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This study adopts a robust systematic literature review (SLR) to investigate the use of mobile devices to support learning (mobile learning) in university science education. It analyses 24 high quality studies over the past decade to generate insights into contemporary mobile learning developments in relation to settings, applications and pedagogical approaches, as well as trends in research methodologies and outcomes. The results show that the use of mobile devices is providing university science learners with peer learning opportunities and supporting their networked interactions with the science community and resources. However, the study also uncovers more constrained use of mobile devices associated with traditional didactic approaches, often in formal settings. The study identifies key differences from other SLR findings on mobile learning in school science education, most notably with respect to adopted pedagogies. It suggests future research directions, including the need for more qualitative studies of mobile learning in university science education. [ABSTRACT FROM AUTHOR]

In this work, we tackle class incremental learning (CIL) for video action recognition, a relatively under-explored problem despite its practical importance. Directly applying image-based CIL methods does not work well in the video action recognition setting. We hypothesize the major reason is the spurious correlation between the action and background in video action recognition datasets/models. Recent literature shows that the spurious correlation hampers the generalization of models in the conventional action recognition setting. The problem is even more severe in the CIL setting due to the limited exemplars available in the rehearsal memory. We empirically show that mitigating the spurious correlation between the action and background is crucial to the CIL for video action recognition. We propose to learn background invariant action representations in the CIL setting by providing training videos with diverse backgrounds generated from background augmentation techniques. We validate the proposed method on public benchmarks: HMDB-51, UCF-101, and Something-Something-v2. • Video-based class incremental learning (video CIL) is important, yet under-explored. • Identify the background bias problem in video CIL setting. • The proposed method diversifies the scenes of training videos in the CIL setting. • The proposed method is a plug-and-play video CIL method. • The proposed method is tested UCF-101, HMDB-51, and Something-Something v2. [ABSTRACT FROM AUTHOR]

The thermodynamic properties and phase diagrams of amorphous magnetic systems described by a disordered Ising model with binary probability are examined using effective field theory (EFT). A ferromagnetic to paramagnetic (FM–PM) phase transition occurs at a critical temperature τ c where the spin susceptibility reveals an acutely sharp peak. By adjusting a disordered probability p , and a fluctuation parameter Δ driving mixed ferromagnetic interactions, we successfully provide a phase diagram illustrating the dependence of the critical temperature τ c on the disordered probability p with various fluctuation strength Δ. The experimentally observed linear behavior of the τ c − p curve is comprehensively explained in the weak disordered regime. Under an external field, we also examine the magnetocaloric effect by observing the magnetic entropy change (MEC) greatly enhanced in the strongly disordered regime where p ≤ 0. 3 and Δ > 0. 4. The linear behavior breaking of the maximal MEC on the fluctuation surprisingly agrees with experimental observations. • Thermodynamic properties of disordered Ising models with a binary probability. • Temperature dependence of thermodynamic quantities with probabilities and fluctuation. • Critical temperature dependence on probability and fluctuation without fields. • Maximal magnetic entropy change (MEC) Δ S M near τ c with external fields. • An inverse relation between the maximal MEC and the critical temperature. [ABSTRACT FROM AUTHOR]

Over the past decades, air pollution has caused severe environmental and public health problems. According to the World Health Organization (WHO), fine particulate matter (PM 2.5), a key component reflecting air quality, is the fourth leading cause of death worldwide after cardiovascular disease, smoking, and diet. Various research efforts have aimed to develop PM 2.5 forecasting models that can be integrated into a solution to mitigate the adverse effects of air pollution. However, PM 2.5 forecasting is challenging because air pollution data are non-stationary and influenced by multiple random effects. This paper proposes an effective multivariate multi-step ensemble machine learning model for predicting continuous 24-h PM 2.5 concentrations, considering meteorological conditions, the rolling mean of PM 2.5 time series, and temporal features. PM 2.5 is strongly correlated with space and time. Therefore, forecasting results from one location are insufficient to represent the level of air pollution for an entire city. In this study, we established six real-time air quality monitoring sites in different regions, including traffic, residential, and industrial areas in Ho Chi Minh City (HCMC), and generated forecasting results for each station. Various statistical methods are incorporated to evaluate the performance of the model. The experimental results confirm that the model performs well, substantially improving its forecasting accuracy compared to existing PM 2.5 forecasting models developed for HCMC. In addition, we analyze to determine the contribution of different feature groups to model performance. The model can serve as a reference for citizens scheduling local travel and for healthcare providers to provide early warnings. [Display omitted] • The proposed model accurately predicts urban PM 2.5 contamination for the next 24 h. • MI-based correlation analysis is valuable for understanding the influence of meteorological variables on PM 2.5 concentration. • Combining rolling mean features of PM 2.5 with meteorological features improves PM 2.5 prediction accuracy significantly. • The forecasting model's training protocol effectively addressed the data's non-stationarity. [ABSTRACT FROM AUTHOR]

With three‐dimensional (3D) laser scanning technology and software packages, the practice of documenting and measuring bullet trajectories has benefited from greater accuracy and reproducibility. This study investigated the accuracy and reproducibility of the bullet trajectory tools in the software package, FARO Zone 3D (FZ3D). Twelve participants were provided laser scanner data for 21 bullet trajectories on drywall panels with impact angles between 25° and 90°. When the impact plane was manually aligned by the operator, 75% of the absolute errors were within 0.91° and 0.98° for the azimuth and vertical angles, respectively. The vertical angle improved to 0.47° when impact plane alignment was taken with respect to gravity (no operator influence). Thus, manual alignment is shown to be subject to greater error than alignment with gravity. However, this study shows that the accuracy and reproducibility of the FZ3D bullet trajectory tools to be comparable with previous research studies. [ABSTRACT FROM AUTHOR]

Streptavidin (SA), and other related proteins, has been isolated from a wide range of organisms, including bacteria, fungi, frogs, fish, and birds. Although their original function is not well understood, they have found an important place in biotechnology based on their unique ability to bind biotin molecules with high affinity and specificity. The SA–biotin interaction is robust and easy to incorporate into different designs, and as such, it is used when reliable molecule interaction is needed under poorly controlled experimental conditions. There are continued efforts to engineer these proteins to modulate their size, valency, and affinity, since the optimum molecular properties vary depending on individual applications. This review will describe recent developments in streptavidin engineering to meet these requirements, including those that form novel oligomeric states, e.g., a monomer, have fewer functional biotin-binding sites, or bind biotin with reduced affinity. We also examine various reported applications of both natural or engineered SA constructs in cell biology, biochemistry, genetics, synthetic chemistry, cancer therapy, drug delivery, and nanotechnology to illustrate the breadth of modern science that is advanced by the endogenous and engineered SA–biotin interactions. [ABSTRACT FROM AUTHOR]

