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Ready-to-fill enteric hard capsule shells are an evolving field of oral drug and nutraceutical products. Lonza Capsugel® Enprotect® capsules were recently proven to provide reliable release in the small intestine after fasted intake, but robustness against postprandial intake needed to be proven. In this study, the capsules were administered to 16 healthy young subjects after intake of a light meal. The Enprotect® capsules were labelled with 5 mg black iron oxide and 25 mg 13C3-caffeine. Magnetic Resonance Imaging was used to identify the localization and visual dispersion of the capsule filling. The salivary appearance of caffeine was considered a second independent and sensitive marker for the initial release. Whereas the fasted gastric residence time of the capsules amounted to 43 ± 32 min, it was increased to 158 ± 36 min after postprandial intake. Therefore, the mean dispersion time according to MRI and the mean caffeine appearance time were increased to 196 ± 37 min and 189 ± 37 min, respectively. But, similar to fasted administration, no capsule disintegration or leakage was observed in the stomach and 38% of the capsules disintegrated in the jejunum and 62% in the ileum. The mean dispersion time after gastric emptying and the mean caffeine appearance time after gastric emptying amounted to 38 ± 21 min and 31 ± 17 min, respectively. Both did not relevantly change compared to the fasted intake. Only the absolute dispersion time and caffeine appearance were prolonged due to the increased gastric residence and no relevant influence of the light meal was observed on the disintegration or release behavior of Enprotect® capsules after gastric emptying. The capsules also showed robust enteric properties after postprandial administration. [ABSTRACT FROM AUTHOR]

[Display omitted] Gastrointestinal fluid volumes are a crucial parameter for dissolution and absorption of orally taken medications. Most often 240 mL are used in clinical standard setups. Nonetheless, surveys in patient populations revealed dramatically lower volumes for intake of oral medications in real life and even in some clinical studies reduced fluid volumes are common. These reductions might have serious impact on pharmacokinetics. Thus, it was the aim of this study to compare the gastric emptying of 240 mL and 20 mL of water in 8 healthy volunteers. For investigation of gastric fluid volumes Magnetic Resonance Imaging with strongly T2 weighted sequences was used. Gastric emptying was additionally quantified via caffeine pharmacokinetics measured in saliva. The absolute gastric volumes after intake of 240 mL or 20 mL obviously differed by factor 10 but relative gastric emptying expressed as fraction per time was nearly comparable. Only slighter slower emptying after intake of 20 mL was observed. Salivary caffeine pharmacokinetics representing mass transfer from stomach to small intestine after intake of different volumes did not differ. The absorbed caffeine fraction and emptied gastric volume fraction correlated well after intake of 240 mL, but not after intake of 20 mL, indicating a higher influence of secretion on gastric volume measurements after intake of smaller volumes. Relative gastric emptying as measured with MRI and salivary caffeine method was only slightly delayed, thus transfer of orally administered drug fraction could be comparable even with lower fluid intake as can be seen by comparable caffeine pharmacokinetics. Nonetheless, the considerably reduced volumes might interfere with dissolution and absorption. [ABSTRACT FROM AUTHOR]

Gastric water emptying as a critical parameter for oral drug absorption can be investigated by several imaging techniques or by the interpretation of pharmacokinetics of appropriate substances. Recently introduced salivary caffeine kinetics is a valuable tool, but the required caffeine abstinence limits its applicability. To avoid the caffeine abstinence, stable isotope-labeled caffeine might be used, but the representability and transferability of kinetics for evaluation of gastric emptying must be demonstrated. Thus, salivary caffeine pharmacokinetics were compared for naturally occurring 12C-caffeine and 13C3-caffeine after the administration of water under fasting conditions in six healthy young subjects. For this purpose, an ice capsule containing the two caffeine species was administered with 50 mL tap water. Gastric water emptying was simultaneously quantified using magnetic resonance imaging (MRI). Gastric emptying of 50 mL of water could be successfully evaluated. The salivary caffeine kinetics of 13C3- and 12C-caffeine were nearly congruent and showed good linear correlations in all subjects, with a mean correlation coefficient of 0.96 in pooled data. Thus, the substitution of natural 12C caffeine with stable isotope-labeled 13C3-caffeine offers the opportunity for broader application of the salivary caffeine gastric emptying technique and increases the robustness of the method against environmental contamination with caffeine. [ABSTRACT FROM AUTHOR]

Survivors of advanced breast cancer (ABC), also known as metavivors, are often left with fewer treatment options in the landscape of a cure culture. Metavivors have unique psychosocial and physical needs distinct from patients with early-stage breast cancer. This analysis delves into side effects commonly experienced by patients with ABC, such as fatigue, anxiety, and cardiotoxicity; how these side effects impact caregiver support, financial toxicity, emotional strain, and spiritual and emotional distress; as well as current strategies for mitigation, including nutrition, exercise, and participation in clinical research. Overall, this analysis is a mandate for additional research to explore novel treatments and implement strategies to maintain and improve patients' quality of life. [ABSTRACT FROM AUTHOR]

Inflammatory bowel disease (IBD) affects patients at a significant time in their lives, often coinciding with family planning or pregnancy. While advances in IBD therapies have afforded women greater opportunities for successful conception and pregnancy outcomes, there still remains considerable maternal fear surrounding continuation of treatment in pregnancy. With the exception of methotrexate, most IBD drugs are safe and well tolerated during pregnancy and are not associated with significant risk of adverse fetal or pregnancy outcomes. Furthermore, the current evidence overwhelmingly suggests that good control of disease activity and clinical remission at time of conception are the greatest prognostic factors for an uncomplicated pregnancy and maintenance of quiescent disease. Management of pregnant women with IBD should involve discussions with the mother and family about fears or concerns surrounding the impact of IBD on pregnancy. Mothers should be supported and counselled carefully on the safety and importance of adherence to therapy in maintaining remission. Optimal management of these women requires an inter-disciplinary team effort, involving the general practitioner, in close consultation with both gastroenterologists and obstetricians. [ABSTRACT FROM AUTHOR]

The instability of various small molecules, vaccines and peptides in the human stomach is a complex challenge for oral drug delivery. Recently, a novel gastro-resistant capsule – the enTRinsic™ Drug Delivery Technology capsule – has been developed. In this work, the salivary tracer technique based on caffeine has been applied to study the in vivo disintegration of enTRinsic™ capsules in 16 healthy volunteers. In addition, magnetic resonance imaging (MRI) was used to visualize GI transit and to verify the disintegration times determined by using the salivary tracer technique. The enTRinsic™ capsules filled with 50 mg of caffeine and 5 mg of black iron oxide were administered in the fed state, i.e. 30 min after a light meal (500 kcal). In the first hour after capsule intake, the subjects were placed in supine position in the MRI scanner and scans were performed in short time intervals. After 1 h, the subjects could leave the MRI scanner in between the MRI measurements, which were performed every 15 min until disintegration of the capsule was confirmed (maximum observation time: 8 h). Saliva samples were obtained simultaneously with MR imaging. Caffeine concentrations in saliva were determined by LC/MS-MS. The starting point of capsule disintegration was determined visually by inspection of the MR images as well as by the onset of salivary caffeine concentrations. In 14 out of 16 subjects, the capsule disintegrated in the small intestine. In one subject, the enTRinsic™ capsule was not emptied from the stomach within the observation time. In another subject, disintegration occurred during gastric emptying in the antropyloric region. In this study, we demonstrated that the enTRinsic™ capsules are also gastro resistant when taken under fed state conditions. Furthermore, we demonstrated the feasibility of using low dose caffeine as a salivary tracer for the determination of the disintegration of an enteric formulation. [ABSTRACT FROM AUTHOR]

