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ImportanceBefore surgery, the best strategy for managing patients who are taking renin-angiotensin system inhibitors (RASIs) (angiotensin-converting enzyme inhibitors or angiotensin receptor blockers) is unknown. The lack of evidence leads to conflicting guidelines.ObjectiveTo evaluate whether a continuation strategy vs a discontinuation strategy of RASIs before major noncardiac surgery results in decreased complications at 28 days after surgery.Design, setting, and participantsRandomized clinical trial that included patients who were being treated with a RASI for at least 3 months and were scheduled to undergo a major noncardiac surgery between January 2018 and April 2023 at 40 hospitals in France.InterventionPatients were randomized to continue use of RASIs (n = 1107) until the day of surgery or to discontinue use of RASIs 48 hours prior to surgery (ie, they would take the last dose 3 days before surgery) (n = 1115).Main outcomes and measuresThe primary outcome was a composite of all-cause mortality and major postoperative complications within 28 days after surgery. The key secondary outcomes were episodes of hypotension during surgery, acute kidney injury, postoperative organ failure, and length of stay in the hospital and intensive care unit during the 28 days after surgery.ResultsOf the 2222 patients (mean age, 67 years [SD, 10 years]; 65% were male), 46% were being treated with angiotensin-converting enzyme inhibitors at baseline and 54% were being treated with angiotensin receptor blockers. The rate of all-cause mortality and major postoperative complications was 22% (245 of 1115 patients) in the RASI discontinuation group and 22% (247 of 1107 patients) in the RASI continuation group (risk ratio, 1.02 [95% CI, 0.87-1.19]; P = .85). Episodes of hypotension during surgery occurred in 41% of the patients in the RASI discontinuation group and in 54% of the patients in the RASI continuation group (risk ratio, 1.31 [95% CI, 1.19-1.44]). There were no other differences in the trial outcomes.Conclusions and relevanceAmong patients who underwent major noncardiac surgery, a continuation strategy of RASIs before surgery was not associated with a higher rate of postoperative complications than a discontinuation strategy.Trial registrationClinicalTrials.gov Identifier: NCT03374449.

BackgroundA limited number of single institutions have published retrospective cohort studies on transoral laser microsurgery for supraglottic laryngectomy (TLM-SGL). These studies have shown that the oncologic outcomes of TLM-SGL are comparable to those of open SGL. However, there is limited information available regarding swallowing rehabilitation and quality of life (QoL).Patients and methodsSUPRATOL is a prospective, multicenter trial assessing the functional outcomes of TLM-SGL +/− adjuvant radio-(chemo)-therapy. The primary endpoint was aspiration-free swallowing at 12 months, as established using fibreoptic endoscopic evaluation of swallowing (FEES) and defined as a grade < 6 on the penetration–aspiration scale. Secondary endpoints were swallowing- and voice-related QoL, the prevalence of temporary and permanent tracheostomy and percutaneous gastrostomy, local control, laryngectomy-free survival, overall survival, and disease-free survival, as well as the influence of treatment centers on outcomes.ResultsFrom April 2015 to February 2018, 102 patients were recruited from 26 German Otorhinolaryngology (ORL) hospitals. All patients had TLM-SGL and 96.1% underwent uni- or bilateral, mostly selective neck dissection. To 47.0% of patients, adjuvant radio-(chemo)-therapy (R(C)T) was administered. The median follow-up period was 24.1 months. At 12-month follow-up, completed by 84.3% of patients, 98.2%, 95.5%, and 98.8% were free of aspiration when tested with saliva, liquid, or pulp. Adjuvant R(C)T, pT category, and type of resection had no significant influence on swallowing rehabilitation. A total of 40.2% of patients had been tracheotomized, and in 46.1% of patients, a PEG tube was inserted. At the 24-month follow-up, 5.3% of patients still required a tracheostomy, and 8.0% continued to use a percutaneous endoscopic gastrostomy (PEG) tube. Deterioration of swallowing- and voice-related QoL was observed immediately after treatment, but patients recovered, and baseline values were reached again. The Kaplan–Meier 2-year rates for local control, laryngectomy-free survival, overall survival, and disease-free survival were 88%, 92%, 93%, and 82%, respectively.ConclusionsOur prospective multicenter trial shows that, at 12 months post-TLM-SGL +/− R(C)T, 95.5%–98.8% of patients achieved aspiration-free swallowing. Morbidity was higher than previously reported. The rates of permanent tracheostomy and gastrostomy tube placement correspond to previous cohort studies. The 2-year oncologic outcomes are within the reported range.Clinical trial registrationhttps://drks.de/search/en/trial/DRKS00004641, identifier (DRKS00004641).

