Search

Background Few studies have assessed life expectancy of patients with tuberculosis (TB) against a comparable background population, particularly in low-income, high-incidence settings. This study aimed to estimate the life expectancy (LE) of patients with TB in the West African country of Guinea-Bissau and compare it with the LE of the background population. Methods This study used data from the Bandim TB cohort from 2004–20 as well as census data from the capital of Guinea-Bissau. LE was estimated using a bootstrapped Kaplan-Meier survival analysis for patients with TB and the background population, stratifying by age of entry and various patient subgroups. The analysis was further stratified by diagnosis period and length of schooling (an indicator of socioeconomic status), to assess their influence on LE. A sensitivity analysis was performed assuming death at loss to follow-up. Results The analysis included 2278 patients and a background population of 169 760 individuals. Overall median LE among 30-year-old patients with TB was 10.7 years (95% CI: 8.7–12.6), compared with 35.8 (95% CI: 35.1–36.5) in the background population. LE was shorter in HIV-infected patients and those who had unsuccessful treatment outcome; however, even among those who were both uninfected with HIV and experienced successful treatment outcome, LE was 20% shorter than in the background population. Longer schooling appeared to decrease mortality. Conclusions TB substantially shortens LE. This effect is present even in patients who are uninfected with HIV and who have successful treatment outcome.

We propose that common elements approaches can advance implementation research and practice and facilitate pragmatic use of intervention and implementation evidence. Common elements are practices or processes frequently shared by interventions or implementations. Traditional common elements methodologies use synthesis, distillation, and statistics to describe and evaluate the merit of common ingredients in effective interventions. Recent developments include identifying and testing common configurations of elements, processes, and context variables across the literature of effective interventions and implementations. While common elements thinking has grown popular in intervention science, it has rarely been utilized in implementation science, and specifically, combined with the intervention literature. The goals of this conceptual methodology paper are to (1) provide an overview of the common elements concept and how it may advance implementation research and usability for practice, (2) give a step-by-step guide to systematic common elements reviews that synthesizes and distills the intervention and implementation literature together, and (3) offer recommendations for advancing element-level evidence in implementation science. A narrative review of the common elements literature was conducted with attention to applications to implementation research. A six-step guide to using an advanced common elements methodology was provided. Examples of potential results are presented, along with a review of the implications for implementation research and practice. Finally, we reviewed methodological limitations in current common elements approaches, and identified steps towards realizing their potential. Common elements methodologies can (a) synthesize and distill the implementation science literature into practical applications, (b) generate evidence-informed hypotheses about key elements and determinants in implementation and intervention processes and mechanisms, and (c) promote evidence-informed precision tailoring of intervention and implementation to context. To realize this potential, common elements approaches need improved reporting of details from both successful and unsuccessful intervention and implementation research, more data availability, and more testing and investigation of causal processes and mechanisms of change from diverse theories.Supplementary informationThe online version contains supplementary material available at 10.1007/s43477-023-00077-4.

In 2019, Norwegian implementation researchers formed a network to promote implementation research and practice in the Norwegian context. On November 19th, 2021, the second annual Norwegian implementation conference was held in Oslo. Ninety participants from all regions of the country gathered to showcase the frontiers of Norwegian implementation research. The conference also hosted a panel discussion about critical next steps for implementation science in Norway. The conference included 17 presentations from diverse disciplines within health and welfare services, including schools. The themes presented included stakeholder engagement, implementation mechanisms, evaluations of the implementation of specific interventions, the use of implementation guidelines and frameworks, the development and validation of implementation measurements, and barriers and facilitators for implementation. The panel discussion highlighted several critical challenges with the implementation of evidence-informed practices in Norway, including limited implementation competence and capacity among practice leaders and workforces, few opportunities for education in implementation science, limited implementation research in the Norwegian context, scarce funding possibilities for implementation research, and a lack of long-term perspectives on implementation processes. Overall, the 2021 Norwegian implementation conference showed an encouraging sign of a maturing field of science in Norway. The more voluminous proceedings from the 2020 conference called for several important advancements to improve implementation science and practice in Norway, and the 2021 conference indicates that steps have already been taken in favorable directions in terms of, for instance, research designs and measurements. However, there are still unexploited potentials for improvements in implementation research, funding, policies, and practice. Norwegian implementation researcher should be mindful of the challenges and potential pitfalls implementation science currently face as a scientific discipline.The online version contains supplementary material available at 10.1007/s43477-022-00069-w.

Purpose: Concomitant use of vitamin K antagonists (VKA) and statins is frequent in cardiovascular patients. However, clinical guidelines on this drug combination are divergent. Therefore, we performed a systematic review to evaluate the effect of statin initiation on coagulation among VKA users. Methods: Following the PRISMA guidelines, we applied two broad search strategies for the drug interaction between VKA and statins in both Embase and Pubmed; 8623 unique hits were obtained. In the final sample, eight studies were included. Results: The most frequently used VKA in the studies was warfarin, while simvastatin was the most commonly initiated statin. All included studies showed a minor increase in the anticoagulant effect of VKA following statin initiation during VKA treatment. The reported increases in mean international normalized ratio (INR) ranged from 0.15–0.65. Conclusion: The anticoagulant effect of statin initiation in patients treated with VKA is likely to be of limited clinical relevance but should be evaluated individually.

