AIM
To analyze the biological effects of prolonged in vitro exposure of HT-29 and LoVo colon cancer cell lines to gefitinib (Iressa), an inhibitor of epidermal growth factor receptor (EGFR) activity, and ZD6474, an inhibitor of both KDR and EGFR activities.

METHODS
Cells were treated with each drug for up to 2 wk using either a continuous or an intermittent (4 d of drug exposure followed by 3 d of washout each week) schedule.

RESULTS
In both cell types, prolonged exposure (up to 14 d) to gefitinib or ZD6474 produced a similar inhibition of cell growth that was persistent and independent of the treatment schedule. The effects on cell growth were associated with a pronounced inhibition of p-EGFR and/or p-KDR expression. Treatment with gefitinib or ZD6474 also inhibited the expression of EGFR downstream signal molecules, p-Erk1/2 and p-Akt, although the magnitude of these effects varied between treatments and cell lines. Furthermore, expression of the drug resistance-related protein ABCG2 was shown to significantly increase after 14 d of continuous exposure to the two drugs.

CONCLUSION
We conclude that long-term exposure of colon cancer cells to gefitinib and ZD6474 does not modify their cytotoxic effects but it might have an effect on sensitivity to classical cytotoxic drugs.


Cued threat conditioning is the most common preclinical model for emotional memory, which is dysregulated in anxiety disorders and post-traumatic stress disorder. Though women are twice as likely as men to develop these disorders, current knowledge of threat conditioning networks was established by studies that excluded female subjects. For unbiased investigation of sex differences in these networks, we quantified the neural activity marker c-fos across 112 brain regions in adult male and female mice after cued threat conditioning compared to naïve controls. We found that trained females engaged prelimbic cortex, lateral amygdala, cortical amygdala, dorsal peduncular cortex, and subparafasicular nucleus more than, and subparaventricular zone less than, trained males. To explore how these sex differences in regional activity impact the global network, we generated interregional cross-correlations of c-fos expression to identify regions that were co-active during conditioning and performed hub analyses to identify regional control centers within each neural network. These exploratory graph theory-derived analyses revealed sex differences in the functional coordination of the threat conditioning network as well as distinct hub regions between trained males and females. Hub identification across multiple networks constructed by sequentially pruning the least reliable connections revealed globus pallidus and ventral lateral septum as the most robust hubs for trained males and females, respectively. While low sample size and lack of non-associative controls are major limitations, these findings provide preliminary evidence of sex differences in the individual circuit components and broader global networks of threat conditioning that may confer female vulnerability to fear-based psychiatric disease.


Abstract. Zonal segmentation of the prostate gland using magnetic resonance imaging (MRI) is clinically important for prostate cancer (PCa) diagnosis and image-guided treatments. A two-dimensional convolutional neural network (CNN) based on the U-net architecture was evaluated for segmentation of the central gland (CG) and peripheral zone (PZ) using a dataset of 40 patients (34 PCa positive and 6 PCa negative) scanned on two different MRI scanners (1.5T GE and 3T Siemens). Images were cropped around the prostate gland to exclude surrounding tissues, resampled to 0.5  ×  0.5  ×  0.5  mm voxels and z-score normalized before being propagated through the CNN. Performance was evaluated using the Dice similarity coefficient (DSC) and mean absolute distance (MAD) in a fivefold cross-validation setup. Overall performance showed DSC of 0.794 and 0.692, and MADs of 3.349 and 2.993 for CG and PZ, respectively. Dividing the gland into apex, mid, and base showed higher DSC for the midgland compared to apex and base for both CG and PZ. We found no significant difference in DSC between the two scanners. A larger dataset, preferably with multivendor scanners, is necessary for validation of the proposed algorithm; however, our results are promising and have clinical potential.


More than a year since the novel coronavirus was first discovered, its presence is still prevalent throughout the world. In such grave situations if technology can help humans combat the spread, then why not explore it. Therefore, keeping this in mind, several researchers have already started investigating artificial intelligence algorithms to find solutions to predict coronavirus using X-ray images of chest. But due to lack of dataset during the initial days of their research, many came up with framework using pre trained image classification models such as VGG-16, Inceptionv3, ResNet-50 and others. In this paper, the performance of two machine learning algorithms which are support vector machine and decision tree has been evaluated. Further developed deep learning model applying convolutional neural network to classify the chest x-ray images as covid-19 or normal. The final CNN model was also integrated with a user interface and hosted on web server for easy access which allows anyone to upload the chest x-ray image from his computer or mobile and check the result.


The ad-hoc retrieval task is to rank related documents given a query and a document collection. A series of deep learning based approaches have been proposed to solve such problem and gained lots of attention. However, we argue that they are inherently based on local word sequences, ignoring the subtle long-distance document-level word relationships. To solve the problem, we explicitly model the document-level word relationship through the graph structure, capturing the subtle information via graph neural networks. In addition, due to the complexity and scale of the document collections, it is considerable to explore the different grain-sized hierarchical matching signals at a more general level. Therefore, we propose a Graph-based Hierarchical Relevance Matching model (GHRM) for ad-hoc retrieval, by which we can capture the subtle and general hierarchical matching signals simultaneously. We validate the effects of GHRM over two representative ad-hoc retrieval benchmarks, the comprehensive experiments and results demonstrate its superiority over state-of-the-art methods.


One well-known method of generating key stream sequences for stream ciphers is to combine the outputs of several linear-feedback shift registers (LFSR) using a combining Boolean function. Here we concentrate on the design of good combining Boolean functions. We provide resilient Boolean functions with currently best known nonlinearity. These functions were not known earlier and the issues related to their existence were posed as open questions in the literature. Some of the functions we construct here achieve the provable upper bound on nonlinearity for resilient Boolean functions. Our technique interlinks mathematical results with classical computer search.


Equilibration to the steady state for a wide class of Luttinger liquid ballistic weakly linked tunnel contacts is extensively studied. Quantum fluctuations of tunnel current are considered in all orders in tunnel coupling and out of the equilibrium in the time domain. Especially, two important mathematical statements: Self-equilibration (SE-)theorem and Self-equilibration (SE-)lemma on the exact re-exponentiation of thermal average from the Keldysh-contour-ordered evolution operator for arbitrary weakly linked Luttinger liquid tunnel contact are proven. Demonstrated proof of SE-theorem and SE-lemma represents first evidence of a novel emergent phenomenon of "self-equilibration" in the dynamics of quantum fluctuations of electron transport through ballistic tunnel junctions. Corresponding differential equation of "self-equilibration" for time-dependent Keldysh partition function of tunnel contact is derived and explained. It is shown that proven SE-theorem can be considered also as the dynamical version of well-known Jarzynski equality for the tunnel electron transport out of the equilibrium. As the result, exact time-dependent cumulant generating functional is derived being valid at arbitrary electron-electron repulsion in the Luttinger liquid leads of the junction, arbitrary temperature and arbitrary bias voltage. Respective general formula in its long-time asymptote turns into a non-perturbative Luttinger liquid generalization of the Levitov-Lesovik type of detailed balance formula for cumulant generating function. As the consequence of obtained results, a universal character of self-equilibration of tunnel current in one-dimensional weakly linked tunnel junctions is revealed and studied on the level of non-equilibrium Fano factor. As well, a new measure of disequilibrium in such systems - the "steady flow" rate - is introduced and discussed.


Modeling soil biogeochemical processes is in a deadlock due to two major limitations: 1. Since most of the biogeochemical processes occur in the soil-water film at surface of solids which compose the hierarchical and aggregated soil structure, coupling biogeochemical models with existing soil water representations is not possible at the process scale without a new paradigm that takes into consideration soil structure and its interaction with soil water. 2. Current pedological mapping and characterization methods do not provide the required soil information and data that are needed for scaling the processes from their scale within the soil to the landscape levels. Such information includes i) delineation of primary soil map units and ii) the functional characteristics which allow for modeling soil internal thermodynamic state that controls the bio and geochemical processes in soil. The new concept of pedostructure and its thermodynamic characterization had lead to a new paradigm for soil water modeling and characterization. This new paradigm provides systematic methodologies for addressing the two challenges introduced above. The physically based soil structure water computer model, Kamel, was built using this paradigm then offers the possibility of 1) coupling disciplinary models (e.g. the organic matter transformation, transport and mineralization) with the soil structure hydro-functioning, at the scale of processes in soil, and 2) integrating results from the local scale in the soil medium to the field scale. In this communication, we present the model Kamel which is available though a dedicated website, along with KamelSoil, a translator of the easily available soil information into pedostructure parameters for Kamel.


ABSTRACT A geoarchaeological and paleobotanical study of a Paleoeskimo and Neoeskimo site was undertaken in order to reconstruct site-formation processes. The study site JfEl-10 is located on Igloo Island, in Diana Bay, on the southern shore of Hudson Strait. It contains a peat-mineral deposit situated between two successive beach crests, close to a small marsh. Samples from the edge of the site, which consists of a remarkable section of stratigraphy 60 cm thick that contains alternating brown organic beds and light-colored sand beds, were examined in the laboratory. Macrofossil data and pollen data were used to reconstruct the local and regional vegetation and to determine climatic changes over the past 1200 years. The geoarchaeological study includes the stratigraphy and the sedimentology of archaeological sediments. The evolution of the site followed three successive environmental phases, and the site was home to two distinct cultures. The first phase (from ca. 1200 to ca. 950 cal. yr B.P.) was characterized by cold and mesic conditions and the Dorset occupation. In the second phase, conditions became more humid beginning ca. 950 cal. yr B.P. and lasted for approximately 450 years. This period is marked by the arrival of Thule Inuit, who hunted marine mammals in the vicinity. Zooarchaeological information indicated a fall/winter occupation during the Thule Inuit period. The third phase corresponds with the onset of the Little Ice Age (A.D. 1500–1850) and associated cooling. During this time, the Thule Inuit abandoned the site. If the increased cooling caused an earlier freeze-up of Diana Bay, this may have prevented the movement of walrus to their haul-out island during fall. Additionally, the faster accumulation of thick ice would have limited the hunting of seals through their breathing holes.