The European Larynx Organ Preservation Study (ELOS; NCT06137378) is a prospective, randomized, open-label, two-armed parallel group controlled, phase II multicenter larynx organ preservation (LOP) trial in locoregionally advanced (LA) stage III, IVA/B head and neck squamous cell carcinoma of the larynx or hypopharynx (LHSCC) amenable for total laryngectomy (TL) with PD-L1 expression within tumor tissue biopsy, calculated as CPS ≥ 1. Induction chemotherapy (IC) with docetaxel and cisplatin (TP) followed by radiation will be compared to TP plus PD-1 inhibition by pembrolizumab (MK-3475; 200 mg i.v. starting day 1 q3w for 17 cycles). After a short induction early response evaluation (ERE) 21 ± 3 days after the first cycle of IC (IC-1), responders achieving endoscopic estimated tumor surface shrinkage (ETSS) ≥30% will get an additional two cycles of IC followed by intensity-modulated radiotherapy 70–72 Gy (EQD2/α/β = 10) aiming at LOP. Nonresponders (ETSS < 30% or progressing disease) will receive TL and bilateral neck dissection followed by postoperative radiation or chemoradiation as recommended by the clinic’s multidisciplinary tumor board. Pembrolizumab treatment will be continued in the intervention arm regardless of ETSS status after IC-1 in both responders and laryngectomized nonresponders, independent of subsequent decisions on adjuvant therapy after TL.Clinical Trial Registrationclinicaltrials.gov, identifier NCT06137378.

We propose the hypothesis that small high-density lipoprotein (HDL) particles reduce the risk of Alzheimers disease (AD) by virtue of their capacity to exchange lipids, affecting neuronal membrane composition and vascular and synaptic functions. Concentrations of small HDLs in cerebrospinal fluid (CSF) and plasma were measured in 180 individuals ≥60 years of age using ion mobility methodology. Small HDL concentrations in CSF were positively associated with performance in three domains of cognitive function independent of apolipoprotein E (APOE) ε4 status, age, sex, and years of education. Moreover, there was a significant correlation between levels of small HDLs in CSF and plasma. Further studies will be aimed at determining whether specific components of small HDL exchange across the blood, brain, and CSF barriers, and developing approaches to exploit small HDLs for therapeutic purposes.

Carrying the apolipoprotein E (ApoE) Ɛ4 allele is associated with an increased risk of cerebral amyloidosis and late-onset Alzheimer's disease, but the degree to which apoE glycosylation affects its development is not clear. In a previous pilot study, we identified distinct total and secondary isoform-specific cerebral spinal fluid (CSF) apoE glycosylation profiles, with the E4 isoform having the lowest glycosylation percentage (E2 > E3 > E4). In this work, we extend the analysis to a larger cohort of individuals (n = 106), utilizing matched plasma and CSF samples with clinical measures of AD biomarkers. The results confirm the isoform-specific glycosylation of apoE in CSF, resulting from secondary CSF apoE glycosylation patterns. CSF apoE glycosylation percentages positively correlated with CSF Aβ42 levels (r = 0.53, p  E3 and increased binding affinity to heparin. These results indicate that apoE glycosylation has a new and important role in influencing brain Aβ metabolism and can be a potential target of treatment.

Panic disorder is a common psychiatric diagnosis characterized by acute, distressing somatic symptoms that mimic medically-relevant symptoms. As a result, individuals with panic disorder overutilize personal and healthcare resources in an attempt to diagnose and treat physical symptoms that are often medically benign. A biobehavioral perspective on these symptoms is needed that integrates psychological and medical knowledge to avoid costly treatments and prolonged suffering. This narrative review examines six common somatic symptoms of panic attacks (non-cardiac chest pain, palpitations, dyspnea, dizziness, abdominal distress, and paresthesia), identified in the literature as the most severe, prevalent, or critical for differential diagnosis in somatic illness, including long COVID. We review somatic illnesses that are commonly comorbid or produce panic-like symptoms, their relevant risk factors, characteristics that assist in distinguishing them from panic, and treatment approaches that are typical for these conditions. Additionally, this review discusses key factors, including cultural considerations, to assist healthcare professionals in differentiating benign from medically relevant symptoms in panic sufferers.

Abstract Carrying the apolipoprotein E (ApoE) Ɛ4 allele is associated with an increased risk of cerebral amyloidosis and late-onset Alzheimer’s disease, but the degree to which apoE glycosylation affects its development is not clear. In a previous pilot study, we identified distinct total and secondary isoform-specific cerebral spinal fluid (CSF) apoE glycosylation profiles, with the E4 isoform having the lowest glycosylation percentage (E2 > E3 > E4). In this work, we extend the analysis to a larger cohort of individuals (n = 106), utilizing matched plasma and CSF samples with clinical measures of AD biomarkers. The results confirm the isoform-specific glycosylation of apoE in CSF, resulting from secondary CSF apoE glycosylation patterns. CSF apoE glycosylation percentages positively correlated with CSF Aβ42 levels (r = 0.53, p E3 and increased binding affinity to heparin. These results indicate that apoE glycosylation has a new and important role in influencing brain Aβ metabolism and can be a potential target of treatment.

Local breeds are key components of livestock farming systems. They are part of livestock biodiversity and this diversity has been threatened since the second half of the 20th century by their replacement with animals from specialized breeds. The multiple benefits of farming systems using local breeds – provision of goods, landscape and environmental management, and uses related to cultural and heritage dimensions – have long been recognized and used to argue for their conservation. However, the notion of ecosystem services is rarely used to analyze those benefits. This article presents a qualitative approach to the provision of ecosystem services by farming systems that use livestock biodiversity. Based on diverse case studies of breeds from several species, we propose an analytical framework that accounts for how a service is qualified, who is concerned by the services identified, the role of the breed in the process of service provision, and interactions between services. Finally, the framework considers the links between the provision of services and the management of the breeds. We discuss to what extent the notion of ecosystem services is useful in dealing with the multiple benefits from farming systems using local breeds.

