The olfactory bulb (OB) is the first central processing center for olfactory information connecting with higher areas in the brain, and this neuronal circuitry mediates a variety of odor-evoked behavioral responses. In the adult mammalian brain, continuous neurogenesis occurs in two restricted regions, the subventricular zone (SVZ) of the lateral ventricle and the hippocampal dentate gyrus. New neurons born in the SVZ migrate through the rostral migratory stream and are integrated into the neuronal circuits of the OB throughout life. The significance of this continuous supply of new neurons in the OB has been implicated in plasticity and memory regulation. Two decades of huge investigation in adult neurogenesis revealed the biological importance of integration of new neurons into the olfactory circuits. In this review, we highlight the recent findings about the physiological functions of newly generated neurons in rodent OB circuits and then discuss the contribution of neurogenesis in the brain function. Finally, we introduce cutting edge technologies to monitor and manipulate the activity of new neurons. Unlike most other central nervous system areas, GABAergic inhibitory interneurons greatly outnumber principal neurons, suggesting that odor representations in the OB are shaped by local inhibitory circuits  of the OB are dominated by dendrodendritic reciprocal synapses between lateral dendrites of M/T cells and GCs, the latter being most numerous type of inhibitory interneurons in the OB. Unlike the neocortex, GABAergic inhibitory interneurons in the OB grealy outnumber principal neurons by 50–100:1 , calbindin-28K , and tyrosine hydroxylase (TH) , only half of them are integrated into pre-existing neural circuits. The remains of them are eliminated by apoptosis during their maturation  , a small number of new neurons migrate into the accessory olfactory bulb (AOB) (Oboti et al., in vivo. Calcium imaging is widely used to image the activity of many neurons simultaneously (Grienberger and Konnerth, in vivo (Akemann et al., Odor information processing is influenced by the activity of OB interneurons, including pre-existing neurons and newly born neurons. As mentioned above, neurogenesis contributes to various olfaction-related behaviors. However, how new neurons contribute to such behaviors is still unclear. New technologies are required to monitor and manipulate the activity of new neurons during such behaviors. Neuronal imaging technologies can help to tackle this issue. During the past decade, two-photon microscope has become a key tool for monitoring the structure, function, and plasticity of neurons Optogenetics is also a powerful tool in the field of OB neurogenesis. Over the last decade, a wide variety of different kinds of opsins have been developed and become available, and now optogenetic approach is a standard methodology for investigating the functional properties of neurons at the circuit and behavioral level (Fenno et al., in vivo, it might be possible to promote adult neurogenesis even in aged brains and lead to restore brain functions.Although neurogenesis continues throughout life, newly generated neurons dramatically decrease in number with age, and this decline may be involved in memory deficit (Seki and Arai, Olfaction is indispensable in mammalian life. GCs are the most common GABAergic inhibitory neurons in the OB and modulate the activity of M/T cells to shape odor representations. The OB neural circuits are reorganized by incorporation and elimination of newly generated granule neurons throughout life. Furthermore, blockade of neurogenesis results in various olfaction-related behavior defects. Therefore, continuous neurogenesis is important to acquire plasticity in the olfactory system and thereby adapt neural circuits to environmental changes. However, there are still a lot of problems about adult neurogenesis to be solved. For example, molecular mechanisms integrating new neurons into the OB neural circuits is still unclear. In addition, there are some discrepancies about behavioral analyses. More sophisticated animal model and standardized behavior paradigms should be established. Further studies will contribute to solution of these problems and lead to the development of therapies and drugs for treatment of neurodegenerative diseases.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.