In eukaryotes, fine-scale maps of meiotic recombination events have greatly advanced our understanding of the factors that affect genomic variation patterns and evolution of traits. However, in bacteria that lack natural systems for sexual reproduction, unbiased characterization of recombination landscapes has remained challenging due to variable rates of genetic exchange and influence of natural selection. Here, to overcome these limitations and to gain a genome-wide view on recombination, we crossed Bacillus strains with different genetic distances using protoplast fusion. The offspring displayed complex inheritance patterns with one of the parents consistently contributing the major part of the chromosome backbone and multiple unselected fragments originating from the second parent. Computational analyses suggested that this bias is due to the action of restriction-modification systems whereas genome features like GC content and local nucleotide identity did not affect distribution of recombination events around the chromosome. Furthermore, we found that the intensity of recombination is uniform across the genome without concentration into hotspots. Unexpectedly, our results revealed that large species-level genetic distance did not affect key recombination parameters. Our study provides a new insight into the dynamics of recombination in bacteria and a platform for studying recombination patterns in diverse bacterial species.


The constitutive relation for open-celled metal foams with random characteristics of cells was constructed based on the mechanical behavior and the distribution of the cells, which implied the effect of the mesoscopic characteristics of the cells on the macroscopic behavior of the foam. The constitutive relation was able to represent the whole three phases of the stress-strain curve of the open-celled metal foam with merely one expression. Besides, the explicit expressions for the foam's yield strain and yield stress were supplied. Experimental data was employed to check the constitutive relation. It was found that the constitutive relation was able to represent accurately the whole compression process of the foams, and the calculated yield points had a good agreement with the experimental results.


In this paper, the terminal falling velocity of the character Mario in Super Smash Bros. Wii U is used to calculate the gravity of the planet shown in the background of the ``Battlefield'' stage of the game. This information is used to calculate a value of gravity g = 0.33 ms^(-2), and a radius of 338 km for the planet, which is used to deduce tectonic activity, a magnetic field and a sea of potentially N2O4 on the planet.


Background
Recent changes in healthcare have placed increased emphasis on price transparency, quality measures, and improving the patient experience. However, limited information is available for patient cost of obtaining a hip MRI and factors associated with cost variability. For a patient with femoroacetabular impingement (FAI), this study sought to report (1) the availability of pricing and quality information for a hip magnetic resonance imaging (MRI) in the state of Iowa, (2) the time investment required to obtain pricing and quality information, and (3) factors that influence hip MRI cost, quality and the time investment required for patients to obtain cost and quality information.

Methods
Within the state of Iowa, 126 unique hospital institutions and 30 active, private orthopaedic practices were identified. All 156 providers were contacted via telephone using a standardized script of a hypothetical 25-year-old adult male patient with FAI requesting a quote for a hip MRI. Cost of the MRI and its components, availability of payment discounts, and MRI magnet tesla (T) were requested. A final bundled cost (FBC) was calculated for each MRI provider with all available services and discounts applied. The total amount of time needed to obtain a quote from each location was recorded.

Results
One hundred and thirty-six of the 156 institutions contacted provided hip MRI services (87%). Median call duration was 9.1 minutes (Range 2.3-25.6). Median FBC was $2,114.00 (Range $484.75-4,463.00) across all providers. Hospital median FBC was $2,261.70 (Range $909.62-4,463.00) versus $1,225.13 (Range $484.75-2,218.40) for independent imaging centers (P<0.0001). No difference in median cost was observed between nine available 3.0 T machines and eighty-nine 1.5 T machines (P=0.2655).

Conclusions
MRI cost varies widely across the state of Iowa and within individual metropolitan areas. Hip MRIs cost less at independent imaging centers compared to hospital locations. The amount of time required to obtain quality and cost data for a hip MRI presents a substantial time burden for patients with FAI. Surgeons, healthcare systems, and policy makers should be cognizant of the large price differences for a hip MRI and the time burden placed on patients with FAI to obtain this information.Level of Evidence: IV.


Chinese cymbidiums are important flowering ornamental plants. Traditional propagation via seed or division cannot satisfy growers' demand for commercialization of new cultivars, and in vitro propagation has a low micropropagation efficiency due to the browning of rhizomes. In this study, rhizomes of Cymbidium '14-16-13' and '14-16-5' were cultured on half-strength Murashige and Skoog (MS) medium supplemented with 6-benzyl aminopurine (BAP), NAA (α-napthaleneacetic acid), or BAP with NAA under either the dark or light. The degree of browning was read, and rhizome proliferation or sprouting (sprout numbers) was evaluated. Results showed that there was significant difference in browning grade of rhizomes between '14-16-13' and '14-16-5' regardless of dark and light culture. Dark culture induced rhizome proliferation but failed to induce sprouts. Light culture slightly elevated the degree of browning but induced sprouting. Among the growth regulators evaluated, BAP was more effective for sprout induction. As rhizome browning appeared to be inevitable in micropropagation of the cymbidiums, a compromise between browning and sprout production could be a realistic approach. Our study showed that rhizomes cultured on half-strength MS medium supplemented with 1.5 mg·L−1 BAP were able to produce more than 16 sprouts per vessel even though browning occurred in the rhizomes. Thus, culturing rhizomes in this medium could be a practical solution for in vitro propagation of Chinese cymbidiums.


Despite the powerful nature of the aza-Michael reaction for generating C-N linkages and bioactive moieties, the bis-Michael addition of 1° amines remains ineffective for the synthesis of functional, step-growth polymers due to the drastic reduction in reactivity of the resulting 2° amine mono-addition adduct. In this study, a wide range of commercial hydrazides are shown to effectively undergo the bis-Michael reaction with divinyl sulfone (DVS) and 1,6-hexanediol diacrylate (HDA) under catalyst-free, thermal conditions to afford moderate to high molecular weight polymers with M n = 3.8-34.5 kg mol-1. The hydrazide-Michael reactions exhibit two distinctive, conversion-dependent kinetic regimes that are 2nd-order overall, in contrast to the 3rd-order nature of amines previously reported. The mono-addition rate constant was found to be 37-fold greater than that of the bis-addition at 80 °C for the reaction between benzhydrazide and DVS. A significant majority (12 of 15) of the hydrazide derivatives used here show excellent bis-Michael reactivity and achieve >97% conversions after 5 days. This behavior is consistent with calculations that show minimal variance of electron density on the N-nucleophile among the derivatives studied. Reactivity differences between hydrazides and hexylamine are also explored. Overall, the difference in reactivity between hydrazides and amines is attributed to the adjacent nitrogen atom in hydrazides that acts as an efficient hydrogen-bond donor that facilitates intramolecular proton-transfer following the formation of the zwitterion intermediate. This effect not only activates the Michael acceptor but also coordinates with additional Michael acceptors to form an intermolecular reactant complex.


The declared intention of Dr Westcott and his colleagues "to demonstrate the general practice answer" is very welcome, and I hope their counter-proposals will share the Court Committee's overriding concern that vested professional interests should not get in tne way of effective services to meet the special needs of children. May I give one example of the problems they will face ? Education authorities will rightly insist that they are provided with a school health service which shares fully in the rising standards which we all seek. Can those who are unhappy about the report's proposals, in this and other respects, suggest an alternative pattern of services which will avoid perpetuating the present divided services ? Experience leads us to believe that such divided services will be divisive: this would be in the interests of no one, least of all children. And that, after all, is what it is all about. MICHAEL ROGERS Principal Clinical Medical Officer, Berkshire Area Health Authority Reading


We present our findings based on a detailed analysis of the binaries of the Hyades, in which the masses of the components are well known. We fit the models of the components of a binary system to observations so as to give the observed total V and B - V of that system and the observed slope of the main sequence in the corresponding parts. According to our findings, there is a very definite relationship between the mixing-length parameter and the stellar mass. The fitting formula for this relationship can be given as a = 9.19(M/M ⊙ - 0.74) 0.053 -6.65, which is valid for stellar masses greater than 0.77 M ⊙ . While no strict information is gathered for the chemical composition of the cluster, as a result of degeneracy in the colour-magnitude diagram, by adopting Z = 0.033 and using models for the components of 70 Tau and θ 2 Tau we find the hydrogen abundance to be X = 0.676 and the age to be 670 Myr. If we assume that Z = 0.024, then X = 0.718 and the age is 720 Myr. Our findings concerning the mixing-length parameter are valid for both sets of the solution. For both components of the active binary system V818 Tau, the differences between radii of the models with Z = 0.024 and the observed radii are only about 4 per cent. More generally, the effective temperatures of the models of low-mass stars in the binary systems studied are in good agreement with those determined by spectroscopic methods.