• Chemical stability of homogeneous α-phase increases with rising Al-content. • Impact of continuity of β-phase on corrosion depends on the surrounding α-Matrix. • Al content of α-phase is more important for control corrosion than β-phase network. The influence of α-phase and β-phase (Mg 17 Al 12) on corrosion of cast binary Mg-Al alloys was investigated by immersion testing in 5 wt.-% NaCl solution saturated with Mg(OH) 2 and by measuring the corrosion potential E corr. The microstructure of the alloys regarding Al-content of α-phase and amount of β-phase was adjusted by solution heat treatments at various temperatures. Subsequently the continuity of β-phase (C β) was measured. With increasing Al-content in the α-phase, the impact of C β decreases. The results show that the Al-content of the α-phase is a very important factor to influence the corrosion resistance. [ABSTRACT FROM AUTHOR]

Graphical abstract Abstract In preclinical research, Beagle dogs are an important model for formulation development and for evaluation of food effects on drug absorption. In this study, the gastrointestinal transit conditions in Beagle dogs were studied with a telemetric motility capsule at different intake conditions. In a cross-over study design, the SmartPill® was given to six Beagle dogs to measure transit times, pH values, pressures and temperatures in the different parts of the canine GI tract. Moreover, the effects of commonly applied pre-treatments as with pentagastrin and famotidine on GI transit conditions were investigated. The gastric transit time in fasted state was short (0.57 ± 0.37 h) and only slightly affected by the pre-treatments. In fed state, gastric transit was clearly prolonged (2.94 ± 0.91 h). The mean intestinal transit time was in the range of 1–2 h and not affected by the intake conditions. The gastric pH values in fasted and fed Beagle dogs were highly variable, but pre-treatment with pentagastrin and famotidine clearly decreased variability. Pre-treatment with pentagastrin resulted in minimum pH values around 0.5 pH units lower than without pre-treatment. Oral administration of famotidine led to constantly elevated pH values of pH 7–8. The maximum pressures in the canine GI tract did not vary significantly between the study arms and typically, maximum pressures of up to 800 mbar were observed in the stomach. The comparison of the data from this study with recent SmartPill® data from humans revealed that major differences could be observed with respect to gastric transit times in fed state, small intestinal transit times as well as maximum pressures arising during GI transit. These differences should be kept in mind if the dog model is used to assess the in vivo performance of solid oral dosage forms intended for use in humans. [ABSTRACT FROM AUTHOR]

Abstract The application areas of hard capsules are currently widened by the introduction of acid-resistant capsule shells. In this study, the gastrointestinal behavior of acid-resistant hard capsule formulations as well as the influence of their density on the gastric residence time were characterized using magnetic resonance imaging (MRI). As labeling material for a reliable identification of the capsules in the MR images, small pieces of dried pineapple were used as they provide a high T1 signal. Tested products were DRcaps™ as capsule in capsule (Cap-in-Cap) system (outer capsule size 00). For the investigation of the influence of the capsule density on the gastric residence time, a floating low-density Cap-in-Cap capsule formulation and a sinking high-density Cap-in-Cap capsule formulation were investigated. The study was performed in eight healthy human subjects under fasting conditions. Besides the transit data of the capsule systems, the intraluminal fluid volume kinetics were determined using T2 weighted sequences. The gastric emptying times of the systems did not differ, with mean values of 45 ± 35 min for floating DRcaps™ and 36 ± 18 min for the sinking DRcaps™. The difference in density had no remarkable influence on gastric emptying. Thus, the concept of floating capabilities for gastroretentive dosage forms seems rather implausible. Furthermore, this assures transferability of common knowledge about dosage form transit for estimation of the performance of acid-resistant capsule shells, which most typically float. The mean disintegration times amounted to 139 ± 35 min for the floating DRcaps™ Cap-in-Cap and 163 ± 55 min for the sinking DRcaps™ Cap-in-Cap. In only one case, a sinking DRcaps™ Cap-in-Cap system disintegrated during gastric emptying, but all other capsules disintegrated in the small intestine, irrespective of their gastric residence time. The use of dried pineapple as labeling material could be successfully demonstrated as a reliable and easy method for the tracking of the transit and disintegration behavior of orally administered drug delivery systems, leading to a thorough understanding of their in vivo performance. Graphical abstract Unlabelled Image [ABSTRACT FROM AUTHOR]

Abstract Community Based Health Insurance Schemes are often confronted to very low uptake. We analyze the impact of a randomized information package on the understanding and adoption of Community Based Health Insurance in Burkina Faso. The sample consists of about 2000 households in the rural community of Ziniaré which we interviewed several times between 2013 and 2016. In contrast to previous studies in the literature, we assess the effects of an intensive information intervention combining tools and repeated interaction instead of only a single event of information provisioning. The information package combines three tools to present different types of information - a brochure presenting factual information, a video presenting a hypothetical health episode and a personalized phone call reminder. The brochure and video are delivered through home visits by specially trained agents. Despite the repeated interaction and the comprehensiveness of the information package, we find only modest improvements in the understanding of insurance principles following our intervention. Investigating treatment heterogeneity, we observe an increase in understanding in poorer households and in households with literate heads. Given the small improvements in insurance knowledge we do not see a significant effect on insurance uptake either. We conclude that information is not enough to increase insurance uptake and discuss the role of other factors that might matter including the political context in which our experiment was implemented. Highlights • An intensive information intervention had no effect on health insurance uptake. • The intervention had modest effects on insurance knowledge. • Knowledge improved especially in literate and poorer households. • Households shared information about the insurance. • Information is a necessary, but not a sufficient encouragement to uptake. [ABSTRACT FROM AUTHOR]

Off-grid solar electric power is a promising technology for remote regions in rural Africa where expansion of the electricity grids is prohibitively expensive. Using household data from a target region of an off-grid solar promotion program in the Kénédougou province in Burkina Faso, this paper explores the role of quality-verified branded solar home systems (SHS) versus non-branded ones. We find that the adoption rate of non-branded SHS is considerably higher at 36% compared to 8% for branded SHS. We compare potential quality differences as well as the cost-effectiveness of branded and non-branded solar products. We show that non-branded SHSs offer a similar service level as branded solar, that they do not fall behind in terms of consumer satisfaction and durability, and that non-branded products are more cost-effective. These findings suggest that promotion programs and branded solar products do not seem to be necessary in Burkina Faso and might also not be needed to establish sustainable off-grid solar markets elsewhere provided that non-branded products are available. The challenge however is to reach the very poor who are unable to bring up investment costs for any electricity. [ABSTRACT FROM AUTHOR]

