Understanding collective behavior of moving organisms and how interactions between individuals govern their collective motion has triggered a growing number of studies. Similarities have been observed between the scale-free behavioral aspects of various systems . Investigation of such connections between the collective motion of non-human organisms and that of humans however, has been relatively scarce. The problem demands for particular attention in the context of emergency escape motion for which innovative experimentation with panicking ants has been recently employed as a relatively inexpensive and non-invasive approach. However, little empirical evidence has been provided as to the relevance and reliability of this approach as a model of human behaviour.This study explores pioneer experiments of emergency escape to tackle this question and to connect two forms of experimental observations that investigate the collective movement at macroscopic level. A large number of experiments with human and panicking ants are conducted representing the escape behavior of these systems in crowded spaces. The experiments share similar architectural structures in which two streams of crowd flow merge with one another. Measures such as discharge flow rates and the probability distribution of passage headways are extracted and compared between the two systems.Our findings displayed an unexpected degree of similarity between the collective patterns emerged from both observation types, particularly based on aggregate measures. Experiments with ants and humans commonly indicated how significantly the efficiency of motion and the rate of discharge depend on the architectural design of the movement environment.Our findings contribute to the accumulation of evidence needed to identify the boarders of applicability of experimentation with crowds of non-human entities as models of human collective motion as well as the level of measurements (i.e. macroscopic or microscopic) and the type of contexts at which reliable inferences can be drawn. This particularly has implications in the context of experimenting evacuation behaviour for which recruiting human subjects may face ethical restrictions. The findings, at minimum, offer promise as to the potential benefit of piloting such experiments with non-human crowds, thereby forming better-informed hypotheses. Understanding collective behavior of complex systems such as the flocking behavior of fish and birds and ant Growing interest towards an understanding of the collective behavior of non-human organisms as well as increasing number of studies that have been carried out to examine patterns of scale-free behaviour of pedestrian crowds under emergency conditions and under the impact of different architectures using biological entities inspired this study. In other words, in recent years, exploring the collective behavior of biological entities during extreme escape has received an increasing attention as an approach of gathering experimental evidence for exploring crowd dynamics under emergency conditions. This approach has been proved most useful for gaining basic insights as to aggregate measures of collective movements. Despite the fact that utilizing this innovative approach has received acceptability in the literature, the reliability of results obtained from this type of experiments remains to be discussed as to whether or not the findings emerged from these experiments, panicking non-human entities, would translate to human behavior in real context.Moreover, modeling pedestrian crowd movement has received a growing recognition in the recent years due to an increase in crowd-related incidents around the world. In the spirit of guaranteeing the safety of pedestrians, an accurate understanding of pedestrian crowd behavior and the rules that govern their motion is of critical importance. As suggested by , the arcOne of the methods of data provisioning that has been employed recently is experimenting with non-human entities particularly under extreme conditions of escape suggesting the practicality of this approach for gaining basic insights towards the collective patterns and characteristics of pedestrian flows under emergency conditions. Despite the great effort made to design and perform animal crowd experiments and despite the great deal of evidence that has emerged as a result, the literature does not offer sufficient evidence as to the extent of relevance of this experimental method. The method is completely non-invasive to humans  and is also often much less expensive compared to its equivalent human-experiment method. However, the literature lacks adequate evidence and systematic studies as to how reliably animal crowd models of behaviour can be used as a proxy for their human peers.As Haghani and Sarvi  recentlyUp to now, mice and ants have been the most common organisms of experimentations. One of the early studies in this field  investigA large number of studies using animal models of escape have explored the effect of architectural designs of the escape environment and their impact on evacuation efficiency. A group of studies of ant experiments –26 invesIn order to understand the impact of conflicting geometries on the emergency response of pedestrian facilities, a number of studies , 30 inveAnother stream of studies has extensively practiced biological entities particularly panicked ants to gain insight towards complex phenomena such as ‘faster is slower’ effect which refers to a situation where elevated desire for escape may actually impede escape efficiency. There are studies that have addressed this particular topic with the use of animal experiments. In a study using ants panicked (repelled) by citronella escaping from triangular chambers with one narrow exit, Soria, Josens  observedSobhani, Sarvi  examinedBased on this overview of the existing literature, there is limited knowledge regarding the consistency between conclusions drawn based on the experiments with non-human entities and what pedestrian crowds actually behave under emergency conditions. There is also limited evidence in the extent to which these conclusions can be generalized to the actual emergency conditions. Additionally, understanding the effect of geometrical features and design of merging streams on the motion patterns of human and non-human entities can be explored using experimental setups. As revealed through a comprehensive literature review, most of the previous studies in pedestrian crowd domain and biological domain have focused on investigating collective movements within simple environments and under normal condition (lower level of rush). However, there are limited studies which conducted to understand the effect of various architectural settings on the collective behavior.In this study, we adopted two main approaches for gathering empirical evidence for examining the aforementioned issues in which humans and ants were the subjects of experiments. We investigate the emergency escape behaviour of pedestrians and ants evacuating crowded confined spaces. We quantitatively contrast the scale free behaviour of non-human entities along with collective movements of humans and estimated the distribution of output rate versus time, the probability distribution of time intervals between the passage of two successive entities and velocity distribution versus time and distance. The impact of different designs of merging configurations on the emergency response rate of escape areas is also investigated.Linepithema humile), as abundantly available species in Melbourne. Further, according to Monash University Animal Ethics Office, animal ethics clearance is exempted for this particular species of ants (Monash University 2015). In these experiments desire to flee and speed are taken to extremes in order to observe how the patterns of movements of these organisms are influenced by the layouts of escape area and presence of conflicting maneuvers. In these experiments, the colonies of Argentina ants were collected from the various sites at the Clayton Campus of Monash University and prepared for experiments following the procedures describes in [Experimentation with non-human subjects allow a wide range of phenomenon to be explored that are otherwise hard to be replicated in experiments with human without concern about participants’ safety. In this study, we performed a wide range of experiments with Argentine ants . In addition, analysis of human experiments reveals that complementary cumulative distribution function (CCDF) of pedestrian’s headway display slowly decaying tail for the asymmetrical merging setups and the corresponding power-law exponent is significantly lower for the asymmetrical merging settings. This suggests that the presence of asymmetrical merging configurations in escape area might increase the possibility of longer headways and blockage in both systems. According to the figure, in the system of panicking ants as well the curves corresponding to the symmetrical layouts are more skewed to the left indicating a shorter headway and less delay which is in consistence with the empirical evidence provided by our experiments with humans.One can note the similarity between the patterns indicated by the left panel of It is also noticeable (more distinctly based on plot 5(c) (ant experiment) and less distinctly based on plot 5(a) (human experiment) that the passage headway in downstream of the merging setup has greater variability in asymmetric setups than in symmetric setups as reflected in the length of the bow-and-whisker plots representing them. This could be a further indirect indication of more frequent traffic instability, flow interruption or transient clogging in such setups making quite large values of time intervals between successive pedestrians to be observable.To investigate the impact of merging configurations in escape areas on the collective movement of evacuees in terms of distribution of speed, average escape velocities along the corridors of the experimental layouts were estimated. We used a particle image velocimetry tool PIVLAB  for the The speed analysis reveals the formation of “stop and go” phenomenon in the flow of the merging branches which causes the flow in one of the merging streams stop or experience a very low speed compared to the other stream. This crowd turbulence phenomenon has been reported by . As can Temporal fluctuations of the velocities in two single branches for human experiments under similar merging configurations are illustrated in Using the trajectories information we also measured the density and average velocity of the subjects at each point in time and space through discretisation of the evacuation space as well as the evacuation time. The calculated spatial averages of velocities and densities were also averaged over time for each scenario and visualised using colour coding methods in order to understand the considerable difference in velocity and density variations and fluctuations associated with the single branches in different merging layouts. Detailed analysis of velocity and density reveals that distribution of densities is not homogeneous and the density near the junctions is higher than other parts of the merging setups resulting in a abrupt reduction of velocity in those areas. In addition average density in the area that two single branches start to join each other in asymmetrical merging configurations is severely high leading to considerably low velocity in this type of merging setups.Whether there is any element of truth to be learnt from such experiments and the type of questions that can be addressed using animal crowd movement experiments as models of their human counterparts have been largely unknown requires replication of crowd motion experiments in both contexts. Systematic links between the contexts of the collective movement of humans and non-humans has so far been scarce in the literature. Given the non-invasiveness and relative logistical easiness of experiments with non-human entities as opposed to staging similar experiments with large groups of people, the answer to this question could have significant implications for the continuation of research in the field of crowd dynamics. Here in this work, we reported on linking between collective motion of humans and ants in experimental conditions as an attempt to bridge this gap.Based on previous studies, some degree of similarity between the collective motions of different biological systems has been observed. However, it is highly unknown that whether or not inferences drawn based on experiments with non-human organisms are consistent with the actual behavior of pedestrian crowds in near field laboratory experiments or to what extent they are deviated from the real human behaviour. In other words, the extent to which and the circumstances and contexts under which findings generated from experimentation with non-human organisms can be relied upon as the proxy of the actual behaviour of pedestrian crowds in natural settings remains to be investigated.In this study, a large number of experiments are conducted with panicking ants and humans providing the possibility of observation and quantitative analysis of the collective movements. A comprehensive data analysis was conducted by examining the motion trajectory of the participants which provides some measures of their scale-free behaviour. This led to findings both in terms of crowd behavior during evacuation from conflicting geometries as well as findings related to degree of resemblance between the collective pattern of movements emerged from both data sets. In other words, the laboratory experiments with human also shed interesting insights into the dynamics of human crowds during escape from environments that impose conflicting maneuvers (i.e. merging corridors).The results inferred from the collective movements of humans under emergency condition (participants were asked to run and evacuate the setting as quick as possible) were in some way the same as those obtained from the experiments with non-human entities. This suggests that extreme emergency conditions might lead to the emergence of scale-free behavior. With regard to the resemblance between the collective movements of humans and ants, our results confirm that the patterns associated with the velocity variations and the fluctuations derived from both set of observations shares a remarkable degree of similarity in terms of the creation of stop-and-go phenomenon and severe imbalance between the distribution of velocities of the two merging branches over space and time. In addition the analysis of the escape rate in both systems suggest that despite the considerable dependency between the average escape rate and its distribution over time and merging angle, the relation between them does not prove to be monotonic.However, there are certain limitations that need to be taken into consideration in terms of drawing possible generalisation to all escape concepts since this single work cannot be regarded as adequate proof for the reliability of ant  crowd experiments, although it offered promising evidence to their possible relevance at least at the level of collective motion and based on aggregate measures. Much further evidence, however, is required for a better understanding of the possible similarities between the dynamics of humans and non-human crowd traffic. We believe data collected from experimentation with two organisms as complements suggesting more of experiments with human is required to make solid conclusions as to the limits of generalizability and applicability of experiments with non-human entities.S1 Video(WMV)Click here for additional data file.S2 Video(WMV)Click here for additional data file.S3 Video(AVI)Click here for additional data file.S4 Video(AVI)Click here for additional data file.S5 Video(AVI)Click here for additional data file.S6 Video(AVI)Click here for additional data file.S7 Video(AVI)Click here for additional data file.S8 Video(AVI)Click here for additional data file.S9 Video(AVI)Click here for additional data file.S10 Video(AVI)Click here for additional data file.S11 Video(AVI)Click here for additional data file.S12 Video(AVI)Click here for additional data file.S1 File(7Z)Click here for additional data file.