ObjectivePrior studies have suggested that self-rated health may be a useful indicator of cardiovascular disease. Consequently, we aimed to assess the relationship between self-rated health, cardiovascular risk factors and subclinical cardiac disease in the Amazon Basin.DesignCross-sectional study.Setting, participants and interventionsIn participants from the Amazon Basin of Brazil we obtained self-rated health according to a Visual Analogue Scale, ranging from 0 (poor) to 100 (excellent). We performed questionnaires, physical examination and echocardiography. Logistic and linear regression models were applied to assess self-rated health, cardiac risk factors and cardiac disease by echocardiography. Multivariable models were mutually adjusted for other cardiovascular risk factors, clinical and socioeconomic data, and known cardiac disease.Outcome measuresCardiovascular risk factors and subclincial cardiac disease by echocardiography.ResultsA total of 574 participants (mean age 41 years, 61% female) provided information on self-rated health (mean 75±21 (IQR 60–90) points). Self-rated health (per 10-point increase) was negatively associated with hypertension (OR 0.87 (95% CI 0.78 to 0.97), p=0.01), hypercholesterolaemia (OR 0.89 (95%CI 0.80 to 0.99), p=0.04) and positively with healthy diet (OR 1.13 (95%CI 1.04 to 1.24), p=0.004). Sex modified these associations (p-interaction ConclusionSelf-rated health was positively associated with health parameters in the Amazon Basin, but not with subclinical cardiac disease by echocardiography. Our findings are of hypothesis generating nature and future studies should aim to determine whether assessment of self-rated health may be useful for screening related to policy-making or lifestyle interventions.Trial registration numberClinicaltrials.gov: NCT04445103; Post-results

PURPOSE: To estimate the life expectancy (LE) of HIV-infected patients in the West African country Guinea-Bissau and compare it with the background population.METHODS: Using data from the largest HIV outpatient clinic at the Hospital Nacional Simão Mendes in the capital Bissau, a retrospective observational cohort study was performed. The study included patients attending the clinic between June 2005 and January 2018. A total of 8958 HIV-infected patients were included. In the analysis of the background population, a total of 109,191 people were included. LE incorporating loss to follow-up (LTFU) was estimated via Kaplan-Meier estimators using observational data on adult HIV-infected patients and background population.RESULTS: The LE of 20-year-old HIV-infected patients was 9.8 years (95% CI 8.3-11.5), corresponding to 22.3% (95% CI 18.5-26.7%) of the LE of the background population. (LE for 20-year-olds in the background population was 44.0 years [95% CI 43.0-44.9].) Patients diagnosed with CD4 cell counts below 200 cells/µL had a LE of 5.7 years (95% CI 3.6-8.2). No increase in LE with later calendar period of diagnosis was observed.CONCLUSIONS: LE was shown to be markedly lower among HIV-infected patients compared with the background population. While other settings have shown marked improvements in prognosis of HIV-infected patients in recent years, no improvement in Bissau was observed over time (9.8 years (95% CI 7.6-12.2) and 9.9 years (95% CI 7.6-12.1) for the periods 2005-2010 and 2014-2016, respectively).

International audience; Climate change increases average temperatures and the occurrence of extreme weather events, in turn accentuating the risk of organism exposure to temperature stress. When thermal conditions become stressful, the sensitivity of insects toward insecticides can be exacerbated. Likewise, exposure of insects to insecticides can subsequently influence their ability to handle stressful temperatures. Here, we investigated the effects of constant temperature and daily heat spikes, in presence/absence of insecticide treatment (cyfluthrin), on the condition (impairment of mobility) and thermal tolerance to cold (-6 °C) and heat (42.5 °C) of the terrestrial beetle Alphitobius diaperinus. The responses of insects from four populations (three farm-collected populations, one laboratory population) to different durations of extreme temperature exposure were compared. The results showed that the laboratory population was generally more sensitive to extreme cold and heat temperatures, with less than 50% of adults recovering after an exposure at -6 or +42.5 °C for 3h. Significant differences in the level of thermal tolerance were also found among insects from poultry farms. Cyfluthrin exposure incurred detrimental effects to insects’ condition in all but one population. For two out of the four populations, mobility impairment was increased when adults were exposed to daily heat spikes (6 h per day at 38 °C) and cyfluthrin simultaneously, compared to cyfluthrin exposure at constant temperatures; yet, no significant interaction between the two stressors was found. Finally, using one farm collected population, effects of pre-exposure to cyfluthrin on extreme temperature tolerance provided another example of the toxicant-induced climate sensitivity in insects.

Most cystic fibrosis (CF) patients referred for lung transplantation are chronically infected with Gram-negative opportunistic pathogens. It is well known that chronic infections in CF patients have a significant impact on lung-function decline and survival before transplantation. The rate and timing of re-colonization after transplantation have been described, but the impact on survival after stratification of bacteria is not well elucidated. We did a single-center retrospective analysis of 99 consecutive CF patients who underwent lung transplantation since the beginning of the Copenhagen Lung Transplant program in 1992 until October 2014. Two patients were excluded due to re-transplantation. From the time of CF diagnosis, patients had monthly sputum cultures. After transplantation, CF-patients had bronchoscopy with bronchoalveolar lavage at 2, 4, 6 and 12 weeks and 6, 12, 18 and 24 months after transplantation, as well as sputum samples if relevant. Selected culture results prior to and after transplantation were stored. We focused on colonization with the most frequent bacteria: Pseudomonas aeruginosa (PA), Stenotrophomonas maltophilia (SM), Achromobacter xylosoxidans (AX) and Burkholderia cepacia complex (BCC). Pulsed-field gel electrophoresis (PFGE) was used to identify clonality of bacterial isolates obtained before and after lung transplantation. Time to re-colonization was defined as the time from transplantation to the first positive culture with the same species. Seventy-three out of 97 (75%) had sufficient culture data for analyses with a median of 7 (1–91) cultures available before and after transplantation. Median colonization-free survival time was 23 days until the first positive culture after transplantation. After 2 years, 59 patients (81%) were re-colonized, 33 (48.5%) with PA, 7 (10.3%) with SM, 12 (17.6%) with AX, and 7 (10.3%) with BCC. No difference in survival was observed between the patients colonized within the first 2 years and those not colonized. Re-colonization of bacteria in the lower airways occurred at a median of 23 days after transplantation in our cohort. In our patient cohort, survival was not influenced by re-colonization or bacterial species.

