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Luiz Eduardo Mateus Brandão,1 Teemu Martikainen,1 Ilona Merikanto,2– 4 Brigitte Holzinger,5,6 Charles M Morin,7– 9 Colin A Espie,10,11 Courtney J Bolstad,12 Damien Leger,13 Frances Chung,14 Giuseppe Plazzi,15 Yves Dauvilliers,16 Kentaro Matsui,17,18 Luigi De Gennaro,19– 21 Mariusz Sieminski,22 Michael R Nadorff,12,23 Ngan Yin Chan,24 Yun Kwok Wing,24 Sérgio Arthuro Mota-Rolim,25– 27 Yuichi Inoue,28 Markku Partinen,29,30 Christian Benedict,31 Bjorn Bjorvatn,32,33 Jonathan Cedernaes1,34 1Department of Medical Sciences, Uppsala University, Uppsala, Sweden; 2Department of Public Health Solutions, Finnish Institute for Health and Welfare, Helsinki, Finland; 3Department of Psychology and Logopedics, University of Helsinki, Helsinki, Finland; 4Orton Orthopaedic Hospital, Helsinki, Finland; 5ZK-Schlafcoaching, Medical University Vienna, Vienna, Austria; 6Institute for Consciousness and Dream Research, Vienna, Austria; 7École de Psychologie, Université Laval, Québec, Canada; 8Centre d’étude des troubles du sommeil, Université Laval, Québec, Canada; 9Centre de recherche CERVO/Brain Research Center, Université Laval, Québec, Canada; 10Sleep & Circadian Institute, University of Oxford, Oxford, UK; 11Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK; 12Department of Psychology, Mississippi State University, Starkville, MS, USA; 13APHP, VIFASOM, Hôtel-Dieu, Centre du Sommeil et de la Vigilance, Université de Paris, Paris, France; 14Department of Anesthesia and Pain Medicine, Toronto Western Hospital, University Health Network, University of Toronto, Toronto, Ontario, Canada; 15Department of Biomedical, Metabolic and Neural Science, University of Modena and Reggio Emilia, Modena, Italy; 16Sleep-Wake Disorders Center, Department of Neurology, Gui-de-Chauliac Hospital, Institute for Neurosciences of Montpellier INM, INSERM, University of Montpellier, Montpellier, France; 17National Center of Neurology and Psychiatry National Institute of Mental Health, Department of Clinical Laboratory and Department of Sleep-Wake Disorders, Tokyo, Japan; 18Tokyo Women’s Medical University, Department of Psychiatry, Tokyo, Japan; 19Department of Psychology, Sapienza University of Rome, Rome, Italy; 20IRCCS Fondazione Santa Lucia, Rome, Italy; 21IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy; 22Department of Emergency Medicine, Medical University of Gdansk, Gdansk, Poland; 23Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, TX, USA; 24Li Chiu Kong Family Sleep Assessment Unit, Department of Psychiatry, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, People’s Republic of China; 25Brain Institute, Federal University of Rio Grande do Norte, Natal, RN, Brazil; 26Physiology and Behaviour Department, Federal University of Rio Grande do Norte, Natal, RN, Brazil; 27Onofre Lopes University Hospital, Federal University of Rio Grande do Norte, Natal, RN, Brazil; 28Department of Somnology, Tokyo Medical University, Tokyo, Japan; 29Helsinki Sleep Clinic, Vitalmed Research Center, Terveystalo Biobank and Research, Helsinki, Finland; 30Department of Neurosciences, Clinicum, University of Helsinki, Helsinki, Finland; 31Sleep Science Laboratory, Department of Neuroscience, Uppsala University, Uppsala, Sweden; 32Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway; 33Norwegian Competence Center for Sleep Disorders, Haukeland University Hospital, Bergen, Norway; 34Department of Medicine, Division of Endocrinology, Metabolism, and Molecular Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USACorrespondence: Jonathan Cedernaes Email jonathan.cedernaes@medsci.uu.sePurpose: Lifestyle and work habits have been drastically altered by restrictions due to the COVID-19 pandemic. Whether the associated changes in sleep timing modulate the risk of suffering from symptoms of insomnia, the most prevalent sleep disorder, is however incompletely understood. Here, we evaluate the association between the early pandemic-associated change in 1) the magnitude of social jetlag (SJL) – ie, the difference between sleep timing on working vs free days – and 2) symptoms of insomnia.Patients and Methods: A total of 14,968 anonymous participants (mean age: 40 years; 64% females) responded to a standardized internet-based survey distributed across 14 countries. Using logistic multivariate regression, we examined the association between the degree of social jetlag and symptoms of insomnia, controlling for important confounders like social restriction extension, country specific COVID-19 severity and psychological distress, for example.Results: In response to the pandemic, participants reported later sleep timing, especially during workdays. Most participants (46%) exhibited a reduction in their SJL, whereas 20% increased it; and 34% reported no change in SJL. Notably, we found that both increased and decreased SJL, as a result of the COVID-19 pandemic, were associated with later sleep midpoint (indicating a later chronotype) as well as more recurrent and moderate-to-severe symptoms of insomnia (about 23– 54% higher odds ratio than subjects with unchanged SJL). Primarily those with reduced SJL shifted their bedtimes to a later timepoint, compared with those without changes in SJL.Conclusion: Our findings offer important insights into how self-reported changes to the stability of sleep/wake timing, as reflected by changes in SJL, can be a critical marker of the risk of experiencing insomnia-related symptoms – even when individuals manage to reduce their social jetlag. These findings emphasize the clinical importance of analyzing sleep-wake regularity.Keywords: BNSQ, ISI, midsleep, MSFsc, PHQ-4, psychological distress