Apolipoprotein ε allele 4 (APOE4) influences the metabolism of polyunsaturated fatty acids (PUFAs) such as docosahexaenoic acid (DHA). The entorhinal cortex (EC) in the brain is affected early in Alzheimer's disease and is rich in DHA. The purpose of this study is to identify the effect of APOE4 and DHA lipid species on the EC. Plasma and cerebrospinal fluid (CSF) lipidomic measurements were obtained from the DHA Brain Delivery Pilot, a randomized clinical trial of DHA supplementation (n = 10) versus placebo (n = 12) for six months in nondemented older adults stratified by APOE4 status. Wild-type C57B6/J mice were fed a high or low DHA diet for 6 months followed by plasma and brain lipidomic analysis. Levels of phosphatidylcholine DHA (PC 38:6) and cholesterol ester DHA (CE 22:6) had the largest increases in CSF following supplementation (P < 0.001). DHA within triglyceride (TG) lipids in CSF strongly correlated with corresponding plasma TG lipids, and differed by APOE4, with carriers having a lower increase than noncarriers. Changes in plasma PC DHA had the strongest association with changes in EC thickness in millimeters, independent of APOE4 status (P = 0.007). In mice, a high DHA diet increased PUFAs within brain lipids. Our findings demonstrate an exchange of DHA at the CSF-blood barrier and into the brain within all lipid species with APOE having the strongest effect on DHA-containing TGs. The correlation of PC DHA with EC suggests a functional consequence of DHA accretion in high density lipoprotein for the brain.

Abstract Background Inducing brain ATP-binding cassette 1 (ABCA1) activity in Alzheimer’s disease (AD) mouse models is associated with improvement in AD pathology. The purpose of this study was to investigate the effects of the ABCA1 agonist peptide CS-6253 on amyloid-β peptides (Aβ) and lipoproteins in plasma and cerebrospinal fluid (CSF) of cynomolgus monkeys, a species with amyloid and lipoprotein metabolism similar to humans. Methods CS-6253 peptide was injected intravenously into cynomolgus monkeys at various doses in three different studies. Plasma and CSF samples were collected at several time points before and after treatment. Levels of cholesterol, triglyceride (TG), lipoprotein particles, apolipoproteins, and Aβ were measured using ELISA, ion-mobility analysis, and asymmetric-flow field-flow fractionation (AF4). The relationship between the change in levels of these biomarkers was analyzed using multiple linear regression models and linear mixed-effects models. Results Following CS-6253 intravenous injection, within minutes, small plasma high-density lipoprotein (HDL) particles were increased. In two independent experiments, plasma TG, apolipoprotein E (apoE), and Aβ42/40 ratio were transiently increased following CS-6253 intravenous injection. This change was associated with a non-significant decrease in CSF Aβ42. Both plasma total cholesterol and HDL-cholesterol levels were reduced following treatment. AF4 fractionation revealed that CS-6253 treatment displaced apoE from HDL to intermediate-density- and low density-lipoprotein (IDL/LDL)-sized particles in plasma. In contrast to plasma, CS-6253 had no effect on the assessed CSF apolipoproteins or lipids. Conclusions Treatment with the ABCA1 agonist CS-6253 appears to favor Aβ clearance from the brain.

Cognitive behavioral therapy (CBT) focuses on decreasing negative affect rather than increasing positive affect and is ineffective for some individuals. A trial comparing novel Positive Affect Treatment (PAT) to Negative Affect Treatment (NAT; a form of CBT) showed that PAT more effectively increased positive affect and decreased negative affect, depression, and anxiety (Craske et al., 2019). The present exploratory study examined threat sensitivity as a treatment moderator. Threat sensitivity was operationalized as pre-treatment skin conductance response and unconditional stimulus (US) expectancy rating during extinction recall. Participants ( N = 43) then received 15 sessions of PAT or NAT. Growth curve models were tested to explore interactions between extinction recall and treatment condition over time. For skin conductance, weaker extinction recall predicted faster improvement in depression and anxiety in NAT than PAT, whereas stronger extinction recall predicted faster improvement in symptoms in PAT than NAT. Reduced US expectancy ratings predicted a faster decrease in symptoms, regardless of treatment condition. Individuals showing greater threat sensitivity, indexed by weaker extinction recall, may benefit more from a treatment that targets threat sensitivity than a treatment that targets reward sensitivity. Individuals showing the converse may benefit more quickly from a treatment that targets reward sensitivity than threat sensitivity.