Background: Left-right movement symmetry is a highly desirable characteristic in sport horses. Objectives: This study compared movement symmetry in well-trained dressage horses in unridden and unrestrained position and ridden in a dressage frame, and investigated possible associations between gaits. Study design: Experimental study. Methods: Seven sound, high-level dressage horses were measured at walk and sitting trot on a treadmill at several speeds under two conditions: with and without rider. Left-right differences in stance duration, stance protraction and retraction based on longitudinal hoof positions, ipsilateral limb tracking, minimum and maximum vertical positions of the dorsal spinous processes of the sixth thoracic (T6), third sacral vertebrae (S3) and wing of atlas, and vertical ground reaction forces were calculated and analysed in mixed models. Results: At walk, five body variables indicated increased asymmetry in the ridden condition compared with unridden condition: forelimb stance duration (unridden/ridden left-right differences 9 vs 13 ms; P = .008), forelimb stance protraction (P = .004), stance retraction (P = .001) and first force peak (P = .003), and hindlimb stance retraction (P = .01). At trot, six body variables were more asymmetrical in the ridden condition: forelimb stance duration (2.5 vs 3.8 ms, P = .004); hindlimb stance protraction (P < .0001) and retraction (P = .01), T6 minimum (4 vs 6 mm, P = .001), T6 maximum (9 vs 11 mm, P = .01) and S3 maximum (6 vs 12 mm, P < .001). Five variables had significant associations between asymmetries at walk and trot, but only three demonstrated a positive slope. Main limitations: A limited number of horses and riders were studied. Measurements were performed on a treadmill. Conclusions: High-level horses moved slightly more asymmetrically when ridden in a dressage frame than in the unridden condition.

Background and purpose Access to evidence-based mental health care for children is an international priority. However, there are significant challenges to advancing this public health priority in an efficient and equitable manner. The purpose of this international colloquium was to convene a multidisciplinary group of health researchers to build an agenda for addressing disparities in mental health care access and treatment for children and families through collaboration among scholars from the United States and Europe engaged in innovative implementation science and mental health services research. Key highlights Guided by the Exploration, Preparation, Implementation, and Sustainment (EPIS) Framework, presentations related to inner, outer, and bridging context factors that impact the accessibility and quality of mental health evidence-based practices (EBPs) for children and families. Three common topics emerged from the presentations and discussions from colloquium participants, which included: 1) the impact of inner and outer context factors that limit accessibility to EBPs across countries, 2) strategies to adapt EBPs to improve their fit in different settings, 3) the potential for implementation science to address emerging clinical and public health concerns. Implications The common topics discussed underscored that disparities in access to evidence-based mental health care are prevalent across countries. Opportunities for cross-country and cross-discipline learnings and collaborations can help drive solutions to address these inequities, which relate to the availability of a trained and culturally appropriate workforce, insurance reimbursement policies, and designing interventions and implementation strategies to support sustained use of evidence-based practices.

We present the effect of exogenous sodium oxybate (GHB) in a severely tormented boy unable to sleep and unable to be anesthetized due to a lesion in the sleep initiation system involving the tracks between the ventrolateral preoptic nucleus and the reticular system. We bypassed the system by using sodium oxybate's effect on the cortical GHB and GABAB receptors involved in the initiation and maintenance of sleep.

This paper deals with collaborative R&D projects, with a considerable number of organizational actors, which generate both new knowledge and innovations, market upstream. It is generally assumed th...

In the clinical nursing practice preceptorship is a widespread method to improve patient care by assisting nurses in developing the right clinical skills. However, little is known about how preceptorship should be practiced to achieve a positive learning outcome. The aim of the study was to investigate how preceptorship can be used in clinical practice to create learning and facilitate competence development. A qualitative study guided by a hermeneutic phenomenological approach and inspired by ethnographic fieldwork included 28 participant observations and 58 interviews. Data were analysed according to Steinar Kvale's three interpretation contexts. The findings showed three themes: Being together: Preceptee and preceptor were physically present in the same room optimising the learning situation with focus on complexity, use of senses and patient safety. Doing together: Preceptee and preceptor performed nursing together to obtain skills focusing on independence, practical skills and communication. Getting along together: Preceptee and preceptor together focused on the patient, relation, comfort and managing how to keep the balance between a professional and a personal relation. Precepetorship is situated learning where knowledge and skills are generated through participation in clinical practice. In this way, nurses develop clinical judgement and independence. In the clinical nursing practice preceptorship is a widespread method to improve patient care by assisting nurses in developing the right clinical skills. However, little is known about how preceptorship should be practiced to achieve a positive learning outcome. The aim of the study was to investigate how preceptorship can be used in clinical practice to create learning and facilitate competence development. A qualitative study guided by a hermeneutic phenomenological approach and inspired by ethnographic fieldwork included 28 participant observations and 58 interviews. Data were analysed according to Steinar Kvale's three interpretation contexts. The findings showed three themes: Being together: Preceptee and preceptor were physically present in the same room optimising the learning situation with focus on complexity, use of senses and patient safety. Doing together: Preceptee and preceptor performed nursing together to obtain skills focusing on independence, practical skills and communication. Getting along together: Preceptee and preceptor together focused on the patient, relation, comfort and managing how to keep the balance between a professional and a personal relation. Precepetorship is situated learning where knowledge and skills are generated through participation in clinical practice. In this way, nurses develop clinical judgement and independence.