Multiple-input multiple-output (MIMO) sonar systems offer new perspectives for area surveillance especially in complex environments where strong multipath and dense clutter can become very challenging. This study proposes a MIMO sonar system based scheme to tackle the difficult problem of harbour surveillance. An emphasis is put on recognition and tracking on low-profile mid-water targets. First, a MIMO simulator which can compute synthetic raw data for any transmitter/ receiver pair in a multipath, cluttered and dynamic environment is presented. The study then proposes two radically different methods for the underwater target tracking problem in complex environment: a digital tracker and an analogue tracker. On the digital side, an implementation of the recently developed hypothesised filter for independent stochastic populations is presented. This filter enables robust multi-object tracking as well as track classification capabilities without the use of heuristics. An analogue filter based on acoustical time reversal techniques is also introduced. This filter directly uses the returned acoustic field from the scene to focus the sound on the expected target position, hence improving the signal-to-noise ratio on the target in complex environments and taking full advantage of the MIMO architecture.


Abstract Three data bases of gridded surface temperature anomalies were used to assess the sensitivity of the average estimated Northern Hemisphere (NH) temperature anomaly to: 1) extreme gridpoint values and 2) zonal band contributions. Over the last 100 year, removal of either the top or bottom 10% of the gridpoint anomalies in any year changes the estimated NH average anomaly by 0.1−0.2°C. Excising extensive zonal bands also produces root-mean-square changes in the estimated NH anomaly of approximately 0.1°C. The estimated NH average anomaly appears to be robust to such perturbations.


Background:The current study was performed to elucidate changes in growth factor expression over time in critical-sized calvarial defects in rats from infancy to skeletal maturity. Materials and Methods:Critical-sized parietal defects of 5, 6, and 8 mm were created in postnatal day 6 (P6), postnatal day (P20), and postnatal day (P84) adult rats, respectively. Dura was harvested at 3, 7, or 14 days after surgery, and serial micro–computed tomography imaging was performed through 12 weeks postoperatively. Absolute quantitative polymerase chain reaction was performed for Bone Morphogenic Protein-2 (BMP-2), Fibroblast Growth Factor-2 (FGF-2), Insulin-like Growth Factor-1 (IGF-1), and Transforming Growth Factor-&bgr;1 (TGF-&bgr;). Results:The P6 (6-d-old) rats showed the greatest difference in gene expression between the dura derived from the defect side and the dura derived from the control side, demonstrating significant differences in TGF-&bgr;1, BMP-2, IGF-1, and FGF-2 at various time intervals. Absolute gene expression in the defect dura was highest in the P6 rats and declined with age. Significant differences were noted at limited time points in the P20 rats for TGF-&bgr;1 and BMP-2 as well as in the P84 rats for TGF-&bgr;1. TGF-&bgr;1 was the only gene studied that showed significant differences at postoperative days 3, 7, and 14 in varying age groups. Conclusions:The P6 rats have a higher osteogenic potential accompanied by a more vigorous alteration in growth factor expression compared with the P20 or P84 rats. Decrease in BMP-2 and FGF-2 as well as relative increase in TGF&bgr;-1 messenger RNA were observed in healing defects. These data provide valuable insight into the mechanism of healing of critical-sized defects and may be of use to engineer factor-releasing implants to correct skull defects.


Forty-eight cases of pathologically verified Alzheimer's disease were examined for the presence of ubiquitin-positive cortical Lewy bodies (CLBs). Thirty-four (71%) of 48 cases of Alzheimer's disease had CLBs compared with 4 (44%) of nine patients with idiopathic Parkinson's disease, and 2 (20%) of 10 patients with multi-infarct dementia. None of the 18 cognitively intact elderly controls we examined had CLBs. Among Alzheimer's disease patients, there was a strong correlation between CLBs and degenerative changes in the substantia nigra. We also found an association between the presence of CLBs and extrapyramidal symptoms. Among Alzheimer's disease patients, there was no association of CLBs with either senile plaques or neurons containing neurofibrillary tangles in hippocampus, neocortex, or ventral striatum. The incidence of CLBs among pathologically verified Alzheimer's disease cases is high when a careful search for these inclusions is performed with a sensitive method such as anti-ubiquitin immunocytochemistry.


Inbreeding depression reduces mean phenotypic value of important traits in livestock populations. The goal of this work was to estimate the level of inbreeding and inbreeding depression for growth and reproductive traits in Argentinean Brangus cattle, in order to obtain a diagnosis and monitor breed management. Data comprised 359,257 (from which 1,990 were genotyped for 40,678 SNP) animals with phenotypic records for at least one of three growth traits: birth weight (BW), weaning weight (WW) and finishing weight (FW). For scrotal circumference (SC), 52,399 phenotypic records (of which 256 had genotype) were available. There were 530,938 animals in pedigree. Three methods to estimate inbreeding coefficients were used. Pedigree-based inbreeding coefficients were estimated accounting for missing parents. Inbreeding coefficients combining genotyped and nongenotyped animal information were also computed from matrix H of the single-step approach. Genomic inbreeding coefficients were estimated using homozygous segments obtained from a Hidden Markov model (HMM) approach. Inbreeding depression was estimated from the regression of the phenotype on inbreeding coefficients in a multiple-trait mixed model framework, either for the whole data set or the data set of genotyped animals. All traits were unfavorably affected by inbreeding depression. A 10% increase in pedigree-based or combined inbreeding would result in a reduction of 0.34 - 0.39 kg in BW, of 2.77 - 3.28 kg in WW and 0.23 cm in SC. For FW a 10% increase in pedigree-based, genomic or combined inbreeding would result in a decrease of 8.05 - 11.57 kg. Genomic inbreeding based on the HMM was able to capture inbreeding depression, even in such a compressed genotyped data set.


Background Several studies have demonstrated the effect of guided Internet-based cognitive behavioral therapy (ICBT) for depression. However, ICBT is not suitable for all depressed patients and there is a considerable level of nonresponse. Research on predictors and moderators of outcome in ICBT is inconclusive. Objective This paper explored predictors of response to an intervention combining the Web-based program MoodGYM and face-to-face therapist guidance in a sample of primary care patients with mild to moderate depressive symptoms. Methods Participants (N=106) aged between 18 and 65 years were recruited from primary care and randomly allocated to a treatment condition or to a delayed treatment condition. The intervention included the Norwegian version of the MoodGYM program, face-to-face guidance from a psychologist, and reminder emails. In this paper, data from the treatment phase of the 2 groups was merged to increase the sample size (n=82). Outcome was improvement in depressive symptoms during treatment as assessed with the Beck Depression Inventory-II (BDI-II). Predictors included demographic variables, severity variables (eg, number of depressive episodes and pretreatment depression and anxiety severity), cognitive variables (eg, dysfunctional thinking), module completion, and treatment expectancy and motivation. Using Bayesian analysis, predictors of response were explored with a latent-class approach and by analyzing whether predictors affected the slope of response. Results A 2-class model distinguished well between responders (74%, 61/82) and nonresponders (26%, 21/82). Our results indicate that having had more depressive episodes, being married or cohabiting, and scoring higher on a measure of life satisfaction had high odds for positively affecting the probability of response. Higher levels of dysfunctional thinking had high odds for a negative effect on the probability of responding. Prediction of the slope of response yielded largely similar results. Bayes factors indicated substantial evidence that being married or cohabiting predicted a more positive treatment response. The effects of life satisfaction and number of depressive episodes were more uncertain. There was substantial evidence that several variables were unrelated to treatment response, including gender, age, and pretreatment symptoms of depression and anxiety. Conclusions Treatment response to ICBT with face-to-face guidance may be comparable across varying levels of depressive severity and irrespective of the presence and severity of comorbid anxiety. Being married or cohabiting, reporting higher life satisfaction, and having had more depressive episodes may predict a more favorable response, whereas higher levels of dysfunctional thinking may be a predictor of poorer response. More studies exploring predictors and moderators of Internet-based treatments are needed to inform for whom this treatment is most effective. Trial Registration Australian New Zealand Clinical Trials Registry number: ACTRN12610000257066; https://www.anzctr.org.au/trial_view.aspx?id=335255 (Archived by WebCite at http://www.webcitation.org/6GR48iZH4).


A nanoparticle-based prodrug formulation consisting of polymeric micelles incorporating the inorganic platinum agent cisplatin with potential antineoplastic activity. In micellar nanoparticle-encapsulated cisplatin NC-6004, cisplatin forms a polymer-metal complex with hydrophilic polyethylene glycol poly(glutamic acid) block copolymers by attaching to the micelle inner core consisting of the hydrophobic polyamino acids. Upon cell entry and release from the polymer-metal complex, cisplatin forms highly reactive, charged platinum complexes that bind to nucleophilic groups such as GC-rich sites in DNA, inducing intrastrand and interstrand DNA cross-linking, DNA-protein cross-linking and, subsequently, tumor cell apoptosis and growth inhibition. Due to the hydrophilic nature of polyethylene glycol, this formulation increases the water-solubility of cisplatin and decreases the nephrotoxicity and neurotoxicity associated with the administration of cisplatin alone. Qeios · Definition, February 7, 2020