Interoception refers to the process by which the nervous system senses, interprets, and integrates signals originating from within the body, providing a moment-by-moment mapping of the body's internal landscape across conscious and unconscious levels. Interoceptive signaling has been considered a component process of reflexes, urges, feelings, drives, adaptive responses, and cognitive and emotional experiences, highlighting its contributions to the maintenance of homeostatic functioning, body regulation, and survival. Dysfunction of interoception is increasingly recognized as an important component of different mental health conditions, including anxiety disorders, mood disorders, eating disorders, addictive disorders, and somatic symptom disorders. However, a number of conceptual and methodological challenges have made it difficult for interoceptive constructs to be broadly applied in mental health research and treatment settings. In November 2016, the Laureate Institute for Brain Research organized the first Interoception Summit, a gathering of interoception experts from around the world, with the goal of accelerating progress in understanding the role of interoception in mental health. The discussions at the meeting were organized around four themes: interoceptive assessment, interoceptive integration, interoceptive psychopathology, and the generation of a roadmap that could serve as a guide for future endeavors. This review article presents an overview of the emerging consensus generated by the meeting.

To inaugurate our series of conversations with scholars in journalism studies with a view to securing some useful insights into the history and practice of journalism education, Prof. Richard Lance Keeble appeared an obvious choice. Now an Honorary Professor at Liverpool Hope University, Prof. Keeble was first director of the International Journalism MA, then director of the Journalism and Social Science BA, at City University, London (1984-2003). He was then appointed Professor of Journalism (2003-present) at Lincoln University where he also became acting head of the Lincoln School of Journalism (2010-2013) and later a Visiting Professor at Liverpool Hope University (2015-2019). Prof. Keeble has been the recipient of prestigious and distinguished prizes, namely the National Teaching Fellowship Award (2011) and the Lifetime Achievement Award for services to journalism education (2014), the latter bestowed by the Association for Journalism Education in the UK. Parallel to his academic career, Prof. Keeble has always been a practising journalist. On completion of his studies in Modern History at Keble College, Oxford University (1967-70), he started a career in journalism, first as sub editor at the Nottingham Guardian Journal/Evening Post (1970-73) and then at the Cambridge Evening News (1973-77). He was deputy editor, then editor, of The Teacher, the weekly newspaper of the National Union of Teachers (1977-84). His dual pedigree in journalism, as a practitioner and a professor, led him to take on many editorial responsibilities. He is emeritus editor of Ethical Space: The International Journal of Communication and Ethics and joint editor of George Orwell Studies and is also on the board of an impressive number of journals, among which are Journalism Studies, Digital Journalism, Journalism Education, International Journal of Media and Cultural Politics, Media Ethics, Journalism: Theory, Practice & Criticism, to name just a few. Prof. Keeble was also Chair of the Orwell Society1 (2013-2020) and has authored or edited no less than 44 books. They include Ethics for Journalists and The Newspapers Handbook,2 respectively on their second and fifth editions, as well as several volumes on George Orwell, investigative journalism, and the British media. It was an honour and privilege to talk to Prof. Keeble in a phone interview on March 25, 2021. The conversation was transcribed while some passages were edited for clarity. I hereby express my immense gratitude for his time, generosity, expertise, and humour. It is such a thrill to start our series of interviews in a way that only makes us want more such conversations.

The discovery of melanopsin and the non-visual impact of light, lead to a new era in lighting design. Using a melanopic action spectrum, the CIE introduced the melanopic efficacy of luminous radiation (MELR), which quantifies the influence of light on melanopsin. A significant amount of research has been conducted on the possible variation of this MELR and other related metrics for various practical lighting settings, but the fundamental spectral boundaries have not yet been disclosed. Without these limits, it is difficult to assess if a certain lighting system really achieves high or low MELR. This paper determines these fundamental MELR boundaries for different CCT and certain minimal TM-30 $R_f$ values, using a a flexible parametrization of the light source spectrum that is optimized with Differential Evolution. The obtained results show that with increasing CCT, the interval between the theoretical MELR extrema increases slightly, while the opposite occurs when increasing the minimal TM-30 $R_f$ value. The same parametric model and optimization approach is also used to determine the maximal Luminous Efficacy of Radiation (LER) within the obtained MELR limits.

Smart lighting systems are capable of producing light when and where it is needed. Such functionality can be achieved with adaptive optical systems, which consist of one or multiple adjustable components, enabling illumination with a variable radiation pattern. This paper introduces the design of a compact, tunable optical system, allowing illumination with variable beam size and beam direction. We demonstrate how this system can be combined with computer vision and a feedback loop, to achieve a fully autonomous, smart illumination system.

Adaptive illumination systems are capable of changing their emission pattern in a dynamic and flexible manner. Such systems can be realized with tunable optical components. We analyse the possibilities and limitations of phase-only spatial light modulators, implemented as a kind of programmable freeform optics, to realize adaptive illumination systems. First, the calculation of the required phase shift patterns to generate specific target irradiance distributions from arbitrary incident wavefronts, is elaborated. Second, the practical limitations of generating prescribed target patterns are experimentally tested and critically discussed.