Artigo escrito a convite do editor do dossiê pelo professor Lorenz Engell, da Universidade Bauhaus em Weimar.

Patient: Male, 70 Final Diagnosis: Acute respiratory failure Symptoms: Cough • fever • lethargy Medication: — Clinical Procedure: — Specialty: Critical Care Medicine Objective: Rare co-existance of disease or pathology Background: Strongyloides stercoralis is an intestinal helminth. Parasitism is caused by penetration of the larvae through the skin. It is endemic in tropical and subtropical regions of the world and in the United States occurs in the southeastern region. It has a tendency to remain dormant or progress to a state of hyper-infection during immunosuppression. Case Report: We present the case of a 70-year-old Nigerian who developed fatal ARDS secondary to Strongyloides infection after been treated with steroids for treatment of autoimmune necrotizing myopathy. Despite adequate management with mechanical ventilation and appropriate antifungal therapy, the patient died on day 19 of hospitalization. Conclusions: S. stercoralis is known to affect every organ in the body. ARDS is often an overlooked complication of Strongyloides hyper-infection, which is often deadly. Immediate diagnosis and treatment are important for patient survival.

Oral vaccination is of major interest because it can be used for mass vaccination of fish of various size and age. Given that their administration is relatively easy and stress-free, oral vaccines have both economic and animal welfare benefits. Yet, mostly due to their limited efficacy, only very few oral vaccines are available to aquaculture industry. Here we present a method for oral vaccine delivery based on the yeast Pichia pastoris. We could express a model antigen, green fluorescent protein (GFP), in this yeast and subsequently show delivery of the GFP protein to the intestine of juvenile flounder or adult carp and trout. We tested this approach in several commercially-relevant fish species, from juvenile to adult stage. To test the oral delivery of antigen to larval fish, the GFP-expressing Pichia pastoris was first fed to planktonic crustacean Daphnia or rotifers that served as ‘bioencapsulation vehicles’ and afterwards, fed to flounder larvae. Again, we could show delivery of intact GFP protein to the intestine. In rainbow trout, the orally-administered GFP-expressing yeast elicited a rapid local innate immune response in the intestine and a subsequent systemic response in the spleen. Our results show that Pichia pastoris is a good vehicle for oral antigen delivery and that it can be used in non-encapsulated form for older fish or in bioencapsulated form for larval fish. We discuss the immunomodulatory properties of the yeast itself, and its potential to enhance local immune responses and act as an adjuvant.

Purpose: The objective of this study was to ascertain vital status of patients considered lost to follow-up at an HIV clinic in Guinea-Bissau, and describe reasons for loss tofollow-up (LTFU).Methods: This study was a cross-sectional sample of a prospective cohort, carried out between May 15, 2013, and January 31, 2014. Patients lost to follow-up, who livedwithin the area of the Bandim Health Project, a demographic surveillance site (DSS), were eligible for inclusion. Active follow-up was attempted by telephone and tracingby a field assistant. Semi-structured interviews were done face to face or by phone by a field assistant and patients were asked why they had not shown up for the scheduledappointment. Patients were included by date of HIV testing and risk factors for LTFU were assessed using Cox proportional hazard model.Results: Among 561 patients (69.5 % HIV-1, 18.0 % HIV-2 and 12.6 % HIV-1/2) living within the DSS, 292 patients had been lost to follow-up and were, therefore,eligible for active follow-up. Vital status was ascertained in 65.9 % of eligible patients and 42.7 % were alive, while 23.2 % had died. Information on reasons for LTFUexisted for 103 patients. Major reasons were moving (29.1 %), travelling (17.5 %), and transferring to other clinics (11.7 %).Conclusion: A large proportion of the patients at the clinic were lost to follow-up. The main reason for this was found to be the geographic mobility of the population inGuinea-Bissau. PURPOSE: The objective of this study was to ascertain vital status of patients considered lost to follow-up at an HIV clinic in Guinea-Bissau, and describe reasons for loss to follow-up (LTFU).METHODS: This study was a cross-sectional sample of a prospective cohort, carried out between May 15, 2013, and January 31, 2014. Patients lost to follow-up, who lived within the area of the Bandim Health Project, a demographic surveillance site (DSS), were eligible for inclusion. Active follow-up was attempted by telephone and tracing by a field assistant. Semi-structured interviews were done face to face or by phone by a field assistant and patients were asked why they had not shown up for the scheduled appointment. Patients were included by date of HIV testing and risk factors for LTFU were assessed using Cox proportional hazard model.RESULTS: Among 561 patients (69.5 % HIV-1, 18.0 % HIV-2 and 12.6 % HIV-1/2) living within the DSS, 292 patients had been lost to follow-up and were, therefore, eligible for active follow-up. Vital status was ascertained in 65.9 % of eligible patients and 42.7 % were alive, while 23.2 % had died. Information on reasons for LTFU existed for 103 patients. Major reasons were moving (29.1 %), travelling (17.5 %), and transferring to other clinics (11.7 %).CONCLUSION: A large proportion of the patients at the clinic were lost to follow-up. The main reason for this was found to be the geographic mobility of the population in Guinea-Bissau.