Transient osteoporosis of the hip (TOH) is a benign, selflimiting condition characterised by acute onset groin pain in adults. Early diagnosis is important to differentiate it from progressive conditions such as osteonecrosis. We report on a middle-aged male who presented with right groin pain without any prior trauma. The diagnosis of transient osteoporosis of hip was confirmed by Magnetic Resonance Imaging (MRI) and he was successfully treated with a course of Alendronate sodium, anti-inflammatory analgesics and a period of non-weight bearing ambulation. Transient osteoporosis of the hip (TOH) is an idiopathic, selflimiting condition observed mostly in men in the fourth or fifth decade of life and women in the third trimester of pregnancy or the immediate postpartum periodA 43 years old Asian gentleman presented with acute onset of right thigh pain, over the anterolateral aspect of two weeks duration. There were no significant findings on clinical examination and he was referred for physiotherapy.On review one month later, the pain was persistent and now localized to the groin with local tenderness and terminal restriction of movements. Blood tests including inflammatory markers, serum uric acid and serum rheumatoid factor were negative. An MRI scan of the pelvis was requested to obtain further detail and it confirmed typical changes of transient osteoporosis of the right hip . The patAt follow up seven weeks later, the patient had complete relief of pain with full painless range of movements. At further review five months after diagnosis and treatment the patient was mobilizing with full weight bearing. He had a full and painless range of movements at the right hip. Repeat MRI scan confirmed complete resolution of changes . With thAt review seven months after diagnosis, the patient was pain free with full range of movement at the affected hip and had resumed normal activities. He was discharged from outpatient follow up care.Transient osteoporosis is a rare clinical syndrome that was first described by Curtiss and Kincaid in 1959. TOH typically involves the middle-aged population and is more frequent in men than women. In women, it is more common during the third trimester of pregnancy. It is idiopathic with no history of traumaThis uncommon condition has been reported in the literature only in the form of case reports and small case seriesEarly differentiation of TOH and osteonecrosis is crucial as the natural history, treatment and outcome of the two conditions are different. TOH is known to have complete clinical and radiological recovery while untreated osteonecrosis of the femoral head leads to progressive damage and arthritis of the hipIn conclusion, a high level of suspicion is needed for early diagnosis of TOH. Typical MRI findings are diagnostic and unnecessary invasive investigation and intervention can be avoided. The treatment of this self-limiting condition is symptomatic and bisphosphonates including alendronate sodium are useful in its management.


Anhanguera-like pterosaurs from the contemporaneous Toolebuc Formation of central Queensland and the global distribution attained by ornithocheiroids during the Early Cretaceous. The morphology of the teeth and their presence in the estuarine- and lacustrine-influenced Griman Creek Formation is likely indicative of similar life habits of the tooth bearer to other members of Anhangueria.The fossil record of Australian pterosaurs is sparse, consisting of only a small number of isolated and fragmentary remains from the Cretaceous of Queensland, Western Australia and Victoria. Here, we describe two isolated pterosaur teeth from the Lower Cretaceous (middle Albian) Griman Creek Formation at Lightning Ridge  and identify them as indeterminate members of the pterodactyloid clade Anhangueria. This represents the first formal description of pterosaur material from New South Wales. The presence of one or more anhanguerian pterosaurs at Lightning Ridge correlates with the presence of ‘ornithocheirid’ and  Pterosaurs first appeared in the Late Triassic and diversified rapidly into the Jurassic. At the peak of their diversity in the Cretaceous, pterosaurs where present on all continents, including Antarctica . During By contrast, the fossil record of pterosaurs in Australia is very sparse and composed solely of isolated and fragmentary remains from the Cretaceous of Queensland, Victoria and Western Australia . The taxMythunga camara  are preserved as isolated crowns, missing the roots and with eroded distal tips.LocalityLRF 759 was excavated in the 1970s from an underground mineral claim at ‘Holden’s Four Mile’ opal field, approximately 4 km south west of Lightning Ridge . LRF 314PreservationBoth LRF 759 and LRF 3142 are isolated tooth crowns with eroded apices; LRF 759 is also missing a portion of the distal part of the crown near the base. Both teeth are preserved as translucent potch, a form of non-precious opal; in LRF 759 the potch displays mauve play of opal colour, whereas LRF 3142 contains areas of dark grey within honey-coloured potch. In LRF 759, the translucency of the potch reveals a thin-walled basal cavity that has been infilled with a body of purple opal and buff-coloured mudstone ; the samDescriptionLRF 759  has an eUnlike LRF 3142, in LRF 759 the tooth crown is ornamented by longitudinal grooves extending essentially apicobasally along the surface . A serieLRF 3142  is a genElongate, conical teeth similar in morphology to those described above have been previously reported from Lightning Ridge, and include plesiosaurs , ichthyoCooyoo australis .in situ dentary and maxillary teeth of Mythunga camara ; and Aussiedraco molnari (QM F10613), both from the Lower Cretaceous of central Queensland. The jaw fragment WAM 68.5.11 , in the absence of articulated or associated skeletal material they typically are insufficient for identification of the tooth-bearer to a specific or generic level. In Australia, this problem is exacerbated by the scarcity of pterosaur remains to which the teeth described here can be compared. It is currently not possible to determine with certainty whether the Lightning Ridge teeth belong to one of the named or unnamed but potential Australian pterosaur taxa, or whether they constituted the dentition of a taxon that is yet to be discovered. Furthermore, given the subtle observed morphological differences between the two teeth  it is also uncertain whether the two teeth are derived from a single taxon or separate taxa. Further finds are needed in order to evaluate whether these differences are indicative of the presence of more than one pterosaur taxon, or whether taphonomic or other processes have affected the appearance of the tooth crowns.The identification of anhanguerian teeth from the Griman Creek Formation is consistent with the reports of anhanguerid-like and ‘ornithocheirid’ skeletal material from the Early Cretaceous of Queensland  and the Isolated teeth excavated from the Lower Cretaceous Griman Creek Formation at Lightning Ridge, New South Wales, are identified as pertaining to pterosaurs. The oval basal cross-section, slight distal recurvature, irregularly-striated enamel ornamentation, and slender crowns bear a striking similarity to those of anhanguerian pterosaurs. This represents the first description of pterosaurs from New South Wales and contributes to the growing diversity of vertebrates from the Griman Creek Formation. The isolated remains cannot be conclusively assigned to any known pterosaur taxon, although their presence is consistent with the known record of anhanguerid-like pterosaurs from the contemporaneous Toolebuc Formation of central Queensland. The simultaneous presence in New South Wales and Queensland of anhanguerian pterosaur remains in sediments displaying characteristics of shallow-water lagoonal and lacustrine depositional environments indicates likely similarities in life habits of these pterosaurs. Further finds and descriptions of Australian pterosaurs are necessary to further characterise the diversity of this poorly understood group of reptiles both locally and in Australia as a whole.