The calcifying cystic odontogenic tumor (CCOT) is a rare cystic odontogenic neoplasm frequently found in association with odontome. This report documents a case of CCOT associated with an odontome arising in the anterior maxilla in a 28-year-old man. Conventional radiographs showed internal calcification within the lesion but were unable to visualize its relation with the adjacent structures and its accurate extent. In this case cone beam computed tomography (CBCT) could accurately reveal the extent and the internal structure of the lesion which aided the presumptive diagnosis of the lesion as CCOT. This advanced imaging technique proved to be extremely useful in the radiographic assessment and management of this neoplasm of the maxilla.  The calcifying odontogenic cyst (COC) is a rare odontogenic lesion of the jaw, characterized by presence of multiple giant cells and internal calcifications. It was first described by Rywkind in 1932; however, it was in 1962 when Gorlin et al. separately identified it as calcifying odontogenic tumor.[In the latest description of odontogenic tumors by the World Health Organization (WHO) in 2005, the name of COC was changed to calcifying cystic odontogenic tumor (CCOT), owing to the neoplastic nature of the lesion. The occuBefore performing any surgery, the extent of maxillofacial lesions and their relationship with the surrounding anatomical structures should be carefully examined in order to determine the appropriate treatment plan and to avoid surgical complications. Neither intraoral nor panoramic radiographs provide the three-dimensional (3D) information of the imaged area needed for optimal preoperative planning. In recent years, cone beam computed tomography (CBCT) has emerged as a reliable tool for preoperative radiological assessment of odontogenic cysts and tumors.The limited number of reported cases indicates the rarity of involvement of maxillary sinus in CCOT.We hereinA 28-year-old male referred to the Department of Oral Medicine and Radiology, Sri Aurobindo College of Dentistry, Indore, India with a complaint of an asymptomatic swelling and heaviness in the left midface region present for one month. On extraoral evaluation, an asymmetry was observed with an approximately 4×5 cm swelling, involving middle half of left side of the face with obliteration of nasolabial fold. Borders of swelling were indistinct. The overlying skin appeared normal.Intraoral examination revealed buccal cortical expansion extending from tooth 22 to 26 and palatal expansion with 22 and 23 .The overlying mucosa appeared normal. On palpation, the swelling was non tender; soft and fluctuant in consistency with 22 and 23 and firm with 24, 25, and 26. No Mobility of teeth was observed. Electric pulp test revealed non vital 23, 24, 25 and delayed pulpal response with 21 and 22.Intraoral clinical inspection did not reveal any specific finding but signs of moderate gingivitis. The patient did not give incidence of local trauma; medical history was largely noncontributory.Intraoral periapical radiograph showed a well-defined radiolucency with internal radiopacity extending from periapical region of teeth 11 up to 26 and into the maxillary sinus. There was external root resorption in teeth 24, 25, and 26 .Occlusal radiograph demonstrated unilocular radiolucency extending anterior-posteriorly from mesial of tooth 11 to distal of 26 with multiple ill-defined radiopaque foci of varying density .Panoramic radiograph was advised  which deAxial section demonstrated lesion extending from the mesial surface of 11 up to the mesial surface of 27 , measuriSagittal section revealed extension of the lesion within the maxillary sinus  with theSurgical enucleation under local anesthesia was performed and a thick cystic wall and mineralized material, compatible with an odontoma in anterior part of the cyst in relation with tooth 21, 22, and 23 was removed, leaving an oval bony defect.  The H&E  the maxilla and mandible.[The CCOT represents approximately 2% of all odontogenic tumors, which momandible. Accordinmandible.CEOT demmandible. CCOT is mandible.Recently, various reports have been published about the computed tomography (CT) examinations of these lesions emphasizing its benefits over the plain film radiography to demonstrate the cystic lining of the tumor, along with the internal calcifications. However, very limited data is available in the literature about the value of CBCT in CCOT diagnosis. CBCT scanners have an edge over CT Scans since it uses a low-energy fixed anode, as used for dental panoramic machines and it rotates only once around the patient, using a cone-shaped x-ray beam to capture the data. These changes allow a less expensive, smaller machine that exposes the patient to approximately 20% of the radiation of a helical CT, equal to the exposure received from a set of full-mouth periapical. Also, due