. In fully adjusted models, black individuals presented with significantly worse CDVA (p < 0.0001) and worse tomographic KCN staging according to the Belin ABCD criteria (p = 0.002) compared to non-blacks. Blacks were also more than four times as likely to present with a thinnest pachymetry < 400 μm (p < 0.0001) and more than three times as likely to have corneal scarring (p = 0.001). Blacks were more than seven times more likely to have keratoplasty recommended as treatment than conservative management such as corneal cross-linking or contact lenses (p = 0.004). Conclusion: Compared with their non-black counterparts, blacks presented with significantly more advanced KCN, which placed them at risk of requiring more invasive treatment plans. Future studies should investigate reasons for such late presentations and aim to mitigate disparities in the presentation and management of KCN. [ABSTRACT FROM AUTHOR]

Depression and dementia are highly prevalent in older adults and often co-occur. This Phase IV study investigated the effectiveness and tolerability of vortioxetine in improving depressive symptoms, cognitive performance, daily and global functioning and health-related quality of life (HRQoL) in patients with major depressive disorder (MDD) and comorbid early-stage dementia. Patients (n = 82) aged 55–85 years with a primary diagnosis of MDD (onset before age 55 years) and comorbid early-stage dementia (diagnosed ≥6 months before screening and after onset of MDD; Mini-Mental State Examination-2 total score, 20–24) received vortioxetine for 12 weeks (initiated at 5 mg/day and up-titrated to 10 mg/day at day 8, with flexible dosing thereafter [5–20 mg/day]). The primary endpoint was change from baseline in Montgomery–Åsberg Depression Rating Scale (MADRS) total score at week 12. Significant improvement in depressive symptom severity was seen from week 1 onwards (P < 0.0001). At week 12, the least-square mean (standard error) change in MADRS total score from baseline was −12.4 (0.78). Significant improvements in cognitive performance were observed (from week 1 for the Digit Symbol Substitution Test and week 4 for the Rey Auditory Verbal Learning Test). Patients also experienced significant improvements in daily and global functioning, and HRQoL. Vortioxetine was well tolerated. From week 4 onwards, more than 50 % of patients were receiving 20 mg/day. Open-label study. Vortioxetine demonstrated effectiveness in clinically significantly improving depressive symptoms, cognitive performance, daily and global functioning, and HRQoL in patients with MDD and comorbid early-stage dementia treated for 12 weeks. ClinicalTrials.gov/ct2/show/NCT04294654. • Depression and dementia are highly prevalent in older adults and often co-occur. • Effectiveness of vortioxetine was assessed in patients with MDD and early-stage dementia. • Significant improvement in depressive symptom severity after vortioxetine initiation. • Cognitive performance significantly improved as assessed by the DSST and RAVLT. • Daily and global functioning and quality of life also improved with vortioxetine. [ABSTRACT FROM AUTHOR]

This scoping study aims to provide an overview of the functions, utilities and limitations of applying "decision support algorithms" (DSAs) in different social work contexts. The study involves searching the Scopus and Web of Science databases, which results in the inclusion of 55 articles in the analysis. We find important differences in the functions, utilities and limitations of DSAs according to the choice of data, variables, technology and social work context. The reviewed literature indicates that social workers are rarely involved in developing DSAs. This seems to result in a limited innovation of DSAs that are capable of stimulating the reflection of social workers and thereby qualifying their decision-making process. This study calls for further research on how to enhance interaction between social workers at the street level and system builders and managers at the system level in developing DSAs designed for reflection. [ABSTRACT FROM AUTHOR]

Patients with major depressive disorder (MDD) often experience comorbid anxiety symptoms. Vortioxetine has demonstrated efficacy in treating anxiety symptoms in patients with MDD; however, efficacy and tolerability have not been assessed across the entire approved dosage range. The efficacy and tolerability of vortioxetine 5–20 mg/day were assessed in patients with MDD and high levels of anxiety symptoms (Hamilton Anxiety Rating Scale [HAM-A] total score ≥ 20) using pooled data from four randomized, fixed-dose, placebo-controlled studies (n = 842). Data from a randomized, double-blind study of vortioxetine 10–20 mg/day versus agomelatine 25–50 mg/day in patients with an inadequate response to prior therapy (n = 299) were analyzed separately. Mean changes from baseline in Montgomery–Åsberg Depression Rating Scale (MADRS), HAM-A, and Sheehan Disability Scale (SDS) total scores were analyzed by vortioxetine dosage. The pooled analysis of fixed-dose studies demonstrated a clear dose–response relationship for vortioxetine 5–20 mg/day for improvements in MADRS, HAM-A, and SDS total scores. Vortioxetine 20 mg/day demonstrated significant effects versus placebo from week 4 onwards. In the post-hoc analysis of the active-controlled study in patients with an inadequate response to prior therapy, vortioxetine 10–20 mg/day was superior to agomelatine across all outcome measures from week 4 onwards. Up-titration of vortioxetine to 20 mg/day was not associated with an increase in adverse events. Short-term trials. Vortioxetine is efficacious and well tolerated in patients with MDD and high levels of anxiety symptoms, including those with an inadequate response to prior therapy. The greatest therapeutic benefits were observed with vortioxetine 20 mg/day. NCT01140906 , NCT01153009 , NCT01163266 , NCT01255787 , NCT01488071. • Patients with major depressive disorder often experience comorbid anxiety symptoms. • Vortioxetine was assessed in patients with MDD and high levels of anxiety symptoms. • Vortioxetine 20 mg/day had the greatest effects on depressive and anxiety symptoms. • Dose-dependent effects were also observed on overall patient functioning. • Dosage increase to 20 mg/day after 1 week did not compromise tolerability. [ABSTRACT FROM AUTHOR]

Background: Generalized anxiety disorder (GAD) is commonly co-morbid with major depressive disorder (MDD) and is associated with greater functional impairment and poorer treatment outcomes than MDD alone. However, studies on treatment with drugs for depression in patients with MDD and co-morbid GAD are limited. Aims: To examine the effectiveness of vortioxetine treatment in patients with MDD and co-morbid GAD in a subgroup analysis of the real-world RELIEVE study. Methods: The analysis included outpatients diagnosed with MDD and co-morbid GAD who initiated vortioxetine treatment at their physician's discretion in the 24-week, observational RELIEVE study. Primary outcome was patient functioning (Sheehan Disability Scale (SDS)) after 12 and 24 weeks of vortioxetine treatment; secondary outcomes included depression severity (9-item Patient Health Questionnaire (PHQ-9)), cognitive symptoms (5-item Perceived Deficits Questionnaire – Depression (PDQ-D-5)) and cognitive performance (Digit Symbol Substitution Test (DSST)). Results: Overall, 180 patients with MDD and co-morbid GAD were included in the analysis. Following vortioxetine initiation, clinically significant improvements in patient functioning (SDS total score) were observed at week 12 (least-squares (LS) mean reduction from baseline, 7.5 points), sustained through week 24 (9.2 points) (both p < 0.0001). LS mean PHQ-9, PDQ-D-5 and DSST scores improved by 7.9, 4.8 and 7.4 points at week 24, respectively (all p < 0.0001 vs baseline). Adverse events were reported by 33.9% of patients (most commonly nausea, 13.3%). Conclusions: In routine clinical practice, vortioxetine was associated with clinically meaningful, sustained improvements in functioning, and depressive and cognitive symptoms, in patients with MDD and co-morbid GAD. Clinical Trials Registry Name and Identifier: Real-life Effectiveness of Vortioxetine in Depression (RELIEVE) (NCT03555136) https://clinicaltrials.gov/ct2/show/NCT03555136 [ABSTRACT FROM AUTHOR]