This comparative study aimed to investigate the differences between the workflow, accuracy, and reproducibility of the area of origin tools in FARO Scene and FARO Zone 3D software. Released in 2018, FZ3D has recently been introduced as an alternative application to FARO Scene's Forensic Wizard plug-in for bloodstain pattern analysis but no accuracy studies have been published at the time of this study. A total of 15 impacts were created using an impact rig at three different positions from two orthogonal walls (50cm, 75cm, 100cm). One researcher conducted the analyses with both software packages, and the total errors using FZ3D were not statistically greater than using FARO Scene (p>0.05). With FZ3D, 50% of the total errors ranged from 6.63cm to 15.68cm with a minimum of 2.45cm, maximum of 27cm, and median of 11.22cm. With FARO Scene, 50% of the total errors ranged from 3.6cm to 15.5cm with a minimum of 2.93cm, maximum of 31.25cm and median of 9.6cm. A blind test with seven participants analyzing the same 15 impacts in FZ3D resulted in 100 out of 105 total errors (95%) to be within the accepted error range of 20cm. Of the five total errors outside 20cm, one was obtained from the 75cm position and four from the 100cm position. 75% of the total errors were below 9.43cm from the 50cm position, 14.88cm from the 75cm position, and 17.39cm from the 100cm position. This could indicate that there is a positive correlation between the distance of the impact from the surfaces and total errors obtained. Based on results of previous literature and comparison to FARO Scene software, FZ3D is shown to have acceptable area of origin analysis tools. [ABSTRACT FROM AUTHOR]

Driven by the need for sustainable eco-friendly materials, natural fibers are increasingly being used as composites reinforcements due to their low cost and their potential in meeting strength and stiffness requirements for nonstructural and semistructural applications. Fewer works, however, have been reported on the acoustic and vibration characteristics of natural fibers. In this article, the sound transmission and absorption performance of flax fiber-reinforced polypropylene (PP) composites in various configurations are assessed experimentally. Natural frequency and damping coefficient of the composites are investigated by modal analysis with an impact hammer. Results from the vibrational analysis showed that thin FF/PP composite panels have resonant frequency ranging between 300 and 1000 Hz which is consistent with the acoustic profile extracted from the sound transmission loss (STL) test. Results of STL tests revealed that higher stiffness of FF/PP composite may lead to higher STL at 100–400 Hz. Resonant frequencies of the composite range from 400 to 900 Hz and STL is show to obey the mass law with nonlinearity in the range of 900–1600 Hz. These results give a better insight into the performance of FF/PP composites in vibroacoustic environments. [ABSTRACT FROM AUTHOR]

A rapid and easy liquid chromatography-tandem mass spectrometry (LC--MS/MS) method was developed, validated, and used to quantify amlodipine besylate and metoprolol succinate in human plasma. Hydrochlorothiazide was used as the internal standard. LC--MS/MS with electrospray ionization in the positive ionization mode was performed under multiple reaction monitoring to examine analytes, which were drawn from human plasma via liquid--liquid extraction using a mixture of diethyl ether and dichloromethane (6:4). The extracts were dried under a nitrogen stream at 40°C, after which the samples were dissolved in a mixture of methanol and water (80:20). The re-dissolved samples were injected onto a C18 column and eluted using a mixture of methanol and 0.4% formic acid (80:20) as the mobile phase. Linear standard calibration was performed, and lower limits of quantification were determined for each analyte. The developed method was fully validated with respect to selectivity and carryover, as well as intra- and inter-day accuracy and precision in accordance with guidelines of the United State Food and Drug Administration and the European Medicines Agency. Mean analyte recovery was between 71.72% and 97.55%, and matrix effects exerted only a minor influence on precision. The validated method was applied in a clinical bioequivalence study to evaluate the in vivo bioequivalence of two commercial products containing 5 mg amlodipine and 50 mg metoprolol. This randomized, single-dose, two-treatment, three-period, two-sequence, open-label, crossover study involved 14 healthy subjects, and a twoweek washout period between the two phases of the research was implemented. Standard pharmacokinetic parameters were calculated to compare a test product with Selomax® as the reference. [ABSTRACT FROM AUTHOR]

The subcortical visual pathway including the superior colliculus (SC), pulvinar, and amygdala has been implicated in unconscious visual processing of faces, eyes, and gaze direction in blindsight. Our previous studies reported that monkey SC and pulvinar neurons responded preferentially to images of faces while performing a delayed non-matching to sample (DNMS) task to discriminate different visual stimuli (Nguyen et al., 2013, 2014). However, the contribution of SC and pulvinar neurons to the discrimination of the facial images and subsequent behavioral performance remains unknown. Since gamma oscillations have been implicated in sensory and cognitive processes as well as behavioral execution, we hypothesized that gamma oscillations during neuronal responses might contribute to achieving the appropriate behavioral performance (i.e., a correct response). In the present study, we re-analyzed those neuronal responses in the monkey SC and pulvinar to investigate possible relationships between gamma oscillations in these neurons and behavioral performance (correct response ratios) during the DNMS task. Gamma oscillations of SC and pulvinar neuronal activity were analyzed in three phases around the stimulus onset [inter-trial interval (ITI): 1000 ms before trial onset; Early: 0–200 ms after stimulus onset; and Late: 300–500 ms after stimulus onset]. We found that human facial images elicited stronger gamma oscillations in the early phase than the ITI and late phase in both the SC and pulvinar neurons. Furthermore, there was a significant correlation between strengths of gamma oscillations in the early phase and behavioral performance in both the SC and pulvinar. The results suggest that gamma oscillatory activity in the SC and pulvinar contributes to successful behavioral performance during unconscious perceptual and behavioral processes. • Superior colliculus and pulvinar constitute the subcortical visual pathway. • Gamma oscillation is implicated in sensory, cognitive and behavioral processes. • Gamma oscillations in response to faces were analyzed using autocorrelograms. • Gamma strength was positively correlated with correct ratios in the task. • Gamma oscillatory activity might support unconscious behaviors in blindsight. [ABSTRACT FROM AUTHOR]

We report an efficient and simple method for the synthesis of core–shell quantum dots CdSe/CdS in aqueous media under normal pressure. This QDs was successfully loaded on the surface of titanium dioxide nanotubes (TNTs) to get the QDs/TNTs composite photocatalysts. The QDs/TNTs composites were successfully applied to the cyclization reaction between arylamines and a series of aldehydes to give the corresponding N-heterocyclic compounds. The results show that the QDs/TNTs composite with the advantages of good catalytic activity, low cost, ease of recovering, and being able to be used for several times. [ABSTRACT FROM AUTHOR]

A stepwise experimental design procedure to obtain reliable data from wastewater treatment plants (WWTPs) was developed. The proposed procedure aims at determining sets of additional measurements (besides available ones) that guarantee the identifiability of key process variables, which means that their value can be calculated from other, measured variables, based on available constraints in the form of linear mass balances. Among all solutions, i.e. all possible sets of additional measurements allowing the identifiability of all key process variables, the optimal solutions were found taking into account two objectives, namely the accuracy of the identified key variables and the cost of additional measurements. The results of this multi-objective optimization problem were represented in a Pareto-optimal front. The presented procedure was applied to a full-scale WWTP. Detailed analysis of the relation between measurements allowed the determination of groups of overlapping mass balances. Adding measured variables could only serve in identifying key variables that appear in the same group of mass balances. Besides, the application of the experimental design procedure to these individual groups significantly reduced the computational effort in evaluating available measurements and planning additional monitoring campaigns. The proposed procedure is straightforward and can be applied to other WWTPs with or without prior data collection. [ABSTRACT FROM AUTHOR]