to the difference in voxel size, CBCT of a limited area is also very effective in achieving high spatial resolution in comparison with conventional CT.CCOT are generally unilocular lesions; although 5–13% of cases have shown multilocular appearance. Variable numbers of radio-opaque bodies are seen in about 50% of CCOT cases. It may have regular outline with well-demarcated margins. Early tumors may appear completely radiolucent. With maturation, they develop calcifications which may show mixed radiolucent-radiopaque appearance. Marx et al. in 2003 discussed three patterns of radiopacity with this tumor; first, salt and pepper pattern of flecks, second, fluffy cloudlike pattern throughout, and third, a crescent-shaped pattern on one side of the radiolucency. Our case had well-defined radiopacity within the center of cystic lumen with lobulated surface, regular margins, and well-defined borders not previously discussed in literature. The presence of internal calcification depicted on CBCT images is an important radiographic characteristic for the presumptive diagnosis of the CCOT. The CBCT examination in this case was useful for complete evaluation of the lesions and related structures involving the maxillofacial complex. Visualization of the overlapping adjacent structures represents the CBCT as a challenge in visualization. Another advantage of CBCT examination in the case was the ability to display the extent and complex relationships of the CCOT and the odontome with the associated teeth in 3D, which could not be provided by conventional radiography. In addition, it could be shown by this case report that the CBCT images can offer higher spatial resolution than the conventional X-rays, reducing the radiation dose and also guiding the treatment of this lesion. In summary, we reported a rare case of CCOT associated with an odontoma. Internal calcification detected on CBCT images aided the presumptive diagnosis of the lesion as CCOT, which was subsequently diagnosed histopathologically as CCOT. CBCT was also useful in determining the extent and relationship of the CCOT and odontome with the adjacent structures.


The diagnosis of mucocutaneous leishmaniasis (MCL) is hampered by the absence of agold standard. An accurate diagnosis is essential because of the high toxicity of themedications for the disease. This study aimed to assess the ability of polymerasechain reaction (PCR) to identify MCL and to compare these results with clinicalresearch recently published by the authors. A systematic literature review based onthe Preferred Reporting Items for Systematic Reviews and Meta-Analyses: the PRISMAStatement was performed using comprehensive search criteria and communication withthe authors. A meta-analysis considering the estimates of the univariate andbivariate models was performed. Specificity near 100% was common among the papers.The primary reason for accuracy differences was sensitivity. The meta-analysis, whichwas only possible for PCR samples of lesion fragments, revealed a sensitivity of 71% and a specificity of 93%  in the bivariate model. The search for measures that could increase thesensitivity of PCR should be encouraged. The quality of the collected material andthe optimisation of the amplification of genetic material should be prioritised. Leishmania genre. The clinical manifestations of ATL are predominantlyclassified as cutaneous (CL) or mucocutaneous leishmaniasis (MCL), depending on the absenceof mucous lesions or on the involvement of mucous membranes, respectively (American tegumentary leishmaniasis (ATL) is caused by parasites of theectively  b.The etiologic diagnosis of ATL in all its forms is a difficult task. This difficulty isincreased in cases of MCL, in which sampling frequently requires invasive techniquesbecause of the potential presence of deep nasopharyngeal lesions .The absence of a gold standard diagnostic test for MCL is a major obstacle. The existingtests cannot be independently used for the diagnosis of MCL because the accuracy of thetests is unsatisfactory. The classical diagnostic methods for MCL include immunological andparasitological tests. The immunological tests include the intradermal leishmanin test (theMontenegro skin test) and serological tests, which are known for their high sensitivity;however, these immunological tests exhibit low diagnostic specificity , offer good sensitivity and specificity and, ultimately, increased accuracycompared with immunological and parasitological tests . HoweverWe performed a systematic literature review of studies of the diagnostic accuracy of PCR indetecting MCL as part of our groups' effort to develop non-invasive collection methods forthe diagnosis of MCL. The primary objective of this study was to assess the status ofvarious molecular biology techniques in recognising MCL and to compare these data with therecent clinical research