The amount and composition of gastrointestinal media are crucial parameters in oral drug delivery. In fasted state, variable residual gastric volumes and gastric emptying behavior often cause variable drug release and absorption from oral drug products. Unfortunately, interindividual and intraindividual variability of the gastric conditions in fasted state are currently insufficiently mapped. In this work, datasets from 5 MRI studies with 16 treatments in total were pooled. The interindividual and intraindividual variability of residual gastric volumes after 10 h overnight fasting and the subsequent emptying of 240 mL of water were compared in healthy human subjects under conditions mimicking clinical studies. This work shows that even under standardized clinical conditions, residual gastric volumes and water emptying are highly variable. Interestingly, interindividual and intraindividual variabilities of both parameters were comparable, suggesting that the variability within the studies was mainly resulting from intraindividual day-to-day variations. The mean resting volumes in all conducted investigations amounted to 25 ± 18 mL (n = 120). Furthermore, 85 ± 13% (n = 22) of initially available gastric volume (resting volume plus 240 mL) was emptied after 30 min. The findings of this work will hopefully contribute to a better comprehension of the variability of oral drug release and absorption. [ABSTRACT FROM AUTHOR]

Decades of intensively applying Green Revolution technologies came at environmental costs, i.e. degraded water and soil quality as well as a loss of biodiversity. This has led to an increased interest in organic farming, yet it remains a marginal activity in many countries. Previous studies highlighted information as an important driver of technology adoption, but little is known about the effect of removing information constraints in the context of organic farming. This study focuses on the role of information provision and training for the adoption of organic farming practices in Indonesia. We use a randomised controlled trial (RCT) complemented by qualitative research methods to identify the impact of a three-day hands-on training in organic farming for smallholder farmers. We find that the training encouraged farmers to experiment with organic inputs and positively affected farmers' knowledge and perceptions of organic farming. Overall, our findings suggest that intensive training is a promising policy tool to enhance the use of organic farming practices. Interestingly, we find that farmers were motivated not only by the price premium, i.e. the price difference between organic and conventional products, that is associated with organic products but also by the prospect of improved soil quality. • Training improves knowledge and shapes perceptions of organic farming. • Training is a promising instrument to increase the adoption of organic farming. • Beyond hands-on learning, endorsement and group mobilization are important triggers. • Experimentation, rather than full conversion within one-year observation window. • Farmers are not just motivated by higher sales prices, but also better soil quality. [ABSTRACT FROM AUTHOR]

In the present study temperature, pH and pressure profiles of nine healthy human volunteers were investigated after ingestion of the SmartPill® under conditions simulating the fasted state treatment in bioavailability and bioequivalence studies. In a previously published study the same subjects received the SmartPill® under fed conditions as recommended by the FDA. Since large non-digestible objects are mainly emptied during phase III of the interdigestive migrating motor complex, the gastric residence time of the SmartPill® was found to be clearly shorter under fasting conditions. Intragastric pH values during the initial 5 min were similar with an identical median value of pH 4.6. Interestingly, the median lowest observed intragastric pH value in fasted state was about one pH unit higher than that under fed conditions. Highest pressure activity was observed within the stomach, in relation to gastric emptying. In fasted state, pressure values upon gastric emptying varied strongly between 30 mbar and 304 mbar, whereas after fed state ingestion values of at least 240 mbar could always be observed. The data showed highly variable gastrointestinal parameters even under fasting conditions which must be considered when evaluating clinical studies and developing biorelevant in vitro test methods especially for large non-disintegrating dosage forms. [ABSTRACT FROM AUTHOR]

Road traffic accident fatalities lead to important private and social costs in the metropolitan areas of most low and middle income countries. An important share of these fatalities is due to injuries to the head and the neck. Helmets can provide efficient protection, but many drivers do not use them. We focus on helmet use behavior among motorbike users in Delhi. We use a detailed data set collected for the purpose of the study. To guide our empirical analysis, we rely on a model in which drivers decide on self-protection and self-insurance. The empirical findings suggest that risk-averse drivers are more likely to wear a helmet and that this has no systematic effect on speed. Helmet use also increases with education. Drivers who show a higher awareness of road risks seem to be both more likely to wear a helmet and to speed less. Controlling for risk awareness, we observe that drivers tend to compensate between speed and helmet use. The results can provide a basis for awareness-raising policies. They also show that improvements to the road infrastructure risk leading to risk-compensating behavior. [ABSTRACT FROM AUTHOR]

Many concepts of oral drug delivery are based on our comprehension of human gastrointestinal physiology. Unfortunately, we tend to oversimplify the complex interplay between the various physiological factors in the human gut and, in particular, the dynamics of these transit conditions to which oral dosage forms are exposed. Recent advances in spatial and temporal resolution of medical instrumentation as well as improved access to these technologies have facilitated clinical trials to characterize the dynamic processes within the human gastrointestinal tract. These studies have shown that highly relevant parameters such as fluid volumes, dosage form movement, and pH values in the lumen of the upper GI tract are very dynamic. As a result of these new insights into the human gastrointestinal environment, some common concepts and ideas of oral drug delivery are no longer valid and have to be reviewed in order to ensure efficacy and safety of oral drug therapy. [ABSTRACT FROM AUTHOR]

We analyze various pathways through which access to electricity affects fertility in Indonesia, using a district difference-in-difference approach. The electrification rate increased by 65 % over the study period, and our results suggest that the subsequent effects on fertility account for about 18 % to 24 % of the overall decline in fertility. A key channel is increased exposure to television. Using in addition several waves of Demographic and Health Surveys, we find suggestive evidence that increased exposure to TV affects, in particular, fertility preferences and increases the effective use of contraception. Reduced child mortality seems to be another important pathway. [ABSTRACT FROM AUTHOR]

Gastrointestinal ( GI) pH and temperature profiles under fasted-state conditions were investigated in two studies with each 10 healthy human subjects using the IntelliCap® system. This telemetric drug delivery device enabled the determination of gastric emptying time, small bowel transit time, and colon arrival time by significant pH and temperature changes. The study results revealed high variability of GI pH and transit times. The gastric transit of IntelliCap® was characterized by high fluctuations of the pH with mean values ranging from pH 1.7 to pH 4.7. Gastric emptying was observed after 7-202 min (median: 30 min). During small bowel transit, which had a duration of 67-532 min (median: 247 min), pH values increased slightly from pH 5.9-6.3 in proximal parts to pH 7.4-7.8 in distal parts. Colonic pH conditions were characterized by values fluctuating mainly between pH 5 and pH 8. The pH profiles and transit times described in this work are highly relevant for the comprehension of drug delivery of solid oral dosage forms comprising ionizable drugs and excipients with pH-dependent solubility. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 104:2855-2863, 2015 [ABSTRACT FROM AUTHOR]