The symmetry of the rider is highly relevant, and in the equestrian community it is generally thought that a symmetrical rider has a better possibility to influence the horse in an optimal way. The aim of the study was to analyse and compare frontal plane kinematics of the core body segments in ten riders while riding and while rocking a balance chair from side-to-side. It was hypothesized that the riders were asymmetrical in relation to their intersegmental strategies when comparing between left and right directions and that individual riders would display the same postural strategies when riding and when rocking the balance chair. Ten moderately-skilled riders wore a full-body marker set that was tracked by a motion capture system as they rocked a balance chair from side to side. Inertial measurement units attached to the head, trunk and pelvis were used to measure the segmental movements while riding in left and right directions. Roll rotation data for head, trunk and pelvis were averaged over available strides/cycles. Results from mixed models showed that the riders were asymmetric when comparing riding in left vs right directions, for example the trunk was rotated 19° to the right on the right circle and 14° to the left on the left circle, on average. Riders adopted the same asymmetrical posture whether they were riding in the left or right direction on straight lines, circles or leg yielding. A significant relationship was found between postural asymmetries when riding and when rocking the balance chair, one degree of pelvis or head roll asymmetry on the chair predicted 2.4 (SE 0.9) degrees of asymmetry while riding. Future studies may investigate the value of seated, off-horse postural training for improving rider symmetry and thereby equestrian performance.

Saddle slip, defined as a progressive lateral displacement of the saddle during ridden exercise, has recently been given attention in the scientific press as a potential sign of lameness. The aim of this study was to objectively quantify the normal lateral movement (oscillations) of the saddle relative to the horse in non-lame horses, and associate this movement to the movements of the horse and rider. Data from seven Warmblood dressage horses competing at Grand Prix (n = 6) or FEI Intermediate (n = 1) level, ridden by their usual riders, were used. Simultaneous kinetic, kinematic and saddle pressure measurements were conducted during sitting and rising trot on a force-measuring treadmill. The maximum lateral movement of the caudal part of the saddle relative to the horse's spine (MAX) was determined for each diagonal step. A mixed model was applied, with MAX as outcome, and T6 and S3 vertical position, rigid body rotation angles (roll, pitch, yaw) of the horse's and rider's pelvis, vertical ground reaction forces, saddle force, and rider position (rising in rising trot, sitting in rising trot or sitting in sitting trot) as explanatory variables. The least square means for MAX were 14.3 (SE 4.7) mm and 23.9 (SE 4.7) mm for rising and sitting in rising trot, and 20.3 (SE 4.7) mm for sitting trot. A 10 mm increase in maximum pelvic height at push off increased MAX by 1.4 mm (p

It is widely accepted that holistic processing is critical for early face recognition, but recent work has suggested a larger role for feature-based processing. The earliest step in familiar face recognition is thought to be matching a perceptual representation of a familiar face to a stored representation of that face, which is thought to be indexed by the N250r event-related potential (ERP). In the current face priming studies, we investigated whether this perceptual representation can be effectively activated by feature-based processing. In the first experiment, prime images were familiar whole faces, isolated eyes, or isolated mouths. Whole faces and isolated eyes, but not isolated mouths, effectively modulated the N250r. In the second experiment, prime images were familiar whole faces presented either upright or inverted. Inverted face primes were no less effective than upright face primes in modulating the N250r. Together, the results of these studies indicate that activation of the earliest face recognition processes is not dependent on holistic processing of a typically configured face. Rather, feature-based processing can effectively activate the perceptual memory of a familiar face. However, not all features are effective primes as we found eyes, but not mouths, were effective in activating early face recognition.HighlightsHolistic processing is not necessary for early identity recognition of familiar faces.Inverted faces and isolated features can effectively activate the perceptual memory of a familiar face.This effectiveness was observed for eyes, but not mouths.

Polymedicated neonates and young infants may be at risk of harmful cumulative exposure to toxic excipients like ethanol, propylene glycol and benzyl alcohol during routine clinical care. The aim of this study was to calculate the cumulative daily alcohol exposure (mg/kg/day) in polymedicated neonates and infants and compare these levels to the tolerance limits found in guidelines published by European Medicines Agency (EMA). As part of the SEEN study, all medicinal products administered to neonates and infants were recorded. All included neonates received ≥2 medicinal products/day and infants ≥3 medicinal products/day. Daily excipient levels were calculated based on quantities obtained from manufacturers or databases. Excipient levels were compared to tolerance limits proposed by the EMA. Altogether, 470 neonates and 160 infants were included, recording 4207 prescriptions and 316 products. In total, 45% (n = 288) of patients were exposed to an alcohol of interest; 2% (n = 14) were exposed to benzyl alcohol (BA), 38% (n = 237) to ethanol and 23% (n = 146) to propylene glycol (PG). Of the total number of prescriptions involving ethanol-containing medicinal products (n = 334), 51% would alone exceed tolerance limit of 6 mg/kg/day. Of the total number of prescriptions involving PG-containing medicinal products (n = 174), 70% would alone exceed a maximum tolerance limit of 50 mg/kg/day. Maximal daily exposure to ethanol (1563 mg/kg/day) or PG (954 mg/kg/day) exceeded the tolerance limits recommended by EMA 260.5 and 19.1 times, respectively. Tolerance limits for ethanol and PG as proposed by the EMA are frequently exceeded in polymedicated neonates and infants due to the cumulative effect of these alcohols. Alternative formulations may minimize excipient exposure.