While considerable attention has been given to the areal expansion of juniper (Juniperus sp.) in the western United States, the presence and ecological significance of old-growth juniper communities has gone largely unnoted. Increased recognition of these communities has prompted questions about how to recognize old-growth, community structure, ecological importance, and appropriate management. As an initial analysis of old-growth western juniper woodlands (Juniperus occidentalis Hook var. occidentalis Vasek) in central Oregon, this study investigated old-growth community structure on eolian-sand derived soils. These woodlands represent the most extensive old-growth western juniper woodlands throughout its range. Nine study plots were established at 7 sites. Within each plot, densities and physical attributes of all live trees and large standing and fallen woody detritus were recorded. Additional measurements for live trees included canopy cover, apparent age class (pre- or postsettlement), and a sampling of tree ages. Aging of trees older than 250 years was complicated by extensive heartwood rot. Shrub density and cover were measured by species. Understory cover was measured by species and functional type. Bare ground, rock, juniper litter, other litter, moss, and cryptogamic crust cover were also measured. Plant cover ranged from 11 to 33% for trees, 0 to 10% for shrubs, 3 to 12% for perennial grasses, 1 to 2% for forbs, and from 0 to 0.1% for annual grasses. The woodlands contained at least 80 trees ha(-1) aged over 200 years. Correlations between tree parameters and understory structure and composition were generally poor. Differences in plant composition among these stands was primarily attributed to elevation, slope, and percent sand content. Structural characteristics that distinguished old-growth stands from younger stands included tree growth form, presence of standing and dead large woody debris, lichen on dead branches, and a relatively open canopy. Results provide a preliminary basis for identifying old-growth Juniperus occidentalis stands, as a prelude to the development of management plans and further research into the functional characteristics of the systems. A definition of old-growth juniper woodlands is presented. DOI:10.2458/azu_jrm_v54i5_waichler


We present an orthogonal frequency division multiple access (OFDMA) cognitive radio medium access control using multichannel ALOHA (OCR MAC). The performance of an infinite population based OCR system is numerically as well as theoretically analyzed in terms of throughput, delay, and data capacity. We evaluate the throughput versus delay tradeoff of OCR MAC with an agile OFDM channel selection. Especially, via simulation with a linear feedback model, we verify the proposed system and its tradeoff characteristics. The numerical results for the proposed CR MAC are compared with conventional non-agile CR MAC as well as pure ALOHA based CR MAC. We also investigate the data capacity for OCR with perfect or imperfect spectrum sensing whose capacity gap is reduced with a large number of channels.


The reliability of the quantification of genetic diversity using only one type of marker has been questioned as compared to the combined use of different markers. To compare the efficiency of the use of single versus multiple markers, the genetic diversity was quantified among 12 diverse pigeonpea germplasm comprised of eight wild and four cultivated using both random amplified polymorphic DNA (RAPD) and simple sequence repeat (SSR) markers, and how well these two types of markers discriminated the diverse pigeonpea germplasm was evaluated. The pigeonpea germplasm including eight wild species and four cultivated varieties was subjected to 40 RAPD and 40 microsatellite primers. The level of polymorphism as revealed by RAPD primers produced a total of 517 DNA fragments and all were found to be polymorphic that is, 100% and in SSR analysis 101 fragments were produced that too showed 100% polymorphism. The high similarity index value revealed by RAPD was 0.931 between GT-100 and ICPL-87 whereas through SSR, it was 1.00 between GTH-1 and GT-100 as well as Rhyncosia rothi and Rhyncosia minima . The least similarity index value revealed by RAPD ( R. rothi and GTH-1) and SSR ( Rhyncosia bracteata and ICPL-87) were 0.07 and 0.133, respectively. Using RAPD marker, the calculated arithmetic mean heterozygosity and the marker index were 0.90 and 22.47, respectively. The R. bracteata and ICPL-87 were found distinct from rest of other cultivars by showing only 13% similarity. Average PIC value shown by RAPD and SSR primers were found to be 0.90 and 0.18, respectively. Keywords : Pigeonpea, random amplified polymorphic DNA (RAPD), simple sequence repeats (SSR) markers. African Journal of Biotechnology Vol. 12(40), pp. 5823-5832


This paper compares stability of international environmental agreements for six different rules of coalition formation under very general conditions (any type of heterogeneity between countries). The rules can be interpreted as different institutional settings in which treaty formations take place and/or different designs of agreements. We consider open and restricted open membership game as well as four exclusive membership games with different degrees of unanimity required to form coalitions. From a policy perspective, counterintuitively, it turns out that stability is higher under exclusive than under open membership and stability increases with the degree of unanimity. We discuss the policy implications of our result for future treaty-making.


This paper describes the rationale and importance of utilizing a priori, model based information to guide segmentation and classification in complex medical images represented by Magnetic Resonance Imaging (MRI). The incorporation of such a priori, model based information requires the development of a "top down" model driven system, rather than the more traditional "bottom up" data driven system. Two different examples which incorporate such model based a priori information are discussed: (1) The segmentation and classification of tissues involved in atherosclerosis; and (2) The segmentation and classification of brain tissue for neurosurgical applications.


: The preanesthetic properties of medetomidine, a novel alpha 2-adrenergic agonist, were compared to the preanesthetic properties of acepromazine, zylazine and meperidine prior to halothane anesthesia. The premedications were given to 23 randomly selected laboratory beagles in doses with sedative effects equal to the 10 micrograms/kg used in the medetomidine group. These dogs also received 0.04 mg/kg of atropine prior to the preanesthetic. A group of 7 dogs with a high medetomidine dose (40 micrograms/kg) was included in the study. Cardiopulmonary and respiratory parameters were recorded at 10 min intervals during surgical stimulus. Dogs receiving 40 micrograms/kg of medetomidine showed bradycardia, but higher blood pressures than dogs in the other groups. Adequate oxygen saturations and perfusion were recorded in all groups. The low 10 micrograms/kg dose of medetomididine had a halothane sparing effect comparable to the other premedications, while the 40 micrograms/kg of medetomidine group showed a clear decrease in halothane consumption. The sedative effect of 10 micrograms/kg of medetomidine was in some instances inadequate for proper manipulation of the dogs, but 40 micrograms/kg produced excessive sedation. Atropine was found to counteract the medetomidine induced bradycardia.


Drought is one of the most important types of abiotic stress that affects stability and amount of yield. This study was conducted to screen for drought tolerance at early seedling stages for 318 ecogeographically diverse wild barley (Hordeum vulgare L. spp. spontaneum) diversity collection (WBDC). Considerable variation was observed for all the seedling characters examined. Seedling growth was significantly reduced by 17% polyethyleneglycol-induced drought stress with significant variation among accessions. Shoot length was the most sensitive trait, however, rootshoot length ratio increased under osmotic stress. Correlation studies indicated that the root length was the most important trait, followed by shoot length and root-shoot length ratio. Principal components analysis (PCA) was performed and the first two principal components (PC) explained 78.3% of the variation present in the WBDC with PC1 (50.1%) associated with shoot length and seedling length. PC2 (28.1%) was related with root length and root-shoot length ratio. PCA showed that accessions from the Fertile Crescent particularly from Jordan and Israel showed high drought tolerance than other geographical regions at the early seedling stage. The accessions WBDC009 (Jordan), WBDC075 (Libya), WBDC211 (Uzbekistan), WBDC242 (Jordan), WBDC254 (Jordan) and WBDC289 (Israel) exhibited the highest drought tolerance index, indicating high level of drought tolerance. Consequently, these accessions showed tolerance to drought at the early seedling stage and are considered to be good sources of drought tolerance for cultivated barley


Original scientific paper Abstract: Today, growing and changing competitive conditions, products, and services, free movement of labor, and businesses with the information they develop strategies that create value to obtain a competitive advantage. Now, final buyers have the convenience of purchasing the products they demand with the features and conditions they want and at the price they accept. In such an environment, businesses use their supply chain and logistics activities more effectively and efficiently than their competitors. Today, achieving a strategic superiority in a global market where the content and quality of the products are the same is only possible by delivering the desired products to the customer at the desired price, at the desired time, in the desired amount, through the right channel, as quickly as possible and without any damage. In such a situation, the desire to focus on the main activities of the enterprises, the need for effective logistics operations, etc. logistics outsourcing has increased rapidly for reasons. Businesses can carry out logistics activities requiring expertise thanks to third party logistics (3PL) service providers in the field such as transportation, storage, customs clearance, without investing in logistics. For logistics outsourcing to be beneficial, a correct logistics service provider must be selected under the needs of the business. Selecting the right logistics service provider is important in increasing the benefit of outsourcing. In this study neutrosophic AHP was used to prioritize the factors.


Abstract. The interannual variability of the South Adriatic Gyre and its relation to the wind vorticity and the large-scale climatic pattern (North Atlantic Oscillation – NAO) was studied using the time series of satellite altimetric data and ocean surface wind products. The cyclonic circulation observed in the southern Adriatic area was partly sustained by the local wind forcing, as suggested by the positive correlation between the rate of change of the current vorticity and the wind-stress vorticity. Nevertheless, the influence of vorticity advection from the adjacent area (northern Ionian Sea) cannot be ignored and it is more significant during the anticyclonic phase of Adriatic–Ionian Bimodal Oscillation System. The geostrophic current vorticities of the southern Adriatic and northern Ionian seas are correlated with a time lag of 14 months, which approximately corresponds to an advection speed of  ∼  1 cm s−1. The different wind patterns observed during two NAO phases in the winter revealed a stronger positive vorticity during the negative NAO phase. Conversely, during the wintertime positive NAO phase the wind vorticity is characterized by lower positive or slightly negative values. Despite a statistically significant negative correlation between the NAO index and the wind vorticity, no unequivocal relationship between large climatic system and the interannual variability of the South Adriatic Gyre intensity was found due to additional effects of the vorticity advection from the Ionian. This can be explained by the fact that the Ionian circulation mode does not depend on the NAO variations. Therefore, the main result of this study is that the interannual variability of the southern Adriatic cyclonic circulation is a result of the combined influence of the vorticity advection from the Ionian and the local wind-curl effect.