Background: The Motivation and Energy Inventory (MEI) is a patient-reported scale for assessment of the impact of mental/cognitive energy, social motivation, and physical energy on daily functioning in patients with major depressive disorder (MDD). This analysis was undertaken to establish the clinically relevant response threshold for the MEI in patients with MDD receiving antidepressant treatment.Methods: Patients with MDD experiencing inadequate response and emotional blunting on selective serotonin reuptake inhibitor or serotonin-noradrenaline reuptake inhibitor monotherapy (adequate dose for ≥6 weeks) were switched to vortioxetine 10-20 mg/day for 8 weeks. Anchor- and distribution-based methods were used to determine the minimal clinically important difference (MCID) in MEI total score.Results: After 8 weeks of vortioxetine treatment, mean (standard deviation) change in MEI total score from baseline was 33.0 (27.3) points. At week 8, mean change in MEI total score from baseline was 37.5 (27.8) points in patients no longer reporting emotional blunting and 28.3 (26.2) points in those still experiencing emotional blunting. In patients considered minimally improved (i.e. Clinical Global Impression-Improvement [CGI-I] score of 3 after 8 weeks of vortioxetine), mean change in MEI total score from baseline was 14.7 (19.1) points. In patients defined as responders (CGI-I score of 2 at 8 weeks), mean change in MEI total score was 33.0 (24.7) points.Limitations: Short study duration.Conclusions: These results provide further validation of the clinical utility of the MEI for assessing treatment response in patients with MDD. The suggested MCID for MEI total score is 15 points.Trial Registration: NCT03835715. [ABSTRACT FROM AUTHOR]

Background: Peyronie's disease (PD) has previously been observed to co‐aggregate in a small number of first‐degree relative pairs (e.g., father–son). However, the familial aggregation of PD in more distant relatives, as well as the aggregation of Dupuytren's disease (DD) in probands and relatives, has not been thoroughly investigated. Objective: This study explored the evidence for familial clustering of PD and DD in close and distant relatives. Materials and methods: The Utah Population Database, which includes genealogy information linked to electronic medical records (available since 1995), was used to identify men and their relatives with PD and DD based on ICD9/10 codes. All cases were required to have high‐quality genealogy data. We estimated relative risk (RR) of PD and DD in first‐ through fifth‐degree relatives compared to matched population rates of disease. We also investigated the average relatedness of cases compared to the average relatedness of sets of matched controls. Outcome measures include estimation of relative risk and excessive relatedness as measured by a Genealogical Index of Familiality (GIF) analysis. Results: We analyzed 307 individuals with PD, and their first‐ through fifth‐degree relatives. Approximately 0.12% of the population had PD, 95% of these were diagnosed over the age of 30 years (age range: 10–92 years), and 1.3% of PD probands had a comorbid diagnosis of DD. RR estimates for PD were significant for first‐ and fifth‐degree relatives. RR estimates for DD were significant only for probands. The average relatedness of cases was significantly greater than matched controls, even after removing first‐ and second‐degree relatives. We also found that 74.9% of identified PD probands belonged to pedigrees with a statistical excess of PD. Conclusion: Despite the low prevalence of PD in our healthcare records, the results provide evidence that support a genetic contribution to at least a subset of PD cases. [ABSTRACT FROM AUTHOR]

Background: The contemporary political discourse about online disinformation has, in many cases, adopted assumptions about the dangers of mass culture that can be traced back to mid-twentieth century theories of mass society. Analysis: To understand how mass society theory has shaped contemporary debates about disinformation, the article examines the Government of Canada's recent framing of the problem in terms of security, regulation, and media literacy. Conclusion and Implications:The article shows that official discourses of disinformation have overemphasized the role of behavioural manipulation by foreign actors and technology companies and underestimated the deeper socio-structural factors that disinformation narratives express. [ABSTRACT FROM AUTHOR]

Simple Summary: Stereotactic ablative radiation therapy (SAbR) is a safe and effective local therapy for renal cell cancer (RCC) with emerging and evolving indications. In this review we provide an overview of the evidence to support SAbR for RCC in a variety of clinical settings. Advancements in radiation delivery technology have made it feasible to treat tumors with ablative radiation doses via stereotactic ablative radiation therapy (SAbR) at locations that were previously not possible. Renal cell cancer (RCC) was initially thought to be radioresistant, even considered toxic, in the era of conventional protracted course radiation. However, SAbR has been demonstrated to be safe and effective in providing local control to both primary and metastatic RCC by using ablative radiation doses. SAbR can be integrated with other local and systemic therapies to provide optimal management of RCC patients. We will discuss the rationale and available evidence for the integration and sequencing of SAbR with local and systemic therapies for RCC. [ABSTRACT FROM AUTHOR]

In international relations, there is regular reflection about the complex relations between academic and various kinds of practical knowledge. In this article, we add to these reflections using the example of democracy promotion expertise. We develop a practice–theoretical methodology based on the sociology of Pierre Bourdieu and extensions of it in the communities of practice literature. We also include a comparative dimension by studying epistemic practices in North America and Germany. Our analysis shows the importance of knowledge translating between academia and democracy promotion practice and the prestige and capital of roaming experts who cross epistemic boundaries that otherwise divide actors. To varying degrees, roaming experts contribute to practice-oriented translations of academic insights and the identification of problems stemming from ongoing practice that are important in democracy promotion. We show that processes of problem construction are regulated by conventions that homogenize epistemic practices and evidence, with only selective attention paid to emancipatory demands or epistemes from the Global South. While our research shows some epistemes and demands conflict with Western norms, Global South epistemes and demands are most often turned into arguments for further liberal democracy promotion. [ABSTRACT FROM AUTHOR]

Background: This international online survey investigated the experience and impact of emotional blunting in the acute and remission phases of depression from the perspective of patients and healthcare providers (HCPs). This paper presents data on the history and severity of psychological trauma and its potential impact on emotional blunting in major depressive disorder (MDD); differences between patient and HCP perceptions are explored. Methods: Patient respondents (n = 752) were adults with a diagnosis of depression who were currently taking antidepressant therapy and reported emotional blunting during the past 6 weeks. HCPs provided details on two eligible patients: one in the acute phase of depression and one in remission from depression (n = 766). Trauma was assessed using questions based on the Childhood Trauma Questionnaire; emotional blunting was assessed using the Oxford Depression Questionnaire (ODQ). Multivariate regression analyses were applied to examine the relationship between trauma and ODQ score. Results: A history of any childhood or recent traumatic event was reported by 97% of patients in the self-assessed cohort and for 83% of those in the HCP-assessed cohort (difference, p < 0.01). Patients were more likely than HCPs to feel that this trauma had contributed to their/the patient's depression (58% vs 43%, respectively; p < 0.01) and that the depression was more severe because of trauma (70% vs 61%, respectively; p < 0.01). Emotional blunting was significantly worse in patients who reported severe trauma than in those who had not experienced severe trauma (mean total ODQ score, 90.1 vs 83.9, respectively; p < 0.01). In multivariate regression analyses, experiencing both severe childhood and recent trauma had a statistically significant impact on ODQ total score (p = 0.001). Conclusions: A high proportion of patients with depression and emotional blunting self-reported exposure to childhood and/or recent traumatic events, and emotional blunting was more severe in patients who reported having experienced severe trauma. However, history of psychological trauma in patients with MDD appeared to be under-recognized by HCPs. Improved recognition of patients who have experienced psychological trauma and are experiencing emotional blunting may permit more targeted therapeutic interventions, potentially resulting in improved treatment outcomes. [ABSTRACT FROM AUTHOR]

Background: Emotional blunting is common in patients with depression. An online survey was undertaken to assess the experience of emotional blunting, and its impact on functioning and quality of life, in the acute and remission phases of depression from the perspective of patients and healthcare providers (HCPs). This paper presents data on the level of concordance between patient and HCP perspectives. Methods: This was a cross-sectional, observational study. Patient respondents were adults with a diagnosis of depression, who were currently using a prescribed antidepressant, and who reported emotional blunting during the past 6 weeks. HCPs completed the survey for the last two eligible patients they had seen, one in each phase of depression. Assessments included the Oxford Depression Questionnaire (ODQ) 'antidepressant as cause' domain and the Functioning Assessment Short Test (FAST). Results: Mean ODQ 'antidepressant as cause' domain scores were significantly higher in the patient-reported cohort (n = 752) than in the HCP-assessed cohort (n = 766) in both the acute (18.0 vs 12.5, respectively; p < 0.01) and remission phases (17.6 vs 12.6; p < 0.01). Overall, 45% of patients believed that their antidepressant medication was negatively affecting their emotions and 39% were considering stopping or had stopped their antidepressant because of perceived emotion-related side effects. In the HCP-assessed cohort, the antidepressant was considered responsible for emotional blunting in 30% of patients and only 18% of patients were believed to be considering stopping their medication due to emotional blunting. Patients reported a greater impact of emotional blunting on activities of daily living than HCPs. Mean FAST score was significantly higher in each phase of depression in the patient-reported cohort than in the HCP-assessed cohort (acute phase, 47.0 vs 39.1; remission phase, 33.5 vs 19.4; both p < 0.01). Conclusions: Compared with previous studies, our results suggest that HCPs may underestimate the prevalence of emotional blunting in patients with depression. HCPs also appear to underestimate the severity and impact of emotional blunting on patient functioning and treatment adherence compared with patients' own perspectives. Differences between patient and HCP perspectives were most pronounced during the acute phase of the disease. [ABSTRACT FROM AUTHOR]