Decades of research have demonstrated that a region of the right fusiform gyrus (FG) and right posterior superior temporal sulcus (pSTS) responds preferentially to static faces and biological motion, respectively. Despite this view, both regions activate in response to both stimulus categories and to a range of other stimuli, such as goal-directed actions, suggesting that these regions respond to characteristics of animate agents more generally. Here we propose a neural model for animacy detection composed of processing streams that are initially differentially sensitive to cues signaling animacy, but that ultimately act in concert to support reasoning about animate agents. We use dynamic causal modeling, a measure of effective connectivity, to demonstrate that the directional flow of information between the FG and pSTS is initially dependent on the characteristics of the animate agent presented, a key prediction of our proposed network for animacy detection.

This paper suggests a method to control the particle size distribution in semi-batch emulsion homopolymerizations under structural plant-model mismatch. In this approach, firstly a nominal monomer feed input trajectory is applied to the plant up to a predefined time instant after the start of the batch (mid-course). By means of a calorimetric observer, all states of the system except the particle size distribution are estimated using the available measurements. The estimated states and the measured PSD at the mid-course of the process are used as the initial condition for an optimization which is done to compute the trajectory of the monomer feed from the mid-course up to the end of the batch. In this optimization, considering a structural plant-model mismatch, a hybrid model which comprises the nominal model of emulsion polymerization and an empirical component that corrects the predictions of this nominal model is used.

For producing sulfur trioxide, sulfur dioxide is oxidized to sulfur trioxide in the presence of a catalyst. Industrially, sulfur trioxide is produced by the contact process which consists of several catalytic beds and inter-cooling stages between them. This process is highly energy intense and inflexible due to long periods of start-up and shut-down caused by the thermal inertia. In order to improve the flexibility of the production process, a new approach for producing sulfur trioxide is currently being investigated. A micro-structured reactor has been constructed by the Karlsruhe Institute for Technology (KIT) which consists of only one cooling passage. In our work, a three dimensional dynamic reactor model was developed that describes the dynamic behavior of the micro-structured reactor. This model was used to simulate the efficiency and the distribution of temperature and reactants in the system and in particular for investigating the start-up of the reactor. A control strategy was developed and tested in simulations in order to react on disturbances and to improve the start-up time. The simulations showed that a conversion of approx. 98.5 % can be reached and by a suitable control strategy the start up time can be improved significantly.

In this contribution we study the application of non-linear model predictive control to a continuous polymerization of acrylic acid in tubular reactors with multiple side injections of monomer. The background of this work is to transfer the polymerization from semi-batch to continuous operation. Model Predictive Control (MPC) is the obvious candidate to control such a multi-input system. The reactor configuration and polymerization reaction make the application of MPC very challenging. The controller employs a discretized dynamic pde model of the process and optimizes the productivity of the plant online while keeping the product quality parameters within the predefined constraints. The spatial domain of the model is discretized by applying the Weighted Essentially Non Oscillatory (WENO) scheme. Besides testing the controller for a nominal case in which the control model is identical to the existing plant, the controller has been simulated for two model-plant mismatch cases, caused by fouling and feed impurities. For the both cases, a moving window estimation scheme is applied to estimate the unknown parameters and to update the model used by NMPC. The results show that the controller can increase the product throughput considerably and has a robust performance in the presence of the model-plant mismatch. Moreover, the effect of formulating the quality constraints as soft constraints is studied.

Summary Background No systematic attempts have been made to estimate the global and regional prevalence of amphetamine, cannabis, cocaine, and opioid dependence, and quantify their burden. We aimed to assess the prevalence and burden of drug dependence, as measured in years of life lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life years (DALYs). Methods We conducted systematic reviews of the epidemiology of drug dependence, and analysed results with Global Burden of Diseases, Injuries, and Risk Factors Study 2010 (GBD 2010) Bayesian meta-regression technique (DisMod-MR) to estimate population-level prevalence of dependence and use. GBD 2010 calculated new disability weights by use of representative community surveys and an internet-based survey. We combined estimates of dependence with disability weights to calculate prevalent YLDs, YLLs, and DALYs, and estimated YLDs, YLLs, and DALYs attributable to drug use as a risk factor for other health outcomes. Findings Illicit drug dependence directly accounted for 20·0 million DALYs (95% UI 15·3–25·4 million) in 2010, accounting for 0·8% (0·6–1·0) of global all-cause DALYs. Worldwide, more people were dependent on opioids and amphetamines than other drugs. Opioid dependence was the largest contributor to the direct burden of DALYs (9·2 million, 95% UI 7·1–11·4). The proportion of all-cause DALYs attributed to drug dependence was 20 times higher in some regions than others, with an increased proportion of burden in countries with the highest incomes. Injecting drug use as a risk factor for HIV accounted for 2·1 million DALYs (95% UI 1·1–3·6 million) and as a risk factor for hepatitis C accounted for 502 000 DALYs (286 000–891 000). Suicide as a risk of amphetamine dependence accounted for 854 000 DALYs (291 000–1 791 000), as a risk of opioid dependence for 671 000 DALYs (329 000–1 730 000), and as a risk of cocaine dependence for 324 000 DALYs (109 000–682 000). Countries with the highest rate of burden (>650 DALYs per 100 000 population) included the USA, UK, Russia, and Australia. Interpretation Illicit drug use is an important contributor to the global burden of disease. Efficient strategies to reduce disease burden of opioid dependence and injecting drug use, such as delivery of opioid substitution treatment and needle and syringe programmes, are needed to reduce this burden at a population scale. Funding Australian National Health and Medical Research Council, Australian Government Department of Health and Ageing, Bill & Melinda Gates Foundation.