The data presented in this article are related to the research article entitled “Options for the remediation of embankment dams using suitable types of alternative raw   Specifications TableValue of the data•The data presents the optimized technology of remediation embankment dams by suitable alternative raw materials and could be used by others researchers.•The rheological properties of grouts were measured by using Mash cone and were compared to others chemical grouts.•This data allows other researchers to extend the statistical analyses.1The dataset of this article provides information about the innovation remediation technology of embankment dams by use the suitable types of alternative raw materials. 22.1The experiments of use the optimal grout were carried out on several types of embankment dams in the Czech Republic. The experiments carried out even before the winter, due to the fact that the dam was ready for the upcoming winter season and especially for the spring floods caused by melting snow, regional or local rainfall. On designed grouts were monitored the effects of mixtures on leaks of the dams. GE clay together with two types of ash  and lime (L) were selected for the design of optimal grouts. When designing, the mixtures were combined with the selected types of additives and their quantities. Before the application of grouts in practice, the tests on grouts were performed in raw and hardened state. On designed grouts were measured the viscosity (in raw state), compressive strength and volumetric shrinkage (in hardened state). The viscosity was determined according to EN 12 715


Mice are arguably the dominant model organisms for studies investigating the effect of genetic traits on the pathways to mammalian skull and teeth development, thus being integral in exploring craniofacial and dental evolution. The aim of this study is to analyse the functional significance of masticatory loads on the mouse mandible and identify critical stress accumulations that could trigger phenotypic and/or growth alterations in mandible-related structures. To achieve this, a 3D model of mouse skulls was reconstructed based on Micro Computed Tomography measurements. Upon segmenting the main hard tissue components of the mandible such as incisors, molars and alveolar bone, boundary conditions were assigned on the basis of the masticatory muscle architecture. The model was subjected to four loading scenarios simulating different feeding ecologies according to the hard or soft type of food and chewing or gnawing biting movement. Chewing and gnawing resulted in varying loading patterns, with biting type exerting a dominant effect on the stress variations experienced by the mandible and loading intensity correlating linearly to the stress increase. The simulation provided refined insight on the mechanobiology of the mouse mandible, indicating that food consistency could influence micro evolutionary divergence patterns in mandible shape of rodents. The developmental pathways related to rodent skull morphogenesis have been extensively studied in the past years, identifying the effect of all traits related to their DNA sequence on the shape of the various skull bones, including mandible . Consequently, food consistency could result in evolutionary divergence patterns triggered through altered mandibular growth. However, the mandible of rodents is exposed to diurnal forces of high complexity and therefore the effects of mechanical loadings remain unclear due to limitations inherent to current experimental models. Computational methods may offer a good alternative to heuristic/experimental methodologies having the potential to answer important endured questions and confirm or not generalized assumptions on the mechanobiology of mandibles.In order to consolidate this hypothesis, we undertook an in situ mechanical response of biological systems  modeling has naturally evolved from traditional engineering disciplines to the study of living tissues, rapidly covering a broad spectrum of clinical applications  and FE modeling techniques were employed to determine whether different masticatory forces and movements are able to significantly alter the stress/strain equilibrium of the mouse mandible. The obtained results indicate that food consistency may be associated with micro evolutionary modifications in rodent mandible morphology that will overall impact on skull shape adaptations.A mouse skull (C57Bl/6-Sv129 genetic background) was scanned by μCT in order to reconstruct a 3D model required for the intended analysis. This technique is capable of producing 2D images of various structures, based on their ability to withstand the emitted X-radiation. As bone and all other hard tissues  have a unique spectrum of X-ray permeability, they shade in different tones of white/gray within a CT slice, thus allowing their relatively unhindered segmentation with some minor overlapping of hard tissue types. This resulted in a 2D outline of the various model entities within every scan, while the 3D geometrical data set was generated by overlaying consecutive slices. Data acquisition was in accordance to DICOM .*.stl files (triangle surface models) of the bone contour through software programs. There exists, however, a consensus throughout literature that highly accurate models  require semi-automated segmentation, supported by manual correction of the threshold results by experienced operators. A multi threshold segmentation technique was employed for the purpose of this study and the mean gray-scale within the image was calculated by employing sensitive edge detection filters, to distinguish the apparent tissue types , and chewing (molar biting) and both of them examined for two load intensities, corresponding to a food type each . Gnawing was simulated with a purely vertical load applied at the tip of the incisors whereas chewing considered a loading direction inclined by 30° to the dorsal-ventral axis of the molars. The fracture strength of these pellet fragments was determined experimentally, based on uniaxial compression tests, and applied as the masticatory load during the two biting scenarios.As the size of the food pellets was disproportionally large to the mouse skull dimensions, the gnawing/chewing load was established on the basis of fragmented pellet bites fitting the animal's mandible size. The fragments, considered during the compression tests, were in these terms similar in size to the rodent's oral cavity e.g., slightly wider than both incisal edges, while height and depth were restricted to the inter-incisor distance. These loads were equally distributed over the molars and incisors (both sides) as literature advocates bilateral biting to be more realistic than unilateral , while not contributing at all to the anteroposterior stabilization of the mandible. Its fibers insert on the medial fossa and the dorsal surface of the angular process and its attachment surface was simulated by a set of 2016 element nodes.➢ The internal pterygoid  was considered to bare 23% of the superoinferior load (Fz) and 30% of the anterior-posterior stabilization force (Fx). It was simulated as being attached on a set of 953 nodes in the area of the masseteric fossa and the masseteric crest ventral to the first and second molars.➢ The medial masseter pars zygomaticomandibularis is a major contributor to proximal movements of the mandible and was thus loaded with 24% of the mandible closing force (Fz) and 30% of the ventral-dorsal load (Fx).➢ The medial masseter pars zygomaticomandibularis was inserted on the ventral margin of the angular process of the mandible . It was considered as the strongest among all masticatory muscles contributing 36% of the vertical (Fz) providing however 40% of the anterior-posterior stabilization (Fx).➢ The posterior fibers of the temporal muscle, only involved in mandible retraction, were not considered during the biting scenarios. The posterior part of the temporal muscle attaches on the anterior border of the ramus of the mandible initiating from the short coronoid process up to the last molar covering a total of 782 element nodes. Due to its small proportions, the temporal muscle was considered to bare only 5% of the mandible closing force . The material properties applied to each tissue type are summarized in Table The final STL model of the mouse skull, reverse engineered through μCT is shown in Figure The forces resulting for each one of the scenarios are summarized in Table The temporomandibular joint was simulated by articulating the mandible surface contacting the temporomandibular disc at its mediolateral axis Figure . An overThe different loading scenarios resulted in significant variations of the stress and strain patterns developing on the mouse teeth and mandible. Biting types  had a dominant effect on the stress fields experienced by the mandible, with loading intensity resulting in an almost linear stress increase.The analysis indicated that the masseter ridge was one of the most stressed areas of the mandible, with incisal biting (gnawing) also resulting in stress augmentations of the mental foramen of the mandible as well as on the temporomandibular joint Figure . This caLoading patterns occurring during chewing were more pronounced in molars when compared to incisors, where the stress was observed at their posterior part Figure . ChewingIt is notable that the mastication forces during chewing were considerably cushioned by the periodontal ligament, thus preventing overloading of the alveolar bone and isolating the masseter ridge from abrupt loading. Although the results indicated a linear correlation of this effect to the applied load, this cushioning is in reality expected to fade along with an increasing masticatory force. This limitation is attributed to the linear-elastic nature of the introduced model, as there is no literature available concerning the nonlinear-viscoelastic material properties of the periodontal ligament. Different stress fields within the periodontal ligament were experienced during the various biting scenarios Figure . It seemDespite the use of dentition and skull morphology to classify both living and extinct species (Machado-Allison and Garcia, in-situ occurring stress fields in the periodontal ligament is vital in assessing its cellular response, as the values provided in Figure in-vitro, to experimentally assess the mechanobiology of the cells endemic to this tissue.This is the first attempt to associate the occurring masticatory forces to evolutionary aspects of rodent mandibles. The masticatory loads, adopted from the pellet compression tests, exhibited significant variations in magnitude and direction (see Table Rodents exhibit two mutually exclusive biting modes (Cox et al., Recent studies observed phenotypic differentiations in laboratory bread mice and associated them to food consistency and muscle driven remodeling (Renaud et al., It remains however unclear whether the trigger for this plastic response is due to environmental influences or genetic effects, as it stands to reason that the recorded stress variations will also affect cell proliferation or differentiation events thus influencing additional bone or other tissue formation based on biting type and intensity (Haudenschild et al., The results shown in this study attest that gnawing can double the stress intensity experienced by areas of the mouse mandible when compared to chewing, while also increasing the strain of both, bony and dental tissue. A response that is in agreement with recent literature findings, which indicated that gnawing induced the highest mean stress across the skull (Cox et al., in vitro (Orr et al., in vivo (Delaine-Smith and Reilly, Since every form of life, from cells to organisms is mechanosensitive, mechanical stimulus is widely accepted to regulate the growth and development of any tissue type under physiological conditions (Farng et al., in-vitro experiments, to determine the in-situ response of cells to masticatory forces. Cells extracted from the periodontal ligament will, in these terms, be subjected to the calculated stress values (presented in Figure Future work includes the use of the presented Finite Element model, in combination with AT and TM: Contributed to the conception of the hypothesis of the study, collaborated in the development of the model and was involved in the evaluation of the results and preparation of the manuscript. He also provided approval for the publication of this version. LJ: Contributed to the development of the model and the interpretation of data for the work. She was also involved in the preparation of the manuscript and provided approval for the publication of this version. EK: Contributed to the development of the model, the acquisition and the analysis of data for the work. He was also involved in the preparation of the manuscript and provided approval for the publication of this version. NM: Contributed to the development of the model, the analysis and the interpretation of data for the work. He was also involved in the preparation of the manuscript and sanctioned the publication of this version.EK was employed by company BETA CAE Systems S.A. The other authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling Editor declared a past co-authorship with two of the authors TM and LJ, and states that the process nevertheless met the standards of a fair and objective review.