NO LONGER IS INTERNATIONAL business the province of the large multinational firm. Many smaller firms recognise that the opportunities offered by Global markets will be increasingly important to the success [...]

This paper investigates the characteristics of different beta estimation techniques in infrequently traded and inefficient stock markets. These markets are artificially created from actual stock market data by removing return observations and by delaying the information transfer from market returns to individual stocks. Alternative beta estimation techniques are reported to behave differently in different types of markets. Key words - estimation, beta estimation, inefficient stock markets, infrequently traded stock markets

A study of the integration of the functions of production and quality control is presented. These functions include for example production lot sizing, assignment under a classification scheme and inspection. Integration of these proceedures is necessary to reduce costs and product defects. A model for a suitable integrated system is presented and suggestions for future research into the issues.

The success of flexible manufacturing systems (FMS) in production management applications has prompted a review of available literature regarding the topic. The aim of the review is to establish existing FMS model applications and to determine the direction of future research work. An appropriate classification scheme has also been developed for identifying literature theory and practice.

A case study is conducted to examine the application of multi-stage production inventory systems. The study focuses on the problem of economic lot sizing and considers the multi-level case for a rayon yarn firm. A multi-level lot sizing model is then applied to the problem. Results show that the model's application minimize costs in setting up and in developing in-process inventory.

RATIONALE: Obesity is the most important risk factor for obstructive sleep apnea (OSA). However, although included in clinical guidelines, no randomized controlled studies have been performed on the effects of weight reduction on mild OSA. OBJECTIVES: The aim of this prospective, randomized controlled parallel-group 1-year follow-up study was to determine whether a very low calorie diet (VLCD) with supervised lifestyle counseling could be an effective treatment for adults with mild OSA. METHODS: Seventy-two consecutive overweight patients (body mass index, 28-40) with mild OSA were recruited. The intervention group (n = 35) completed the VLCD program with supervised lifestyle modification, and the control group (n = 37) received routine lifestyle counseling. The apnea-hypopnea index (AHI) was the main objectively measured outcome variable. Change in symptoms and the 15D-Quality of Life tool were used as subjective measurements. MEASUREMENTS AND MAIN RESULTS: The lifestyle intervention was found to effectively reduce body weight (-10.7 +/- 6.5 kg; body mass index, -3.5 +/- 2.1 [mean +/- SD]). There was a statistically significant difference in the mean change in AHI between the study groups (P = 0.017). The adjusted odds ratio for having mild OSA was markedly lowered (odds ratio, 0.24 [95% confidence interval, 0.08-0.72]; P = 0.011) in the intervention group. All common symptoms related to OSA, and some features of 15D-Quality of Life improved after the lifestyle intervention. Changes in AHI were strongly associated with changes in weight and waist circumference. CONCLUSIONS: VLCD combined with active lifestyle counseling resulting in marked weight reduction is a feasible and effective treatment for the majority of patients with mild OSA, and the achieved beneficial outcomes are maintained at 1-year follow-up. [ABSTRACT FROM AUTHOR]