Local beer breweries in Burkina Faso absorb a considerable amount of urban woodfuel demand. We assess the woodfuel savings caused by the adoption of improved brewing stoves by these micro-breweries and estimate the implied welfare effects through the woodfuel market on private households as well as the environmental effect. We find substantial wood savings among the breweries, 36% to 38% if they fully switch to an improved stove. In absolute amounts, they save about 0.176 kg of fuelwood per litre of dolo brewed. These savings imply huge reductions in CO2-emissions and reduce the overall demand for woodfuel, which is predominantly used by the poorer strata for cooking purposes. We provide estimates for the price decrease that might result from this and show that the urban poor are likely to benefit. Thus, the intervention under study is an example for a green growth intervention with pro-poor welfare gains – something green growth strategies should look for. [ABSTRACT FROM AUTHOR]

Chronic activation of Ca 2 + /calmodulin-dependent protein kinase II (CaMKII) has been implicated in the deleterious effects of β-adrenergic receptor (β-AR) signaling on the heart, in part, by enhancing RyR2-mediated sarcoplasmic reticulum (SR) Ca 2 + leak. We used CaMKIIδ knockout (CaMKIIδ-KO) mice and knock-in mice with an inactivated CaMKII site S2814 on the ryanodine receptor type 2 (S2814A) to investigate the involvement of these processes in β-AR signaling and cardiac remodeling. Langendorff-perfused hearts from CaMKIIδ-KO mice showed inotropic and chronotropic responses to isoproterenol (ISO) that were similar to those of wild type (WT) mice; however, in CaMKIIδ-KO mice, CaMKII phosphorylation of phospholamban and RyR2 was decreased and isolated myocytes from CaMKIIδ-KO mice had reduced SR Ca 2 + leak in response to isoproterenol (ISO). Chronic catecholamine stress with ISO induced comparable increases in relative heart weight and other measures of hypertrophy from day 9 through week 4 in WT and CaMKIIδ-KO mice, but the development of cardiac fibrosis was prevented in CaMKIIδ-KO animals. A 4-week challenge with ISO resulted in reduced cardiac function and pulmonary congestion in WT, but not in CaMKIIδ-KO or S2814A mice, implicating CaMKIIδ-dependent phosphorylation of RyR2-S2814 in the cardiomyopathy, independent of hypertrophy, induced by prolonged β-AR stimulation. [ABSTRACT FROM AUTHOR]

Around 3 billion people in developing countries rely on woodfuels for their daily cooking needs with profound negative implications for their workload, health, and budget as well as the environment. Improved cooking stove (ICS) technologies appear to be an obvious solution in many cases. Indeed we find that users of a very simple ICS in urban Burkina Faso need between 20 and 30 percent less firewood compared to traditional stoves, making the investment highly profitable. In spite of these high returns and great efforts made by the international community to disseminate ICSs, take-up rates are – similar to many other high-return innovations – strikingly low; in our case a mere 10 percent. When exploring adoption decisions of households, we find suggestive evidence that a major deterrent to adoption is the upfront investment costs. They seem to be much more important than access to information, taste preferences, or the woman's role in the household. These findings suggest that perhaps more direct promotion strategies such as subsidies would help households to overcome liquidity constraints, and would hence improve adoption rates. [ABSTRACT FROM AUTHOR]

Asbestos has been classified as a human carcinogen, and exposure may increase the risk of diseases associated with impaired respiratory function. As the range of health effects and airborne concentrations that result in health effects across asbestos-related natural mineral fiber types are not fully understood, the National Institute of Environmental Health Sciences has established a series of research studies to characterize hazards of natural mineral fibers after inhalation exposure. This paper presents the method development work of this research project. A prototype nose-only exposure system was fabricated to explore the feasibility of generating natural mineral fiber aerosol for in vivo inhalation toxicity studies. The prototype system consisted of a slide bar aerosol generator, a distribution/delivery system and an exposure carousel. Characterization tests conducted using Libby Amphibole 2007 (LA 2007) demonstrated the prototype system delivered stable and controllable aerosol concentration to the exposure carousel. Transmission electron microscopy (TEM) analysis of aerosol samples collected at the exposure port showed the average fiber length and width were comparable to the bulk LA 2007. TEM coupled with energy dispersive spectrometry (EDS) and selected area electron diffraction (SAED) analysis further confirmed fibers from the aerosol samples were consistent with the bulk LA 2007 chemically and physically. Characterization of the prototype system demonstrated feasibility of generating LA 2007 fiber aerosols appropriate for in vivo inhalation toxicity studies. The methods developed in this study are suitable to apply to a multiple-carousel exposure system for a rat inhalation toxicity testing using LA 2007. [ABSTRACT FROM AUTHOR]

Exposure to asbestos is associated with malignant and nonmalignant respiratory disease. To strengthen the scientific basis for risk assessment on fibers, the National Institute of Environmental Health Sciences (NIEHS) has initiated a series of studies to address fundamental questions on the toxicology of naturally occurring asbestos and related mineral fibers after inhalation exposure. A prototype nose-only exposure system was previously developed and validated. The prototype system was expanded to a large-scale exposure system in this study for conducting subsequent in vivo rodent inhalation studies of Libby amphibole (LA) 2007, selected as a model fiber. The exposure system consisting of six exposure carousels was able to independently deliver stable LA 2007 aerosol to individual carousels at target concentrations of 0 (control group), 0.1, 0.3, 1, 3, or 10 mg/m3. A single aerosol generator was used to provide aerosol to all carousels to ensure that exposure atmospheres were chemically and physically similar, with aerosol concentration as the only major variable among the carousels. Transmission electron microscopy (TEM) coupled with energy dispersive spectrometry (EDS) and selected area electron diffraction (SAED) analysis of aerosol samples collected at the exposure ports indicated the fiber dimensions, chemical composition, and mineralogy were equivalent across exposure carousels and were comparable to the bulk LA 2007 material. The exposure system developed is ready for use in conducting nose-only inhalation toxicity studies of LA 2007 in rats. The exposure system is anticipated to have applicability for the inhalation toxicity evaluation of other natural mineral fibers of concern. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate whether short-term primary preventive cardioverter- defibrillator (ICD) implantation as bridge to heart transplantation (HTX) provides any survival benefit. Thirty-three patients awaiting HTX were randomized to either conventional therapy (control group) or primary preventive ICD implantation (ICD group). Fourteen patients had ischemic cardiomyopathy (ICM) and 19 patients had dilated cardiomyopathy (DCM). Sixteen patients were randomized to the ICD group and 17 patients were randomized to the control group. Twenty patients (61%) were transplanted after a waiting time of 10 ± 9 months. The remaining 13 patients (39%) were not transplanted because of clinical improvement (n = 5), cerebral hemorrhage (n = 3), or death (n = 5). On the waiting list, 3 ICD patients with DCM developed slow VTs without ICD intervention, two patients with ICM (6%) had fast VT terminated by the ICD, and no arrhythmic death was observed. After 11.9 years (median), 13 of 20 HTX patients (65%) and 5 of 13 non-HTX patients (38%) were alive. Survivors had a higher LVEF (22 ± 6 vs. 17 ± 4%, P = 0.0092) and a better exercise capacity (75 ± 29 vs. 57 ± 24 Watt, P = 0.0566) at baseline as compared to nonsurvivors. This study may not support the general use of primary preventive ICDs as a short-term bridge to heart transplantation. [ABSTRACT FROM AUTHOR]