Spatial hearing is crucial in real life but deteriorates in participants with severe sensorineural hearing loss or single-sided deafness. This ability can potentially be improved with a unilateral cochlear implant (CI). The present study investigated measures of sound localization in participants with single-sided deafness provided with a CI. Sound localization was measured separately at eight loudspeaker positions (4°, 30°, 60°, and 90°) on the CI side and on the normal-hearing side. Low- and high-frequency noise bursts were used in the tests to investigate possible differences in the processing of interaural time and level differences. Data were compared to normal-hearing adults aged between 20 and 83. In addition, the benefit of the CI in speech understanding in noise was compared to the localization ability. Fifteen out of 18 participants were able to localize signals on the CI side and on the normal-hearing side, although performance was highly variable across participants. Three participants always pointed to the normal-hearing side, irrespective of the location of the signal. The comparison with control data showed that participants had particular difficulties localizing sounds at frontal locations and on the CI side. In contrast to most previous results, participants were able to localize low-frequency signals, although they localized high-frequency signals more accurately. Speech understanding in noise was better with the CI compared to testing without CI, but only at a position where the CI also improved sound localization. Our data suggest that a CI can, to a large extent, restore localization in participants with single-sided deafness. Difficulties may remain at frontal locations and on the CI side. However, speech understanding in noise improves when wearing the CI. The treatment with a CI in these participants might provide real-world benefits, such as improved orientation in traffic and speech understanding in difficult listening situations.

High-density lipoproteins (HDLs) are complex, heterogenous lipoprotein particles, consisting of a large family of apolipoproteins, formed in subspecies of distinct shapes, sizes, and functions and are synthesized in both the brain and the periphery. HDL apolipoproteins are important determinants of Alzheimer’s disease (AD) pathology and vascular dementia, having both central and peripheral effects on brain amyloid-beta (Aβ) accumulation and vascular functions, however, the extent to which HDL particles (HLD-P) can exchange their protein and lipid components between the central nervous system (CNS) and the systemic circulation remains unclear. In this review, we delineate how HDL’s structure and composition enable exchange between the brain, cerebrospinal fluid (CSF) compartment, and vascular cells that ultimately affect brain amyloid metabolism and atherosclerosis. Accordingly, we then elucidate how modifications of HDL-P have diagnostic and therapeutic potential for brain vascular and neurodegenerative diseases.

Objective: Positive and negative affect play critical roles in depression and anxiety treatment, but the dynamic processes of how affect changes over treatment in relation to changes in symptoms is unclear. The study goal was to examine relationships among changes in positive and negative affect with changes in depression and anxiety symptoms. Method: This secondary analysis used a combined sample (N = 196) of two trials (Craske et al., 2019, 2023) comparing positive affect treatment (PAT) to negative affect treatment. Longitudinal cross-lag panel models explored whether changes in positive and negative affect (Positive and Negative Affect Schedule; Watson et al., 1988) predicted subsequent changes in depression and anxiety symptoms (Depression Anxiety Stress Scales; Lovibond & Lovibond, 1995), whether symptoms predicted subsequent changes in affect, and whether treatment condition moderated these relationships. Results: Increases in positive affect predicted subsequent decreases in depression and anxiety symptoms, regardless of treatment condition. Symptoms did not reciprocally predict changes in positive affect. For individuals in PAT, decreases in negative affect predicted subsequent decreases in symptoms. Moreover, decreases in symptoms predicted subsequent decreases in negative affect, regardless of treatment condition. Conclusions: Results did not support a reciprocal relationship between positive affect and symptoms of depression and anxiety since positive affect predicted depression and anxiety symptoms but not vice versa. Results supported a reciprocal relationship between negative affect and symptoms of depression and anxiety since negative affect predicted depression and anxiety symptoms in PAT, and depression and anxiety symptoms predicted negative affect in both treatment conditions. What is the public health significance of this article?: This study highlights the importance of considering the different and dynamic ways in which changes in positive affect and negative affect contribute to subsequent changes in depression and anxiety symptoms and vice versa over the course of psychotherapy. [ABSTRACT FROM AUTHOR]

There is growing interest in designing platforms for coherent electron-driven photon sources for hybrid light and electron spectroscopy. Here the authors demonstrate generation of coherent broadband ultrashort light pulses upon electron irradiation to nanostructured gold plated film.

BackgroundSleep quality may be an important, yet relatively neglected, predictor of treatment outcome in cognitive-behavioral therapy (CBT) for anxiety disorders. Specifically, poor sleep quality may impair memory consolidation of in-session extinction learning. We therefore examined sleep quality as a predictor of treatment outcome in CBT for social anxiety disorder and the impact of d-cycloserine (DCS) on this relationship.MethodsOne hundred sixty-nine participants with a primary diagnosis of DSM-IV generalized social anxiety disorder were recruited across three sites. Participants were enrolled in 12 weeks of group CBT. Participants randomly received 50 mg of DCS (n = 87) or pill placebo (n = 82) 1 hr prior to sessions 3-7. Participants completed a baseline measure of self-reported sleep quality and daily diaries recording subjective feelings of being rested upon wakening. Outcome measures including social anxiety symptoms and global severity scores were assessed at each session.ResultsPoorer baseline sleep quality was associated with slower improvement and higher posttreatment social anxiety symptom and severity scores. Moreover, patients who felt more "rested" after sleeping the night following a treatment session had lower levels of symptoms and global severity at the next session, controlling for their symptoms and severity scores the previous session. Neither of these effects were moderated by DCS condition.ConclusionsOur findings suggest that poor sleep quality diminishes the effects of CBT for social anxiety disorder and this relation is not attenuated by DCS administration. Therapeutic attention to sleep quality prior to initiation of CBT and during the acute treatment phase may be clinically indicated.