Background: Emotional blunting is a common symptom in people with depression and an important factor preventing full functional recovery. This international survey investigated the experience of emotional blunting in the acute and remission phases of depression from the perspective of patients and healthcare providers. This paper presents data on the impact of emotional blunting on overall functioning and health-related quality of life from the patient perspective. Methods: Respondents were adults diagnosed with depression by a physician, currently prescribed an antidepressant, and reporting emotional blunting during the past 6 weeks. Assessments included the Oxford Depression Questionnaire (ODQ), the Functioning Assessment Short Test (FAST), and the World Health Organization-Five Well-being Index (WHO-5). Pearson correlation and multivariate regression analyses were applied to examine the relationship between ODQ and FAST scores. Results: Data are available for 752 patients (62% female; mean age, 45 years). Mean ODQ total score was 94.8 in patients in the acute phase of depression (n = 300) and 85.7 in those in remission (n = 452; possible maximum, 130). Mean FAST total scores were 47.0 and 33.5, respectively (possible maximum, 72). Patients in the acute phase of depression had significantly greater impairment in functioning across all FAST domains than those in the remission phase (all differences, p < 0.01). Mean WHO-5 scores were 6.4 and 9.8 in the acute and remission phases, respectively (lower scores indicate poorer well-being). Overall, 65% of patients in the acute phase and 36% of those in remission reported that emotional blunting had a significant impact on their quality of life. Pearson correlation analysis showed a moderate positive correlation between ODQ and FAST total scores (r = 0.52) and a weak negative correlation between ODQ total score and WHO-5 score (r = − 0.26; both p < 0.01). In multivariate regression analysis, ODQ total score (in combination with other covariates) was the strongest significant predictor of poor patient functioning. Conclusions: Emotional blunting has a substantial negative impact on patients' daily functioning, well-being, and quality of life in both the acute and remission phases of depression. These findings highlight the importance of recognizing and treating emotional blunting in patients with major depressive disorder in order to achieve full functional recovery. [ABSTRACT FROM AUTHOR]

Background: Major depressive disorder (MDD) and generalized anxiety disorder (GAD) are frequently comorbid. Aims: To assess the effectiveness of vortioxetine in patients with MDD and comorbid GAD. Methods: Open-label, 8-week study (NCT04220996) in 100 adult outpatients with severe MDD and severe comorbid GAD receiving vortioxetine as first treatment for the current depressive episode or switching to vortioxetine due to inadequate response to another drug for depression. Vortioxetine starting dosage was 10 mg/day, with forced up-titration to 20 mg/day after 1 week. Response was defined as ⩾50% decrease in Montgomery–Åsberg Depression Rating Scale (MADRS) and/or Hamilton Anxiety Rating Scale (HAM-A) total score from baseline; remission defined as MADRS and/or HAM-A total score ⩽10. Results: Clinically meaningful and statistically significant improvements from baseline in symptoms of depression and anxiety, and overall functioning and health-related quality of life, were observed after 8 weeks' vortioxetine treatment (all changes p < 0.0001 vs baseline). At week 8, rates of MADRS response and remission were 61% and 35%, respectively. Corresponding rates of HAM-A response and remission were 55% and 42%. Response on both the MADRS and HAM-A scales was achieved by 52% of patients; 31% achieved remission on both scales. Vortioxetine dose up-titration was well tolerated; no unexpected adverse events were reported. Conclusion: Vortioxetine demonstrates effectiveness in significantly reducing symptoms of both depression and anxiety in patients with severe MDD comorbid with severe GAD. Findings support increasing vortioxetine dosage to 20 mg/day early in the course of therapy, and show that this may be achieved without compromising tolerability. [ABSTRACT FROM AUTHOR]

Background: Emotional blunting—inability to feel positive or negative emotions, detachment, or reduced emotional responsiveness—is common in people with depression. However, there is a paucity of studies comprehensively investigating this symptom and its functional impact. This study investigated the experience of emotional blunting, and its impact on overall functioning and quality of life, in the acute and remission phases of depression from the perspective of patients and healthcare providers. This paper presents data on the clinical presentation of emotional blunting in depression from the patient perspective. Methods: Cross-sectional, observational study conducted in Brazil, Canada, and Spain between April 15 and May 18, 2021. Data were collected via a self-completed online survey. Respondents were adults with depression (acute or remission phase), who were currently using a prescribed antidepressant, and who reported emotional blunting during the past 6 weeks. Emotional blunting was assessed using the Oxford Depression Questionnaire (ODQ; total score range 26–130, higher scores indicate greater emotional blunting). Results: In all, 752 patients completed the survey (62% female; mean age, 45 years). Overall, 44% of patients rated their emotional blunting as extremely severe (acute phase [n = 300], 72%; remission phase [n = 452], 25%; difference, p < 0.01). In all, 56% of patients considered their emotional blunting to be caused by their depression (acute phase, 62%; remission phase, 52%). Mean ODQ total score was 94.8 for patients in the acute phase of depression and 85.7 for those in remission (difference, p < 0.01). Mean score for the ODQ 'antidepressant as cause' domain (maximum possible score, 30) was 18.0 in patients in the acute phase and 17.6 in those in remission. Overall, 45% of patients believed that their antidepressant medication was blunting their emotions and 39% were considering stopping or had already stopped their antidepressant because of perceived emotion-related side effects. Conclusions: Almost three-quarters of patients in the acute phase of depression and one-quarter of those in remission reported severe emotional blunting. Approximately 56% of patients considered their emotional blunting to be caused by their depression, while 45% believed that their antidepressant medication was negatively affecting their emotions. Just over one-third of patients were considering stopping or had stopped their antidepressant as a result. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the effect of each of the tip sizes available for the Oertli CataRhex3® phacoemulsification machine on efficiency. Methods: Porcine lenses were fixed in formalin for 2 hours, then cut into 3.0 mm cubes. We studied three Oertli tips, all of which had a 30-degree bevel: easyTip 2.2 mm (20G), easyTip 2.8 mm (19G), and CO-MICS (21G). For the 19G and 20G tips, vacuum was set at 600 mmHg, irrigation rate at 50 mL/min, continuous power 70%, and bottle height 85 cm. For the 21G tip, vacuum was set at 450 mmHg; irrigation and power settings were identical to those used for the easyTip tips. We measured time to removal and chatter events to determine efficiency. Results: Results from 20 trials for each tip showed that the larger the gauge size, the more quickly lens fragments were removed. Chatter events demonstrated an increasing trend with smaller tip gauge. The 19G tip used an average time to fragment removal of 2.8 seconds; the 20G, 3.2 seconds; and the 21G, 4.6 seconds. Increasing tip diameter from 21G to 20G decreased emulsification time by 33% (P = 0.02). Increasing the diameter from 21G to 19G further decreased time to emulsification by 42% (P = 0.003). The 21G tip had a mean 1.4 events/cube; 20G, 0.35 events; and 19G, 0.1 events. Differences in mean chatter events for each tip were each statistically significant. Conclusion: These data suggest that when evaluated by chatter events and emulsification time, the 2.8 mm (19G) easyTip proves to have greatest efficiency. [ABSTRACT FROM AUTHOR]