In warehousing systems, the speed of the removal and distribution of goods often represents a bottleneck as it limits the achievable throughput and, thus, the efficiency of the complete warehousing system. Consequently, an optimal management of the distribution of goods can lead to large efficiency and financial gains. In this contribution, it is shown for an accurate model of an industrial real-world high-rise warehouse (HRW), which is connected to a polymer production plant, that rigorous optimization of the distribution procedure can lead to a large efficiency increase in comparison to standard techniques. To this end, the distribution problem is modelled using timed automata (TA) in which the jobs arrive one after the other and are not known in advance. The TA-based approach, which was originally developed for standard scheduling problems, is extended to a reactive moving window approach that employs a cost-optimal reachability algorithm to compute optimal plans for the goods distribution. We show that compared to a typical first-come first-served dispatching rule, this approach can lead to throughput gains of more than 40%.

Siden valget af Hamas i 2006 er der opstået en opposition af al-Qaidainspirerede bevægelser i Gaza. Ideologiske modsætninger har ført til konflikt mellem disse grupper og Hamas. Men hvem truer hvem i denne situation? Og hvad er konsekvenserne for fredsprocessen?

In this contribution we discuss an extension of a recent approach to solve batch scheduling problems using reachability analysis for timed automata (TA) with embedded lower bound computations. We propose two bounding procedures embedded in the reachability algorithm to handle scheduling problems with sequence-dependent changeovers: (i) a MILP formulation (originally proposed by Manne 1960) extended with additional constraints to model setup and changeover operations and (ii) an improved minimum remaining processing time (MRPT) procedure. The efficiency of the proposed bounding procedures is evaluated on job shop problems with sequence-dependent changeovers. The comparative study shows that the MRPT-based bounding procedure is efficient and increases the overall performance significantly in comparison to the MILP-based bounding procedure.

For continuously operated processes, even a small increase in the efficiency pays important dividends in terms of energy savings and profit. Therefore, tighter and more efficient control of chemical plants is becoming a strategic objective. In this work, we demonstrate the use of dynamic process optimization to improve the business performance of chemical processes. Model predictive control techniques are widely applied to coupled multivariable control problems. The reference values in these problems are usually adjusted by infrequent optimizations based upon a static rigorous nonlinear model of the plant. In between these optimizations, however, the process may undergo sub-optimality of operation due to the presence of disturbances. In this paper, nonlinear model-based optimization with different schemes is proposed to combine optimal operation and feedback control. The work demonstrates the feasibility and the potential of using optimizing as well as economics-oriented tracking control techniques for a challenging example, a catalytic distillation process. The performances of the proposed controllers are investigated and compared. This work points out that by using direct optimizing NMPC, the plant economics can be handled better while guaranteeing the product specifications.

In this paper, an online adaptation scheme for tuning of PID parameters is presented. This scheme is based upon our previous works on using a data-driven method to obtain a sufficient condition for robust stability and integrating robustness into the Unfalsified Control framework. Here, a modified bumpless transfer approach to facilitate the adaptation of the PID controller parameters is presented. The proposed scheme is demonstrated using a PID benchmark problem.

Emulsion polymerization processes are characterized by exothermic reactions with complicated nonlinear dynamics. A very precise temperature control is necessary in order to ensure that the end product satisfies the quality demands. In industry, this issue is addressed by adopting a conservative monomer feed policy such that a robust operation is guaranteed under various disturbing influences. A combination of a monomer feed controller based on jacket temperature constraint and a monomer feed controller based on droplet phase avoidance constraint that optimizes the batch time is analysed in terms of robustness and performance. The simulation results show that the scheme reduces the batch time without harming the quality of the temperature control.

Background and purpose The genetic/environmental etiology of Scheuermann's disease is unclear. We estimated the heritability of the disease using an etiological model adjusted for sex and time of d...

In this paper, a data-driven adaptive control scheme is presented which is based upon Unfalsified Control theory. The presented work extends our previous works on suitable cost functions in Unfalsified Control and the use of optimization to obtain new optimal controllers. A data-driven method is used here to obtain a sufficient condition for robust stability. This condition is used to falsify the non-robust controllers. Additionally it is used along with a signal-to-peak norm constraint in the optimization of the candidate controller parameters, to obtain robust controllers and to avoid the controller saturation. A case study using a well known example from chemical engineering shows the application of the extended scheme.

Perception of both gaze-direction and symbolic directional cues (e.g. arrows) orient an observer’s attention toward the indicated location. It is unclear, however, whether these similar behavioral effects are examples of the same attentional phenomenon and, therefore, subserved by the same neural substrate. It has been proposed that gaze, given its evolutionary significance, constitutes a ‘special’ category of spatial cue. As such, it is predicted that the neural systems supporting spatial reorienting will be different for gaze than for non-biological symbols. We tested this prediction using functional magnetic resonance imaging to measure the brain’s response during target localization in which laterally presented targets were preceded by uninformative gaze or arrow cues. Reaction times were faster during valid than invalid trials for both arrow and gaze cues. However, differential patterns of activity were evoked in the brain. Trials including invalid rather than valid arrow cues resulted in a stronger hemodynamic response in the ventral attention network. No such difference was seen during trials including valid and invalid gaze cues. This differential engagement of the ventral reorienting network is consistent with the notion that the facilitation of target detection by gaze cues and arrow cues is subserved by different neural substrates.

In this paper, an improved algorithm for data-driven adaptive control that includes ideas from Unfalsified Control is presented. This work extends our previous work on suitable cost functions in Unfalsified Control and the use of optimization to improve the set of controllers by an additional sufficient condition for robust stability that is derived only from the measured data. This condition is also used to falsify controllers in order to avoid that a non-robust controller is put into the loop.