In this paper, a new Wilkinson balun is proposed using the asymmetrical T-structure power divider connected with the metamaterial and conventional transmission lines at outputs to improve the phase response flatness. Since the asymmetrical T-structure power divider can be designed to provide a output phase difference, it can be applied to compensate the nonlinear phase difference between the metamaterial and conventional transmission lines. The Wilkinson balun is designed at the center frequency 1.5 GHz. Over the frequency range of 1.15-2.45 GHz, namely a 72.2% relative bandwidth, the phase difference of the developed Wilkinson balun is within 180±3°, and the amplitude imbalance is less than 0.6 dB.


This article outlines how Germany has sought to project a strategic narrative of the Eurozone crisis. Germany has been placed center stage in the Eurozone crisis, and as a consequence, the German government's crisis narrative matters for the future of the common currency. We highlight how the German government has sought to narrate a story of the cause of the Eurozone crisis and present policy solutions to influence policy decisions within the EU and maintain domestic political support. This focus on the public communication of the crisis is central to understanding the development of Germany's policy as it was negotiated with EU partners, the U.S. and international financial institutions. We draw on speeches and interviews by Chancellor Angela Merkel and two of her senior cabinet ministers delivered at key moments of the Eurozone crisis between May 2010 and June 2012. The article argues that while Merkel and her governments have been able to shore up domestic support for her Eurozone policies, she has struggled to find a coherent strategic narrative that is both consistent with German domestic preferences and historical memory, and with those of other Eurozone members.


Abstract PorphyStruct, a new digital tool for the analysis of non‐planar distortion modes of different porphyrinoids, and its application to corrole structures is reported. The program makes use of the normal‐coordinate structure decomposition technique (NSD) and employs sets of normal modes equivalent to those established for porphyrins in order to describe the out‐of‐plane dislocation pattern of perimeter atoms from corroles, norcorroles, porphycenes and other porphyrinoids quantitatively and in analogy to the established terminology. A comparative study of 17 porphyrin structures shows very similar results to the original NSD analysis and no systematic error. Application to corroles is successful and reveals the necessity to implement an extended basis of normal modes for a large share of experimental structures. The results frequently show the concomitant occurence of several modes but remain interpretable. For group XI metal corroles the phenomenon of supersaddling was unravelled, allowing for more in‐depths discussions of structure‐function correlations.


Retinal fundus images acquired with non-mydriatic digital fundus cameras are a versatile tool for the diagnosis of various retinal diseases. Even with relative ease of use, the images produced sometimes suffer from reflectance artefacts mainly due to the nerve fibre layer (NFL) or camera lens related reflections. We propose a technique that employs multiple fundus images to obtain a single higher quality image without these reflectance artefacts, which also compensates for a sub-optimal illumination. The removal of bright artefacts, can have great benefits for the reduction of false positives in the detection of retinal lesions by automatic systems or manual inspection. The fundus images are acquired by changing the stare point of the patient but keeping the camera fixed. Between each shot, the apparent shape and position of all the retinal structures that do not exhibit isotropic reflectance (e.g. bright artefacts) change. This physical effect is exploited by our algorithm.


extremefit is a package to estimate the extreme quantiles and probabilities of rare events. The idea of our approach is to adjust the tail of the distribution function over a threshold with a Pareto distribution. We propose a pointwise data driven procedure to choose the threshold. To illustrate the method, we use simulated data sets and three real-world data sets included in the package.


With the rapid development of powerful image editing software, digital image forgery has been a serious problem. One of the most commonly used forgery technique is the Copy-move forgery that copies a part of an image and pastes it on the other region in the same image. Some methods in the literature divide suspicious image into overlapped blocks and extract some features from them to judge the forgery. Similarity among the feature vectors gives a clue about the forgery. In this work, we used first three-color moments to extract feature vectors from the blocks. The method assumes that the color distribution of a block cannot be changed even if it is compressed or blurred. Color Moments has not been used to detect image forgery in the literature before. The proposed method has higher accuracy ratios compared to other works when the forged image is post processed using some operations.


Analysis of compositional variations along profiles from tholeiitic sills provides insights into syn- and post-emplacement magmatic differentiation processes. We present here 18 whole-rock compositional profiles sampled from a saucer-shaped sill emplaced in the Karoo Basin (South Africa), the Golden Valley Sill. We show that different compositional profile patterns previously described in basic-ultrabasic sills may be found in different parts of a single saucer-shaped sill. The detailed examination of the mineral grain assemblage and compositions suggests that processes taking place in hundred-meter-thick sills relate to early and late fractional crystallization. Our observations in the Golden Valley Sill suggest that a significant part of fractionation takes place at a late stage of cooling when a crystalline skeleton or mush zone is formed. We show that porous flow of interstitial melt driven by forces related to the particular geometry (saucer-shaped) of the sill may result in a post-emplacement compositional evolution. We propose that the process of post-emplacement melt flow regionally overprinted compositional patterns produced by earlier crystal segregation from the cooling magma at fluid-like stages during the emplacement.


Today producers are beginning to use social media as the field product promotion them. From various media like television, newspapers, youtube, facebook, instagram, youtube.Vivo is one of the brands which when it appears often in the media. With advertising expenditure reached rp462,4 billion have been very intents explain excellence vivo to consumers. Thus should vivo is one of a smartphone owns the most attractive to in indonesia. But the intensity of the movement vivo in advertising their products it does make vivo become a smartphone most attractive to in indonesia. The purpose of this study is to find the relationship between double-digit vivo advertising in the media interest in buying products with a smartphone. Vivo The theory used in this research is a theory a response cognitive. This is quantitative research research covered with type eksplanatori.Researchers used the technique of non probability the sampling method of to the total number of samples from 100 people with the 18-30 age of years in the city of semarang that has been exposed to advertising exposure vivo smartphone. Based on the hypothesis test conducted using kendall' s know correlation, analysis it shows that there is a relationship it on each variable. The highest correlation value is the exposure of television ads by 0.532, and advertising through the newspaper of exposure 0.622, and advertising exposure through facebook with niali of 0.525.The higher the exposure to ads, vivo the higher the interest of the people buying towards. vivo products and vice versaWith the results suggested to vivo to create ads with a variety of of messages create ads with various of messages according to the desired, segmentation in order to reach the consumer segmentation in order to have interest in buying products. smartphone vivo


Learning structures of 3D shapes is a fundamental problem in the field of computer graphics and geometry processing. We present a simple yet interpretable unsupervised method for learning a new structural representation in the form of 3D structure points. The 3D structure points produced by our method encode the shape structure intrinsically and exhibit semantic consistency across all the shape instances with similar structures. This is a challenging goal that has not fully been achieved by other methods. Specifically, our method takes a 3D point cloud as input and encodes it as a set of local features. The local features are then passed through a novel point integration module to produce a set of 3D structure points. The chamfer distance is used as reconstruction loss to ensure the structure points lie close to the input point cloud. Extensive experiments have shown that our method outperforms the state-of-the-art on the semantic shape correspondence task and achieves comparable performance with the state-of-the-art on the segmentation label transfer task. Moreover, the PCA based shape embedding built upon consistent structure points demonstrates good performance in preserving the shape structures. Code is available at https://github.com/NolenChen/3DStructurePoints


In this work, an investigation of efficiency enhancing methods and cross-section data in the BEAMnrc Monte Carlo (MC) code system is presented. Additionally, BEAMnrc was compared with VMC++, another special-purpose MC code system that has recently been enhanced for the simulation of the entire treatment head. BEAMnrc and VMC++ were used to simulate a 6 MV photon beam from a Siemens Primus linear accelerator (linac) and phase space (PHSP) files were generated at 100 cm source-to-surface distance for the 10 x 10 and 40 x 40 cm2 field sizes. The BEAMnrc parameters/techniques under investigation were grouped by (i) photon and bremsstrahlung cross sections, (ii) approximate efficiency improving techniques (AEITs), (iii) variance reduction techniques (VRTs), and (iv) a VRT (bremsstrahlung photon splitting) in combination with an AEIT (charged particle range rejection). The BEAMnrc PHSP file obtained without the efficiency enhancing techniques under study or, when not possible, with their default values (e.g., EXACT algorithm for the boundary crossing algorithm) and with the default cross-section data (PEGS4 and Bethe-Heitler) was used as the "base line" for accuracy verification of the PHSP files generated from the different groups described previously. Subsequently, a selection of the PHSP files was used as input for DOSXYZnrc-based water phantom dose calculations, which were verified against measurements. The performance of the different VRTs and AEITs available in BEAMnrc and of VMC++ was specified by the relative efficiency, i.e., by the efficiency of the MC simulation relative to that of the BEAMnrc base-line calculation. The highest relative efficiencies were approximately 935 (approximately 111 min on a single 2.6 GHz processor) and approximately 200 (approximately 45 min on a single processor) for the 10 x 10 field size with 50 million histories and 40 x 40 cm2 field size with 100 million histories, respectively, using the VRT directional bremsstrahlung splitting (DBS) with no electron splitting. When DBS was used with electron splitting and combined with augmented charged particle range rejection, a technique recently introduced in BEAMnrc, relative efficiencies were approximately 420 (approximately 253 min on a single processor) and approximately 175 (approximately 58 min on a single processor) for the 10 x 10 and 40 x 40 cm2 field sizes, respectively. Calculations of the Siemens Primus treatment head with VMC++ produced relative efficiencies of approximately 1400 (approximately 6 min on a single processor) and approximately 60 (approximately 4 min on a single processor) for the 10 x 10 and 40 x 40 cm2 field sizes, respectively. BEAMnrc PHSP calculations with DBS alone or DBS in combination with charged particle range rejection were more efficient than the other efficiency enhancing techniques used. Using VMC++, accurate simulations of the entire linac treatment head were performed within minutes on a single processor. Noteworthy differences (+/- 1%-3%) in the mean energy, planar fluence, and angular and spectral distributions were observed with the NIST bremsstrahlung cross sections compared with those of Bethe-Heitler (BEAMnrc default bremsstrahlung cross section). However, MC calculated dose distributions in water phantoms (using combinations of VRTs/AEITs and cross-section data) agreed within 2% of measurements. Furthermore, MC calculated dose distributions in a simulated water/air/water phantom, using NIST cross sections, were within 2% agreement with the BEAMnrc Bethe-Heitler default case.