Disinformation and other forms of post-truth politics are clearly a threat to global democracy. One way to better understand this post-truth moment is to re-examine the recent history of how political actors have tried to build or defend democratic institutions. This article turns to the field of international democracy promotion to examine the problem of legitimacy and trust in democratic institutions. While it has evolved from its late Cold War roots in pro-democracy propaganda campaigns, democracy promotion has increasingly become a field of expert knowledge aimed at professionalizing or improving the capacity of democratic institutions. This research follows the recent practice turn in IR theory to examine how expert knowledge is enacted through everyday organisational practices and argues that the recent rise of post-truth politics was not coincidental to the professionalisation of the field. Through interviews, ethnographic research, and document analysis of North American democracy promotion organisations, the following presents an analysis of contemporary democracy promotion as a set of practices emerging out of a global backlash against democracy that started in the early 2000s. The findings of this research suggest that performances of expertise in this field tend to be de-politicised, indeterminate, and narrowly focused on institutional legitimacy. [ABSTRACT FROM AUTHOR]

OBJECTIVE To determine if increased mortality could be detected with the administration of ceftriaxone and IV calcium in infants through an analysis of a large repository of electronic health records. METHODS Patients were split into 3 groups: 1) neonates, 2) infants, and 3) infants <1 year whose age was not specified. Deaths were classified into mutually exclusive categories based on the administration and timing of ceftriaxone and IV calcium. Crude death rates were calculated, and logistic regression modeling was used to calculate adjusted relative odds of death with associated covariates. RESULTS A total of 259,149 infants were identified. Of 79,038 neonates, the proportion of patients that received ceftriaxone and IV calcium within 48 hours who died was 3.8%, compared with 1.95% (IV calcium), 0.3% (ceftriaxone), 1.54% (IV fluids), and 2.03% (parenteral nutrition). For 102,456 infants, the proportions of deaths were 5.47% (ceftriaxone and IV calcium within 48 hours), 0.45% (IV calcium), 0.15% (ceftriaxone), 0.39% (IV fluids), and 5.5% (parenteral nutrition). Multivariate analysis showed increased odds of death in infants who received ceftriaxone and IV calcium within 48 hours, regardless of age, and propensity score-matched analysis showed a more than 2-fold increased risk for death. CONCLUSIONS The increased risk for death following ceftriaxone and IV calcium administration was noted not only in neonates, but among older infants as well. [ABSTRACT FROM AUTHOR]

Background: The Oxford Depression Questionnaire (ODQ) is a patient-reported scale for assessing emotional blunting in patients with major depressive disorder (MDD). This analysis was undertaken to further validate the scale in patients experiencing emotional blunting while receiving antidepressant treatment.Methods: Patients with MDD who experienced inadequate depressive-symptom resolution and emotional blunting on selective serotonin reuptake inhibitor or serotonin-noradrenaline reuptake inhibitor monotherapy (adequate dose for ≥6 weeks) were switched to vortioxetine 10-20 mg/day. ODQ total scores were assessed excluding and including the "antidepressant-as-cause" domain (ODQ-20 and ODQ-26, respectively). Anchor- and distribution-based methods were used to determine the minimal clinically important difference in ODQ scores in terms of change from baseline to week 8 of antidepressant treatment.Results: After 8 weeks of vortioxetine treatment, the mean change in ODQ-20 and ODQ-26 scores from baseline was -24.8 and -30.1 points, respectively. Greater mean changes from baseline in ODQ-20 and ODQ-26 scores were seen in patients reporting no emotional blunting vs those still experiencing emotional blunting after 8 weeks of vortioxetine treatment (ODQ-20: -27.0 vs -22.6 points; ODQ-26: -32.8 vs -27.5 points, respectively). In patients considered clinically minimally improved (Clinical Global Impression-Improvement score, 3) after 8 weeks of vortioxetine treatment, respective mean (standard deviation) change in ODQ-20 and ODQ-26 score from baseline was -15.5 (18.1) and -20.0 (20.5) points.Limitations: Short study duration.Conclusions: These results provide further validation of the clinical utility of the ODQ for assessing emotional blunting in patients with MDD. The suggested minimal clinically important difference for change in ODQ-20 and ODQ-26 scores is 16 and 20 points, respectively, after 8 weeks of antidepressant treatment.Trial Registration: ClinicalTrials.gov identifier: NCT03835715. [ABSTRACT FROM AUTHOR]

• Zarf is a lambda calculus-based instruction set architecture for program analysis. • We formally describe the ISA's syntax and semantics and prove its safety. • We verify an assembly-level implementation of an ICD application specified in Coq. • We guarantee timing requirements and prove non-interference via integrity types. Building a trustworthy life-critical embedded system requires deep reasoning about the potential effects that sequences of machine instructions can have on full system operation. Rather than trying to analyze complete binaries and the countless ways their instructions can interact with one another — memory, side effects, control registers, implicit state, etc. — we explore a new approach. We propose an architecture controlled by a thin computational layer designed to tightly correspond with the lambda calculus, drawing on principles of functional programming to bring the assembly much closer to myriad reasoning frameworks, such as the Coq proof assistant. This approach allows assembly-level verified versions of critical code to operate safely in tandem with arbitrary code, including imperative and unverified system components, without the need for large supporting trusted computing bases. We demonstrate that this computational layer can be built in such a way as to simultaneously provide full programmability and compact, precise, and complete semantics, while still using hardware resources comparable to normal embedded systems. To demonstrate the practicality of this approach, our FPGA-implemented prototype runs an embedded medical application which monitors and treats life-threatening arrhythmias. Though the system integrates untrusted and imperative components, our architecture allows for the formal verification of multiple properties of the end-to-end system. We present a proof of correctness of the assembly-level implementation of the core algorithm in Coq, the integrity of trusted data via a non-interference proof, and a guarantee that our prototype meets critical timing requirements. [ABSTRACT FROM AUTHOR]

Increasing numbers of hospitalized children, institutionalized elderly, and other vulnerable populations around the world are receiving special treatments from "clownical" members of clinical teams. Integrating humor into healthcare is flourishing and for good reason; feeling good is good for us. [ABSTRACT FROM AUTHOR]

This article examines humour and its connectedness to spatiality in social work by drawing on examples from fieldwork involving vulnerable young people. The article argues that the relationship between a spatial perspective and humour as a phenomenon in social work is an underdeveloped area of social work research. The article draws on De Certeau's concepts of tactical behaviour and strategically defined spaces, both of which involve a dynamic spatial approach. Connecting these concepts to humour, the article concludes that applying a humour-affective spatial theoretical approach to social work research greatly aids the identification of power dynamics and the tensions that can arise in social situations. In short, the article offers another way of conceptualising the production of the spatial dynamics of power, inclusion and exclusion. The empirical basis for the article is a comprehensive field study carried out at a 24-hour residential institution for children and youth in vulnerable positions. [ABSTRACT FROM AUTHOR]

Background: This analysis investigates the efficacy of vortioxetine in adults with major depressive disorder (MDD) who report childhood or recent trauma.Methods: Patient-level data were analyzed from 4 double-blind, randomized, placebo-controlled short-term studies investigating the efficacy of vortioxetine (5-20 mg/day) versus placebo in patients (18-75 years old) with DSM-IV-TR-defined MDD. Changes from baseline to week 8 on the Montgomery-Åsberg Depression Rating Scale (MADRS), Hamilton Anxiety Rating Scale (HAM-A), Clinical Global Impression - Improvement (CGI-I), and Sheehan Disability Scale (SDS) were examined at the individual study level and as in meta-analysis. A long-term relapse prevention study of 5 and 10 mg of vortioxetine was also analyzed. Traumatic events history was recorded at baseline.Results: Sixty-one percent of subjects (1113/1811) reported trauma history in the short-term studies. A significant effect vs. placebo was observed for vortioxetine on MADRS (10 mg, -2.2, P = .025; 20 mg, -4.4, P < .001), HAM-A (20 mg, -1.60, P = .012), CGI-I (5 mg, -0.3, P = .028; 10 mg, -0.3, P = .013; 20 mg, -0.50, P = .009), and SDS (20 mg, -2.3, P = .007) in patients with any trauma (childhood and/or recent). In the relapse prevention study, 51% (198/392) of subjects reported a history of trauma. Subjects with any trauma (childhood and/or recent) randomized to placebo were significantly more likely to relapse than subjects treated with vortioxetine (hazard ratio 2.8, P = .0019).Limitations: An exploratory analysis.Discussion: Vortioxetine showed significant short- and long-term efficacy on depressive and anxiety symptoms and overall functioning in this large subpopulation of MDD patients with a history of trauma. A significantly lower risk of relapse was also observed with vortioxetine. [ABSTRACT FROM AUTHOR]