Atrial fibrillation is the most common arrhythmia to occur after cardiac surgery, with an incidence of 10% to 50%. It is associated with postoperative complications including increased risk of stroke, prolonged hospital stays and increased costs. Despite new insights into the mechanisms of atrial fibrillation, no specific etiologic factor has been identified as the sole perpetrator of the arrhythmia. Current evidence suggests that the pathophysiology of atrial fibrillation in general, as well as after cardiac surgery, is multifactorial. Studies have also shown that new-onset postoperative atrial fibrillation following cardiac surgery is associated with a higher risk of short-term and long-term mortality. Furthermore, it has been demonstrated that prophylactic medical therapy decreases the incidence of postoperative atrial fibrillation after cardiac surgery. Of note, the incidence of postoperative atrial fibrillation has not changed during the last decades despite the numerous preventive strategies and operative techniques proposed, although the perioperative and postoperative care of cardiac patients as such has improved., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Physical exercise-especially at high intensity-is known to impose cardiac stress, as mirrored by, e.g., increased blood levels of cardiac stress biomarkers such as cardiac Troponin T (cTnT) and NT-proBNP. We examined healthy young participants to determine whether a few nights of short sleep duration alter the effects of acute exercise on these blood biomarkers., Methods: Sixteen men participated in a randomized order in a crossover design, comprising three consecutive nights of a) normal sleep duration (NS, 8.5 h of sleep/night) and b) sleep restriction (SR, 4.25 h of sleep/night). Blood was repeatedly sampled for determination of NT-proBNP and cTnT serum levels before and after a high-intensity exercise protocol (i.e., 75% VO 2 maxReserve cycling on an ergometer)., Results: Under pre-exercise sedentary conditions, blood levels of cTnT and NT-proBNP did not significantly differ between the sleep conditions (P > 0.10). However, in response to exercise, the surge of circulating cTnT was significantly greater following SR than NS (+37-38% at 120-240 min post-exercise, P ≤ 0.05). While blood levels of NT-proBNP rose significantly in response to exercise, they did not differ between the sleep conditions., Conclusion: Recurrent sleep restriction may increase the cardiac stress response to acute high-intensity exercise in healthy young individuals. However, our findings must be further confirmed in women, older subjects and in patients with a history of heart disease., (Copyright © 2022 The Author(s). Published by Elsevier GmbH.. All rights reserved.)

The hormone fibroblast growth factor 21 (FGF21) modulates tissue metabolism and circulates at higher levels in metabolic conditions associated with chronic sleep-wake disruption, such as type 2 diabetes and obesity. In the present study, we investigated whether acute sleep loss impacts circulating levels of FGF21 and tissue-specific production, and response pathways linked to FGF21. A total of 15 healthy normal-weight young men participated in a randomised crossover study with two conditions, sleep loss versus an 8.5-hr sleep window. The evening before each intervention, fasting blood was collected. Fasting, post-intervention morning skeletal muscle and adipose tissue samples underwent quantitative polymerase chain reaction and DNA methylation analyses, and serum FGF21 levels were measured before and after an oral glucose tolerance test. Serum levels of FGF21 were higher after sleep loss compared with sleep, both under fasting conditions and following glucose intake (~27%-30%, p = 0.023). Fasting circulating levels of fibroblast activation protein, a protein which can degrade circulating FGF21, were not altered by sleep loss, whereas DNA methylation in the FGF21 promoter region increased only in adipose tissue. However, even though specifically the muscle exhibited transcriptional changes indicating adverse alterations to redox and metabolic homeostasis, no tissue-based changes were observed in expression of FGF21, its receptors, or selected signalling targets, in response to sleep loss. In summary, we found that acute sleep loss resulted in increased circulating levels of FGF21 in healthy young men, which may occur independent of a tissue-based stress response in metabolic peripheral tissues. Further studies may decipher whether changes in FGF21 signalling after sleep loss modulate metabolic outcomes associated with sleep or circadian disruption., (© 2021 The Authors. Journal of Sleep Research published by John Wiley & Sons Ltd on behalf of European Sleep Research Society.)

Background: Atrial fibrillation (AF) is the major cause of stroke since approximately 25% of all strokes are of cardioembolic-origin. The detection and diagnosis of AF are often challenging due to the asymptomatic and intermittent nature of AF., Hypothesis: A wearable electrocardiogram (ECG)-device could increase the likelihood of AF detection. The aim of this study was to evaluate the feasibility and reliability of a novel, consumer-grade, single-lead ECG recording device (Necklace-ECG) for screening, identifying and diagnosing of AF both by a cardiologist and automated AF-detection algorithms., Methods: A thirty-second ECG was recorded with the Necklace-ECG device from two positions; between the palms (palm) and between the palm and the chest (chest). Simultaneously registered 3-lead ECGs (Holter) served as a golden standard for the final rhythm diagnosis. Two cardiologists interpreted independently in a blinded fashion the Necklace-ECG recordings from 145 patients (66 AF and 79 sinus rhythm, SR). In addition, the Necklace-ECG recordings were analyzed with an automatic AF detection algorithm., Results: Two cardiologists diagnosed the correct rhythm of the interpretable Necklace-ECG with a mean sensitivity of 97.2% and 99.1% (palm and chest, respectively) and specificity of 100% and 98.5%. The automatic arrhythmia algorithm detected the correct rhythm with a sensitivity of 94.7% and 98.3% (palm and chest) and specificity of 100% of the interpretable measurements., Conclusions: The novel Necklace-ECG device is able to detect AF with high sensitivity and specificity as evaluated both by cardiologists and an automated AF-detection algorithm. Thus, the wearable Necklace-ECG is a new, promising method for AF screening., Clinical Trial Registration: Study was registered in the ClinicalTrials.gov database (NCT03753139)., (© 2021 The Authors. Clinical Cardiology published by Wiley Periodicals LLC.)