The correct description of cell cultures is vital for the understanding of underlying processes and optimisation of production processes. The brewer's yeast Saccharomyces cerevisiae is a commonly used and well explored organism for the production of amino acids, antibiotics, recombinant proteins, and others. In this paper, an existing single cell model of the cell cycle of S. cerevisiae is extended in order to correctly describe mass, age, and cell cycle distributions of a cell culture. For this, a model of the aging process of the cell has been integrated into the cell cycle model. The model can be used to gain insight into the distribution of mutant populations. Also, it can be regarded as a first step for the development of optimisation strategies for production processes where the production and secretion rates of products vary over the cell cycle.

Tumor infiltration with Valpha24-invariant NKT cells (NKTs) associates with favorable outcome in neuroblastoma and other cancers. Although NKTs can be directly cytotoxic against CD1d+ cells, the majority of human tumors are CD1d-. Therefore, the role of NKTs in cancer remains largely unknown. Here, we demonstrate that CD68+ tumor-associated monocytes/macrophages (TAMs) represented the majority of CD1d-expressing cells in primary human neuroblastomas. TAMs stimulated neuroblastoma growth in human cell lines and their xenografts in NOD/SCID mice via IL-6 production. Indeed, TAMs produced IL-6 in primary tumors and in the BM of patients with metastatic neuroblastoma. Gene expression analysis using TaqMan low-density arrays of 129 primary human neuroblastomas without MYCN amplification revealed that high-level expression of TAM-specific genes (CD14, CD16, IL6, IL6R, and TGFB1) was associated with poor 5-year event-free survival. While NKTs were not cytotoxic against neuroblastoma cells, they effectively killed monocytes pulsed with tumor cell lysate. The killing of monocytes was CD1d restricted because it was inhibited by a CD1d-specific mAb. Cotransfer of human monocytes and NKTs to tumor-bearing NOD/SCID mice decreased monocyte number at the tumor site and suppressed tumor growth compared with mice transferred with monocytes alone. Thus, killing of TAMs reveals what we believe to be a novel mechanism of NKT antitumor activity that relates to the disease outcome.

Affection of the optic nerves play a central role in multiple sclerosis (MS) symptomatology. In reported autopsy series the prevalence of optic neuropathy has approached 100%. In the present study subclinical affection of the optic nerves was investigated by visual evoked response (VER), Farnworth-Munsell 100 Hue test (FM 100 Hue test) and Ishihara plates in 17 patients with normal visual acuity and without a history of acute optic neuritis. Optic neuropathy was demonstrated in 72% of the eyes. The occurrence of optic neuropathy was also investigated by the same methods in 16 patients with previous acute optic neuritis, which was bilateral in 5 patients. Affection of the optic nerves was demonstrated in 95% in this group. The affection of also the fellow eye in patients with previous monolateral optic neuritis is unexplained. It may be an analogue to the symmetry of plaques found in the brain and the spinal cord. The cause of this peculiar distribution of lesions is, like the ethiology of MS, unexplained at present. In compairing the different methods of demonstrating optic neuropathy, VER is recommended as the method of choice.

The reported findings of periphlebitis retinae (PR) at autopsy, in which brain autopsy was also performed, in 2 patients with multiple sclerosis (MS) are, so far as the authors are aware, the first histological account of this manifestation of the disease. The similarity between the cellular accumulations around the veins of the central nervous system seen in multiple sclerosis and the periphlebitic cellular accumulations here described suggests that periphlebitis is an initial event in plaque formation.

Periphlebitis retinae (PR) in multiple sclerosis (MS) is seen as cuffs around veins in the otherwise normal retinae. The frequency of PR in MS varies considerably between different series, approximately from 5 to 25%. The aim of the present study was to investigate if PR, when present, is correlated to neurological disease activity. No similar study has been performed to the author's knowledge. The prevalence of PR in a hospital material of 135 MS patients was 15%, compared to the frequency of 5% found in 168 MS patients examined at a Rehabilitation Center. Thus a three times higher frequency was found in the hospital material which comprised more patients with active disease. The status of neurological disease activity was assessed in 27 patients at the occurrence of PR. One patient only had stationary disease. The frequency of malignant MS in the 27 PR patients was 26% versus 9%. The present study suggests a correlation between neurological disease activity and PR in MS patients.

Abstract Today, many supermarket refrigeration systems are operated by decentralized control systems that often lead to excessive starting and stopping of the compressors which drive the cooling cycle and, consequently, to a large wear of the process equipment. In our previous work, a hierarchical model-predictive control scheme was proposed for supermarket refrigeration systems that overcomes this drawback. In this scheme, simple low-level temperature controllers are employed, and the high-level optimization task is the optimal adjustment of the parameters of these controllers. While this approach yields a good control performance, it is computationally too expensive for larger systems. In this paper, a more efficient approach is presented that is based on an approximation of the system dynamics using simple models that are computed from system sensitivities around simulated reference trajectories. The application of the new approach to a large hybrid model proves the real-time capabilities of the new technique.

Abstract In this paper, a new scheme for adaptive unfalsified control with non-ideal measurements is presented and demonstrated for a well-known example of a nonlinear plant, the continuous stirred tank reactor (CSTR) with the van-der-Vusse reaction scheme. In our adaptive control algorithm, there are two adaptation mechanisms: 1. Switching of the active controller in a fixed set of candidate controllers by the e-hysteresis switching algorithm. 2. Adaptation of the set of controllers performed by a population-based evolutionary algorithm. In this paper, the effect of measurement errors on the adaptive control scheme is investigated. The total least squares method is used to perform the deconvolution of noisy signals.