Peyronie's disease (PD) is a superficial fibrosing disorder that causes penile deformity and can interfere with sexual intercourse and reproduction, as well as diminish quality of life. While the exact mechanism of PD is still being investigated, there is likely a genetic component to the predisposition to penile plaque formation. Ultimately, however, perturbations in normal wound healing and aberrant deposition of extracellular matrix components lead to fibrotic tissue deposition. Fibrosis in PD is regulated by a complex pathway of inflammatory and fibrotic mediators. Currently there are no treatments for PD that address an underlying cause or disease progression. In this review, we provide an overview of the known inflammatory and fibrotic mediators of PD and explore the pathophysiology of other human superficial fibrosing disorders to develop further insights into PD. [ABSTRACT FROM AUTHOR]

Objective: To determine the cost-effectiveness of vortioxetine vs duloxetine in adults with moderate-to-severe major depressive disorder (MDD) in Norway using a definition of a successfully treated patient (STP) that incorporates improvement in both mood symptoms and functional capacity.Methods: Using the population of patients who completed the 8-week CONNECT study, the cost-effectiveness of vortioxetine (n = 168) (10-20 mg/day) vs duloxetine (n = 176) (60 mg/day) was investigated for the treatment of adults in Norway with moderate-to-severe MDD and self-reported cognitive dysfunction over an 8-week treatment period. Cost-effectiveness was assessed in terms of cost per STP, defined as improvement in mood symptoms (≥50% decrease from baseline in Montgomery-Åsberg Depression Rating Scale total score) and change in UCSD [University of California San Diego] performance-based skills assessment [UPSA] score of ≥7. The base case analysis utilized pharmacy retail price (apotek utsalgspris (AUP)) for branded vortioxetine (Brintellix) and branded duloxetine (Cymbalta).Results: After 8 weeks of antidepressant therapy, there were more STPs with vortioxetine than with duloxetine (27.4% vs 22.5%, respectively). The mean number needed to treat for each STP was 3.6 for vortioxetine and 4.4 for duloxetine, resulting in a lower mean cost per STP for vortioxetine (NOK [Norwegian Kroner] 3264) than for duloxetine (NOK 3310) and an incremental cost per STP of NOK 3051. The use of a more challenging change in the UPSA score from baseline (≥9) resulted in a mean cost per STP of NOK 3822 for vortioxetine compared with NOK 3983 for duloxetine and an incremental cost per STP of NOK 3181.Conclusions: Vortioxetine may be a cost-effective alternative to duloxetine, owing to its superior ability to improve functional capacity. The dual-response STP concept introduced here represents a more comprehensive analysis of the cost-effectiveness of antidepressants. [ABSTRACT FROM AUTHOR]

Achnatherum inebrians is a perennial grass widely distributed in northwest China. Nearly all wild A. inebrians plants are infected by Epichloë endophytes. In this study, bacteria from the phyllosphere were isolated from leaves of both endophyte‐free and endophyte‐infected A. inebrians and sequenced for identification. Pseudomonas, comprising 48.12% of the culturable bacterial communities, was the most dominant bacterial genus. Thirty‐four strains from 12 Pseudomonas species were used to inoculate A. inebrians seeds and plants. Results indicated that Epichloë significantly increased the diversity and richness index of the phyllosphere. Pseudomonas Sp1, Sp3, Sp5 and Sp7 had a significantly positive effect on plant growth and photosynthesis, whereas Sp10, Sp11 and Sp12 had a significantly negative effect. Whole‐genome and pan‐genome analysis suggested that the variability in the effects of Pseudomonas on A. inebrians was related to differences in genome composition and genomic islands. [ABSTRACT FROM AUTHOR]

Despite common practice, inhomogeneous and/or anisotropic diffusion cannot be considered without regarding the microscopic details breaking the translational and/or angular symmetry. The macroscopic diffusion equation and the stationary solution are determined by the microscopic model and depend in general on all the microscopic parameters and not simply on the combination in the diffusion tensor. The traditional diffusion equation is only valid under special conditions and it cannot, in general, be used for anisotropic diffusion. An alternative form of the diffusion equation has a wider range of applicability. It is shown that for isotropic diffusion all variants of the diffusion equation are mathematically (but not physically) equivalent and can be transformed into each other by introduction of effective potentials. This is not the case for anisotropic diffusion where the traditional diffusion equation in most cases will give incorrect results. Two examples illustrate the differences between the two dynamic equations with respect to stationary solutions and detailed balance. © 2003 American Institute of Physics. [ABSTRACT FROM AUTHOR]

Highlights • Delaying sowing date shortened time of emergence of maize, Sudan grass, foxtail millet and Japanese millet. • Variation of leaf area per plant of three forage crops was caused by leaf area elongation rate (LAER). • The relationship between final leaf number on main culm and climatic conditions varied with forage species. • Maize, Sudan grass, foxtail millet and Japanese millet displayed a strong phenotypic plasticity. Abstract Annual forage crops attract more attention to researchers for it can be used as both forage in animal production and ethanol production in industry. Sowing date are critical to increase crop yield potential in semi-arid environments. Successful establishment and canopy develop are two key aspects ensuring the final yield of forage crop. Therefore, emergence time, leaf appearance and solar radiation interception by the canopy were measured with four annual forage grasses [maize (Zea mays), Sudan grass (Sorghum sudanense Stapf., S), foxtail millet (Setaria italic) and Japanese millet (Echinochloa crus-galli var. frumentacacea)] during the period of 2011–2013 in the western Loess Plateau of China. The results showed that a delay of sowing date could decrease the time for crop emergence. In addition, a decrease in the final leaf number (FLN) and the individual leaf area (ILA) (maize, foxtail millet and Japanese millet) from delayed sowing resulted in less light interception (RI). The variation FLN was closely related to day length (DL) and initial soil water and rainfall at flowering (W s +R f) for maize and foxtail millet, thermal time (TT), DL and W s +R f for Sudan grass and Japanese millet. Changes in leaf area per plant (LA single) in Sudan grass, foxtail millet and Japanese millet were caused by leaf area elongation rate (LAER). Sowing date did not affect leaf appearance rate (LAR) in Japanese millet while decreased in Sudan grass and increased in foxtail millet when the sowing date was delayed, mainly due to changes in DL, TT and W s +R f. Variations in individual leaf area (ILA) and LAER indicated the strong plasticity of the four crop species. Therefore, the results of this study improved the understanding of the relationship between sowing date and canopy development and provide important information in crop management and breeding to increase the crop yield. [ABSTRACT FROM AUTHOR]

Background: The University of California San Diego Performance-based Skills Assessment (UPSA) has been validated as a functional measure in patients with major depressive disorder (MDD). The study herein aims to both replicate and extend the initial validation incorporating data sets from two additional studies.Methods: NCT02279966 and NCT02272517 were multinational, double-blind, placebo-controlled studies in adult outpatients with moderate-to-severe MDD and a current major depressive episode of ≥3 months and less than 1 year, respectively. Subjects were randomized to vortioxetine (10 or 20 mg), placebo or active reference drug (paroxetine [20 mg], or escitalopram [10 or 20 mg]) for 8 weeks. Pearson correlation coefficients were estimated for baseline UPSA-Brief (UPSA-B), demographic/disease characteristics, Montgomery-Åsberg Depression Rating Scale (MADRS), Perceived Deficit Questionnaire-20 items (PDQ-20), and Digit Symbol Substitution Test (DSST), to examine construct validity. Distribution- and anchor-based methods examined clinically important difference (CID) threshold. A pooled analysis with data from NCT01564862 (initial validation study) was performed to increase the statistical power of the estimations.Results: In pooled analysis of the two new studies, UPSA-B score correlated with the DSST (r = 0.32, P < 0.0001), but not the MADRS (r = -0.07, p = 0.302) or the PDQ-20 (r = -0.10, p = 0.109), replicating initial validation results. Estimated CID range was 7.1-11.2 and 5.5-6.1 points for anchor- and distribution-based methods, respectively. In pooled analyses of all three studies, the CID was 7.0 and 6.4 for anchor- and distribution-based methods, respectively.Conclusions: These results confirm the construct validity of UPSA for assessing functional capacity in patients with MDD. Estimated CID using UPSA is approximately 6-7 points.Trial Registration: ClinicalTrials.gov identifier: NCT01564862; NCT02272517; NCT02279966. [ABSTRACT FROM AUTHOR]