The tumor-draining lymph nodes (TDLNs) are primary sites for induction of tumor immunity. They are also common sites of metastasis, suggesting that tumor-induced mechanisms can subvert anti-tumor immune responses and promote metastatic seeding. The high endothelial venules (HEVs) together with CCL21-expressing fibroblastic reticular cells (FRCs) are essential for lymphocyte recruitment into the LNs. We established multicolor antibody panels for evaluation of HEVs and FRCs in TDLNs from breast cancer (BC) patients. Our data show that patients with invasive BC display extensive structural and molecular remodeling of the HEVs, including vessel dilation, thinning of the endothelium and discontinuous expression of the HEV-marker PNAd. Remodeling of the HEVs was associated with dysregulation of CCL21 in perivascular FRCs and with accumulation of CCL21-saturated lymphocytes, which we link to loss of CCL21-binding heparan sulfate in FRCs. These changes were rare or absent in LNs from patients with non-invasive BC and cancer-free organ donors and were observed independent of nodal metastasis. Thus, pre-metastatic dysregulation of core stromal and vascular functions within TDLNs reflect the primary tumor invasiveness in BC. This adds to the understanding of cancer-induced perturbation of the immune response and opens for prospects of vascular and stromal changes in TDLNs as potential biomarkers.

Aims: Atrial fibrillation (AF) is the most common tachyarrhythmia and a significant cause of cardioembolic strokes. Atrial fibrillation is often intermittent and asymptomatic making detection a major clinical challenge. We evaluated a photoplethysmography (PPG) wrist band in individual pulse detection in patients with AF and tested the reliability of two commonly used algorithms for AF detection., Methods and Results: A 5-min PPG was recorded from patients with AF or sinus rhythm (SR) with a wrist band and analysed with two AF detection algorithms; AFEvidence and COSEn. Simultaneously registered electrocardiogram served as the golden standard for rhythm analysis and was interpreted by two cardiologists. The study population consisted of 213 (106 AF, 107 SR) patients. The wrist band PPG achieved individual pulse detection with a sensitivity of 91.7 ± 11.2% and a positive predictive value (PPV) of 97.5 ± 4.6% for AF, with a sensitivity of 99.4 ± 1.5% [7.7% (95% confidence interval, 95% CI 5.5% to 9.9%); P < 0.001] and PPV of 98.1 ± 4.1% [0.6% (95% CI -0.6% to 1.7%); P = 0.350] for SR. The pulse detection sensitivity was lower 86.7 ± 13.9% with recent-onset AF (AF duration <48 h, n = 43, 40.6%) as compared to late AF (≥48 h, n = 63, 59.4%) with 95.1 ± 7.2% [-8.3% (95% CI -12.9% to -3.7%); P = 0.001]. For the detection of AF from the wrist band PPG, the sensitivities were 96.2%/95.3% and specificity 98.1% with two algorithms., Conclusion: The wrist band PPG enabled accurate algorithm-based detection of AF with two AF detection algorithms and high individual pulse detection. Algorithms allowed accurate detection of AF from the PPG. A PPG wrist band provides an easy solution for AF screening., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Objective: The authors studied the incidence of postoperative delirium among cardiac surgery patients using the Intensive Care Delirium Screening Checklist (ICDSC)., Design: Prospective screening., Setting: Two university hospitals., Participants: A total of 1,036 consecutive patients., Interventions: None., Measurements and Main Results: Patients were prospectively screened from day 1 to day 10 after surgery or until hospital discharge. Appropriate perioperative data were collected. The overall incidence of postoperative delirium was 11.5%. In the multivariate logistic regression analysis, age over 70 years, higher EuroSCORE points, longer aortic occlusion time, and profuse drainage increased the incidence of delirium. The duration of mechanical ventilation and intensive care unit length of stay were longer in the group of patients with delirium (10.6 hours [6.6-19.5] v 6.4 hours [4.9-8.6], p < 0.001, and 1.7 days [0.9-4.2] v 0.9 days [0.9-1], p < 0.001)., Conclusions: Postoperative delirium is common after cardiac surgery, and it is associated with the duration of mechanical ventilation., (Copyright © 2017 Elsevier Inc. All rights reserved.)