Apolipoproteins C-I, C-II, and C-III interact with ApoE to regulate lipoprotein metabolism and contribute to Alzheimer's disease pathophysiology. In plasma, apoC-I and C-II exist as truncated isoforms, while apoC-III exhibits multiple glycoforms. This study aimed to 1) delineate apoC-I, C-II, and C-III isoform profiles in cerebrospinal fluid (CSF) and plasma in a cohort of nondemented older individuals (n = 61), and 2) examine the effect of APOE4 on these isoforms and their correlation with CSF Aβ42, a surrogate of brain amyloid accumulation. The isoforms of the apoCs were immunoaffinity enriched and measured with MALDI-TOF mass spectrometry, revealing a significantly higher percentage of truncated apoC-I and apoC-II in CSF compared with matched plasma, with positive correlation between CSF and plasma. A greater percentage of monosialylated and disialylated apoC-III isoforms was detected in CSF, accompanied by a lower percentage of the two nonsialylated apoC-III isoforms, with significant linear correlations between CSF and plasma. Furthermore, a greater percentage of truncated apoC-I in CSF and apoC-II in plasma and CSF was observed in individuals carrying at least one APOE Ɛ4 allele. Increased apoC-I and apoC-II truncations were associated with lower CSF Aβ42. Finally, monosialylated apoC-III was lower, and disialylated apoC-III greater in the CSF of Ɛ4 carriers. Together, these results reveal distinct patterns of the apoCs isoforms in CSF, implying CSF-specific apoCs processing. These patterns were accentuated in APOE Ɛ4 allele carriers, suggesting an association between APOE4 genotype and Alzheimer's disease pathology with apoCs processing and function in the brain.

BackgroundPsychomotor change is a core symptom of depression and one of the criteria in diagnosing depressive disorders. Research suggests depressed individuals demonstrate deviations in gait, or walking, compared to non-depressed controls. However, studies are sparse, often limited to older adults and observational gait assessment. It is also unclear if gait changes are due to dysregulation of affect, a core feature of depression. The current study addressed this gap by investigating the relation between positive and negative affect, depressive symptom severity, and gait in young adults.MethodsUsing three-dimensional motion capture, gait parameters (velocity, stride length, and step time) were attained from 90 young adults during a task where they walked ten meters at their own pace overground in a laboratory for ten minutes. Self-report measures of mood and affect were collected.ResultsOn average, the study population reported high negative and low positive affect. Contrary to our hypotheses, hierarchical regressions demonstrated no significant associations between gait parameters and affective or depressive symptoms (ps>.05).ConclusionsOur findings do not support a relation between affective symptoms and gait parameters. The results may indicate age-dependent gait pathology or that other symptoms of depression may influence gait more strongly than affect. They may also reflect an observational bias of gait changes in depressed young adults, one that is unsupported by objective data. Replication is warranted to further examine whether affective symptomology is embodied via gait differences in young adults.

Abstract Background Demands placed on individuals in occupational and social settings, as well as imbalances in personal traits and resources, can lead to chronic stress. The Trier Inventory for Chronic Stress (TICS) measures chronic stress while incorporating domain-specific aspects, and has been found to be a highly reliable and valid research tool. The aims of the present study were to confirm the German version TICS factorial structure in an English translation of the instrument (TICS-E) and to report its psychometric properties. Methods A random route sample of healthy participants (N = 483) aged 18–30 years completed the TICS-E. The robust maximum likelihood estimation with a mean-adjusted chi-square test statistic was applied due to the sample’s significant deviation from the multivariate normal distribution. Goodness of fit, absolute model fit, and relative model fit were assessed by means of the root mean square error of approximation (RMSEA), the Comparative Fit Index (CFI) and the Tucker Lewis Index (TLI). Results Reliability estimates (Cronbach’s α and adjusted split-half reliability) ranged from .84 to .92. Item-scale correlations ranged from .50 to .85. Measures of fit showed values of .052 for RMSEA (Cl = 0.50–.054) and .067 for SRMR for absolute model fit, and values of .846 (TLI) and .855 (CFI) for relative model-fit. Factor loadings ranged from .55 to .91. Conclusion The psychometric properties and factor structure of the TICS-E are comparable to the German version of the TICS. The instrument therefore meets quality standards for an adequate measurement of chronic stress.