When expressing the margin of stability as a distance, it does not directly estimate the perturbation magnitude needed to change stability states. Additionally, it is unknown how body size may influence this measure. Therefore, we propose other expressions of stability margins, including that of an impulse, a change in center of mass velocity, and a scaled, unitless impulse. The purpose of this study was to determine the influence of body size on these margin expressions using walking data from children and adults. We anticipated that margins expressed as an impulse would have strong correlations with body mass and height, as well as large between-group differences. We predicted that scaling this impulse value would result in small correlations and between-group effect sizes. We calculated each stability margin at minimum lateral values and in the anteroposterior directions at mid-swing and foot strike. In the lateral direction, margins expressed as an impulse had strong correlations with body size (r≥0.58, p<0.01) and large between-group differences (|d|≥1.07, p<0.01). The other expressions did not have strong positive correlations (|r|≤0.20) or large between-group effects (|d|≤0.44). In the anteroposterior directions, impulse margins had strong correlations with body size (|r|≥0.83, p<0.01) and large between-group differences (|d|≥1.74, p<0.01). The scaled, unitless impulse margin was the only variable that resulted in small, non-significant differences (|r|≤0.22, p≥0.24) as well as small between-group effect sizes (|d|≤0.46, p≥0.22). We propose expressing stability margins as an impulse. If scaling is needed, we encourage using the scaled, unitless impulse. [ABSTRACT FROM AUTHOR]

OBJECTIVE To evaluate age, adjunctive antiseizure medication (ASM), and specific ASMs on lacosamide (LCM) weight normalized dose-to-concentration ratio (DCR) and US Food and Drug Administration (FDA) dosing guidelines in pediatric patients. METHODS Patients 1 mo to ≤18 years with a LCM serum concentration between October 2009 and June 2017 were considered. Demographics, LCM DCR, and adjunctive ASM were recorded. LCM DCR/hr was used as a surrogate for clearance. Data were stratified by age (1 mo-< 2 yr; ≥ 2–6 yr; ≥ 6–12 yr; and ≥12–≤18 yr), FDA dosing weights, and ASM potential to interaction with LCM. RESULTS There were 646 sera (380 patients) with median dose 8.36 mg/kg/day (IQR, 5.92–11.16). 50.2% of doses were within FDA-weight guidelines; however, 40.4% exceeded recommendations. Most (81.3%) LCM concentrations were between 2 and 12 mg/L. A difference existed in DCR between ages, with those <2 years having the highest DCR (p < 0.001). Moving across age groups, the DCR decreases by 30.7%, 50.5%, and 63.4%. There was a weak (r2 = 0.073) but significant (p < 0.001) negative correlation between DCR and age. 84.8% received adjunctive ASM consisting of at least one of 31 different ASMs. DCR was higher with adjunctive ASMs compared with monotherapy [0.061 (0.039–0.095) vs 0.043 (0.030–0.062)], respectively (p < 0.001) and was greatest with inducers. Phenobarbital increased DCR by 2.6-fold, topiramate by 72.1%, and clobazam by 32.6%. Inhibitors had no effect. CONCLUSIONS The correlation between age and DCR was weak, accounting for 6% of variability. Strong inducers significantly increased DCR. Synergy may exist when multiple inducers are given. Weak inhibitors did not affect DCR. Those ≥6 to 11 kg, ≥30 to 50 kg, and those given strong inducers may require larger initial LCM doses. Serum concentrations should be used to individualize dosing, especially in those receiving strong inducers. [ABSTRACT FROM AUTHOR]

Inactin is a long lasting anesthetic agent commonly used in rat studies, but is also shown to exert physiological effects such as reducing renal blood flow, glomerular filtration rate and depressing tubular transport capacity. The effect of inactin on isolated kidney mitochondria is unknown and may be important when studying related topics in anaesthetized animals. The aim of this study was to determine whether inactin exerts effects on mitochondrial function and production of reactive oxygen species. Kidney mitochondrial function and production of reactive oxygen after acutely (5 min) or longer (1.5 hour) anesthetizing rats with inactin was evaluated using high-resolution respirometry. The results demonstrate that inactin significantly improves respiratory control ratio, inhibits complex I in the mitochondrial respiratory chain, reduce both unregulated proton leak and time dependently reduce the regulated proton leak via uncoupling protein-2 and adenine nucleotide translocase. Inactin also contributes to increased mitochondrial hydrogen peroxide production. In conclusion, inactin exerts persistent effects on mitochondrial function and these profound effects on mitochondrial function should to be considered when studying mitochondria isolated from animals anesthesized with inactin. [ABSTRACT FROM AUTHOR]

Abstract: The immense amount of electronic health data (pharmacy and administrative claims, electronic health records, and clinical registries) that is being generated every day in the care of patients has the potential to be leveraged for improving clinical decisions at the point of care, uncovering or validating drug efficacy and drug safety. The potential use of big data for improving safe and effective use of medications is especially important in children because of their low drug exposure relative to adults. Electronic health data is collected primarily for clinical or billing purposes and not for research purposes. The major steps involved in data acquisition, extraction, aggregation, analysis, modeling, and interpretation are discussed. It is important to understand the limitation of big data and utilize appropriate study design and statistical methods. Possible applications are presented along with specific examples of how big data has been used in drug research to find that blip on the radar screen that may give an efficacy or safety signal that can lead to further investigation. [ABSTRACT FROM AUTHOR]

Background: Efficacy has been proven for vortioxetine in short-term and long-term treatment of major depressive disorder (MDD), with broad beneficial effects on emotional, physical and cognitive symptoms. Limited specific data on the effects of vortioxetine on depression-related physical symptoms have been published.Methods: A meta-analysis was carried out of five short-term multinational, double-blind, placebo-controlled studies. These studies were conducted in a total of 2105 adult MDD outpatients (18-75 years) with a major depressive episode of ⩾3 months' duration. Only patients treated with a dose of 5 or 10 mg vortioxetine (therapeutic doses) or placebo were included in this analysis. Efficacy assessment of vortioxetine on the physical symptoms of depression included all items of the Hamilton Depression Scale (HAM-D) assessing physical symptoms, and all somatic items in the Hamilton Anxiety Scale (HAM-A). A subgroup analysis in MDD patients with coexisting anxiety symptoms (i.e. those with a HAM-A ⩾20 at baseline) was also performed.Results: A significant improvement ( p<0.05) of vortioxetine versus placebo was observed on all HAM-D items measuring physical symptoms, except for the somatic gastrointestinal symptoms and loss of weight items. Significant effects were also observed on the HAM-A somatic items: general somatic symptoms, gastrointestinal symptoms, and autonomic symptoms. In patients with a high baseline level of anxiety, a significant effect of vortioxetine was also observed on the physical symptoms of depression.Conclusions: These analyses indicate that patients with MDD, including those with a high level of anxiety symptoms, have significant improvements in MDD-associated physical symptoms when treated with vortioxetine. [ABSTRACT FROM AUTHOR]