This paper presents a novel method to position electric vehicles for inductive charging purposes. The approach is to get position information by measuring the magnetic flux density caused by the charging coil located in the ground of the parking place. However, the sensors are mounted at the high-permeable undersurface of the vehicle, which leads to field distortions and, consequently, to high measurement errors. In this paper, these distortions were investigated by means of the finite-element method. Thereby, the vehicle was designed as finite expanded cuboid of high permeability. From these results, a simple mathematical model was derived, which maps the original field to the distorted one. In the following, this model and its validity constraints are discussed more in detail. [ABSTRACT FROM AUTHOR]

This article examines the dynamics of the informal sector in Madagascar during the 1995-2004 period, which was characterized by sustained growth that ended due to a major political crisis. As conventionally assumed by simple dualistic models, the informal sector indeed fulfils a labor-absorbing function in times of crisis. However, informal business creation was also a major trend both during macroeconomic growth and during crisis and recovery. Growth in the informal sector was mostly extensive, with little job creation or capital accumulation. Although such a situation would be consistent with the existence of poverty traps, estimated marginal returns to capital are decreasing, which tends to reject this hypothesis. [ABSTRACT FROM AUTHOR]

Using the method of narrative bioethics, this article analyzes Julian Schnabel's film "The Diving Bell and the Butterfly" (USA/France 2007), the story of the French journalist Jean-Dominique Bauby, who was trapped in his body as the result of a cerebral infarction (Locked-in-syndrome). The ethical themes of the film are identified and evaluated as part of a public ethical discourse: euthanasia, search for identity in the disturbing experience of desease, care and compassion, spirituality and religion as dimensions of an illness narration. The results are connected with experiences of health care chaplaincy in a neurological clinic. Working with "The Diving Bell and the Butterfly" in an ethical training could help doctors, nurses and therapists to reflect their care interactions and sensitize them to the dignity of neurological patients. Thereby the call for euthanasia can be reduced. [ABSTRACT FROM AUTHOR]

Software-defined radio technology is experiencing more and more attention in modern communication and radar systems. The main practical challenge in deploying such technology is related to achieving sufficient linearity and spurious-free dynamic range in the RF front-end, especially in low-cost mass-product devices. This paper focuses on the analysis and digital mitigation of nonlinear distortion in software-define radio devices, building on wideband multicarrier/multiradio direct-conversion receiver principle where a wide collection of radio frequencies is in-phase/quadrature down-converted as a whole. A complete behavioral model for the total nonlinear distortion of the whole receiver chain is first derived, taking into account the third-order nonlinear distortion effects in all individual components, namely, RF low-noise amplifier, in-phase/quadrature mixer, and baseband in-phase/quadrature amplifiers. Stemming from this modeling, an adaptive digital feed-forward linearization structure is then developed to efficiently mitigate the joint nonlinear distortion of the whole receiver. The effectiveness of this approach is verified through extensive simulations and actual RF system measurements with a commercially available software-defined radio platform, which clearly outperforms the existing state-of-the-art methods that do not jointly consider RF and baseband nonlinearities. [ABSTRACT FROM PUBLISHER]

S'il est largement reconnu que l'accès à l'électricité joue un rôle important dans la performance des entreprises, les données empiriques sur la question sont mitigées. Qui plus est, peu d'informations sont disponibles concernant les petites et micro-entreprises opérant dans le secteur informel. Nous constatons, à partir d'un échantillon représentatif d'entreprises informelles de sept villes d'Afrique occidentale, qu'il n'existe aucune donnée démontrant un effet positif systématique et significatif de l'accès à l'électricité sur la performance des entreprises. Cependant, en examinant de près un échantillon plus homogène de tailleurs travaillant à Ouagadougou, nous observons un effet positif de l'électricité, l'accès à cette dernière favorisant l'adoption de machines modernes et contribuant au fonctionnement des entreprises. Nos résultats offrent une nouvelle illustration de l'hétérogénéité du secteur informel, qui doit être prise en compte lors de l'élaboration de politiques publiques destinées à aider les entreprises opérant dans ce segment de l'économie à surmonter les obstacles à la croissance. [ABSTRACT FROM AUTHOR]

Abstract: The two-phase flow in the gas channels of a proton exchange membrane fuel cell (PEMFC) is studied with an ex situ setup using a gas diffusion layer (GDL) as the sidewall of the channels. Air is supplied at the channel inlet manifold and water is supplied continuously and uniformly through the GDL along the length of the channel. This is different from the simultaneous air and water introduction at the inlet of the channel as studied by previous two-phase flow researchers. The GDL is compressed between the gas channels and the water chambers to simulate PEMFC conditions. The superficial velocity for air and water ranged from 0.25 to 34.5 m/s and 1.54 × 10−5 to 1.54 × 10−4 m/s, respectively. The ex situ setup was run in both vertical and horizontal orientations with two GDLs, – Baseline (Mitsubishi Rayon Co. MRC 105 with 5 wt.% PTFE and coated with an in-house MPL by General Motors) and SGL 25 BC – and three channel treatments – hydrophobic, hydrophilic, and untreated Lexan, with contact angles of 116°, 11° and 86°, respectively. No appreciable effect was noted because of the orientation, GDL type or channel coatings. The flow regime is observed at different locations along the channel and is expressed as a function of the superficial air and water velocities. Flow regime criteria are developed and validated against the range of ex situ data observations. A new variable water flow rate pressure drop model is developed in order to account for the variation of water entering the channel at multiple locations along the flow length. Pressure drop models are developed for specific flow regimes and validated against experimental data. The models are able to predict the experimental pressure drop data with a mean error of less than 14%. [Copyright &y& Elsevier]

Summary: The informal sector is typically characterized as being very heterogeneous and possibly composed of two clearly distinct segments, sometimes called the lower and upper tiers. However, empirical evidence shows that even among lower tier entrepreneurs profitability can be quite high. We combine these findings and develop an innovative approach to identify what we call “constrained gazelles”, next to the well-known survivalists in the lower tier and growth-oriented top-performers in the upper tier. Our sample of informal entrepreneurs in seven West-African countries allows to link the relative size of these three groups to the structural and macroeconomic environment in these countries. [Copyright &y& Elsevier]

Abstract: Household income has been shown to matter for children’s school enrolment, in particular in settings where households face tight liquidity constraints caused by the lack of insurance and limited possibilities to smooth consumption through credit and savings. However, so far only few studies have made an effort to quantify the income elasticity of school enrolment, in particular in the Sub-Saharan African context. The empirical problem in identifying the causal impact of income on enrolment is to control for parental ability, which is largely unobserved, and to deal with reverse causality and measurement error. This paper uses for identification a natural experiment in Burkina Faso, a country with particularly low enrolment rates. The results show that naive estimates largely underestimate the true income elasticity of school enrolment. The results can provide a basis for safety net policies. [Copyright &y& Elsevier]

Here, we compare the entire compound collections of Bayer HealthCare and Schering AG with respect to structural identities, similarities and physico-chemical properties. We discuss possible consequences stemming from unexpected findings in light of new collaborative models in pharmaceutical research. [ABSTRACT FROM AUTHOR]