The purposes of this study are to prepare the generic extended release tablet of potassium chloride (PC) 600 mg and to compare the absorption of potassium ion from the experimental tablets to that of Kaleorid® LP 600 mg (Leo Pharmaceutical Products, Denmark). Carnauba wax was used as retardant in the matrix core tablets. The core tablets were coated with blends of ethyl cellulose (EC) and hydroxypropyl methyl cellulose (HPMC) to modulate the drug release. Results of a selective two-level, three-factor experiment design revealed that a blend of 41.75% of EC and 58.25% of HPMC at 4.5% weight gained could produce the coated tablets having dissolution profiles similar to those of Kaleorid®. A two-treatment, two-period, two-sequence crossover bioequivalence study was carried out on 24 healthy volunteers to compare the absorption of potassium ion from experimental tablets to that from Kaleorid®. The potassium ion in the urine was measured by a selective electrode of the ADVIA 1650 system (Bayer) and used to calculate cumulative urinary excretion and urinary excretion rate. Results of 90 percent confidence interval analysis showed that the limits for natural log-transformed cumulative urinary potassium excretion (Ln Ae0-24 ) of test product were in the range of 3.73-3.79 mEq, corresponding to 99.08%-100.92% of Kaleorid ®, respectively, and the limits for natural log-transformed maximal potassium excretion rate (Rmax) of test product were in the range of 1.72-1.82 mEq/h, corresponding to 97.34%-102.66% of reference product, respectively. Both of them fell within the bioequivalence interval (80%-125%) of reference product, proving that experimental product is bioequivalent to Kaleorid ®. [ABSTRACT FROM AUTHOR]

Evidence exists of a fast increase in the returns to education in Vietnam in the 1990s and 2000s. However, there was a huge change in education policy in the mid-2000s, opening up opportunities for education providers to expand enrolment. This may lead to a decline in the returns to education in later years when the changes have generated sufficient effect. To provide up-to-date estimates of the returns, we re-visit the returns using updated large survey data up to 2014. We apply the OLS and Heckman selection estimators which can correct for selection bias and find that both estimators provide a consistent trend of the returns, which increased quickly up to the global financial crisis in 2008/2009 and then declined afterwards. This raises a question whether higher educated labour force is oversupplied. [ABSTRACT FROM AUTHOR]

In today’s integrated global economy, business executives of multinational corporations are required to have a flexible global mindset in order to cope with the driving forces of globalization. Thus, the global market forces stress the importance for business schools to graduate students with skill sets pertinent to functioning competitively in the ever-changing business environment. In this article, we conducted a survey of 165 students in the Albers School of Business and Economics at Seattle University to examine whether international cocurricular activities help achieve the goal of cultivating a global mindset in students. The results suggest that international cocurricular activities enhance students’ global mindset. Short-term study tours and international internships do have a significant impact on students’ global mindset as other long-term cocurricular activities, which may cost more time and money. We recommend that short-term study tours be used as an alternative cost-effective way to engaging business students in the internationalization of the business curriculum at their institutions. [ABSTRACT FROM AUTHOR]

Soldiers and supporting engineers are frequently exposed to high low-frequency (<500 Hz) cabin noise in military vehicles. Despite the use of commercial hearing protection devices, the risk of auditory damage is still imminent because the devices may not be optimally customised for such applications. This study considers flax fibre-reinforced polypropylene (Flax-PP) as an alternative to the material selection for the ear cups of commercial earmuffs, which are typically made of acrylonitrile butadiene styrene (ABS). Different weaving configurations (woven and nonwoven) and various noise environments (pink noise, cabin booming noise, and firing noise) were considered to investigate the feasibility of the proposed composite earmuffs for low-frequency noise reduction. The remaining assembly components of the earmuff were kept consistent with those of a commercial earmuff, which served as a benchmark for results comparison. In contrast to the commercial earmuff, the composite earmuffs were shown to be better in mitigating low-frequency noise by up to 16.6 dB, while compromising midfrequency acoustical performance. Consequently, the proposed composite earmuffs may be an alternative for low-frequency noise reduction in vehicle cabins, at airports, and at construction sites involving heavy machineries. [ABSTRACT FROM AUTHOR]

Air pollution concentrations in Ho Chi Minh City (HCMC) have been found to surpass the WHO standard, which has become a very serious problem affecting human health and the ecosystem. Various machine learning algorithms have recently been widely used in air quality forecasting studies to predict possible impacts. Training and constructing several machine learning models for different air pollutants, such as NO 2 , SO 2 , O 3 , and CO forecasts, is a time-consuming process that necessitates additional effort for deployment, maintenance, and monitoring. In this paper, an effort has been made to develop a multi-step multi-output multivariate model (a global model) for air quality forecasting, taking into account various parameters such as meteorological conditions, air quality data from urban traffic, residential, and industrial areas, urban space information, and time component for the prediction of NO 2 , SO 2 , O 3 , CO hourly (1 h to 24 h) concentrations. The global forecasting model can anticipate multiple air pollutant concentrations concurrently, based on past concentrations of covariate characteristics. The datasets on air pollution time series were gathered from six HealthyAir air quality monitoring sites in HCMC between February 2021 and August 2022. Darksky weather provided the hourly concentrations of meteorological conditions for the same period. This is the first model built using real-time air quality data for NO 2 , SO 2 , CO, and O 3 forecasting in HCM city. To assess the effectiveness of the proposed model, it was evaluated using real data from HealthyAir stations and quantified using Root Mean Squared Error (RMSE), Mean Absolute Percentage Error (MAPE), and correlation indices. The results show that the global air quality forecasting model beats earlier models built for air quality forecasting of each specific pollutant in HCMC. [ABSTRACT FROM AUTHOR]

In aerobic granular sludge (AGS), the growth of nitrite oxidizing bacteria (NOB) can be uncoupled from the nitrite supply of ammonia oxidizing bacteria (AOB). Besides, unlike for conventional activated sludge, Nitrobacter was found to be the dominant NOB and not Nitrospira. To explain these experimental observations, two possible pathways have been put forward in literature. The first one involves the availability of additional nitrite from partial denitrification (nitrite-loop) and the second one consists of mixotrophic growth of Nitrobacter in the presence of acetate (ping-pong). In this contribution, mathematical models were set up to assess the possibility of these pathways to explain the reported observations. Simulation results revealed that both pathways influenced the nitrifier distribution in the granules. The nitrite-loop pathway led to an elevated NOB/AOB ratio, while mixotrophic growth of Nitrobacter guaranteed their predominance among the NOB population. Besides, mixotrophic growth of Nitrobacter could lead to NO emission from AGS. An increasing temperature and/or a decreasing oxygen concentration led to an elevated NOB/AOB ratio and increased NO emissions. [ABSTRACT FROM AUTHOR]

Service learning has been used to supplement a standard business curriculum, but not typically in an international business context. We report the results of two short-term study abroad programs in which we incorporated service learning projects, one in Cambodia and the other in Vietnam. Our objective is to assess how we organized and delivered effective service learning projects in short-term study tours, and to assess students’ learning outcomes on global poverty issues in a business curriculum. We used both quantitative and qualitative assessment measures. The findings suggest that several types of learning outcomes did occur through the service learning projects, as the literature suggested. Seeing poverty firsthand and doing something about it through service learning may be a first experience for many students, but it seems to be a transformational one for many. We conclude that students may approach business and even political decisions with a greater understanding of their impact on poverty in the developing world. [ABSTRACT FROM PUBLISHER]

The objective of this study was to examine the impact of a number of variables on the perceptions of women entrepreneurs' success and motivational factors. We partnered with PeaceTrees Vietnam, a Seattle-based NGO and the Women's Union of Vietnam to conduct field work in Quang Tri province in central Vietnam. A survey was administered to 20 women entrepreneurs in 6 different communes. Of the 120 surveys administered, 109 usable surveys were received. We found that women owners of businesses in Quang Tri Province perceived success to be a result of their values and perceptions of entrepreneurship. Similarly, the women were motivated by both their perceptions of values and perceptions of entrepreneurship. [ABSTRACT FROM AUTHOR]