The coastal waters of Nigeria are a difficult environment to build structures to control the local morphology and hydrodynamic conditions to ones desire. This difficulty is a consequence of the persistent high-energy swell wave climate and Longshore Sediment Transport (LST) in the order of one million cubic metres per year. Besides these tough conditions, the costs of conventional coastal mitigation solutions are high because of the lack of suitable material (rock) close by. These characteristics of the Nigerian coast led to the interest, whether it is possible to design and construct a 'Sand Breakwater' for a planned port on the Nigerian coastline at Badagry. A 'Sand Breakwater' is the complete construction which functions as the protection of the port and creates shelter from incoming waves for ships inside, consisting out of components (partly) made out of sand and hard structures. Especially the very uni-directional and consistent character of the wave climate creates an opportunity to embrace natural processes in the design. In addition, much sand needs to be dredged for the creation of the approach channel along with the port's basin. This volume of sand might possibly be re-used for a sand breakwater. This report presents the feasibility of a sand breakwater on the Nigerian coastline at Badagry. This feasibility is determined both morphologically and economically. Long term coastline development was modelled with the one-line coastline evolution model LITPACK. Results show that the persistent uni-directional character of the wave climate prevailing at the coast of Badagry forces an equilibrium coastline orientation of 277.5 degrees with respect to True North (TN). Because of this, all other orientations of coast rather than the equilibrium orientation are vulnerable and will develop to the equilibrium orientation over time. The implementation of this equilibrium orientation in the design along with some hard structures led to multiple long term morphological stable conceptual variants for a sand breakwater. The coastline impacts of these variants west of the sand breakwater were examined on large scale. In 38 years after construction a maximum of 20 meters coastline retreat occurs, which is considered acceptable. After this period, only shoreline accretion takes place. To establish complete conceptual designs, the cross-shore profiles are first determined. The submerged part of the profile up to the top of the intertidal profile is constructed by integration of measured data in the design. The emerged part of the profile concerns the cross-section of a dune and was the critical part for the designing objective. To determine these profiles, first the design crest height is determined by applying maxmimum acceptable overtopping volumes (Tilmans, 1983). Knowing the design crest height, the dune width is determined by modelling storm impact. This width is established by examining storm impact and determine what minimal required width needs to be present for the sand breakwater to live up to its design criteria. Storm impact for the found conceptual variants is examined with the numerical software XBeach to determine cross-shore sediment transport during storm impact. The impact of storms with shorter return periods results to be relatively high in comparison to the storms with longer return periods. This is taken into account by adapting the design conditions. The design storm conditions are based on the impact of a storms with a 1/100 year return period along with an expansion for a consecutive storm with a return period of 1/1 year. With this storm impact known, the required crest width is determined and with that the minimal required cross-shore profiles for the multiple variants are established. Consequently, besides long term morphologically stable, the conceptual designs are capable to design storm impact, confirming the morphological feasibility. In order to define the economical feasibility of a sand breakwater, a comparison between the different conceptual variants and a conventional design is made. This comparison is conducted via a rough cost comparison along with examining future prospects. In order to be able to make this cost comparison, rough volume estimations are done for all conceptual variants and conventional design. These volume estimations combined with unit prices lead to a rough cost comparison. From this rough cost comparison appears that a sand breakwater showed to be in the same price range as a conventional design. Three future prospects of a sand breakwater are determined. First of all the by-pass of sand is compared for the conceptual designs to the conventional design. The characteristic LST is problematic due to the occurrence of sand by-passing causing sedimentation in the approach channel and port. One of the conceptual variants shows that a sand breakwater is proven to be able to provide a period without by-passing of sand in the same order of magnitude as a conventional design. Another future prospect is the required maintenance necessary to execute for the sand breakwater. The XBeach results of lower storm conditions show that maintenance costs are high. However, these results are assumed to be heavily overestimated. Results with more specific 'Nigerian conditions' create reason to believe that maintenance for lower storm conditions will be much lower and in acceptable range. The last future prospect concerns the accreted land which arises due to the blockage of LST. A sand breakwater creates the possibility of acquiring land for new port space which is not possible with a conventional breakwater. In addition, the value of a Building with Nature component is present in this project and could enhance its economical interest. Not only the morphological but also the economical feasibility of a sand breakwater is confirmed. The 'Sand Breakwater' succeeded to convert the drivers of the problem to its solution, leading to an innovative and in all likeliness even more cost-effective solution compared to the traditional approach.


Cytosine residues in 32P-labeled E. coli tRNA Leu 1 were modified by treatment of the tRNA with the semicarbazide-bisulfite reagents [Hayatsu, H. (1976) Biochemistry 15, 2677-2682]. Analysis of the modification sites showed that only four cytidine residues, i.e. C35, C53, C85 and C86, reacted. They were identical with the cytidines of this tRNA accessible to methoxyamine [Chang, S. E. and Ish-Horowicz, D. (1974) J. Mol. Biol. 84, 375-388] and the accessibility was consistent with the conformational features recognized for tRNA in general. The rapidity and the simple nature of this modification demonstrate that the semicarbazide-bisulfite reaction is a useful tool in studying conformations of polynucleotides.


Hydrogel coatings have been widely researched as a nonfouling surface modification of materials for cardiovascular applications. In this study, we examined cell- surface interactions between a poly(acrylamide-co- polyethylene glycol/acrylic acid) interpenetrating network (IPN) hydrogel and aortic endothelial cells (ECs). The IPN was covalently attached to polystyrene to form a nanometer scale thick hydrogel, and the IPN layer was activated by conjugation of the cell adhesion peptide Arg-Gly-Asp (RGD). On IPN surfaces lacking the RGD peptide, EC did not adhere and spread even after long-term incubation. The IPN was able to support greater EC adhesion and spreading with increasing RGD surface concentrations. Upon adequate adhesion and spreading, ECs migrated and proliferated at high rates regardless of the RGD surface concentration. These results suggest that this IPN can be used to promote endothelialization of vascular implants made of polymeric and metal materials for cardiovascular applications.


Accumulating evidence suggests that platelet-type 12-lipoxygenase (p12-LOX) plays an important role in tumor development. However, how p12-LOX contributes to tumorigenesis is still not understood. The role of p12-LOX was therefore examined in tumor promotion using mouse epidermal JB6 P+ cells that are sensitive to 12-O-tetradecanoylphorbol-13-acetate-induced transformation. The expression of p12-LOX was significantly higher in JB6 P+ cells than in JB6 P- cells that were resistant to transformation, and its expression was further increased by tumor necrosis factor (TNF)-alpha. Importantly, the inhibition of p12-LOX in JB6 P+ cells by baicalein, a specific inhibitor or small interfering RNA significantly suppressed TPA-induced transformation. Moreover, treatment with 12(S)-hydroxyeicosatetraenoic acid (HETE), a metabolite of p12-LOX, enhanced TPA-induced neoplastic transformation either in the presence or absence of baicalein. These results indicate that p12-LOX is required for tumor promotion of epidermal cells and that 12(S)-HETE functions as a rate-limiting factor. Notably, treatment with baicalein significantly suppressed the proliferation of JB6 P+ cells when cells were seeded at a low density in a culture plate. Moreover, the cloning efficiency of JB6 P+ cells was dramatically decreased by inhibition of p12-LOX. In contrast, baicalein treatment did not affect the cloning efficiency of most malignant cancer cells. These results indicate that p12-LOX is induced by the inflammatory cytokine TNF-alpha in the early stage of tumorigenesis, and is required for tumor promotion through enhancing efficient proliferation of a small number of initiated cells. The present results suggest that the p12-LOX pathway may be an effective target of chemoprevention for skin carcinogenesis.


This study of the Wada of Maharashtra (India) attempts the first systematic overview of the courtyard house form in the present day state of Maharashtra, across its five traditional regions. Between 1700 AD and 1900 AD the wada received royal patronage and proliferated. It was first the Marathas, and later their successors the Peshwas, who patronized this house form which was found not only in Maharashtra but areas around as well, where their rule spread. Previous scholarships concentrated on small geographical regions, whereas this study attempts to evaluate the generalities and the variations across the entire state of Maharashtra. Regional and social variations have been identified while documenting 75 wadas across the five traditional regions of the state, covering over 30 towns. The data is organized in regional and sociological typologies, arriving at a classification of images, plans, sections and elevations. From this classification, the variables and commonalities become evident. These typologies have been studied in relation to the town plan, establishing a link with the broader urban context. Reasons for the development of the plan, its continuity and disruption, have been examined, while considering the determinants of space and form. Socio cultural, historical and geographical factors have been taken into account to understand their implications on space and form. The


A great earthquake of magnitude 8.0 occurred on May 12, 2008 (Beijing Time) in Wenchuan, Sichuan Province of China. Leigu town, which adjoins Beichuan county, was the most seriously damaged place in this earthquake. The teaching buildings were destroyed severely and the earthquake disaster phenomena is very typical. In this paper, firstly, the characteristics of structures and the earthquake damage of the teaching buildings in Leigu town are introduced in detail. Secondly, their damage states are calculated by means of structure vulnerability analysis, which are used for comparative analysis with actual damage states, and the influencing factors on seismic behavior are analyzed. Finally, some reasonable suggestions on the reconstruction of teaching buildings after disaster have been given.