High prevalence of hypertension is observed in diabetic patients of both the types. Diabetic nephropathy is one of the major reason for high morbidity, mortality and financial burden in such hypertensive diabetic patients. For this review, electronic databases including PubMed/Medline, Embase, Cochrane and Google scholar were searched from 1990-2013. Multiple inter-related factors are responsible for the development of hypertension and therefore nephropathy in the chronic diabetic patients. Majority of such factors are identified to lead to extensive sodium reabsorption and peripheral vasoconstriction and thus leading to microvascular complications like nephropathy. Management of hypertension by targeting such mediators is the highly recommended therapy for controlling and treating diabetic nephropathy. Clinical trials suggests that drugs inhibiting the renin-angiotensin-aldosterone pathway should be used as the first-line agents for the management of hypertensive diabetic nephropathy patients. These agents are effective in slowing the progression of the end-stage kidney disease as well as lowering albuminuria. Researchers are also investigating the effectiveness of drug combination for better management of hypertension and diabetic nephropathy. The present article is a review of the evidences which explains the underlying pathological changes which leads to the development of nephropathy in a hypertensive diabetic patients. The review also observes the clinical trials for different anti-hypertensive drugs which are recommended for the treatment of such patients. High prevalence of hypertension is observed in diabetic patients of both the types. Diabetic nephropathy is one of the major reason for high morbidity, mortality and financial burden in such hypertensive diabetic patients.Prevalence rates of diabetes has been observed to increase drastically in past two decades due to both the ageing population around the world as well as unhealthy lifestyles which is increasing obesity and overweight problems. For this review, electronic databases including PubMed/Medline, Embase, Cochrane and Google scholar were searched from 1990-2013. Diabetic patients are always on a high risk of developing diabetes related complications like hypertension, neuropathy, nephropathy, retinopathy, stroke and others. Observations over-the-years suggest that one-third of the diabetic patient develops diabetic nephropathy which on long turn leads to chronic renal problems. Diabetic nephropathy is a one of the commonest problems responsible for diabetes related morbidity, mortality, and financial burdens. It is therefore essential to isolate the menace issues associated with the advancement of diabetic nephropathy. It is also highly advisable to have better knowledge of early treatment procedures so that extensive morbidity and mortality can be avoided  (.4% (4). For the type 2 diabetes mellitus patients, hypertension usually co-exist before the onset of kidney diseases. This can be explained by the fact that obesity and overweight problem is a common risk factor which is responsible for both the glucose intolerance as well as hypertension. Different studies suggest that prevalence of hypertension in the diabetic mellitus type 2 patients who are yet not having proteinuria is 58-70%. The research also clarifies that chronic diabetes is less associated with the development of hypertension than the impaired renal function. In fact, hypertension further exaggerate and worsen the dysfunction of kidneys and therefore directly contributes to exaggeration of the cardiovascular conditions .The overall findings of the entire research suggest that microalbuminuria always precedes the hypertensive stage in both the types of diabetes patients and then the worsened renal functions contributes in degradation of the cardiovascular functions and the vicious cycle continues. The severity of high tension in diabetic nephropathy patient rises with every phase of the chronic kidney disease which in turn worsen the kidney functions and ultimately 90% of the patients are approached to final-phase renal ailment. An individual’s susceptibility to the development of both the high tension and renal ailment is caused due to various metabolic and hemodynamic changes which are shared by most diabetic patients. Genetic determinant are important decisive factors to dictate patient’s vulnerability. While certain inherited genes may make the person prone to the disease while some are renoprotective. Although this is yet unclear if these genetic factor defines the incidences of nephropathy diabetes or only make the person more vulnerable to the renal diseases in general context along with the other risk factors .The international statistics for the prevalence of diabetic nephropathy reveals striking epidemiological variations even within the European nations. The proportion of the diabetic nephropathy sufferers requiring renal replacement treatment is more in Germany than the Unites States of America. Reports suggest that in the year 1995, 59% of the patients admitted in Southwest Germany hospitals for renal replacement were having any form of diabetes while 90% of them were having type 2 diabetes mellitus. A high correlation between final phase renal ailment and type 2 blood sugar has also been observed for the countries like Denmark and Australia where the overall prevalence of diabetes is low compared to the other states. Equal prevalence rate of the disease has been found in both the male and female patients. Epidemiological data of the condition in context of patient’s age suggest that diabetic nephropathy is rarely observed during the initial 10 year of the type 1 diabetes mellitus duration. On the other hand, peak incidences of the condition i.e. 3% per year has been found in the patients with diabetes for more than 15-20 years. Patients who usually requires management for final phase renal ailment are of average 60 years. While the reports from around the world suggest higher incidence of diabetic nephropathy in hypertensive diabetes sufferers of geriatric age, still the part of age in the progression of the ailment in younger sufferers is not clear. The Pima Indians having type 2 diabetes mellitus that are susceptible to the development of diabetes at younger age are also equally prone to the advancement of final phase renal ailment. Till a 20 year age, about fifty percent of every diabetic Pima Indian has acquired blood sugar nephropathy, where 15 percentile of these persons have advanced to end-stage renal disease (ESRD). Race based epidemiology of diabetic nephropathy reveals that the severity as well as occurrence rates of the condition are higher in the blacks who are around 3-6 times more affected by the condition than the whites, Mexican Americans, and Pima Indians who are having non-insulin reliant diabetic mellitus. The high prevalence of blood sugar nephropathy in black not only suggest the underlying genetic factors but also points out the effect of poor socioeconomic conditions which is the causative factor for poor diet, uncontrolled hyperglycemia, poorly managed hypertension and obesity. All these socioeconomic factors are also the threat aspects for the progress of diabetes, hypertension and thus blood sugar nephropathy. These facts also suggest that familial clustering may also be present in these population .The overall pathogenesis of blood sugar nephropathy is highly complex and is hugely driven by the altered internal milieu around the renal apparatus which initiates multiple pathways leading to the advancement of the ailment. Extensive hyperglycemia is a chief culprit in causing renal dysfunction as it leads to glomerular hyperfiltration along with endothelial dysfunction. Both the conditions together contributes to the changes in the basement membrane properties which are characterised by hypertrophy and hyperplasia of the intraglomerular cells. Other such basement membrane changes as observed by researchers are nodular intercapillary glomerulosclerose and glomerular matrix changes. Detection of albumin in the urine of patient is usually considered an indicative sign of such changes happening inside the body . All theThe altered renin-angiotensin aldosterone system (RAAS) in the blood sugar patient also is a significant contributor to the advancement of blood sugar nephropathy. The altered RAAS system affects the systemic as well as glomerular blood pressure along with affecting the sodium reabsorption process by virtue of its angiotensin II and aldosterone effects on the pro-fibrotic level . AdditioThe observations that control of hypertension from the initial phases of blood sugar reduces the progression of blood sugar nephropathy suggest the important part of hypertension in the development of the condition. Prolonged systemic hypertension is an important contributor of the endothelial injuries to the kidneys. Human studies suggest that lowering the blood pressure with any of the pharmacological agent in a type 2 diabetes mellitus patient acts as a powerful intervention in the prevention of this complication .The pathogenesis of diabetic nephropathy can be summarised by three distinctive mechanisms. 1) The expansion of mesangial membrane due to prolonged hyperglycemia which leads to heightened creation of matrix and/or glycosylation of the proteins in the matrix. 2) Coagulating of the glomerular cellar tissue because of various inflammatory processes. 3) Factors like expansion of the afferent renal artery or ischemic wound caused by the contracting of the blood vessels innervating the glomerular apparatus due to hyaline deposition . The majAssociation of hereditary aspects in the growth and progression of blood sugar nephropathy can be explained by the fact that all the patients with either type of diabetes do not develops the condition. This suggests that inherited genetic factors in the family predisposes the person both to diabetes as well as diabetic nephropathy. According to a theory, a person born with comparatively lesser number of nephrons is highly susceptible to the growth of renal problems like nephropathy in the later life. Animal studies show that if the mothers are exposed to extensive hyperglycemia during pregnancy, the child is highly susceptible to the progress of diabetes in initial phases of life and also to the progress of final phase renal ailments. If this fact is extrapolated in case of humans, it suggest that certain maternal factors might also be responsible for the development of such complications .Genetics along with the other risk factors like age, obesity, smoking, history of hypertension, and the length of the diabetic condition predisposes a diabetic patient to the development of diabetic nephropathy . Family-While the contribution of each of these genes in the progress of blood sugar nephropathy is not yet ascertained, extensive research in the field of diabetes related genetics may provide important information about the underlying pathophysiology of diabetic nephropathy as well as useful treatment targets in future. Two such genes which are presently extensively researched are CNDP1 and CCR2. Both the genes and their impacts are discussed below:CNDP1: The gene is an allelic variant of the carnosinase gene and has been strongly connected the development of blood sugar nephropathy by altering the carnosine pathway. The gene is responsible for encoding the enzyme carnosinase which functions as hydrolyzing enzyme to the substrate L-carnosine. Carnosine is also known as β-alanyl-L-histidine dipeptide and is found inside most of the cells in the body. Maximum amount of the amino-acid is found in the muscles and from there it is released inside the serum. The amino acid is also available from the nutritive sources. The main function of the carnosine is to inhibit the ACE in a natural environment and also hinder the production of the progressive glycation end-yields. The amino acid also reduces the oxidative stress by scavenging. Animal experimentation of the