In this paper we attempt to analyze the impact of an integrated microcredit program on the empowerment of women in rural Vietnam. We conduct a longitudinal study in 2008 and 2012 on a sample of 50 microcredit recipients. The finding indicates the importance of the empowerment components in the Peace Trees microcredit program, which serves as leverage for higher income generation and greater gender equality. The study emphasizes the role of the Women's Union in designing and implementing the microcredit program with the objective of empowering women. This study supports the importance of the feminist empowerment paradigm in which empowerment is a best practice when a gender equality approach is embedded in program design, rather than an add-on benefit. The microcredit program has also integrated the poverty alleviation paradigm and the financial self-sustainability paradigm. [ABSTRACT FROM AUTHOR]

• New compression moulding process for thermoplastic composites with metal inserts. • FE model accurately predicts pull-out strengths for a wide range of geometries. • Multi-objective optimisation method for high strength and low mass inserts. Fibre reinforced plastics have great potential for the design of lightweight structures with high stiffness and strength. However, in practical engineering applications, there is a frequent requirement to join composite parts together or to join composite parts with metallic parts, creating hybrid connections. The ability to join such parts without performance degradation is a challenging task. This paper presents a near-netshape compression moulding manufacturing methodology for direct embedment of lightweight metallic load introduction inserts into composite laminates. The paper investigates the optimal pull-out strength design of these inserts considering a wide range of insert parameters. Extensive experimental characterisation is undertaken with both steel and titanium cone inserts, considering variation of insert diameter, cone height and vertical position within the laminate. The experimental results are used to validate a finite element model, which is then used for multi-objective optimisation and the generation of design charts, considering both maximum strength and minimum weight multi-objective design requirements. For each insert material, a Pareto front is determined, which defines the set of optimal insert geometries related to its vertical position. [ABSTRACT FROM AUTHOR]

There is growing evidence from both behavioral and neurophysiological approaches that primates are able to rapidly discriminate visually between snakes and innocuous stimuli. Recent behavioral evidence suggests that primates are also able to discriminate the level of threat posed by snakes, by responding more intensely to a snake model poised to strike than to snake models in coiled or sinusoidal postures (Etting and Isbell 2014). In the present study, we examine the potential for an underlying neurological basis for this ability. Previous research indicated that the pulvinar is highly sensitive to snake images. We thus recorded pulvinar neurons in Japanese macaques (Macaca fuscata) while they viewed photos of snakes in striking and non-striking postures in a delayed non-matching to sample (DNMS) task. Of 821 neurons recorded, 78 visually responsive neurons were tested with the all snake images. We found that pulvinar neurons in the medial and dorsolateral pulvinar responded more strongly to snakes in threat displays poised to strike than snakes in non-threat-displaying postures with no significant difference in response latencies. A multidimensional scaling analysis of the 78 visually responsive neurons indicated that threat-displaying and non-threat-displaying snakes were separated into two different clusters in the first epoch of 50 ms after stimulus onset, suggesting bottom-up visual information processing. These results indicate that pulvinar neurons in primates discriminate between poised to strike from those in non-threat-displaying postures. This neuronal ability likely facilitates behavioral discrimination and has clear adaptive value. Our results are thus consistent with the Snake Detection Theory, which posits that snakes were instrumental in the evolution of primate visual systems. [ABSTRACT FROM AUTHOR]

In this paper, we design a novel three-order autonomous system. Numerical simulations reveal the complex chaotic behaviors of the system. By applying the undetermined coefficient method, we find a heteroclinic orbit in the system. As a result, the Ši'lnikov criterion along with some other given conditions guarantees that the system has both Smale horseshoes and chaos of horseshoe type. [ABSTRACT FROM AUTHOR]

We study constructive generalized synchronization (GS) for bidirectional discrete arrays of difference systems (BDADSs). The result provides a general representation of GS in BDADSs. Numerical simulations are presented to show the effectiveness of the theoretical results. [ABSTRACT FROM AUTHOR]

Context: Congenital hyperinsulinism (HI) is a common cause of hypoglycemia in infancy. The medical treatment of diazoxide-unresponsive HI is based on a somatostatin analogue. Objective: This study aims at replacing three daily s.c. octreotide (Sandostatin, Novartis) injections by a single and monthly i.m. injection of long-acting release (LAR) octreotide (Sandostatin LP, Novartis) in HI patients. Subjects and method: LAR octreotide was injected every 4 weeks during 6 months and s.c. octreotide injections were stopped after the third injection of LAR octreotide. After this 6-month study, LAR octreotide was continued, with an average follow-up of 17 months. Ten HI pediatric patients unresponsive to diazoxide and currently treated with s.c. octreotide were included in the trial. Glycemias and other parameters (HbA1c, IGF1, height, weight, quality of life (QoL), and satisfaction) were monitored at each monthly visit. Results: For all ten patients, glycemias were maintained in the usual range, HbAlc (mean 5.5%; 95% CI: 4.6-6.2) and IGF1 (mean 89.7 ng/ml; 95% CI: 26-153) were unchanged. Patients gained height significantly (mean 2.7 cm; 95% CI: 1.9-3.4) and no side effect was noted during the study and the later follow-up. Plasma octreotide levels were stable under LAR octreotide. Parents' questionnaires of general satisfaction were highly positive whereas children's QoL evaluation remained unchanged. Conclusion: In these diazoxide-unresponsive HI patients, LAR octreotide was efficient, well tolerated and contributed to a clear simplification of the medical care. [ABSTRACT FROM AUTHOR]

Abstract: Finding structural similarities between proteins often helps reveal shared functionality, which otherwise might not be detected by native sequence information alone. Such similarity is usually detected and quantified by protein structure alignment. Determining the optimal alignment between two protein structures, however, remains a hard problem. An alternative approach is to approximate each three-dimensional protein structure using a sequence of motifs derived from a structural alphabet. Using this approach, structure comparison is performed by comparing the corresponding motif sequences or structural sequences. In this article, we measure the performance of such alphabets in the context of the protein structure classification problem. We consider both local and global structural sequences. Each letter of a local structural sequence corresponds to the best matching fragment to the corresponding local segment of the protein structure. The global structural sequence is designed to generate the best possible complete chain that matches the full protein structure. We use an alphabet of 20 letters, corresponding to a library of 20 motifs or protein fragments having four residues. We show that the global structural sequences approximate well the native structures of proteins, with an average coordinate root mean square of 0.69 Å over 2225 test proteins. The approximation is best for all α-proteins, while relatively poorer for all β-proteins. We then test the performance of four different sequence representations of proteins (their native sequence, the sequence of their secondary-structure elements, and the local and global structural sequences based on our fragment library) with different classifiers in their ability to classify proteins that belong to five distinct folds of CATH. Without surprise, the primary sequence alone performs poorly as a structure classifier. We show that addition of either secondary-structure information or local information from the structural sequence considerably improves the classification accuracy. The two fragment-based sequences perform better than the secondary-structure sequence but not well enough at this stage to be a viable alternative to more computationally intensive methods based on protein structure alignment. [Copyright &y& Elsevier]