Purpose: The objective of this study was to determine the associations of strabismus surgery reoperation rates in a large national database of provider payments with geographic region, practice type and volume, and the availability of adjustable suture technique.Methods: Fee-for-service payments to providers for medicare beneficiaries having strabismus surgery between 2012 and 2015 were retrospectively analyzed to identify reoperations in the same calendar year. The adjustable-suture technique was considered to be available to the patient if the patient's surgeon billed for adjustable sutures. Predictors of reoperation in the same calendar year were determined by multivariable logistic regression.Results: Availability of the adjustable suture technique was not associated with reoperation rate in multivariable analysis among 5971 patients having horizontal muscle surgery (odds ratio, [OR] 0.86, P = 0.29), 2840 patients having vertical muscle surgery (OR 0.98, P = 0.93), or 1199 patients having surgery with scarring or restriction (OR 0.86, P = 0.61). For horizontal surgery, the reoperation rate was higher in academic practices (OR 1.67), as compared with community practices, and in the South (OR 2.85) and West (OR 1.92, all P < 0.001). The reoperation rate was unchanged with surgeons in the lowest-quartile of surgical volume. Among surgeons paid for horizontal surgery, 45% of surgeons in the Northeast, the West, or Florida coded for adjustable sutures, compared with 8% of surgeons elsewhere (P < 0.001).Conclusion: The availability of the adjustable-suture technique was not associated with reoperation rate after strabismus surgery in this large national database. Having surgery by a lower-volume surgeon was not associated with a higher reoperation rate. The reoperation rate was higher when surgery was conducted in an academic practice, or in certain regions of the country. Adjustable sutures are largely a bicoastal practice. [ABSTRACT FROM AUTHOR]

Background: Major depressive disorder (MDD) is associated with significant impairments in health-related quality of life (HRQoL) and everyday functioning. This cohort study investigated the long-term development of HRQoL in patients with MDD and its association with patient characteristics, including depressive symptom severity and cognitive symptoms.Methods: The Prospective Epidemiological Research on Functioning Outcomes Related to Major depressive disorder (PERFORM) study was a longitudinal cohort study conducted in 1,159 outpatients aged 18–65 years with MDD in France, Germany, Spain, Sweden, and the UK. The patients were either initiating antidepressant monotherapy or undergoing their first switch of antidepressant. HRQoL was assessed using the Medical Outcomes Study Short-Form 12-item Health Survey (SF-12) up to month 12 and the EuroQol Five Dimensions questionnaire up to month 24 (UK only). Depressive symptom severity was assessed up to month 24 by the patient-reported Patient Health Questionnaire and cognitive symptoms by the Perceived Deficit Questionnaire. Multivariate analyses were performed to identify patient characteristics associated with HRQoL.Results: Mental HRQoL was severely impaired at baseline versus normative data (mean [SD] SF-12 mental component summary [MCS], 26.5 [9.2]); mean (SD) physical component summary (PCS) total score was 45.2 (12.1). SF-12 MCS improved over 12 months of follow-up (38.7 [11.6] at month 12), while SF-12 PCS remained stable (45.3 [11.1]). At each assessment time point, there was a clear pattern of lower SF-12 MCS and PCS total score in patients experiencing greater cognitive problems. The mean EuroQol Five Dimensions questionnaire utility index score generally decreased (i.e., worsened) with increasing severity of cognitive and depressive symptoms at all time points up to 24 months. Multivariate analyses identified both depression severity and cognitive symptoms as strongly and significantly associated with poor HRQoL.Conclusion: These findings highlight the importance of recognizing and managing residual symptoms in patients with MDD, including the cognitive symptoms, to restore long-term psychosocial functioning. [ABSTRACT FROM AUTHOR]

Background and aims: This study explored the effects of Epichloë gansuensis endophyte on water use efficiency (WUE), nutrient content and biomass accumulation of Achnatherum inebrians (drunken horse grass, DHG) under varying water availability. It also examined possible transgenerational effects (TGE) on above indicators.Methods: DHG with (EI) and without endophyte (EF), from seed of plants of the same seed-line that had been grown in Yuzhong (YZ-D, relatively dry) and Xiahe (XH-W, relatively wet), were grown under limited water conditions (LWC). Plant height, leaf number and chlorophyll content were monitored dynamically. After 10 weeks, the biomass, photosynthetic indexes and C, N, P content of plants was determined.Results: The endophyte increased plant height and chlorophyll content, but decreased plant leaf number, and the CO2 concentration, while increasing other photosynthetic indexes. The biomass, N and P content were higher in EI than EF plants of the YZ-D DHG, but not the C content and root weight. However, there were almost no significant affects on these factors between EI and EF plants of the XH-W DHG.Conclusions: The endophyte enhanced WUE and maintained the growth of plants under LWC by improving photosynthetic efficiency and promoting nutrient absorption. However, TGE also affected this process. [ABSTRACT FROM AUTHOR]

Background: With symptomatic remission and functional recovery as the overarching therapeutic objectives of antidepressant therapy, composite endpoint measures that conjointly consider both aspects of treatment are needed. This analysis evaluated the combined effect of vortioxetine on depressive symptoms and functional capacity in adults with MDD.Methods: NCT01564862, a multinational, double-blind, placebo-controlled, duloxetine-referenced study, conducted between April 2012 and February 2014, in 602 adult outpatients (18-65 years) with moderate-to-severe MDD (Montgomery-Åsberg Depression Rating Scale (MADRS) ≥ 26), a major depressive episode of ≥ 3 months' duration, and self-reported cognitive symptoms were randomized to once-daily vortioxetine (10 or 20mg), duloxetine (60mg), or placebo for 8 weeks. Assessments included the University of California San Diego Performance-based Skills Assessment (UPSA) and the MADRS. Two versions of UPSA were utilized; UPSA ‒Validation of Intermediate Measures and UPSA Brief form. An aligned UPSA-B (communication and finance items) was examined for sensitivity analysis. Efficacy was analyzed versus placebo according to the dual response (change from baseline in UPSA ≥ 7 and ≥ 9 and reduction in MADRS total score from baseline ≥ 50%).Results: Significantly more vortioxetine-treated patients were classified as dual responders for change in MADRS total score and UPSA score of ≥ 7 (clinically important difference [CID]) (27.4% vs 14.5%; P = 0.004), and change above CID (≥ 9) (23.4% vs 13.9%; P = 0.025). Duloxetine did not differ significantly from placebo for these dual response criteria. Sensitivity analysis using the aligned UPSA-B confirmed these results for vortioxetine.Limitations: An exploratory analysis of a new dual outcome measure in patients with MDD.Conclusions: Vortioxetine, but not duloxetine, demonstrated a robust combined effect on depressive symptoms and functional capacity in patients with MDD.Trial Registration: ClinicalTrials.gov identifier: NCT01564862; European Clinical Trials Database [EudraCT] Number 2011-005298-22. [ABSTRACT FROM AUTHOR]

Background: This retrospective chart review compared the higher-order aberrations (HOAs) among photorefractive keratectomy (PRK), laser-assisted in situ keratomileusis (LASIK), and small incision lenticule extraction (SMILE) alongside changes in spherical equivalent (SEQ) and corneal shape (Q-value). Methods: Analyzing 371 myopic eyes, including 154 LASIK, 173 PRK, and 44 SMILE cases, Pentacam imaging was utilized pre-operatively and at one-year post-operative visits. Results: All procedures resulted in 100% of patients achieving an uncorrected distance visual acuity (UDVA) of 20/40 or better, with 87% of LASIK and PRK, and 91% of SMILE patients having 20/20 or better. Significant increases in HOAs were observed across all procedures (p < 0.05), correlating positively with SEQ and Q-value changes (LASIK (0.686, p < 0.05), followed by PRK (0.4503, p < 0.05), and SMILE (0.386, p < 0.05)). Vertical coma and spherical aberration (SA) were the primary factors for heightened aberration magnitude among the procedures (p < 0.05), with the largest contribution in SMILE, which is likely attributed to the centration at the corneal apex. Notably, PRK showed insignificant changes in vertical coma (−0.197 µm ± 0.0168 to −0.192 µm ± 0.0198, p = 0.78), with an increase in oblique trefoil (p < 0.05). Conclusions: These findings underscore differences in HOAs among PRK, LASIK, and SMILE, helping to guide clinicians. [ABSTRACT FROM AUTHOR]