amino-acid as well as its laboratory cultures has proved that it hugely influence the breakdown of glucose in the physique and therefore reduces the risk of hyperglycemia. This in turn allows carnosine to protect the mesangial cells of the renal apparatus from the inflammatory effects and oxidative stress due to high blood glucose levels. In this manner carnosine prevents or at least slow down the progress of microvascular problems of blood sugar such as nephropathy . ExtensiCCR2: CCR2 encodes for chemokine receptor-2 gene. The chemokine receptor also acts as a co-receptor for macrophages and therefore plays an important role in inflammatory pathway. Mutation in the gene recognized as CCR-V64I is responsible for altering the monocyte chemoattractant protein-1 (MCP-1)-receptor and therefore induces the inflammatory processes under the influence of environmental conditions. The cascades initiated by such genes causes the development of inflammation mediated microvascular conditions like diabetic nephropathy .While so many different menace issues for the blood sugar nephropathy was recognised, none of them are globally accepted as an accurate predictor of the condition. Presently the healthcare professionals use the signs of microalbuminuria as an early predictor of diabetic nephropathy. Albumin excretion as measured in the urine falling between 30 to 300 mg per day is considered as microalbuminuria. Also albumin creatinine ratio of 2.5-25 and 3.5-35 mg/mmol in men and female patients correspondingly is also considered as microalbuminuria. The ratio is identified from a random urine sample. These assessment not only predicts nephropathy but also indicates towards the progressive renal complications and therefore provides a prognosis related to mortality in both types of diabetes patients . While tAlternate non-invasive procedures for the early prediction of diabetic nephropathy are under investigation. Researchers have identified various urinary markers which acts as early predictors of renal complications. These new biomarkers are kidney injury molecule-1 (KIM-1), α-1 microglobulin and neutrophil gelatinase-associated lipocalin (NGAL). These biomarkers along with their practical application methods are further researched so that they can be used for prediction of both the acute as well as chronic renal damages caused due to diabetes .Urine proteome analysis is another non-invasive technique which can be used for the early prediction of diabetic nephropathy. The method uses capillary electrophoresis coupled mass spectrometry to identify specific biomarkers in the patient’s urine sample . The proVarious randomised control trial has proved that strict control of hyperglycaemic condition reduces the occurrence rate of albuminuria in the diabetic patients of both the types . It is nInhibition of the renin-angiotensin aldosterone arrangement having an ACE inhibitor as well as angiotensin receptor blocker is presently considered as best treatment for preventing the development of overt blood sugar nephropathy to the final phase renal ailment. A relative risk reduction rate for reduced renal functioning as observed with the curing with ACE inhibitors in blood sugar sufferers is 50%. However the risk reduction with similar treatment plan was found to be only 15% for the final phase renal ailment for the non-insulin reliant blood sugar sufferers with fully established diabetes nephropathy .Different strategies for effective blockade of RAAS have been proposed which even includes increased dosing of the drugs or even the utilisation of two or three different RAAS blocking drugs simultaneously. But such treatment plan implementation requires watchful observation of the patients hemodynamic balance as all these drugs when taken together may lead to hyperkalaemia in the patient .All these data together suggest that even the rigorous management of hypertension and albuminuria has limited part in restricting the development of microvascular complications of blood sugar and thus adjunctive treatments are required which can directly affect the pathological pathway for the development of this conditions. Only pathway targeted treatment plans can effectively diminish the advancement of the diabetic nephropathy and added complications especially in type 2 diabetes mellitus patients.Animal studies on benfotiamine found that the drug can prove to be an effective treatment option as it can act on the three major pathways of the hyperglycaemic damage. This sterol solvable thiamine derivative was proved to inhibit the hexosamine pathway, inhibit the forming of high level glycation final products, and can inhibit the diacylglycerol (DAG)-protein kinase C (PKC) pathway. The drug is also capable of blocking the initiation of the proinflammatory transcript issue NF-κB which is triggered by hyperglycemia. Instigation of the NF-κB conduit by hyperglycemia leads to the extensive production of triphosphates and superoxides which are responsible for the induction of metabolic pseudohypoxia. Ischemic damage caused by this pseudohypoxia is characterised by mitochondrial dysfunction and damage of renal cells by free oxygen radicals which ultimately leads to permanent vascular damage . MoleculCMJN was the single author of the paper.The author declared no competing interests.Ethical issues  have been completely observed by the author.None.


This article offers an overview of what has been done until now on restorative research with children and opens up new inquires for future research. Most of the work has studied children's exposure to nature and the restorative benefits this contact provides, focusing on the renewal of children's psychological resources. The paper begins with an introduction to children's current tendency toward an alienation from the natural world and sets out the objectives of the article. It is followed by four main sections. The first two sections report on what we already know in this research area, distinguishing between children with normal mental capabilities and those suffering from attention-deficit hyperactivity disorder (ADHD). The findings gathered in these sections suggest that children's contact with nature improves their mood and their cognitive functioning, increases their social interactions and reduces ADHD symptoms. The next section describes five suggestions for future research: (1) the need for considering the relational dynamics between the child and the environment in restoration research, and the concept of constrained restoration; (2) the possibility of restorative needs arising from understimulation; (3) the importance of considering children's social context for restoration; (4) the relationship between restoration and pro-social and pro-environmental behaviors; and (5) children's restorative environments other than nature. We close by making some final remarks about the importance of restoring daily depleted resources for children's healthy functioning. Studies conducted within research areas as environmental psychology, public health, and outdoor recreation suggest that exposure to nature can alleviate some of the negative symptoms of our children's contemporary lifestyle. Time spent in green outdoors reduces children's probability of being overweight , one could think that being under close parental surveillance while being involved in non-organized activities in nature might constrain children's restorative experiences .The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Ghana is classified as being in the malaria control phase, according to the global malaria elimination program. With many years of policy development and control interventions, malaria specific mortality among children less than 5 years old has declined from 14.4% in 2000 to 0.6% in 2012. However, the same level of success has not been achieved with malaria morbidity. The recently adopted 2015–2020 Ghana strategic action plan aims to reduce the burden of malaria by 75.0%. Planning and policy development has always been guided by evidence from field studies, and mathematical models that are able to investigate malaria transmission dynamics have not played a significant role in supporting policy development. The objectives of this study are to describe the malaria situation in Ghana and give a brief account of how mathematical modelling techniques could support a more informed malaria control effort in the Ghanaian context. A review is carried out of some mathematical models investigating the dynamics of malaria transmission in sub-Saharan African countries, including Ghana. The applications of these models are then discussed, considering the gaps that still remain in Ghana for which further mathematical model development could be supportive. Because of the collaborative approach adopted in their development, some model examples Ghana could benefit from are also discussed. Collaboration between malaria control experts and modellers will allow for more appropriate mathematical models to be developed. Packaging these models with user-friendly interfaces and making them available at various levels of malaria control management could help provide the decision making tools needed for planning and a platform for monitoring and evaluation of interventions in Ghana. Globally, about 3.2 billion people were at risk of malaria infection in 2015, with the number of cases being 214 million. Deaths attributable to malaria were estimated to be 438,000, most of which occurred in sub-Saharan Africa. These interventions were predominantly deployed in major cities. Insecticide Treated Bed nets (ITNs) were deployed nationally in 2004, following evidence from field trials of their effectiveness in 1996 in Ghana and elsewhere. A policy was also made to subsidise delivery of ITNs in 2007.Since 2005, IRS activities have been recommended; however their deployment has been on a limited scale. Figure 3Despite the high levels of coverage of the interventions, the level of malaria morbidity in Ghana remains relatively high, making iWithin the frame of the 2030 targets set by the Global Malaria Programme (GMP), appropriate mathematical models could help to find deployment strategies for existing and new intervention packages across the three distinct epidemiological zones of the country. These models should also provide a suitable platform for monitoring and evaluating the impact of deployed interventions and track progress towards set goals at both the zonal and national level.Mathematical modelling techniques have been in use for centuries to study transmission dynamics of various infectious diseases.The foundations of modern mathematical modelling techniques specifically for malaria transmission dynamics were laid by Ronald Ross in the early part of the eighteenth century when he demonstrated the link between mosquitoes and malaria transmission and subsequently developed a simple mathematical model to describe transmission of malaria.,22 The RIn Ghana, attempts have been made to develop similar mathematical models to describe the dynamics of malaria. Using ordinary differential equations, compartments representing susceptible, exposed, infected and recovered/removed (SEIR) and susceptible, exposed infected (SEI) for both human and mosquito populations respectively were developed. The focus of these models was on investigating the basic reproductive number, conducting stability analyses and simulation studies to determine when Ghana could achieve malaria free status. The secoAnother model was developed with two infectious classes for the human population using differential equations. This modModifying the Kermack–Makendrick model, a suscepWhile the results of all the aforementioned models were informative, potentially key factors of malaria epidemiology in Ghana are yet to be considered. Factors including the varying epidemiological settings of populations across the country and available monthly aggregated data from all health facilities in all districts rather than the annualised data could offer more insights to the transmission dynamics of malaria in Ghana at the specific ecological zone level, given the varying meteorological factors across the country that lead to different incidence of malaria.Despite the potential usefulness of country-specific mathematical models in studying infectious diseases such as malaria, there seems to be no evidence to suggest that they have guided malaria intervention strategies in Ghana.Models have been developed elsewhere in Africa where the diversity in malaria transmission across regions is taken into account through the incorporation of meteorological factors such as rainfall and temperature. These models were successfully used to investigate the impact of interventions such as IRS and ITNs on the transmission of malaria.