The estimated volume of the swing path is referred to as the Path Volume Envelope (PVE) which defines a volume in space from which the path of a blood-releasing object is contained within. FARO Zone 3D is a software program that allows for the calculation of the PVE; however, there are no current studies which look at how well this method performs across various analysts for a simple, human created cast-off pattern. A total of seventeen participants were provided data for a single cast-off pattern that was produced from human motion using a wooden dowel rod as the "weapon". The known three-dimensional motion of the object which created the cast-off pattern was documented using a motion capture system but remained unknown to the participants. The results show that an approximate maximum width of the PVE of±15 cm is enough to encompass the results of all participants in this study. In addition, the X, Y and Z position of the center of the PVE was found to have a standard deviation of 0.1 cm, 5.1 cm, and 9.9 cm, respectively. The standard deviations of the rotations for the PVE around the horizontal and vertical axes (i.e., yaw and pitch) were found to be 2.6° and 1° respectively. Overall, the combined results of all participants were able to fit within a rectangular prism with an overall width of± 15 cm which appears to be a reasonable value for simple scenarios, since it can define an approximate location from where an object was swung relative to a wall or another object at a crime scene. A PVE of greater or lesser maximum width may be required depending on the complexity of the cast-off pattern, the weapon used, and other factors. [ABSTRACT FROM AUTHOR]

Abstract: Introduction. – Codeine is an opioid drug used as an antitussive and an analgesic. One of the metabolic pathways of codeine leds to morphine formation: the cytochrome P450 enzyme (CYP450-2D6) catalyses the transformation of codeine to morphine. Synthesis of facts. – This complex pathway exhibits a great variability among individuals. The global distribution in the population can be divided into three groups according to their metabolic capacities, i.e. low, normal and high metabolizers. The genetic polymorphism partly explains this great heterogeneity. Moreover, health conditions as well as environment are involved. Conclusion. – This variability is important for interpretation of doping control based on the urinary determination of codeine and morphine. [Copyright &y& Elsevier]

Retinoids have been shown to inhibit the growth of many human tumor cells including breast, ovarian and squamous cell carcinoma (SCC). While the exact mechanism of retinoid mediated growth suppression is not known, a role for the retinoic acid receptors (RARs) and retinoid X receptors (RXRs) has been established in both the breast and ovarian tumor cell models. We set out to determine if modulation of RAR/RXR function would alter the retinoid sensitivity of oral SCC cells. We found that the growth of SCC cells was significantly inhibited by treatment with either all-trans-retinoic acid (trans-RA) or the synthetic, conformationally restricted RARγ selective retinoids MM11254 and MM11389. In order to demonstrate a role for RAR/RXR function in this process, stable oral SCC cell clones constitutively overexpressing the dominant negative mutant RARβ2 (R269Q) were prepared and shown to exhibit reduced RAR/RXR transcriptional transactivation activity. We found that oral SCC cells exhibiting reduced RAR/RXR function became resistant to growth inhibition by all-trans-RA, MM11254 and MM11389. Likewise, treatment of oral SCC cells with the RARγ antagonist MM11253 was found to block the ability of MM11254 and MM11389 to inhibit SCC cell growth. Thus, modulation of RAR function through the use of RAR-γ selective agonists, an RAR-γ selective antagonist or a pan-RAR dominant negative mutant significantly alters the growth inhibitory response of oral SCC cells to retinoids. Oncogene (2000) 19, 1457–1465. [ABSTRACT FROM AUTHOR]

The development of new drugs that combine active ingredients for the treatment hypertension is critically essential owing to its offering advantages for both patients and manufacturers. In this study, for the first time, detailed development of a scalable process of film-coated bi-layer tablets containing sustained-release metoprolol succinate and immediate-release amlodipine besylate in a batch size of 10,000 tablets is reported. The processing parameters of the manufacturing process during dry mixing-, drying-, dry mixing- completion stages were systematically investigated, and the evaluation of the film-coated bi-layer tablet properties was well established. The optimal preparation conditions for metoprolol succinate layer were 6 min- dry mixing with a high-speed mixer (120 rpm and 1400 rpm), 30-min drying with a fluid bed dryer, and 5 min- mixing completion at 25 rpm. For the preparation of amlodipine besylate layer, the optimal dry-mixing time using a cube mixer (25 rpm) was found to be 5 min. The average weight of metoprolol succinate layers and bi-layer tablets were controlled at 240–260 mg and 384–416 mg, respectively. Shewhart R chart and X ¯ charts of all three sampling lots were satisfactory, confirming that the present scalable process was stable and successful. This study confirms that the manufacturing process is reproducible, robust; and it yields a consistent product that meets specifications. [ABSTRACT FROM AUTHOR]

Sustainable investing allocates investments based on environmental, social and governance factors (ESG). The societal value of sustainable investment is becoming progressively relevant as investors are increasingly recognizing the importance of investing in companies that seek to combat climate change, environmental destruction, while promoting corporate responsibility. Environmental policy and sustainable growth initiatives at a country-level are also being influenced by the UN's Sustainable Development Goals (SDGs). Situated within the current trend of declining foreign direct investment flows (FDI), our study examines the role of ESG factors in attracting FDI and enabling progress toward SDGs. We econometrically examine the linkages between ESG and FDI inflows for a sample of 161 counties. We also focus on low- and middle-income emerging economies and low- and middle-income commodity exporters as these countries face unique challenges of mobilizing financing to achieve SDGs and generating sustainable economic growth. Results suggest that FDI inflows to the full sample of countries are positively attracted by good governance in a destination country. We observe that good scores on HDI deters FDI, that higher FDI flows are associated with higher levels of carbon emissions in the case of emerging markets. Sustainability reporting attracts FDI to commodity exporting countries. The study provides possibilities for future research in a post-pandemic future. [ABSTRACT FROM AUTHOR]

The effects of moisture on the mechanical and acoustic properties of flax fibers embedded in polypropylene (PP) were investigated in the present study. Flax/PP and hybrid flax-carbon/PP samples were immersed in water at controlled temperatures. The water intake over time in flax/PP was shown to approach Fickian behavior at room temperature while hybrids showed strong deviations. Through hybridization with 13% carbon fibers, water uptake in flax-carbon PP was reduced by 25%. For thin hybrid laminates, positioning carbon fibers at the outer edges caused no significant difference in the rate of moisture uptake. Micrographic analysis revealed that carbon fiber bundles are more susceptible to resin deficiency in flax-carbon/PP hybrids due to its densely packed thin fibers. The stiffness of moisture-saturated flax/PP samples was 50% lower than dry specimens, with 35% increase in failure strain. The tensile strength, however, was almost unaffected, and both, dry and wet samples, exhibited similar damage characteristics. The stiffness reduction affected the acoustic performance: the resonant frequency was reduced, and the STL were lowered in the stiffness-controlled frequency domain. To determine the unknown water uptake at saturation, an accelerated method was presented as an alternative time-efficient solution for designers. [ABSTRACT FROM AUTHOR]