Denture stomatitis is a disease involving C. albicans, which can affect elderly and immuno-compromised people. To avoid any recurrence of this pathology, it is necessary to treat patients regularly and disinfect dentures. However, the denture cleansers’ efficacy is not optimal and often leads to adverse color effects on the denture base resins. The aim of this study was to investigate the efficacy of a low-pressure non-thermal O2 plasma (NTP) treatment on C. albicans seeded on ProBase®Hot resin (Ivoclar Vivadent). The viability reduction of C. albicans was assessed by colony forming units (CFU) analysis and by scanning electron microscopy (SEM). The effect of repeated treatments on the resin color was evaluated by spectrophotometry. The resin samples were placed in a sealed bag in which O2 plasma was generated in low-pressure conditions. The results showed that a 120-min O2 NTP treatment led to a 6-log reduction of C. albicans viability (p < 0.05) and to yeasts’ major alterations observed by SEM. Furthermore, significant slight color changes of the resin (∆E00 = 1.33) were noted only after six plasma treatments (p < 0.05). However, the denture aesthetic was preserved, as the color changes were not perceptible and remained below the acceptability threshold (∆E00 < 4).

The Peutinger Table refers to a relay station called Sipia along the route linking the capital cities of Rennes and Angers. This can probably be located southeast of what is today the town of Visseiche (Ille-et-Vilaine). It has recently been the subject of a range of archaeological observations which, although incomplete, have enabled its principal features to be outlined.

Patients treated for head and neck cancer (HNC) often suffer from severe and visible loss of function as the cancer itself and the side effects of aggressive treatments have the potential to severely affect quality of life. Therefore, the aim of follow-up is not only the early detection of potentially curable recurrences and second primary tumors but also the diagnosis and rehabilitation of functional impairments. Clear guidelines determining the frequency of follow-up visits are missing, and the impact of follow-up visits on patient's prognosis is unclear. An intensive post-treatment follow-up is needed to detect functional impairments and to initiate their treatment. The aim is an optimal rehabilitation of the patients. This article focusses on goals of aftercare treatment and describes the spectrum of long-term sequelae, and the impact of Patient Reported Outcome (PRO) instruments of which three will be introduced.

Laser diodes are very promising solid-state devices for the development of high-luminance white light sources. Currently, the most simple and efficient way to produce white light with solid-state sources is to combine them with color-converting luminescent materials or phosphors. The quantum yield (i.e., the potential to convert light to another color) of these materials has complex dependence on temperature. In the case of high-power white light sources based on laser diodes, high temperatures are reached inside the phosphor material, which decrease its quantum yield (thermal quenching) and result in a nonstable light output. While this thermal quenching effect is well known, the tools used today to design and optimize optical systems do not include it in a realistic way. This work fills that gap by proposing an automated framework that simulates both the optical and thermal effects and the interplay between them. Additionally, an adapted version of the framework is also proposed, which is more computationally efficient. The resulting shorter simulation time is crucial for the efficient optimization of the optothermal performance of lighting systems, which requires several iterations of the framework for each optimization variable. The optothermal simulation framework has been applied to some optical designs to study them by changing certain optical and thermal properties and evaluating how these affect the overall performance. It is clearly demonstrated that even for optical designs that use LED sources, neglecting the thermal effects of luminescent materials can lead to an incorrect assessment of the system's capabilities and performance.

Vingt-cinq ans après leur arrivée en France, les loups sont régulièrement ou épisodiquement présents dans plus de 30 départements, avec 57 zones de présence permanente. Depuis 2008, la progression interannuelle des animaux d’élevage retrouvés prédatés (ovins, caprins, bovins, équins…) est linaire, avoisinant les 12 000 en 2017. Il faut y ajouter les animaux disparus et les dégâts indirects : stress à effet durable, avortements, blessures internes et baisse de fertilité. La France a pourtant mis en oeuvre et généralisé depuis 2004 une protection élaborée des troupeaux : présence humaine renforcée, chiens de protection et parcs de nuit électrifiés. Comment expliquer alors cet échec ? Il y a deux principales raisons. D’abord, les paysages composés de prairies, pelouses, haies, lisières et sous-bois, favorisent la prédation. Mais surtout, les loups se sont adaptés. Très intelligents et opportunistes, ils profitent en France de leur statut légal de protection stricte, n’associant visiblement plus les troupeaux aux humains et les humains au danger. Face à des troupeaux regroupés en parc de nuit, ils opèrent la moitié de leurs attaques en cours de journée, y compris en présence de chiens et d’humains. Dans les pays où les humains sont autorisés à défendre les troupeaux activement et promptement, y compris par des tirs létaux, les loups se tiennent plus à distance et les pertes d’élevage sont bien moindres. Sans une régulation ciblée des loups en fonction de leur comportement vis-à-vis des troupeaux, c’est la viabilité de nos élevages de plein air qui est profondément remise en question.

Remote phosphor light-emitting diode (LED) modules could offer advantages over intimate white phosphor converted LEDs in terms of phosphor operation temperature, light extraction efficiency, and angular color uniformity. Existing commercial devices show a large variety with respect to the dimensions of the mixing cavity, which raises a question about the optimization of the topology. A simplified simulation model applying a two-wavelength approach and considering the remote phosphor as one virtual surface to which three bidirectional scattering distribution functions are attributed (respectively, describing the blue-blue, blue-yellow, and yellow-yellow interactions) is developed and validated. This model has been used to analyze the impact of the cylindrical mixing cavity parameters such as the absolute reflectance, the diffuse-to-specular reflectance ratio, and the height of the mixing cavity, as well as the pitch and angular full-width at half-maximum of the LEDs on the extraction efficiency, the yellow-to-blue ratio, and the irradiance uniformity. It can be concluded that in order to increase the efficacy substantially, the recuperation of the backward emission of the converted light can only be increased by avoiding further interaction with the phosphor plate. To this extent, topologies other than cylindrical mixing cavities must be considered.