–35The earliest mathematical model for malaria transmission in Africa was the Garki model, which was developed and tested in a large field trial in northern Nigeria in 1974. The GarkOther models in Nigeria, Ivory Coast and Mali aided the investigation of malaria transmission dynamics, the condMathematical models have also been successfully developed in eastern Africa. Some investigated malaria transmission dynamics in mosquitoes and humans,–45 otherEven though South Africa is largely malaria free, the dynamics of malaria in the northern provinces of South Africa were investigated using various mathematical models.–51 TheseWhile the results from these studies are useful, one major drawback is often the seeming lack of awareness of these models by programme managers at the national and district level. Providing these models, built with the involvement of programme managers, on user friendly platforms will be the next necessary step that may prove to be invaluable in helping to combat incidence of malaria on the African continent.The National Malaria Control Program (NMCP) in Ghana has made laudable strategic plans to reduce the burden of the disease by 75% across the country by 2020. The aim is to achieve this goal by intensifying the distribution of treated bednets (ITNs) and scaling up monitoring and evaluation (M&E) activities.However, the NMCP will need the tools to adequately justify the approach in which interventions are deployed across different epidemiological settings across the country. Their inRegardless of the availability of health facility level reported cases on the DHIMS, which are analysed periodically to assess progress of malaria morbidity at the regional level, these analyses can only be carried out retrospectively. The ability to provide evidence prospectively to support decision making that could form a basis for intervention deployment may not be available with the usual approach of analysing the data.The retrospective limitations of conventional approaches may also not allow evaluation of the impact and cost effectiveness of existing or new interventions  without Although a few attempts have been made to develop malaria transmission models in Ghana, there are some limitations in their implementation. While some models  aim at GThis project therefore aims to develop a suite of mathematical models that could be used to predict the transmission of the disease in all the different epidemiological/ecological zones of Ghana and can also be used to assess the optimal impact of interventions individually or in combination. The study also aims to extend these models for evaluation of the cost effectiveness of interventions. Finally a friendly user interface visualising the data and incorporating these models will be developed for use at various levels of malaria control. These tools will support the development of relevant policies for the effective control of malaria with limited resources.A spatially explicit population level dynamic mathematical model that takes into account the varying epidemiology of malaria morbidity in Ghana, validated using routine health facility data from all districts, will be developed to investigate the impact of malaria interventions and support planning.To develop and validate a suite of mathematical models that can be used to predict malaria transmission and to investigate the impact and cost of malaria interventions in Ghana.Determine the relationship between malaria morbidity and weather variables in Ghana using statistical methods.Develop dynamic spatially explicit population level mathematical models and assess the optimal combination of various interventions in different epidemiological settings in Ghana.Evaluate the cost effectiveness of these interventions on various populations.Assess prospects of achieving proposed local and international set targets, based on the formulated mathematical models.Develop an interactive and user friendly interface of the mathematical models using the R software and making them available to policy makers and managers of malaria control, at the regional and national level.Specific objectives:The proposed mathematical models will be developed using nonlinear ordinary differential equations. The basic model structure will include coupling compartments for populations that are susceptible, infected and recovered for humans and susceptible, infected and infectious for mosquitos. Due to the endemicity of malaria transmission in Ghana, the concTransitions between compartments will be modelled incorporating appropriate rate parameters estimated from observed data or from the literature. Seasonality of malaria transmission will be captured through forcing functions or functions of meteorological variables of the various ecological zones as covariates.The impact of interventions will be tested by simulating various levels of intervention coverages (singly or in combination) on the potential reduction on transmission of disease in the various zones. Similarly the prospects of reducing the prevalence and incidence of malaria to desired set targets, by the NMCP and those for malaria elimination, will be tested based on the impact of varying coverage levels of interventions on transmission.Cost effectiveness of various interventions will also be calculated based on the net intervention cost. That is, benefits in terms of cost reduction derived to the health system following implementation of the interventions. Average cost effectiveness ratio (ACER) will then be calculated as the ratio of the net cost of interventions and the net effect of interventions. Other deModels will be fitted with the aim to matching the features and trajectory of observed monthly reported cases within each zone and the best parameter set obtained through maximum likelihood methods.Clinical data for this study will be obtained from the health facility records of confirmed uncomplicated and severe malaria cases, malaria attributable deaths and records of pregnant women confirmed to have malaria. These data are captured and stored on the DHIMS platform and are available to the NMCP. Aggregated monthly records of all confirmed cases of malaria for all age groups and districts from 2000 to 2016 will be used.Data for the cost effectiveness analysis will also be obtained from NMCP and other published literature. These will include budget estimates and previous expenditures for malaria interventions and malaria specific activities and programs in Ghana.For the purposes of studying the relationships between malaria morbidity and meteorological variables, monthly average precipitation (mm) and temperature (minimum and maximum) (°C) from all 10 regions in Ghana for the period 2000–2016 will be used. These data will be obtained from the Ghana Meteorological Agency (GMET).Ethical approval will be sought from the Navrongo Health Research Centre Institutional Review Board and the Faculty of Science Ethics Committee of the University of Cape Town. Permission to use the data will also be sought from the NMCP.Towards malaria control and elimination in Ghana: challenges and decision making tools to guide planning.Investigating the relationship between seasonal dynamics of reported malaria cases and weather variability in Ghana.Accounting for regional transmission variability and the impact of malaria interventions in Ghana .Cost effectiveness of malaria control interventions in Ghana: a mathematical modelling approach.Expected outcomes will include the following proposed articles that will be submitted for peer review and publication:There seems to be no evidence of country-specific mathematical models playing a role in supporting policy decision making with regards to malaria intervention strategy development, although a number of studies, as mentioned earlier, have been conducted as part of efforts to understand the epidemiology of malaria in Ghana.One of reasons accounting for this may include the non-availability of data, prior to the DHIMS platform, needed to be used to validate model parameters. Another reason could be limited interaction between modellers and policy makers. Tapping the full potential of mathematical models to support policy may require a collaborative effort between model builders and malaria control stakeholders such as the National Malaria Control Program, Ministry of Health, and Ghana Health Service.Examples of collaborative research into building mathematical models include one in Cambodia and another in Thailand. In Cambodia, the National Institute for Health designed and implemented, collaboratively with policy makers and other stakeholders of malaria control, a malaria early warning system supported by seasonal climate forecasting, weather monitoring, statistical and dynamic models. The system was implemented at the municipal level and was made available for use by malaria control managers. A user-fIn Ghana, developing a mathematical model to support policy development will require detailed parameterisation and validation using results of the numerous epidemiological studies available in published literature as well as data unpublished and available to malaria control stakeholders. The recent analyses undertaken by the NMCP to generate an updated malaria prevalence map for Ghana using data from 1960 to 2011 is one very useful source of data. Additionally, aggregated monthly health facility data maintained on the DHIMS ,59 will Therefore, the mathematical model development process proposed in this study will consider both population and sub-population level dynamics of malaria transmission along the varying epidemiological settings of Ghana. This will be done by factoring in local disease transmission dynamics of malaria and also by engaging policy makers, such as the NMCP to gain more insights, including the practical difficulties of intervening in malaria transmission in the country.It is envisaged that the process of conducting this research collaboratively with the NMCP in Ghana will afford the opportunity to support policy makers and stakeholders in the field of malaria control through country-specific mathematical models. These models should be useful for investigating malaria transmission dynamics for purposes of disease control and policy evaluation.Specifically, the challenges that may be addressed by the earlier proposed modelling venture are well articulated by the NMCP of Ghana in the following statement: ‘Among the challenges facing the future of effective control include a more rational basis for stratified intervention delivery, better planning information and an ability to generate sufficient evidence to demonstrate impact and value for money’ (p. 1) .More importantly, the opportunity for interaction between malaria control experts and modellers will create a platform for information sharing, presenting a unique platform for the development of more practically focused models for guiding malaria control activities in Ghana.Subsequently, packaging these mathematical modelling tools into user friendly interfaces and making them available for use by malaria control management teams at various levels across Ghana will be the way to exploit synergies for a common goal of a possible malaria elimination by 2030 as envisaged by the Global Malaria Programme.