Neural stem cells (NSCs) play vital roles in brain homeostasis and exhibit a broad repertoire of potentially therapeutic actions following neurovascular injury. One such injury is stroke, a worldwide leading cause of death and disability. Clinically, extensive injury from ischemic stroke results from ischemia-reperfusion (IR), which is accompanied by inflammation, blood-brain barrier (BBB) damage, neural cell death, and extensive tissue loss. Tissue plasminogen activator (tPA) is still the only US Food and Drug Administration–approved clot-lysing agent. Whereas the thrombolytic role of tPA within the vasculature is beneficial, the effects of tPA (in a non-thrombolytic role) within the brain parenchyma have been reported as harmful. Thus, new therapies are needed to reduce the deleterious side effects of tPA and quickly facilitate vascular repair following stroke. The Stroke Treatment Academic Industry Roundtable (STAIR) recommends that stroke therapies "focus on drugs/devices/treatments with multiple mechanisms of action and that target multiple pathways". Thus, based on multifactorial ischemic cascades in various stroke stages, effective stroke therapies need to focus on targeting and ameliorating early IR injury as well as facilitating angiogenesis, neurogenesis, and neurorestorative mechanisms following stroke. This review will discuss the preclinical perspectives of NSC transplantation as a promising treatment for neurovascular injury and will emphasize both the subacute and chronic phase of ischemic stroke. [ABSTRACT FROM AUTHOR]

In recent years, natural fiber polymer composites have demonstrated great potential for reducing noise. This study reports sound transmission loss (STL) of hybrid flax fabric-reinforced polypropylene composites. The STL values were determined by the BSWA impedance tube and evaluated by ISO 10534 standard test procedure in the frequency range of 64 to 1600 Hz. Measurements show that the STL per areal density of flax/polypropylene is two times higher compared to aluminum. A noteworthy result is that upon hybridization with 13% carbon fibers (carbon-flax/polypropylene), the STL per areal density increases by 2.4 times. This study also presents the finite element (FE) simulation of sound transmission through the composites. Good agreement between FE predicted and experimentally measured STL is obtained. Moreover, parametric sensitivity studies are performed using the developed FE model to examine the effect of possible variation in the mechanical properties of the natural fiber composites on the STL performance. It is found that within 15% variation, no significant effect on STL is obtained and that STL is only sensitive to the in-plane elastic moduli. [ABSTRACT FROM AUTHOR]

Background: Achondroplasia is a genetic disorder that inhibits endochondral ossification, resulting in disproportionate short stature and clinically significant medical complications. Vosoritide is a biologic analogue of C-type natriuretic peptide, a potent stimulator of endochondral ossification.Methods: In a multinational, phase 2, dose-finding study and extension study, we evaluated the safety and side-effect profile of vosoritide in children (5 to 14 years of age) with achondroplasia. A total of 35 children were enrolled in four sequential cohorts to receive vosoritide at a once-daily subcutaneous dose of 2.5 μg per kilogram of body weight (8 patients in cohort 1), 7.5 μg per kilogram (8 patients in cohort 2), 15.0 μg per kilogram (10 patients in cohort 3), or 30.0 μg per kilogram (9 patients in cohort 4). After 6 months, the dose in cohort 1 was increased to 7.5 μg per kilogram and then to 15.0 μg per kilogram, and in cohort 2, the dose was increased to 15.0 μg per kilogram; the patients in cohorts 3 and 4 continued to receive their initial doses. At the time of data cutoff, the 24-month dose-finding study had been completed, and 30 patients had been enrolled in an ongoing long-term extension study; the median duration of follow-up across both studies was 42 months.Results: During the treatment periods in the dose-finding and extension studies, adverse events occurred in 35 of 35 patients (100%), and serious adverse events occurred in 4 of 35 patients (11%). Therapy was discontinued in 6 patients (in 1 because of an adverse event). During the first 6 months of treatment, a dose-dependent increase in the annualized growth velocity was observed with vosoritide up to a dose of 15.0 μg per kilogram, and a sustained increase in the annualized growth velocity was observed at doses of 15.0 and 30.0 μg per kilogram for up to 42 months.Conclusions: In children with achondroplasia, once-daily subcutaneous administration of vosoritide was associated with a side-effect profile that appeared generally mild. Treatment resulted in a sustained increase in the annualized growth velocity for up to 42 months. (Funded by BioMarin Pharmaceutical; ClinicalTrials.gov numbers, NCT01603095, NCT02055157, and NCT02724228.). [ABSTRACT FROM AUTHOR]

Résumé La fibrodysplasie ossifiante progressive (FOP) ou maladie de Münchmeyer, est une pathologie génétique rare, autosomique dominante, se manifestant par des poussées d'ossification hétérotopique, progressives et cumulatives, aboutissant à une douloureuse métamorphose en « homme de pierre », ankylose irrémédiable laissant les familles et les professionnels de santé souvent désemparées devant l'immuable progression de la pathologie. L'implication d'une mutation récurrente du gène activine-like kinase gene, ACVR1/ALK2 , mutation activatrice de la voie du (TGF)-β/BMP a été démontrée en 2006 par F. Kaplan, E. Shore et un consortium international. Cette découverte majeure a lancé de nombreux travaux de recherche permettant d'appréhender les bases physiopathologiques et d'aborder des pistes thérapeutiques spécifiques. Le suivi et la prise en charge de cette pathologie incluent pour l'instant essentiellement des mesures préventives et le traitement symptomatique des poussées inflammatoires douloureuses précédant le phénomène d'ossification. Plusieurs thérapeutiques innovantes sont en cours de développement préclinique et clinique, visant à bloquer les voies de signalisation d'amont et d'aval de ACVR1/ALK2. Elles marquent une nouvelle ère pour la communauté de personnes concernées engagées auprès des patients FOP. L'hétéroplasie ossifiante progressive (progressive osseous heteroplasia , POH, OMIM 166350) appartient aussi au groupe des ossifications hétérotopiques, caractérisé par la survenue anormale de formation osseuse au sein des tissus conjonctifs. Il s'agit d'une pathologie ultra-rare (moins de 100 cas décrits à ce jour), progressive, d'évolution très variable. Cette grande rareté semble être liée à une pénétrance incomplète avec large variabilité des manifestations. Le phénomène d'ossification est épisodique, comme dans la FOP. Par contre, ces deux pathologies sont distinguées par le fait que la POH implique un phénomène d'ossification principalement d'origine intramembraneuse, qu'il n'existe pas de facteur déclenchant aux poussées, qu'il n'existe pas la progression selon un schéma caractéristique prédictible et par l'absence de facteur inflammatoire concomitant. Il existe une différenciation directe des progéniteurs mésenchymateux en ostéoblastes. La POH est associée à des mutations inactivatrices du gène GNAS. Les traitements sont actuellement limités aux mesures symptomatiques, notamment assurer une asepsie cutanée, une antalgie adaptée et aux anti-inflammatoires non stéroïdiens. Abstract Fibrodysplasia ossificans progressiva (FOP), or Münchmeyer's disease, is a rare, autosomal dominant genetic disorder, characterized by episodic progressive and cumulative heterotopic ossification, leading to a disabling metamorphosis into a "stone man", with irremediable joint immobility, leaving families and health professionals often distraught, faced to the immeasurable progression of the disease. The involvement of a recurrent mutation of the activin-like kinase gene, ACVR1/ALK2 gene, an activating mutation of the (TGF)-β/BMP pathway, was demonstrated in 2006 by F. Kaplan, E. Shore and an international consortium. This major discovery has launched many research projects for understanding the pathophysiological basis and targeting specific therapies approaches. The present management of this pathology includes mainly preventive measures, and symptomatic treatment of disease flare-ups preceding the phenomenon of ossification, by various anti-inflammatory agents. Several innovative therapies are currently undergoing preclinical and clinical development, aimed at blocking the upstream and downstream signaling pathways of ACVR1/ALK2, marking a new era for the community of affected individuals and people engaged with FOP patients. Progressive osseous heteroplasia (POH) also belongs to the group of genetic disorders with extensive heterotopic ossification, characterized by the abnormal formation of bone within the connective tissues. It is an ultra-rare pathology (less than 100 cases described to date), severely progressive. This great rarity seems to be related to incomplete penetrance with wide variability of manifestations. The onset of ossification is episodic, as in FOP. On the other hand, these two conditions may be distinguished by the facts that POH is due to heterotopic ossification mainly of intramembranous origin, that there is no triggering factor leading to bone formation, there is no progression according to a characteristic pattern and by the absence of concomitant inflammatory factor. There is a direct differentiation of mesenchymal progenitors into osteoblasts. POH is associated with inactivating mutations of the GNAS gene. Treatments are currently limited to symptomatic measures, including ensuring cutaneous asepsis, adequate analgesia and non-steroidal anti-inflammatory drugs. [ABSTRACT FROM AUTHOR]