Purpose To assess the effect of varying levels of torsional power on phacoemulsification efficiency using an active-fluidics phacoemulsification platform with a 0.7 mm Sonata tip. Setting John A. Moran Eye Center Laboratories, University of Utah, Salt Lake City, Utah, USA. Design Experimental study. Methods A 0.7 mm tip was used to emulsify 2.0 mm porcine lenses that had been hardened in formalin. The torsional power was varied from 10% to 100% at intervals of 10%, and efficiency and chatter were recorded. A comparison of the 0.7 mm tip with the 0.9 mm Balanced tip was also performed. Using a torsional power setting of 90% and 100%, the 0.7 mm tip and the 0.9 mm tip efficiency times were recorded. Results The study showed an increase in efficiency as torsional power increased. The relationship was linear and more efficient up to 90% ( R 2 = .8025, P = .0005). Chatter was only observed at a torsional power setting of 60%. In addition, a head-to-head comparison of the 0.7 mm tip with the 0.9 mm tip showed that both tips were statistically similar in efficiency times, despite the smaller diameter of the 0.7 mm tip. Conclusions The optimum torsional power setting with the Centurion platform in conjunction with the 0.7 mm tip was 90%. The efficiency of the 0.7 mm tip and the 0.9 mm tip was statistically similar. [ABSTRACT FROM AUTHOR]

Lespedeza davurica, a major semi-shrub leguminous plant of the vast semi-arid grasslands in northwest China, has decreased greatly in abundance due to overgrazing. Seed characteristics and fungal pathogens affect seedling recruitment from soil seed banks. However, little is known about how grazing affects seed characteristics and fungal colonization on seeds. Seeds of L. davurica were obtained both from plants and from soil from plots where four intensities of grazing (0, 2.7, 5.3 and 8.7 sheep/ha) had been applied for 13 years. The morphological and germination characteristics and colonization of seed by fungi were examined. Seed size showed a hump-shaped trend with increasing grazing intensity. With freshly harvested seed, the intensity of 8.7 sheep/ha significantly enhanced germination and extended the time over which germination occurred. The occurrence of pathogenic Fusarium species on seeds decreased with increasing grazing intensity. Our study strongly suggests that the intensity of grazing can alter seed morphological and germination characteristics, as well as the colonization of fungi on seeds. Additional studies involving more members of the plant community are needed to determine whether the intensity of grazing results in a compensatory mechanism that serves to enhance the possibility of plant recruitment from seeds under field conditions. [ABSTRACT FROM AUTHOR]

Aims: Plant-soil feedbacks (PSFs) and grazing drive community dynamics in grasslands. We examined how the intensity of grazing and PSF interact to affect plant growth and explored what drives the observed feedback effects. Methods: Three dominant perennial plant species; Artemisia capillaris, Lespedeza davurica, and Stipa bungeana were grown in field-conditioned soil (sterilized or unsterilized) collected from four grazing intensities in a semiarid grassland of northwest China. Soil nutrient concentrations and root fungal communities were determined. Results: Plant biomass increased with grazing intensity for the three plant species. Within each grazing intensity, plant growth in sterilized soil relative to unsterilized soil differed markedly among species. Soil inorganic nitrogen (N) concentration tended to increase with increasing grazing intensity. Arbuscular mycorrhizal fungi (AMF) colonization was high for all grazing intensities for L. davurica. Fusarium tricinctum, the most common pathogenic Fusarium species, had the highest frequency from the control for A. capillaris and tended to increase with increasing grazing intensity for S. bungeana. Conclusions: Our results suggest that in grasslands plant growth can be modified by the intensity of grazing via grazing-induced changes in soil nutrient availability and fungal communities. Additional studies are needed to determine how grazing intensity affects species co-existence through PSFs to mixed communities. [ABSTRACT FROM AUTHOR]

Background: Intracerebral hemorrhage (ICH) is the deadliest and most disabling form of stroke. Little is known about the causes of persistent neurological impairment among ICH survivors.Methods: Factor seven for acute hemorrhagic stroke (FAST) was a randomized, multicenter, double-blind, placebo-controlled trial conducted at 122 sites in 22 countries. Neurological impairment was evaluated according to the NIHSS in all patients at hospital admission, and at days 1, 2, 3, 15 and day 90 after ICH onset. Multivariate stepwise logistic regression was applied to identify predictors of neurological impairment 90 days after hospital admission.Results: A total of 821 patients were enrolled; 638 survivors were evaluated with the NIHSS at day 90. Mean NIHSS score at admission was 13.2 (SD 6.6), decreasing to 9.6 (SD 7.7) at day 15 and 5.1 (SD 5.5) at day 90. Twenty-five percent of patients had severe neurological impairment (NIHSS ≥ 15) at baseline compared to 6% of those alive at day 90. Neurological worsening within the first 72 h (defined as worsening of GCS of two or more points or increase in NIHSS score ≥ 4) predicted greater neurological impairment at day 90 in all models. A decrease of <10% in systolic blood pressure (SBP) within the first 24 h was significantly associated with less severe neurologic impairment compared to more severe reductions.Conclusion: Neurological deterioration within 24 h of ICH onset is a powerful determinant of persistent neurological impairment. Careful reduction of the SBP by 1–10% in the first 24 h may lower the risk. [ABSTRACT FROM AUTHOR]

For decades, epineurial electrodes have been used in clinical therapies involving the stimulation of peripheral nerves. However, next generation peripheral nerve interfaces for applications such as neuroprosthetics would benefit from an increased ability to selectively stimulate and record from nerve tissue. This increased selectivity may require the use of more invasive devices, such as the Utah Slanted Electrode Array (USEA). Previous research with USEAs has described the histological response to the implantation of these devices in cats and rats; however, no such data has been presented in humans. Therefore, we describe here the degree of penetration and foreign body reaction to USEAs after a four-week implantation period in human median and ulnar nerves. We found that current array designs penetrate a relatively small percentage of the available endoneurial tissue in these large nerves. When electrode tips were located within the endoneurial tissue, labels for axons and myelin were found in close proximity to electrodes. Consistent with other reports, we found activated macrophages attached to explanted devices, as well as within the tissue surrounding the implantation site. Despite this inflammatory response, devices were able to successfully record single- or multi-unit action potentials and elicit sensory percepts. However, modifying device design to allow for greater nerve penetration, as well as mitigating the inflammatory response to such devices, would likely increase device performance and should be investigated in future research. [ABSTRACT FROM AUTHOR]

Mechanical stimulation of cell cultures has been shown be an effective means of enhancing ECM production. ECM produced from vocal fold fibroblast cultures has the potential for therapeutic use for vocal fold repair. However, current bioreactor designs generally fail to produce physiological relevant frequency and strain values. Here we present an approach for using commercial oscillatory rheometers and an elastic ring bilayer system to produce physiologically relevant strain values at frequencies in the range of 20–100 Hz. We demonstrate the ability to target specific strain and frequency values by manipulating system parameters, and also show that it is possible to maintain high oscillatory strains for extended periods of time. Such a system could be used to mechanically stimulate cell cultures contained within gel carrier systems and has the potential to be extended to other applications requiring high strains at low frequencies. [ABSTRACT FROM AUTHOR]

Considerable progress has been made in pediatric drug development. Despite these gains there remain certain therapeutic areas where a high percentage of drugs approved for use in adults do not gain approval for use in children. Lack of sufficient US Food and Drug Administration (FDA)-approved labeling correlates with diminished therapeutic efficacy and increased risk for adverse drug reactions. Despite the increasing prevalence and important clinical challenge with pediatric type 2 diabetes mellitus (T2DM), only 1 drug (metformin) of the first 4 T2DM drugs to complete testing in children gained FDA approval. This analysis reviews 4 pediatric drug development programs for orally administered antidiabetic agents that have undergone FDA review and discusses factors influencing failure to meet specified end points for approval. Recommendations to guide future study are also provided. [ABSTRACT FROM AUTHOR]

Voter studies conducted in the United States during the first decades after World War II transformed social scientific research on democracy. Especially important were the rapid innovations in survey research methods developed by two prominent research centers at Columbia University and the University of Michigan. This article argues that the Columbia and Michigan voter studies presented two visions for research on democracy. Where the Michigan research produced quantitative measures expressing the 'political behavior' of the electorate, the Columbia studies, and especially Paul F. Lazarsfeld, presented an alternative vision for qualitative research on political choice. Largely ignored by later voter studies, this vision prefigured much contemporary research on democracy that embraces a qualitative or interpretive approach. This article reconstructs Lazarsfeld's alternative vision, describes the institutional context in which scholars disregarded it in favor of formal quantitative models, and argues for its recognition as a forerunner to qualitative research on democratic processes. [ABSTRACT FROM AUTHOR]