Clouds represent a major paradigm shift from contemporary systems, inspiring the contemporary approach to computing. They present fascinating opportunities to address dynamic user requirements with the provision of flexible computing infrastructures that are available on demand. Clouds, however, introducing novel challenges particularly with respect to security that require dedicated efforts to address them. This study is focused at one such challenge, that is, determining the extent of damage caused by an intrusion for a victim virtual machine. It has significant implications especially with respect to effective response to the intrusion. This study presents the efforts to address this challenge for Clouds in the form of a novel scheme for intrusion damage assessment for Clouds. In addition to its context-aware operation, the scheme facilitates protection against multi-stage attacks. The study also includes the formal specification and evaluation of the scheme, which successfully demonstrate its effectiveness to achieve rigorous damage assessment for Clouds.


The behavior problem pupil in the public school classroom is of continual and vexing concern to educators and to the parents of the child. Many valid environmentally oriented theories have been advanced to explain patterns of aberrant conduct but the plausibility of these postulations may obscure questions raised about the organic fitness of some children. We cannot ignore the close relationship of brain activity to overt behavior. 1 The present paper is concerned with the effects of amphetamine on the so-called hyperkinetic syndrome of behavior, so ably described by Laufer and Denhoff 2,3 and the very similar "organic syndrome of behavior" defined by Bradley. 4 It is characterized mainly by hyperactivity, short attention span, impulsivity, explosiveness, erratic school performance, and poor social adjustment. Teachers find these children extremely trying and make them the subject of recurrent referrals to guidance personnel. Laufer and Denhoff


By use of dark-field light microscopy, secretory granules isolated from the anglerfish endocrine pancreas were observed to attach to and release from microtubules assembled in vitro from brain homogenates. Secretory granules only bound to microtubules assembled in the presence of microtubule-associated proteins (MAPs) and not to microtubules assembled from purified tubulin. The addition of a MAP fraction to purified tubulin restored secretory granule binding. The secretory granules were released from MAP-containing microtubules by the addition of Mg-ATP but not by other nucleotides. The number of secretory granules bound to MAP-containing microtubules was increased in the presence of cyclic AMP. In addition to the associations of secretory granules with microtubules, MAP-containing microtubules also associated with each other. These laterally associated microtubules were dispersed by the addition of Mg-ATP. Electron micrographs confirmed that the associations between MAP-containing microtubules and secretory granules as well as the associations of microtubules with one another were mediated by the high molecular weight MAPs known to project from the surface of in-vitro-assembled microtubules.


Background Rising levels of alcohol and drug abuse as reported by NACADA, Kenya, especially in the central part of Kenya necessitated a crisis intervention which was ordered by the President of Kenya in June 2015. Breakdown of family units, social and moral decadence and threat of loss of a whole generation to the dangers of addiction was evident. A one of a kind, ninety Day mass Rehabilitation program was started in Murang'a as a county initiative. The program attracted approximately 1,500 addicts. Methods Tents were pitched in the stadium and make shift facilities provided to facilitate the process. A team of qualified counsellors were invited to offer voluntary services. Medical staff were deployed from the county hospitals under the supervision of a psychiatrist. The Clients would go through a process of intake and to determine their level of addiction, different tools were used and if there was need for hospitalisation this would be facilitated at the local hospital. A program of rehabilitation that involved the twelve steps and life skills psycho education was put together. Results The Rehabilitation centre currently holds eight hundred recovering addicts. The process of rehabilitation has reviewed well educated people who lost hope and immersed themselves into addiction and are now being structured to reenter into job markets and business as opportunities arise. Major issues of life threatening dangers have been addressed. A larger number of addicts from across the county, which has a documented 30,000 addicts, await to be admitted for rehabilitation. Conclusions The battle against alcohol and drug addiction in Murang'a and in Kenya is far from complete but massive resources are required. Rehabilitation will help heal the country, socially, economically and emotionally.


Background: Digital supply chain twins (DSCT) are gaining increased attention in academia and practice and their positive impact on logistics and supply chain management (LSCM) performance is often highlighted. Still, LSCM executives are hesitant regarding DSCT implementation. One reason is the difficulty of making a reasonable cost–benefit comparison, because the benefits of using a DSCT are rarely quantified. Moreover, there seems to be no method of quantifying these benefits as of today. Methods: This article builds upon an extensive simulation study of a constructed organic food supply chain (FSC), containing as many as 40 simulation experiments. In this simulation study, three volatility scenarios in the FSC were simulated and their effects on LSCM performance were measured. Subsequently, dynamic simulation experiments were run to emulate DSCT use. The benefits of using a DSCT were then quantified using a newly developed approach. Results: A conclusive method for quantifying the benefits of using a DSCT is presented and validated. Moreover, the performance evaluation of using a DSCT for the multi-echelon inventory management of an organic FSC is given. Conclusions: The study leads towards a method for quantifying the use of DSCTs that is of importance for research and practice alike. For managers, it additionally provides an exemplary application of said method in the context of organic FSCs.


Summary.  Background: After a first unprovoked venous thromboembolism (VTE), many patients have residual pulmonary and/or lower limb vascular obstruction following completion of short‐term anticoagulation. Residual vascular obstruction may complicate the diagnosis of recurrent VTE. Whether baseline imaging, conducted after completion of anticoagulation, helps in interpreting diagnostic testing in patients who subsequently have suspected recurrent VTE is unknown. Study design: The REVERSE study is a cohort study whose primary aim was to derive a clinical decision rule to guide the duration of anticoagulation after a first unprovoked VTE. All patients underwent baseline imaging after completing 5–7 months of anticoagulant therapy. We performed a post hoc randomized controlled comparison among 121 patients investigated for a suspected recurrent VTE during follow‐up: the decision on recurrent VTE with or without baseline imaging was made available to two independent adjudicators. Results: The proportion of patients not classifiable for recurrent VTE was statistically significantly higher in the group with no baseline imaging than in the group with baseline imaging: one in five as compared with one in 25. The interobserver agreement between the two adjudicators was better in the group with baseline imaging than in the group with no baseline imaging: κ‐values were 0.78 and 0.54, respectively. Conclusions: In patients with a first unprovoked VTE, baseline imaging at completion of anticoagulant therapy helps in interpreting diagnostic tests performed in cases of suspected recurrent VTE.


A novel free-standing air electrode with various structural and electrochemical merits was designed for a highly reversible lithium–oxygen battery. Interconnected NiCo2O4 nanosheets were grown almost perpendicular to the surface of carbon foam acting as a gas diffusion layer via a hydrothermal method combined with low temperature calcination and then decorated with palladium (Pd). Basically, this novel class of heterostructured catalysts consists of hierarchical nanosheets that can provide enough catalytic surface and open space, which is advantageous for oxygen or lithium ion transfer. In addition, the intrinsic porous structure of carbon foam better facilitates barrier-free oxygen transport and electrolyte penetration, while the introduction of Pd can modify the electronic structure of NiCo2O4, thereby enhancing electron transport all over the electrode. Because Pd incorporation also evolves the surface oxygen vacancies, which helps the discharge product (Li2O2) grow into a flower-like form, its formation or decomposition in the free-standing Pd@NiCo2O4 electrode could be rendered extremely reversible, finally realizing low charge over-potential, high discharge capacity (the maximum capacity reaches about 4000 mA h g−1) and long cycle life (extremely stable cyclic retention almost up to 100 cycles under the capacity limitation of 1000 mA h g−1).


Prototype-based meta-learning has emerged as a powerful technique for addressing few-shot learning challenges. However, estimating a deterministic prototype using a simple average function from a limited number of examples remains a fragile process. To overcome this limitation, we introduce ProtoDiff, a novel framework that leverages a task-guided diffusion model during the meta-training phase to gradually generate prototypes, thereby providing efficient class representations. Specifically, a set of prototypes is optimized to achieve per-task prototype overfitting, enabling accurately obtaining the overfitted prototypes for individual tasks. Furthermore, we introduce a task-guided diffusion process within the prototype space, enabling the meta-learning of a generative process that transitions from a vanilla prototype to an overfitted prototype. ProtoDiff gradually generates task-specific prototypes from random noise during the meta-test stage, conditioned on the limited samples available for the new task. Furthermore, to expedite training and enhance ProtoDiff's performance, we propose the utilization of residual prototype learning, which leverages the sparsity of the residual prototype. We conduct thorough ablation studies to demonstrate its ability to accurately capture the underlying prototype distribution and enhance generalization. The new state-of-the-art performance on within-domain, cross-domain, and few-task few-shot classification further substantiates the benefit of ProtoDiff.


In the so-called new neoclassical synthesis, expected future output and
inflation enter the model equations for demand and supply, since house-
holds and firms take into account forecasts of endogenous variables in their
consumption and pricing decisions. However, the linear model equations
of the new neoclassical synthesis reflect the behavior of risk-neutral eco-
nomic subjects and firms, since market participants are indifferent to devi-
ations of actual values of endogenous variables from previously predicted
levels, which is in contrast to the risk-aversion reflected in the utility func-
tions used in the underlying microfoundation. In this paper, we show
that risk-averse economic subjects and firms form rational expectations
not only regarding the expected values but also regarding uncertainty in
future variables, impacting the model equations for demand and supply
and the conduct of monetary policy (JEL D81, E10, E52).