The abnormal expression in the T-type calcium channels is involved in various cancer types, thus inhibiting T-type calcium channels is one of approaches in cancer treatment. The fact that KTt-45 acted as a T-type calcium channel inhibitor as well as a pain-relief agent prompts us to address if KTt-45 plays any role against cancer cells. The results showed that KTt-45 caused cytotoxic effects towards HeLa cervical, Raji lymphoma, MCF-7 breast cancer, and A549 lung cancer cell lines with IC50 values less than 100 μM, in which highly selective toxicity was against HeLa cells (IC50 = 37.4 μM, SI > 3.2). Strikingly, the KTt-45 induced an accumulation of cytoplasmic vacuoles after 48 h treatment and mitochondrial-dependent apoptosis activation as evidenced by morphological features, chromatin condensation, nuclear fragmentation, and significant activation of caspase-9 as well as caspase-3. In conclusion, KTt-45 could inhibit cell growth and trigger mitochondrial-dependent apoptosis in HeLa cervical cancer cells. The results, taken together, strongly demonstrated that KTt-45 is a potential agent for further study on anticancer drug development which not only targets cancer cells but also helps to relieve neuropathic pain in cancer patients. [ABSTRACT FROM AUTHOR]

The shadow economy has emerged as a challenging issue for countries globally, particularly emerging markets. An increased budget deficit prevents the governments from using public expenditure to control the increased shadow economy. This paper examines the effect of government expenditure on the shadow economy and the moderating role of budget deficit affecting this impact for the ASEAN-7 countries from 1990 to 2019. We find that increased government spending is associated with an increased shadow economy in ASEAN countries. Interestingly, the effects of government expenditure on the shadow economy intensify with increased budget deficit in the short and long term. [ABSTRACT FROM AUTHOR]

Stem growth habit dictates plant architecture and influences flowering and podding (seed setting), making it an essential morphological and breeding agronomic trait of soybean (Glycine max). Stem growth habit in soybean is affected by photoperiod and environment and is determined by genetic variation at major genes. Classical genetic analysis identified two critical loci, designated Determinacy 1 (Dt1) and Determinacy 2 (Dt2). Dt1 is an ortholog of Arabidopsis thaliana TERMINAL FLOWER1 (TFL1) and specifies an indeterminate stem growth habit, whereas Dt2 specifies a semi-determinate growth habit. MADS-box proteins, including Dt2, SUPPRESSOR OF OVEREXPRESSION OF CO1 (GmSOC1) and MADS-box genes downregulated by E1 (GmMDE), repress Dt1 expression. Photoreceptors encoded by the E3 and E4 loci regulate the expression of soybean FLOWERING LOCUS T (GmFT) orthologs via circadian clock genes and E1, and GmFTs compete with Dt1 to regulate stem growth habit. Study of the molecular mechanism underlying the regulation of stem growth habit in soybean has focused on the repression of Dt1 expression. Here we provide an overview of progress made in elucidating the genetic and molecular bases of stem growth habit in soybean, with emphasis on the molecular components responsible for integrating photoperiodic flowering and stem growth habit. [ABSTRACT FROM AUTHOR]

Background: The design of clinical trials in rare diseases is often complicated by a lack of real-world translational knowledge. Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare genetic disorder characterized by skeletal malformations and progressive heterotopic ossification (HO). Palovarotene is a selective retinoic acid receptor gamma agonist. Here, we describe the methodology of three studies in the palovarotene clinical development program in FOP and discuss insights that could inform future research, including endpoint suitability and the impact of trial design. Methods: PVO-1A-001 (NCT02322255) was a prospective, protocol-specified, longitudinal FOP natural history study (NHS). PVO-1A-201 (NCT02190747) was a randomized, double-blind, placebo-controlled phase II trial; PVO-1A-202 (NCT02279095) was its open-label extension. Trial designs, including treatment regimens and imaging assessments, were refined between PVO-1A-201 and PVO-‍1A-202, and within PVO-1A-202, based on emerging data as the studies progressed. Palovarotene doses were administered using a flare-up treatment regimen (higher dose for 2/4 weeks, followed by lower dose for 4/≥8 weeks; from flare-up onset), with or without accompanying chronic (daily) treatment. Flare-up and disease progression outcomes were assessed, including incidence and volume of new HO during flare-ups and/or annually, as well as other clinical, patient-reported, and exploratory outcomes. Safety was monitored throughout all studies. Results: Overall, 114 and 58 individuals with FOP were enrolled in the NHS and phase II trials, respectively. Results of the NHS and PVO-1A-201 were published in 2022; complete results of PVO-1A-202 will be publicly available in due course. Together the studies yielded important information on endpoint suitability, including that low-dose whole-body computed tomography was the optimum imaging modality for assessing HO progression annually and that long study durations are needed to detect substantial changes in functional and patient-reported outcomes. Conclusions: A flexible clinical development program is necessary for underexplored rare diseases to overcome the many challenges faced. Here, the NHS provided a longitudinal evaluation of FOP progression and interventional trials were based on emerging data. The studies described informed the design and endpoints implemented in the phase III MOVE trial (NCT03312634) and provide a foundation for future clinical trial development. Trial registration: NCT02322255 (registered 23/12/2014); NCT02190747 (registered 15/07/2014); NCT02279095 (registered 30/10/2014). [ABSTRACT FROM AUTHOR]

Background: Fibrodysplasia ossificans progressiva (FOP) is a rare, severely disabling, and life-shortening genetic disorder that causes the formation of heterotopic bone within soft connective tissue. Previous studies found that the FOP prevalence was about one in every two million lives. The aim of this study is to estimate the FOP prevalence in France by probabilistic record-linkage of 2 national databases: 1) the PMSI (Programme de médicalisation des systèmes d'information), an administrative database that records all hospitalization activities in France and 2) CEMARA, a registry database developed by the French Centres of Reference for Rare Diseases.Results: Using a capture-recapture methodology to adjust the crude number of patients identified in both data sources, 89 FOP patients were identified, which results in a prevalence of 1.36 per million inhabitants (CI95% = [1.10; 1.68]). FOP patients' mean age was 25 years, only 14.9% were above 40 years, and 53% of them were males. The first symptoms - beside toe malformations- occurred after birth for 97.3% of them. Mean age at identified symptoms was 7 years and above 18 years for only 6.9% of patients. Mean age at diagnosis was 10 years, and above 18 years for 14.9% of the patients. FOP patients were distributed across France.Conclusions: Despite the challenge of ascertaining patients with rare diseases, we report a much higher prevalence of FOP in France than in previous studies elsewhere. We suggest that efforts to identify patients and confirm the diagnosis of FOP should be reinforced and extended at both national and European level. [ABSTRACT FROM AUTHOR]