The dataset on the effects of social demographic on job satisfaction was obtained through self-administered questionnaire. The survey was situated in a Nigerian manufacturing company and the valid ninety two copies of the questionnaire were analyzed by AMOS 21. Structural Equation Modelling (SEM) analysis was carried out on the constructs. In addition, further analysis of the data will assist in establishing the significant level of demographic on job satisfaction. Specifications TableValue of the data•The outcomes of the data can assist in managerial decisions such as recruitment and selection processes.•The analyzed data can provide insights into the generational differences and how each affects job satisfaction.•Managers can also leverage on the data for workforce diversity management.1The dataset contained effects of social demographic on job satisfaction. The survey is premised on quantitative method and the Structural Equation Modelling (SEM) statistical tool was adopted to identify the significant effects of demographic characteristics of employees of a manufacturing company on job satisfaction 2The statistics presented in this data set was based on the quantitative study conducted that examined the influence of social demographic variables on job satisfaction in a manufacturing company in Nigeria. Descriptive survey research design which help to assess sample at the specific time without inconsistencies was adopted. One of the leading manufacturing firms in Ogun State, Nigeria was sampled. The study population consisted all employees of the sampled manufacturing firm. Researchers used complete enumeration of employees because the population of the study is relatively small. Data was collected with the use of a structured questionnaire. However, Structural Equation Modeling (AMOS 22) was used for the analysis of data


Introduction. The use of cyclosporine (CsA) in the treatment of nephrotic syndrome (NS) contributed to a significant reduction in the amount of corticosteroids used in therapy and its cumulative side effects. One of the major drawbacks of CsA therapy is its nephrotoxicity. Prolonged CsA treatment protocols require sensitive, easily available, and simple to measure biomarkers of nephrotoxicity. NGAL is an antibacterial peptide, excreted by cells of renal tubules in response to their toxic or inflammatory damage. Aim of the Study. The aim of this study was to assess the suitability of the NGAL concentration in the urine as a potential biomarker of the CsA nephrotoxicity. Material and Methods. The study was performed on a group of 31 children with NS treated with CsA. The control group consisted of 23 children diagnosed with monosyptomatic enuresis. The relationship between NGAL excreted in urine and the time of CsA treatment, concentration of CsA in blood serum, and other biochemical parameters was assessed. Results. The study showed a statistically significant positive correlation between urine NGAL concentration and serum triglycerides concentration and no correlation between C0 CsA concentration and other observed parameters of NS. The duration of treatment had a statistically significant influence on the NGAL to creatinine ratio. Conclusions. NGAL cannot be used alone as a simple CsA nephrotoxicity marker during NS therapy. Statistically significant correlation between NGAL urine concentration and the time of CsA therapy indicates potential benefits of using this biomarker in the monitoring of nephrotoxicity in case of prolonged CsA therapy.  Since the 1980s calcineurin inhibitors have been the basis of immunosuppressive therapy in the prevention of transplant rejection and in the treatment of various autoimmune diseases. A significant limitation to their long-term use is a specifically defined nephrotoxicity. The nephrotoxic action of calcineurin inhibitors depends on genetically determined drug pharmacodynamics and demonstrates a dependence on their serum concentrations and on the duration of the therapy . In the Ischaemic nephron injury, caused by afferent arteriole constriction, develops in early stages of cyclosporine-induced nephropathy . The druThe most precise way to assess the nephrotoxic effect of CsA is a kidney biopsy. A histopathological analysis reveals features of arteriolopathy , band-like interstitial fibrosis, and ischaemic atrophy of the renal tubules. The detection of changes typical for the CsA toxicity in a renal biopsy specimen attests to a considerable advancement of the process and has a nature of chronic and progressing remodelling of the nephron and tubulointerstitial compartment .Numerous studies have reported that ischaemic, osmotic, or toxic injury  of the epithelial cells of the proximal tubules induces the synthesis of a large amount of neutrophil gelatinase-associated lipocalin (NGAL) by the cells of the distal tubules and intercalated cells of the arcuate tubules , 9.NGAL, which is called “renal troponin,” is a sensitive marker of acute renal injury . It is pNGAL excreted in urine is a sum of the protein filtered in the renal glomeruli , synthesized de novo by cells of the nephron loop thick limb and arcuate renal tubules, as well as a pool of protein produced by neutrophils and macrophages that infiltrate the organ during an ongoing inflammation –15.Thus, an increase in NGAL concentration in urine may indicate the impairment of the reabsorption of this protein by the proximal tubule cells, increased NGAL synthesis by the distal parts of nephron as a reaction to inflammatory or ischaemic injury, and activation of immune cells in the renal parenchyma and migrant cells , 16.In the available literature there are single reports concerning the usefulness of determining the level of NGAL in urine for the detection of the early stages of cyclosporine A nephrotoxicity in children chronically treated with this drug due to glomerulopathy with nephrotic syndrome .The aim of the study was to evaluate the usefulness of determining the NGAL urine concentration as a potential biomarker of cyclosporine A nephrotoxicity.2) were included in the study, after exclusion of active foci of infection, UTIs, urinary tract anomalies, and liver diseases.The examined group consisted of 31 patients, children and adolescents, at the age of 3–17 (mean 9.2), including 19 boys and 12 girls. The patients were treated in the Department and Outpatient Clinic of Paediatric Nephrology of Chorzow Centre for Paediatrics and Oncology due to steroid-dependent or steroid-resistant nephrotic syndrome. Characteristics of the examined group are showed in All patients received cyclosporine A for at least 3 months. The mean duration of the therapy was 26.5 months. The daily dose ranged from 3 to 6 mg/kg of the body weight.During the entire treatment, the serum drug concentration was systematically monitored, with C0 level between 80 and 120 ng/ml. All the children were in the stage of complete remission of nephrotic syndrome at the time of the study. Apart from cyclosporine A patients enrolled into the study were treated with steroids at different doses; also they received antihistaminic drugs, proton pump inhibitors, and supplemented calcium, magnesium, and vitamin D. None of the patients enrolled into the study did not use ACE inhibitors at the time of the blood and urine samples collection.All of the patients had cyclosporine C0 and C2 levels determined and they underwent biochemical tests as well to assess renal function  and tests of inflammation markers and biochemical parameters, which are typical disorders for nephrotic syndrome .GFR from the serum creatinine concentration was calculated with the use of the Schwartz formula:k  × height [cm]/creatinine [mg/dl] .eGFR = l/cys C)].GFR from the serum cystatin C concentration was calculated with the use of the Filler formula: eGFR = 1.962 × [1.123 × log). We collected a morning urine sample prior to the administration of CsA (NGAL 1) and another sample was gathered 2 to 4 hours after the CsA administration (NGAL 2) from all the patients to determine urine NGAL concentration. Urine samples collected for NGAL determination were frozen at −70 degrees Celsius. Enrollment of patients into the study and the collection of blood and urine samples lasted for six months.After sample collection, the NGAL level was determined with the use of an immunoenzyme test by Bioporto Diagnostics, with strict adherence to the manufacturer's instructions. All samples were diluted to optimal density. The results of the immunoenzyme reaction were read with the use of a microplate spectrophotometer. The measurements were expressed as nanograms per millilitre. The limit of detection was 0.1 ng/ml.The control group consisted of 23 children aged 4–17 (mean 10.1), including 14 boys and 9 girls, diagnosed in the Chorzow Centre for Paediatrics and Oncology due to monosymptomatic nocturnal enuresis. In the control group the first morning urine samples were obtained to measure NGAL and creatinine concentration and laboratory tests were performed to confirm a normal systemic metabolism.The examination protocol was approved by the Bioethical Commission of the Medical University of Silesia, decision number 10/2009.t-test was used to analyse the differences between the groups.The statistical comparison of the study and control groups was preceded by the verification of continuous variable distributions with the normal distribution based on the Shapiro-Wilk test. For continuous variables with normal distribution, a parametric Student's For the variables not demonstrating normal distribution, a nonparametric Wilcoxon test was used.r-Pearson correlation, Kendall Tau correlation, and linear robust regression models were used.To analyse the influence of the duration of cyclosporine A therapy on NGAL excretion and the influence of various factors on NGAL concentration changes and NGAL/creatinine ratio changes during CsA therapy, the The data presented in A significant negative correlation was shown between the difference of the NGAL/creatinine ratio in urine samples collected before and after CsA administration and the C0 cyclosporine level. The higher the baseline concentration of the medicine, the lesser the influence of the next dose of the medicine on urinary NGAL excretion, expressed as a ratio of NGAL concentration to creatinine concentration. We found no statistically significant correlation between the C0 cyclosporine concentration and the difference of absolute urinary NGAL concentration expressed in ng/ml .Significant positive correlation was found between the NGAL/creatinine ratio in the urine samples and the serum concentration of triglyceride. The higher the serum triglyceride concentration, the higher the urinary NGAL excretion Figures  and 3.The similar dependence was observed between the absolute levels of NGAL excreted in urine expressed in ng/ml and the concentration of serum triglycerides. Relationship between NGAL concentration in the urine sample prior to and 2 hours after CsA administration and serum triglyceride levels is shown in Figures The statistical analyses performed using the regression robust model demonstrated an influence of the duration of cyclosporine A therapy on urinary NGAL excretion in the examined group.The duration of treatment had a statistically significant influence on the NGAL to creatinine ratio in the urine sample collected before the administration of the drug. The concentration changes are presented in The similar dependence concerns NGAL urine excretion expressed in ng/ml .The difference in the NGAL to creatinine ratio before and after the administration of CsA positively correlated with GFR calculated using the Filler formula .Such a relationship with GFR calculated using Schwartz formula from the creatinine concentration was not observed.The difference in the NGAL to creatinine ratio before and after the CsA administration negatively correlated with total serum cholesterol concentration .In available literature there are only a few reports concerning the comportment of NGAL in children suffering from different types of nephrotic syndrome. It has been shown that in course of chronic glomerulonephritis plasma NGAL concentration and the urinary excretion of this protein are higher than in healthy people, but that does not apply to all types and periods