One of the most frequent critiques of the HDI is that is does not take into account inequality within countries in its three dimensions. In this paper, we apply a simply approach to compute the three components and the overall HDI for quintiles of the income distribution. This allows a comparison of the level in human development of the poor with the level of the non-poor within countries, but also across countries. This is an application of the method presented in Grimm et al. (World Development 36(12):2527–2546, 2008) to a sample of 21 low and middle income countries and 11 industrialized countries. In particular the inclusion of the industrialized countries, which were not included in the previous work, implies to deal with a number of additional challenges, which we outline in this paper. Our results show that inequality in human development within countries is high, both in developed and industrialized countries. In fact, the HDI of the lowest quintiles in industrialized countries is often below the HDI of the richest quintile in many middle income countries. We also find, however, a strong overall negative correlation between the level of human development and inequality in human development. [ABSTRACT FROM AUTHOR]

Abstract: The multifunctional Ca2+/calmodulin-dependent protein kinase II (CaMKII) targets a number of Ca2+ homeostatic proteins and regulates gene transcription. Many of the substrates phosphorylated by CaMKII are also substrates for protein kinase A (PKA), the best known downstream effector of β-adrenergic receptor (β-AR) signaling. While PKA and CaMKII are conventionally considered to transduce signals through separate pathways, there is a body of evidence suggesting that CaMKII is activated in response to β-AR stimulation and that some of the downstream effects of β-AR stimulation are actually mediated by CaMKII. The signaling pathway through which β-AR stimulation activates CaMKII, in parallel with or downstream of PKA, is not well-defined. This review considers the evidence for and mechanisms by which CaMKII is activated in response to β-AR stimulation. In addition the potential role of CaMKII in β-AR regulation of cardiac function is considered. Notably, although many CaMKII targets (e.g., phospholamban or the ryanodine receptor) are central to the regulation of Ca2+ handling, and effects of CaMKII on Ca2+ handling are detectable, inhibition or gene deletion of CaMKII has relatively little effect on the acute physiological contractile response to β-AR. On the other hand CaMKII expression and activity are increased in heart failure, a pathophysiological condition characterized by chronic stimulation of cardiac β-ARs. Blockade of β-ARs is an accepted therapy for treatment of chronic heart failure although the rationale for its beneficial effects in cardiomyocytes is uncertain. There is growing evidence that inhibition or gene deletion of CaMKII also has a significant beneficial impact on the development of heart failure. The possibility that excessive β-AR stimulation is detrimental because of its effects on CaMKII mediated Ca2+ handling disturbances (e.g., ryanodine receptor phosphorylation and diastolic SR Ca2+ leak) is an intriguing hypothesis that merits future consideration. [Copyright &y& Elsevier]

The inflammatory bowel diseases have undergone an explosion of discovery in the last 10 years. The overwhelming focus of this has been in genetics and immune mechanisms of disease. While the former has provided critical information on predisposing factors, the latter has resulted in a panoply of novel immune-based therapies and technologies. These range from an improved approach to the use of conventional immunomodulators, such as azathioprine and 6-mercaptopurine, to commonplace availability of anti-tumor necrosis factor agents such as infliximab and adalimumab, through to small molecule inhibition of immune mediators. Unusual treatments, such as helminth infestation, stem cell transplantation, and leucocytapheresis, all derive from the burgeoning understanding of pathogenesis. Most important to our successful use of these therapies will be a fundamental understanding of the patient phenotypes and genotypes that will dictate particular treatment approaches in the future. [ABSTRACT FROM AUTHOR]

Summary: One of the most frequent critiques of the HDI is that it does not take into account inequality within countries. We suggest a methodology which allows to compute the three components and the overall HDI for quintiles of the income distribution. This allows comparisons of the level in human development of the poor and non-poor within and across countries. An empirical illustration shows large discrepancies in human development within the countries, especially in Africa. These discrepancies are lower the higher the HDI is, but only weakly so. Inequality in income is generally higher than inequality in education and life expectancy. [Copyright &y& Elsevier]

• Rural households depend on informal transfers for income support. • Transfers decline with recipient's income among the poorest of the poor. • Transfers in response to income fluctuations in particular are subject to crowding-out. • Formal regular cash transfers might induce less crowding-out than formal insurance. Households in rural areas depend on informal transfers to meet subsistence needs and cope with shocks. Yet, to provide monetary support, formal safety nets are increasingly being introduced in developing countries. However, it remains unclear whether such social-protection policies will have the desired redistributive welfare effects. This article addresses this question from an ex ante perspective by analyzing the private-transfer response to changes in the income of rural recipients in Burkina Faso. We use novel dyadic household panel data from two periods that offers information on both recipient and sender incomes. This allows us to address the endogeneity concerns that other studies have thus far not been able to account for. Our hypothesis is that the transfer-income relationship is nonlinear and that transfer motives, and therefore also transfer responses, vary with the recipient's position within the income-distribution. Our findings support this view. We find a pronounced, negative private-transfer response among the poorest of the poor. This observation has important policy implications: those households that depend most on private transfers are the ones most likely affected by crowding-out effects. The negative relationship for the lowest income class is consistent with transfers being altruistic in nature. Furthermore, we observe, that with increasing income levels, transfers cease being altruistic suggesting that then exchange motives dominate. Yet, the observed transfer pattern is also indicative of an (informal) insurance role of private transfers. Rural households receive higher private transfers in response to negative shocks. These results can serve as a basis for the design of formal social-protection mechanisms in a context where informal redistribution still plays an important role. [ABSTRACT FROM AUTHOR]

The optimum length of a monolith tube is one for which near-hundred percent conversion is attained, and at the same time, the catalyst over the entire length of the tube is utilized. In practice, the length is adjusted by stacking monolith plugs end-to-end. In this study, the repercussions of such a practice are investigated numerically with the goal to determine if a tube of length 2L demonstrates the same behavior as two tubes of length L each, stacked end-to-end. Catalytic combustion of methane–air mixture on a platinum catalyst is considered. The studies are conducted using a multi-step reaction mechanism involving 24 surface reactions between 19 species. Two different materials are considered for the walls of the monolith tube, namely silicon carbide and cordierite. Both steady state and transient simulations are performed. Results indicate that the ignition and blowout limits can be significantly different between split and continuous tubes when the wall is made up of a high thermal conductivity material, such as silicon carbide. For steady state combustion, for both wall materials, the point of attachment of the flame to the wall is altered by splitting the tube—the effect being more pronounced for silicon carbide and at relatively high Reynolds numbers. These results imply that axial heat conduction, or lack thereof due to thermal contact resistance, through the walls of the monolith results in thermal non-equilibrium between the solid and fluid phase, and subsequently affects ignition and flame stability in catalytic combustion. [Copyright &y& Elsevier]