Objective: This review examines the evidence for psychosocial influences in asthma and behavioral medicine approaches to its treatment. Method: We conducted a systematic review of the literature on psychosocial influences and the evidence for behavioral interventions in asthma with a focus on research in the past 10 years and clinical trials. Additional attention was directed at promising new developments in the field. Results: Psychosocial factors can influence the pathogenesis and pathophysiology of asthma, either directly through autonomic, endocrine, immunological, and central nervous system mechanisms or indirectly through lifestyle factors, health behaviors, illness cognitions, and disease management, including medication adherence and trigger avoidance. The recent decade has witnessed surging interest in behavioral interventions that target the various pathways of influence. Among these, self-management training, breathing training, and exercise or physical activation programs have proved particularly useful, whereas other essential or promising interventions, such as smoking cessation, dietary programs, perception and biofeedback training, and suggestive or expressive psychotherapy, require further, more rigorous evaluation. Given the high comorbidity with anxiety and mood disorders, further evaluation of illness-specific cognitive behavior therapy is of particular importance. Progress has also been made in devising community-based and culturally tailored intervention programs. Conclusion: In concert with an essential medication treatment, behavioral medicine treatment of asthma is moving closer toward an integrated biopsychosocial approach to disease management. (Contains 1 table and 1 footnote.)

Cognitive and biobehavioral coping skills are central to psychosocial therapies and are taught to facilitate and improve exposure therapy. While traditional coping skills are aimed at controlling maladaptive thoughts or dysregulations in physiology, newer approaches that explore acceptance, defusion, and values-based direction have been gaining interest. Acceptance and Commitment Therapy (ACT) involves creating an open, nonjudgmental stance toward whatever thoughts, feelings, and bodily sensations arise in a given moment, experiencing them for what they are, and moving toward them while inner experiences such as anxiety are present. This approach can be seen as consistent with exposure therapies and may be utilized to organize and facilitate engagement in exposure exercises. This study examines the feasibility and efficacy for combining a brief ACT protocol with traditional exposure therapy. Eleven patients with panic disorder with or without agoraphobia received 4 sessions of ACT followed by 6 sessions of exposure therapy, with data collected on a weekly basis. Acquisition of ACT skills and their application during exposure was monitored using a novel "think-aloud" technology. Treatment was associated with clinically significant improvements in panic symptom severity, willingness to allow inner experiences to occur, and reductions in avoidant behavior. Although preliminary, results suggest that our brief training in ACT only (as assessed prior to exposure exercises) and in combination with exposure therapy was acceptable to patients and offered benefits on the order of large effect sizes. Clinical and research implications are discussed. (Contains 1 table, 2 figures, and 8 videos.)

Objective: Determine whether a novel psychosocial treatment for positive affect improves clinical status and reward sensitivity more than a form of cognitive behavioral therapy that targets negative affect and whether improvements in reward sensitivity correlate with improvements in clinical status. Method: In this assessor-blinded, parallel-group, multisite, two-arm randomized controlled clinical superiority trial, 85 treatment-seeking adults with severely low positive affect, moderate-to-severe depression or anxiety, and functional impairment received 15 weekly individual therapy sessions of positive affect treatment (PAT) or negative affect treatment (NAT). Clinical status measures were self-reported positive affect, interviewer-rated anhedonia, and self-reported depression and anxiety. Target measures were eleven physiological, behavioral, cognitive, and self-report measures of reward anticipation-motivation, response to reward attainment, and reward learning. All analyses were intent-to-treat. Results: Compared to NAT, individuals receiving PAT achieved superior improvements in the multivariate clinical status measures at posttreatment, b =.37, 95% CI [.15,.59], t(109) = 3.34, p =.001, q =.004, d =.64. Compared to NAT, individuals receiving PAT also achieved higher multivariate reward anticipation-motivation, b =.21, 95% CI [.05,.37], t(268) = 2.61, p =.010, q =.020, d =.32, and higher multivariate response to reward attainment, b =.24, 95% CI [.02,.45], t(266) = 2.17, p =.031, q =.041, d =.25, at posttreatment. Measures of reward learning did not differ between the two groups. Improvements in reward anticipation-motivation and in response to reward attainment correlated with improvements in the clinical status measures. Conclusions: Targeting positive affect results in superior improvements in clinical status and reward sensitivity than targeting negative affect. This is the first demonstration of differential target engagement across two psychological interventions for anxious or depressed individuals with low positive affect. What is the public health significance of this article?: This study demonstrates that positive affect treatment was significantly more effective than an intervention that targeted negative affect for adults with severely low positive affect, moderate-to-severe depression or anxiety, and functional impairment. The findings of this study suggest that positive affect treatment improves positive affect and aspects of reward hyposensitivity. [ABSTRACT FROM AUTHOR]