Background: Infants presenting with lysosomal acid lipase deficiency have marked failure to thrive, diarrhea, massive hepatosplenomegaly, anemia, rapidly progressive liver disease, and death typically in the first 6 months of life; the only available potential treatment has been hematopoietic stem cell transplantation, which is associated with high morbidity and mortality in this population. The study objective was to evaluate safety and efficacy (including survival) of enzyme replacement with sebelipase alfa in infants with lysosomal acid lipase deficiency. This is an ongoing multicenter, open-label, phase 2/3 study conducted in nine countries. The study enrolled infants with growth failure prior to 6 months of age with rapidly progressive lysosomal acid lipase deficiency; they received once-weekly doses of sebelipase alfa initiated at 0.35 mg/kg with intrapatient dose escalation up to 5 mg/kg. The main outcome of interest is survival to 12 months and survival beyond 24 months of age.Results: Nine patients were enrolled; median age at baseline was 3.0 months (range 1.1-5.8 months). Sixty-seven percent (exact 95% CI 30%-93%) of sebelipase alfa-treated infants survived to 12 months of age compared with 0% (exact 95% CI 0%-16%) for a historical control group (n = 21). Patients who survived to age 12 months exhibited improvements in weight-for-age, reductions in markers of liver dysfunction and hepatosplenomegaly, and improvements in anemia and gastrointestinal symptoms. Three deaths occurred early (first few months of life), two patients died because of advanced disease, and a third patient died following complications of non-protocol-specified abdominal paracentesis. A fourth death occurred at 15 months of age and was related to other clinical conditions. The five surviving patients have survived to age ≥24 months with continued sebelipase alfa treatment; all have displayed marked improvement in growth parameters and liver function. Serious adverse events considered related to sebelipase alfa were reported in one of the nine infants (infusion reaction: tachycardia, pallor, chills, and pyrexia). Most infusion-associated reactions were mild and non-serious.Conclusion: Sebelipase alfa markedly improved survival with substantial clinically meaningful improvements in growth and other key disease manifestations in infants with rapidly progressive lysosomal acid lipase deficiency TRIAL REGISTRATION: Clinicaltrials.gov NCT01371825 . Registered 9 June 2011. [ABSTRACT FROM AUTHOR]

Prior research in the behavioral sciences has demonstrated that reminders can be an effective tool for encouraging health-related behavior changes. This article extends that literature by reporting the outcome of a randomized controlled trial of mailed vaccination reminders. In addition to making a substantive contribution regarding the efficacy of mailed reminders, this article also makes a methodological contribution: it illustrates how researchers can study the causal impact of an intervention even when a pure parallel trial is not possible. In this study, the Louisiana Department of Health sent postcard reminders regarding four recommended vaccinations (influenza, tetanus, shingles and pneumonia) to 208,867 senior residents of Louisiana. We used block randomization and a stepped wedge design to assess the efficacy of the intervention. Individuals were blocked by their prior vaccine record and randomized to receive the postcard in one of four consecutive months (October–January). The reminder postcard had an overall positive effect on vaccination rates. The statistically significant and substantively small increase in overall vaccination rates was driven by participants who received the postcard reminder early in the intervention period. [ABSTRACT FROM AUTHOR]

Nitisinone (NTBC) was recently approved to treat alkaptonuria (AKU), but there is no information on its impact on oxidative stress and inflammation, which are observed in AKU. Therefore, serum samples collected during the clinical studies SONIA1 (40 AKU patients) and SONIA2 (138 AKU patients) were tested for Serum Amyloid A (SAA), CRP and IL-8 by ELISA; Advanced Oxidation Protein Products (AOPP) by spectrophotometry; and protein carbonyls by Western blot. Our results show that NTBC had no significant effects on the tested markers except for a slight but statistically significant effect for NTBC, but not for the combination of time and NTBC, on SAA levels in SONIA2 patients. Notably, the majority of SONIA2 patients presented with SAA > 10 mg/L, and 30 patients in the control group (43.5%) and 40 patients (58.0%) in the NTBC-treated group showed persistently elevated SAA > 10 mg/L at each visit during SONIA2. Higher serum SAA correlated with lower quality of life and higher morbidity. Despite no quantitative differences in AOPP, the preliminary analysis of protein carbonyls highlighted patterns that deserve further investigation. Overall, our results suggest that NTBC cannot control the sub-clinical inflammation due to increased SAA observed in AKU, which is also a risk factor for developing secondary amyloidosis. [ABSTRACT FROM AUTHOR]

Abstract: The complexes {[Cu(L)(μ1,5-dca)](ClO4)} n (1, L=bepza; 2, L=bedmpza) and [Cu(L)(μ1,5-dca)(dca)] n (3, L=bepza; 4, L=bedmpza), where dca=dicyanamide anion, bepza=bis[2-(1-pyrazolyl)ethyl)]amine and bedmpza=bis[2-(di-2,5-dimethyl-1-pyrazolyl)ethyl)]amine, were synthesized and characterized by spectroscopic techniques. The crystal structures of complexes 1 and 3 confirmed their polymeric 1D chain nature through the two terminal nitrile groups of the μ1,5-bridging dicyanamido ligand. The magnetic susceptibility measurements of the two complexes 1 and 3 revealed the occurrence of very weak antiferromagnetic coupling with J values of −0.17 and −0.03cm−1, respectively. [Copyright &y& Elsevier]

Abstract: We studied thyroid function in 81 long-term survivors of allogeneic stem cell transplantation (allo-SCT), with a median follow-up of 84 months (range, 45 to 166 months). Median age at transplantation was 35 years (range, 6 to 66). Seventy-two of the patients received a total body irradiation (TBI)–containing conditioning regimen (n = 23, 12 Gy; n = 49, 13 Gy). Twenty-one of the patients (25.9%) had subclinical hypothyroidism, and 9 (11.1%) developed overt hypothyroidism at a median of 28 months (range, 3 to 78 months) after allo-SCT. Multivariate logistic regression analysis demonstrated that prolonged immunosuppressive therapy (IST) was significantly associated with subclinical hypothyroidism (odds ratio [OR] = 3.8) and overt hypothyroidism (OR = 2.6). Antithyroglobulin and thyroid peroxidase antibody were detected in 12 of 60 patients tested (20%). No correlation was found between the occurrence of thyroid antibodies and hypothyroidism (P = .13) or chronic graft-versus-host disease (cGVHD) (P = .55). In conclusion, thyroid dysfunction is relatively common after allo-SCT and is more likely to occur in patients receiving prolonged IST for cGVHD; however, thyroid dysfunction does not appear to be related to an antibody-mediated autoimmune process. [Copyright &y& Elsevier]

Abstract: In this paper, first burst-mode transmitter for 2.5-Gb/s gigabit-capable passive optical networks (GPON) system is evaluated. Small form factor (SFF) type optical network unit (ONU) generates 2.5-Gb/s optical eyes with commercial distributed feedback-laser diode (DFB-LD). For the fast burst signal access, burst enable (BEN) connection on the evaluation board utilizes DC-coupling configuration. Resultant optical output waveform shows 16.30dB extinction ratio with wide eye opening for GPON mask test. No significant eye degradation is detected in high temperature operation and after 10km distance transmission. Proposed GPON ONU successfully shows fast timing characteristics of 2.17nsec for Tx enable stage and 1.17ns for Tx disable stage. [Copyright &y& Elsevier]