Emotion primitive descriptions are an important alternative to classical emotion categories for describing a human’s affective expressions. We build a multi-dimensional emotion space composed of the emotion primitives of valence, activation, and dominance. In this study, an image-based, text-free evaluation system is presented that provides intuitive assessment of these emotion primitives, and yields high inter-evaluator agreement. An automatic system for estimating the emotion primitives is introduced. We use a fuzzy logic estimator and a rule base derived from acoustic features in speech such as pitch, energy, speaking rate and spectral characteristics. The approach is tested on two databases. The first database consists of 680 sentences of 3 speakers containing acted emotions in the categories happy, angry, neutral, and sad. The second database contains more than 1000 utterances of 47 speakers with authentic emotion expressions recorded from a television talk show. The estimation results are compared to the human evaluation as a reference, and are moderately to highly correlated (0.42< r <0.85). Different scenarios are tested: acted vs. authentic emotions, speaker-dependent vs. speaker-independent emotion estimation, and gender-dependent vs. gender-independent emotion estimation. Finally, continuous-valued estimates of the emotion primitives are mapped into the given emotion categories using a k-nearest neighbor classifier. An overall recognition rate of up to 83.5% is accomplished. The errors of the direct emotion estimation are compared to the confusion matrices of the classification from primitives. As a conclusion to this continuous-valued emotion primitives framework, speaker-dependent modeling of emotion expression is proposed since the emotion primitives are particularly suited for capturing dynamics and intrinsic variations in emotion expression. [Copyright &y& Elsevier]

Abstract: The sustained positive inotropic effect of α-adrenoceptor agonists in the heart is associated with a small increase in intracellular Ca2+ transients together with a larger sensitization of myofilaments to Ca2+. The multifunctional Ca2+ and calmodulin-dependent protein kinase II (CaMKII) could contribute to this effect, either by affecting the Ca2+ release (ryanodine receptor) or by an uptake mechanism (via phospholamban [PLB] and SR Ca2+ ATPase). Here we examined the role of CaMKII in the positive inotropic effect of the α-adrenoceptor agonist phenylephrine in left atria isolated from a genetic mouse model of cardiac CaMKII inhibition (AC3-I). Compared to atria from wild-type (WT) or AC3-C (scrambled peptide), AC3-I atria showed the following abnormalities. PLB phosphorylation at Thr17, a known CaMKII target, was significantly lower (∼20%). Post-rest (30 s, 1 Hz, 37 °C) potentiation of force was absent (AC3-C, 190% of pre-rest amplitude). Basal force was ∼20% lower at 1.8 mM Ca2+, but normal at high Ca2+ concentration (>4.5 mM). The maximal positive inotropic effect of phenylephrine, which was more pronounced at low frequencies in WT and AC3-C atria, lost its frequency dependence (1 Hz to 8 Hz). Thus, the effect of phenylephrine was reduced by ∼50% at 1 Hz, but was normal at 8 Hz. All three groups showed a negative force–frequency relation, and did not differ in the frequency-dependent acceleration of relaxation. Our data indicate a role of CaMKII in post-rest potentiation and the positive inotropic effect of α-adrenergic stimulation at low frequencies. [Copyright &y& Elsevier]

Objective--To determine whether mares are a clinically important source of Rhodococcus equi for their foals. Sample Population--171 mares and 171 foals from a farm in Kentucky (evaluated during 2004 and 2005). Procedures--At 4 time points (2 before and 2 after parturition), the total concentration of R equi and concentration of virulent R equi were determined in fecal specimens from mares by use of quantitative bacteriologic culture and a colony immunoblot technique, respectively. These concentrations for mares of foals that developed R equi-associated pneumonia and for mares with unaffected foals were compared Data for each year were analyzed separately. Results--R equi-associated pneumonia developed in 53 of 171 (31%) foals. Fecal shedding of virulent R equi was detected in at least 1 time point for every mare; bacteriologic culture results were positive for 62 of 171 (36%) mares at all time points. However, compared with dams of unaffected foals, fecal concentrations of total or virulent R equi in dams of foals with R equi-associated pneumonia were not significantly different. Conclusions and Clinical Relevance--Results indicate that dams of foals with R equi-associated pneumonia did not shed more R equi in feces than dams of unaffected foals; therefore, R equi infection in foals was not associated with comparatively greater fecal shedding by their dams. However, detection of virulent R equi in the feces of all mares during at least 1 time point suggests that mares can be an important source of R equi for the surrounding environment. [ABSTRACT FROM AUTHOR]

The present study examined the role of myosin light chain kinase (MLCK), PKC isozymes, and inositol 1,4,5-trisphosphate (IP3) receptor in the positive inotropic effect of α1-adrenergic stimulation in atrial myocardium.We measured inotropic effects of phenylephrine (0.3–300 μM) in isolated left atrial preparations (1 Hz, 37°C, 1.8 mM Ca2+, 0.3 μM nadolol) from male 8-week FVB mice (n=200). Phenylephrine concentration-dependently increased force of contraction from 1.5±0.1 to 2.8±0.1 mN (mean±s.e.m., n=42), which was associated with increased MLC-2a phosphorylation at serine 21 and 22 by 67% and translocation of PKCɛ but not PKCα to membrane (+30%) and myofilament (+50%) fractions.MLCK inhibition using ML-7 or wortmannin right-shifted the concentration–response curve of phenylephrine, reducing its inotropic effect at 10 μM by 73% and 81%, respectively.The compound KIE1-1 (500 nM), an intracellularly acting PKCɛ translocation inhibitor peptide, prevented PKCɛ translocation and augmented the maximal inotropic effect of phenylephrine by 40%. In contrast, inhibition of Ca2+-dependent PKC translocation (KIC1-1, 500 nM) had no effect. Chelerythrine, a PKC inhibitor, decreased basal force without changing the inotropic effect of phenylephrine.The IP3 receptor blocker 2-APB (2 and 20 μM) concentration-dependently decreased basal force, but did not affect the concentration–response curve of phenylephrine.These results indicate that activation of MLCK is required for the positive inotropic effect of α1-adrenergic stimulation, that the Ca2+-independent PKCɛ negatively modulates this effect, and that PKCα and IP3 receptor activation is not involved.British Journal of Pharmacology (2006) 148, 991–1000. doi:10.1038/sj.bjp.0706803; published online 19 June 2006 [ABSTRACT FROM AUTHOR]

Background: Artificial intelligence (AI)-based computation methods have been recently shown to be applicable in several clinical diagnostic fields. The purpose of this study was to introduce a novel AI method called evolutionary algorithms (EAs) to clinical predictions. The technique was used to create a pharmacokinetic model for the prediction of whole blood levels of cyclosporine (CyA). Methods: One hundred one adult cardiac transplant recipients were randomly selected and included in this study. All patients had been receiving oral cyclosporine twice daily, and the trough levels in whole blood were measured by monoclonal-specific radioimmunoassay. An evolutionary algorithm (EA)-based software tool was trained with pre- and post-operative variables from 64 patients. The results of this process were then tested on data sets from 37 patients. Results: The mean value of the predicted CyA level throughout the measurement period for the test data was 175 ± 27 ng/ml, which compared well with the mean observed CyA level of 180 ± 31 ng/ml. The system bias expressed as the mean percent error (MPE) for the training and test data sets were 7.1 ± 5.4% (0.1% to 26.7%) and 8.0 ± 6.7% (0.8% to 28.8%), respectively. The prediction accuracy ranged from 80% to 90%. The correlation coefficient between predicted and observed CyA concentration for the training data were 0.93 (p < 0.001) and for the test data were 0.85 (p < 0.001), respectively. Conclusions: The results of this study suggest that the use of evolutionary algorithms to identify pharmacokinetic models yields accurate prediction of cyclosporine whole blood levels in heart transplant recipients. This and other similar technologies should be considered as future clinical tools to reduce costs in our health systems. [Copyright &y& Elsevier]