Abstract: Chronic wasting disease (CWD) is an infectious and fatal prion disease occurring in the family Cervidae. To update the research community regarding the status quo of CWD epidemic models, we conducted a meta-analysis on CWD research. We collected data from peer-reviewed articles published since 1980, when CWD was first diagnosed, until December 2018. We explored the analytical methods used historically to understand CWD. We used 14 standardized variables to assess overall analytical approaches of CWD research communities, data used, and the modeling methods used. We found that CWD modeling initiated in the early 2000s and has increased since then. Connectivity of the research community was heavily reliant on a cluster of CWD researchers. Studies focused primarily on regression and compartment-based models, population-level approaches, and host species of game management concern. Similarly, CWD research focused on single populations, species, and locations, neglecting modeling using community ecology and biogeographic approaches. Chronic wasting disease detection relied on classic diagnostic methods with limited sensitivity for most stages of infection. Overall, we found that past modeling efforts generated a solid baseline for understanding CWD in wildlife and increased our knowledge on infectious prion ecology. Future analytical efforts should consider more sensitive diagnostic methods to quantify uncertainty and broader scale studies to elucidate CWD transmission beyond population-level approaches. Considering that infectious prions may not follow biological rules of well-known wildlife pathogens (i.e., viruses, bacteria, fungi), assumptions used when modeling other infectious disease may not apply for CWD. Chronic wasting disease is a new challenge in wildlife epidemiology.


Mechanisms of development of cardiogenic vagosympathetic depressor reflexes during adrenergic heart stimulation and local immune and ischemic damages of the left ventricle were studied in anesthetized dogs and cats by recording afferent and efferent impulsation from cardiac nerves as well as cardiodynamic indices. Impulse activity in cardiac nerves showed reciprocal changes: an increase in frequency of afferent impulsation in vagal nerves and inhibition of efferent impulsation in sympathetic nerves. The data obtained suggest that stimulation of heart mechanoreceptors due to the increase of myocardial contractility and asynergy of the left ventricle, is a triggering mechanism for reflex inhibition of sympathetic impulsation and depressor reflex.


Patient Experience of the Trauma System (PETS) Trauma care is highly organised, time critical medicine. Changes to patient management in trauma care are often the result of Random Control Trials, and expert opinion following rigorous evaluation of the evidence. Highly efficient, injury focused care is required to achieve the best outcomes for patients. One area that has not been researched so thoroughly however, is the patient experience of trauma care. As evidence already suggests that patients with high stress levels have poorer outcomes, we wanted to investigate the patient perception of the trauma system. We were particularly interested to find out if there were any areas where patient anxieties could be reduced or eliminated. Methodology A ten-person qualitative study was initially conducted to test for feasibility and reproducibility. The methodology involved semi-structured interviews investigating outcome measures such as the patient's perception of being looked after, biggest concerns and understanding of care, among others. Interviews were undertaken by a medical student and a Foundation Year 2 doctor (at the end of the Emergency Medicine block, post sign-off) trained in the methodology. The initial study was carried out over one month in early 2017 and involved adult patients (>18 years) admitted via the trauma care pathway who were Glasgow Coma Score 15/15. Interviews took place within 48 hours of admission in the Emergency Department (prior to transfer), the observation ward or the extended care trauma unit. Barriers to patient interviews included: severity of injuries; patient refusal; language proficiency and patient recollection (some had no recollection of being in resus). Despite this we managed an initial sample of 10 patients, with rich data. Following on from the pilot study we have made some amendments to our questions and have conducted a further set of 20 interviews. Conclusions A significant proportion of patients have concerns during trauma care that they feel unable to voice. This has the potential to increase their stress levels and have an adverse impact on their recovery. The concerns are varied and not always predictable, often unrelated to the injury. Thus we feel there may be patient benefit from the use of a single open question towards the end of the primary survey. We suggest AMPLE-AE for 'is there Anything Else you would like to tell me or ask about?'


Abstract. This paper presents a comprehensive review and analysis of the available literature and information on droughts to build a continental, regional and country level perspective on geospatial and temporal variation of droughts in Africa. The study is based on the review and analysis of droughts occurred during 1900–2013, as well as evidence available from past centuries based on studies on the lake sediment analysis, tree-ring chronologies and written and oral histories and future predictions from the global climate change models. Most of the studies based on instrumental records indicate that droughts have become more frequent, intense and widespread during the last 50 years. The extreme droughts of 1972–1973, 1983–1984 and 1991–1992 were continental in nature and stand unique in the available records. Additionally, many severe and prolonged droughts were recorded in the recent past such as the 1999–2002 drought in northwest Africa, 1970s and 1980s droughts in western Africa (Sahel), 2010–2011 drought in eastern Africa (Horn of Africa) and 2001–2003 drought in southern and southeastern Africa, to name a few. The available (though limited) evidence before the 20th century confirms the occurrence of several extreme and multi-year droughts during each century, with the most prolonged and intense droughts that occurred in Sahel and equatorial eastern Africa. The complex and highly variant nature of many physical mechanisms such as El Nino–Southern Oscillation (ENSO), sea surface temperature (SST) and land–atmosphere feedback adds to the daunting challenge of drought monitoring and forecasting. The future predictions of droughts based on global climate models indicate increased droughts and aridity at the continental scale but large differences exist due to model limitations and complexity of the processes especially for Sahel and northern Africa. However, the available evidence from the past clearly shows that the African continent is likely to face extreme and widespread droughts in future. This evident challenge is likely to aggravate due to slow progress in drought risk management, increased population and demand for water and degradation of land and environment. Thus, there is a clear need for increased and integrated efforts in drought mitigation to reduce the negative impacts of droughts anticipated in the future.


The objective of this work was to evaluate whether insulin, like norepinephrine (NE), exerts direct growth effects in brown adipocytes, as assessed by changes in rates of protein labeling with [35S]methionine. Mouse brown adipocytes isolated by tissue collagenase digestion were incubated for up to 24 h with or without NE in Dulbecco's modified Eagle's medium with albumin, calf serum, and antibiotics. There was a 40% cell loss and a 50% decrease in cell content of succinate dehydrogenase (SDH) activity over 24 h. Both cell recovery and SDH content significantly improved in the presence of NE. In addition, NE increased [35S]methionine incorporation into proteins in both cytosolic and mitochondrial compartments. These effects of NE were inhibited by propranolol. Both insulin and insulin-like growth factor-1 (IGF-1) receptors were detected in brown adipocytes, with insulin receptors in much greater concentration. Increased protein labeling was observed when brown adipocytes were incubated for 4 h with 0.2-5 nM insulin in the absence of serum. This effect was small (30% stimulation) compared with the 200-350% increase observed with NE, and 5 nM IGF-1 had no effect. These results indicate direct trophic actions of both NE and insulin in mouse brown adipocytes, with the effects of NE an order of magnitude greater than those of insulin.


In this amazingly prophetic work, done late in his career, Herbert Spencer offers an approach to ethics that anticipates developments throughout the twentieth century. He moves away from the twin evils of ethical doctrines bequeathed to us by an ancient past that are simply no longer feasible but also avoids modern standards of ethical conduct that are simply impossible to attain. "By association with rules that cannot be obeyed," Spencer writes, "rules that can be obeyed lose their authority." The volume opens with three chapters on conduct: its evolution, good and bad, and ways of judgment. This is followed by a series of chapters that examine ethics from a variety of scientific perspectives: physics, biology, psychology, and sociology. The work then moves on to specific issues of deep human concern: the relativity of pleasures and pain, egoism versus altruism in explaining actions, and trial and compromise in decision-making about ethical concerns. Spencer's work anticipates the movement toward pragmatic, naturalistic, and even positivist approaches to ethics. He emphasizes that a relativist approach while in keeping with the spirit of the industrial age, also poses a variety of problems that admit only of empirical solutions. He understands that his critical stance on absolutism should not blind researchers to the ideals assumed by the ancients that assist people in their everyday living. In short, this is a remarkable work, entirely modern, and yet containing a sharp evaluation of how ethical data serve to enhance ethical conduct.


ABSTRACT Glycosylphosphatidylinositols (GPIs), the anchor molecules of some membrane proteins of Plasmodium species, have been implicated in the induction of immunopathology during malaria infections. Hence, neutralization of GPIs by antibodies may reduce the severity of clinical attacks of malaria. To test this hypothesis, we have assessed the levels of anti-GPI antibodies in plasma from children and adults living in areas of seasonal malaria transmission in The Gambia. In a prospective study of susceptibility to clinical or asymptomatic infection, the levels of anti-GPI antibodies were measured before and after the transmission season. Samples were also obtained from children recruited into a hospital-based study of severe malaria. We find that in malaria-exposed individuals both the prevalence and the concentration of anti-GPI antibodies increase with age and that antibody levels are significantly higher at the end of the malaria transmission season than at the start of the season. Antibody levels are also higher in children with asymptomatic infections (i.e., those with a degree of clinical immunity) than in children who developed clinical malaria and high parasitemia, although this difference is not statistically significant. Importantly, antibodies appear to be rapidly boosted by clinical malaria infection, but children under the age of two years are seronegative for anti-GPI antibodies, even during an acute infection. While GPIs may be involved in the pathogenesis of human malaria, the data from this study do not provide any strong evidence to support the notion that anti-GPI antibodies confer resistance to mild or severe malarial disease. Further case-control studies, ideally of a prospective nature, are required to elucidate the role of antiglycolipid antibodies in protection from severe malaria.