of chronic glomerulonephritis –20. NishOur research in children treated for various types of nephrotic syndrome demonstrated no differences in the mean concentration of NGAL in the urine samples compared to the control group. This may be due to the fact that all the children in the study group were in the remission period and in any case there was no significant proteinuria. This is essential for further consideration of cyclosporine's nephrotoxicity and the comportment of NGAL in children treated with this drug. It allows us to assume that NGAL in the urine is not a biomarker of only nephrotic syndrome. Cyclosporine A used in its treatment induces ischemia and the damage of the epithelial cells of renal tubules by the vasoconstriction of afferent arterioles. In experimental tests and the culture of human tubular cells in vitro it has been demonstrated that ischemic injury increases the NGAL mRNA , 22.Because the nephrotoxic effects of many drugs, including CsA, are a huge clinical problem, attention was drawn to the potential usefulness of the NGAL urine concentration measurement, as an early biomarker of this complication , 23. SieTo this date, there were very few reports in literature evaluating the usefulness of NGAL in the detection of nephrotoxicity of calcineurin inhibitors in patients after organ transplantation and those treated with other clinical indications. Wasilewska et al. conducted a survey concerning NGAL serum concentration and urinary NGAL excretion in children treated with cyclosporine A due to various types of nephrotic syndrome .The study included 19 children with steroid-dependent nephrotic syndrome on the ground of MCD and FSGS. In the study group the serum concentrations of NGAL and NGAL excretion in the urine, expressed as a ratio of NGAL to creatinine in the urine sample, were measured four times. The first measurement was performed during exacerbation of nephrotic syndrome, prior to the initiation of CsA therapy. The subsequent measurements were performed in the 3rd, 6th, and 12th months of treatment.The NGAL urine excretion differed between the study and the control group before the initiation of treatment. The difference increased up to 6 months of the therapy and after that the time differences in NGAL excretion were reduced, which may be connected with the reduction of cyclosporine dosage. In our study, we observed no differences in the urinary NGAL excretion between the study group and the control group.The NGAL excretion in the urine in the study of Wasilewska et al. remained without any relation to the cyclosporine A blood concentration. This observation corresponds to our results.In this study, the urinary NGAL excretion expressed as a ratio of NGAL to creatinine increased up to the 6th month of therapy and then decreased. In our observation, the urinary NGAL excretion converted per mg of creatinine increased in direct proportion to the duration of the cyclosporine treatment. The cyclosporine dependence, observed in a large number of patients, determines the elongation of CsA treatment. The treatment with this drug was initially predicted for a year or two. In many centers at the moment, patients are treated with cyclosporine even for several years. In this context increasing the concentrations of NGAL in urine during the treatment time observed in our study may be an important diagnostic clue indicating slow but steadily progressing renal tubular damage.On one hand using CsA to treat nephrotic syndrome reduces lipid metabolism disorders, but on the other hand, it may itself cause hyperlipidemia. Cyclosporine as a lipophilic substance binds with lipoproteins in the plasma. Lipid disorders may therefore have an effect on drug metabolism and bioavailability. In examining the impact of various metabolic disorders in nephrotic syndrome on the urinary NGAL excretion in children treated with CsA, we found a strong, statistically significant positive correlation between NGAL and creatinine, calculated from both urine samples and the serum concentration of triglycerides. Moreno-Navarrete et al., investigating lipocalin 2 serum concentrations in patients with metabolic syndrome, insulin resistance, and excessive intake of fats, found a statistically significant positive correlation between changes in the concentration of triglycerides in the serum of subjects and changes in serum concentrations of NGAL . FassettAt the moment, lipocalin 2 aspires to the role of a “renal troponin.” Acute renal failure, as well as chronic kidney disease, is conditions that often coexist with the dysfunction of other organs and systems. A high proportion of patients diagnosed with renal diseases have serious lipid disorders. The influence of a concentration of serum triglycerides on the urinary NGAL excretion found in our study certainly requires further research and maybe it will be included in the interpretation of tests in the future.In our study we found a negative correlation between the total cholesterol level and the difference in the NGAL urine concentration in the samples collected before and 2 hours after the administration of CsA. The theoretically high concentration of CsA two hours after the administration of the drug should stimulate ischemic nephron injury, which would enhance lipocalin excretion by the proximal tubule and collecting duct cells. However, our study did not reveal such a correlation, which seems to be connected with very high cholesterol levels in children with nephrotic syndrome. Cyclosporine as an active lipophilic substance binds with lipoproteins present in excess in the serum of sick children. Perhaps for this reason, its vasoconstrictive reaction in these children is not as rapid as expected.The difference in urinary NGAL excretion before the administration of CsA and at the peak of its serum concentration in the examined children demonstrated a positive correlation with the GFR calculated using the Filler method (but not the Schwartz method).The results of our study demonstrate that the concentration of NGAL in urine (expressed as a NGAL to creatinine ratio in the urine sample) cannot be used to detect early stages of CsA nephrotoxicity in children with nephrotic syndrome that is treated with this drug. This observation is consistent with evidence obtained from the only available study in literature evaluating NGAL as a potential marker of CsA nephrotoxicity in children with nephrotic syndrome. The complex correlation between the urine lipocalin excretion and characteristic for the nephrotic syndrome metabolic disorders complicates the interpretation of the results. The positive correlation between the urine NGAL concentration over the course of the CsA treatment seems to have a big practical meaning in the context of prolonged CsA treatment observed in recent years.The examination of the urinary NGAL concentration is a simple and noninvasive test delivering certain information concerning the condition of renal parenchyma. Its periodic measurement and interpretation together with other available parameters of nephrotoxicity may be beneficial in the individualization and optimization of CsA therapy.The concentration of NGAL in urine cannot act as an early detector of CsA nephrotoxicity in children with nephrotic syndrome treated with this drug.The concentration of NGAL excreted in the urine demonstrates a statistically significant correlation with serum triglycerides concentration.A statistically significant correlation between the urinary NGAL concentration and the duration of the CsA treatment indicates the potential usefulness of this marker in the monitoring of CsA nephrotoxicity, but only in relation to the other available indicators of kidney function.


Transglutaminase catalyzes the formation of intermolecular isopeptide crosslinks in polypeptides . Because2+ that occurs during synaptic transmission [Glutamine residues  are necessary for the formation of the crosslinks and most transglutaminase substrates contain a segment of short tandem sequence repeats . A numbeIn addition to diseases of polyQ expansion, neurological diseases associated with the formation of protein aggregates include Alzheimer’s disease, Parkinson’s disease, prion diseases and some forms of amyotrophic lateral sclerosis. All of these diseases are characterized by the deposition of specific proteins: the amyloid β-peptide and hyperphosphorylated tau in Alzheimer’s disease, ɑ-synuclein in Parkinson’s disease and the conformationally altered Prion protein in Prion disease. Numerous reports have provided supporting evidence linking neurological diseases and the formation of aggregates to the action of transglutaminase . The rolIn view of the likely participation of transglutaminase in neurodegenerative diseases and of the elusive function of transglutaminase in brain, we endeavored to identify the transglutaminase substrates present in brain thus hoping to clarify the function of the enzyme in brain. For this we developed a functional proteomics strategy in which incorporation of biotinylated amine-donor and amine-acceptor probes is used to affinity-purify the transglutaminase substrates, which are then identified by mass spectrometry. The biological significance of the 166 substrates that we found was determined using the Ingenuity Pathway Analysis. We were surprised to find that most of the brain substrates identified were known to interact with huntingtin, the amyloid precursor protein or α-synuclein and that neurological disease was the most significant canonical pathway associated with the substrates. In view of the likely association of transglutaminase substrates with neurological disease, we wondered whether the aggregates associated with the diseases contained such substrates. This was demonstrated in two ways. First transglutaminase promoted very efficiently the incorporation of the amine-acceptor probe into both the inclusions of Huntington disease brain, and huntingtin-containing polymers purified from a patient’s cerebral cortex. Second, we randomly selected some substrates and tested their presence within the inclusions by in-situ immunolabeling. All the substrates that we examined could be detected in the inclusions  were randomly selected for the experiment and all three were found to be selectively polymerized in neuronal cells when cytosolic calcium concentration was raised. These results strongly support the idea that the crosslinking activity of brain transglutaminase participates in the formation of the protein aggregates found in diseases of the central nervous system and reinforce the notion that transglutaminase might constitute a useful target in the search for prophylactic or therapeutic molecules inhibiting the aggregation process [Since the substrates that we had found had been identified in an  process .


The last decade witnessed an explosion of interest in cancer stem cells (CSCs). The realization of epithelial ovarian cancer (EOC) as a CSC-related disease has the potential to change approaches in the treatment of this devastating disease dramatically. The etiology and early events in the progression of these carcinomas are among the least understood of all major human malignancies. Compared to the CSCs of other cancer types, the identification and study of EOC stem cells (EOCSCs) is rather difficult due to several major obstacles: the heterogeneity of tumors comprising EOCs, unknown cells of origin, and lack of knowledge considering the normal ovarian stem cells. This poses a major challenge for urgent development in this research field. This review summarizes and evaluates the current evidence for the existence of candidate normal ovarian epithelial stem cells as well as EOCSCs, emphasizing the requirement for a more definitive laboratory approach for the isolation, identification, and enrichment of EOCSCs. The present review also revisits the ongoing debate regarding other cells and tissues of origin of EOCs, and discusses early events in the pathogenesis of this disease. Finally, this review discusses the signaling pathways that are important regulators of candidate EOCSC maintenance and function, their potential role in the distinct pathogenesis of different EOC subtypes, as well as potential mechanisms and clinical relevance of EOCSC involvement in drug resistance.