Abstract: Objective: Mechanisms of the positive inotropic response to α1-adrenergic stimulation in the heart remain poorly understood, but recent evidence in rat papillary muscle suggests an important role of regulatory myosin light chain (MLC2) phosphorylation. This study investigated α1-adrenergic contractile effects and the role of MLC kinase (MLCK)-dependent phosphorylation of MLC2 in human atrial muscle strips. Methods: Force measurement was performed on electrically stimulated atrial muscle strips (n=140; 20 hearts) in the presence of the beta-blocker nadolol. MLC2a phosphorylation was determined by 2D-polyacrylamide gel electrophoresis and Western blotting of muscle strips that were immediately freeze-clamped following force measurements. Results: The α1-agonist phenylephrine (PE; 0.3–100 μM) exerted a concentration-dependent, monophasic, sustained positive inotropic effect (86% above basal) that was accompanied by an 80% increase in MLC2a phosphorylation. Desinhibition of MLC phosphatase by the Rho kinase inhibitor Y-27632 (10 μM) reduced the effect of PE by 16%. The MLCK inhibitor wortmannin (10 μM) completely abolished both the PE-induced increase in force and MLC2a phosphorylation. The structurally unrelated MLCK inhibitor ML-7 (10 μM) had similar effects. Neither Y-27632 nor wortmannin or ML-7 affected β-adrenergic force stimulation. In contrast to our findings in atrial muscle strips, we observed no increase in MLC2v phosphorylation after PE in human ventricular muscle strips and wortmannin failed to inhibit PE-induced force of contraction. Conclusion: α1-Adrenergic receptors mediate a prominent increase in contractile force in human atria that depends on MLCK activity and is accompanied by an increase in MLC2 phosphorylation. [Copyright &y& Elsevier]

The interplay between fertility decisions and per capita growth of income by investment decisions in human capital constitutes the key element of growth models based on the microeconomic theory of family behavior. A strategy that raises the fixed cost per child, reduces the cost of education, stimulates the accumulation of human capital, diminishes the opportunity cost of parents to send their children to school, encourages female activity, accelerates economic development and contributes to a reduction of inequality. [ABSTRACT FROM AUTHOR]

Objective: Neurocognitive deficit is an important complication in patients undergoing open heart surgery. The aim of this prospective, contemporary study was to objectively measure neurocognitive brain function following mechanical mitral valve replacement and mitral valve repair. Methods: Forty consecutive, unselected patients (mechanical valve replacement n=20, mean age 65±14; valve repair n=20, mean age 64±7, P=0.896) entered this prospective, contemporary study. Neurocognitive function was objectively measured by means of P300 auditory evoked potentials (peak latencies, ms) and two standard psychometric tests (Mini Mental State Examination, Trailmaking Test A (TTA)), preoperatively, 7 days and 4 months postoperatively. Results: Before operation, neurocognitive brain function was comparable in both patients groups (mechanical valve replacement versus valve repair: P300 potentials 374±25 versus 378±46 ms; P=0.791 and TTA 57±15 versus 54±10 s; P=0.552). Following mechanical valve replacement, neurocognitive function continuously worsened (7 day-follow-up: P300 potentials 392±28, P=0.001 versus preop and TTA 65±17, P=0.0001; 4-month follow-up: P300 potentials 406±39, P=0.0004; TTA 69±17, P=0.0001). Interestingly, neurocognitive brain function was unaffected in patients undergoing valve repair (7-day follow-up: P300 potentials 386±40, P=0.890 versus preop and TTA: 53±10, P=0.644; 4-month follow-up: P300 potentials 374±36, P=0.166 and TTA 54±11, P=0.147). At 4-month follow-up, patients with mechanical prostheses performed worse as compared to valve repair (P300 potentials: P=0.024; TTA P=0.014). Conclusion: As shown by P300 auditory evoked potentials and Trailmaking Test A, there is marked neurocognitive damage related to mechanical valve replacement, whereas mitral valve repair does not affect neurocognitive function. This finding supports the beneficial effect of mitral valve repair over mechanical valve replacement in the decision-making tree of borderline cases, which are suitable for both types of procedure. [Copyright &y& Elsevier]

Presents a study which investigated the evolution of urban policy in its various dimensions in C ô te d'Ivoire since the 1980s through 2002. Statistics on monetary poverty in the 1990s; Monetary analysis of living standards; Analysis of subsistence conditions.

There are no methods for specific local application of active substances to the mucosa of the esophagus to treat eosinophilic esophagitis or other esophageal diseases. This publication describes the principal in vivo functionality and acceptance of a novel modular drug delivery concept, called EsoCap system, by 12 healthy volunteers. For the first time, the EsoCap system enables targeted placement on the esophageal mucosa of a mucoadhesive polymer film. Acceptance was determined by means of a standardized questionnaire after administration and functionality of the device by MRI scans. Two different setups of the EsoCap system were tested: one setup with a density of 0.4 g/cm3 and one with a density of 1.0 g/cm3. Acceptability of the dosage form was also confirmed in addition to functionality, by measuring the applied film length. It was found that acceptance of the variant with the higher density was significantly better. This novel drug delivery technology could enable a targeted, local and long-lasting therapy of the esophagus for the first time, depending on the polymer film used. [ABSTRACT FROM AUTHOR]

OBJECTIVES Barlow's disease is a specific sub-form of mitral valve (MV) disease, characterized by diffuse excessive tissue and multi segment prolapse. The anterolateral mini-thoracotomy represents the standard access for MV regurgitation in many centres. It still remains unclear which surgical technique provides the best results. Therefore, the aim of this study was to compare operative safety and mid-term outcomes after (i) isolated annuloplasty, (ii) use of additional artificial chordae or (iii) leaflet resection in patients suffering from Barlow's disease undergoing minimally invasive MV repair. METHODS A consecutive series of patients suffering from Barlow′s disease undergoing minimally invasive MV surgery between 2001 and 2020 were analysed (n  = 246). Patients were grouped and analysed according to the used surgical technique. The primary outcome was a modified Mitral Valve Academic Research Consortium combined end-point of mortality, reoperation due to repair failure or reoccurrence of severe mitral regurgitation within 5 years. The secondary outcome included operative success and safety up to 30 days. RESULTS No significant difference was found between the 3 surgical techniques with regard to operative safety (P  = 0.774). The primary outcome did not differ between groups (P  = 0.244). Operative success was achieved in 93.5% and was lowest in the isolated annuloplasty group (77.1%). Conversion to MV replacement was increased in patients undergoing isolated annuloplasty (P  < 0.001). CONCLUSIONS Isolated annuloplasty, use of additional artificial chordae and leaflet resection represent feasible techniques in Barlow patients undergoing minimally invasive MV surgery with comparable 5-year results. In view of the increased conversion rate in the annuloplasty group, the pathology should not be oversimplified. [ABSTRACT FROM AUTHOR]