published by our group .This systematic literature review was performed based on recommendations by thePreferred Reporting Items for Systematic Reviews and Meta-Analyses: the PRISMAStatement, with adjustments for evaluating the diagnostic accuracy of the studies OR mucocutaneous) OR mucous)) AND leishmaniasis) ANDdiagnosis) AND Polymerase Chain Reaction", using the advanced search system on thePubMed site (PubMed Advanced Search Builder) following the recommendations for searcheswith comprehensive criteria. Because MCL is a highly endemic disease in South America,predominantly in Brazil, we included the non-MeSH terms "mucous" and "mucosal", whichare frequently translated from the Portuguese words leishmaniosemucosa.Two researchers were recruited to search the related references in the followingdatabases or virtual libraries: PubMed, EMBASE, Web of Knowledge, SciELO and LILACS,using the same terms and connectors through each specific advanced search tool . No specInclusion criteria - Papers that fulfilled all of the followingcriteria were selected and included. Addressed the topic: using PCR techniques for thediagnosis of MCL leishmaniasis, studies in humans, cases of mucosal leishmaniasispotentially associated with skin lesions, more than seven cases of mucosalleishmaniasis, any number of controls without a diagnosis of mucosal leishmaniasis, norestriction for defining the controls  andwritten in English, French, Portuguese or Spanish.Exclusion criteria - Fewer than eight cases of mucosal leishmaniasis,studies without controls, studies that used known cured cases of ATL as controls,studies in which patients with CL and mucosal leishmaniasis were included without beingexplicitly separated, PCR tests conducted with cultured patient samples, only thepresence of exclusively CL forms of ATL and written in languages other than English,French, Portuguese or Spanish.No restrictions were imposed on the paper selection process regarding the year ofpublication and no additional limits were set. Additionally, no restrictions wereimposed regarding the reference composite standard for the diagnostic criteria of MCL.This characteristic was considered for the classification of selected papers and for theinclusion in the final meta-analysis model.via electronic correspondence.The papers were accessed using the periodicals portal available through the BrazilianFederal Agency for Support and Evaluation of Graduate Education on theinternet-connected network of the University of Brasília and through direct contact withthe authors After the search and review by the researchers, any disagreements were resolved by athird evaluator, who was blind to the identity of the researchers who conducted theprevious selection. Electronic communications were sent to all of the correspondingauthors of the selected papers with an inquiry regarding whether they knew of anypublished or unpublished study that addressed the criteria of interest. Additionally,the references cited in the pre-selected papers were examined for additional relevantstudies. Thesis databases at several internationally recognised universities weresearched as well (Supplementary data I).(r) v.3.01 . After this procedure, the corresponding authors of the selected paperswere again contacted by email with the intent of retrieving the data of papers in whichit was impossible to construct the 2 x 2 table and to confirm the precision of theaccuracy data obtained after reading the papers.The researchers constructed a 2 x 2 table based on the information contained in thepapers with the aim of calculating the sensitivity, specificity, predictive values andaccuracy using OpenEpiAnalysis of the selected papers - Two reviewers conducted thequalitative analysis and paper critiques. The qualitative assessment was based on thecompletion of the tables, which were constructed during the above-mentioned clinicalstudy previously published by this group .Analysis of the heterogeneity of the papers - In the first step, thepapers were separated according to the composite reference standard used to define thecases and controls. The papers were classified according to the use of clinical,immunological, or/and parasitological criteria  software  and thebivariate model was fitted in R(r) software, v.3.1.2, using the mada package. Thislibrary estimates the parameters by the restricted maximum likelihood method. All of thetests were bimodal (2-sided) and applied a 5% type I error rate.erformed . The uniAt the end of the selection process, 14 papers were included based on theabove-mentioned criteria  braziliensisspecies are endemic. Five studies were conducted in Peru, one in Colombia and one inArgentina. Five of the 14 papers included only patients with MCL. The remaining studiescombined cases of MCL and CL.One of the main reasons for heterogeneity among the selected papers was the compositereference standard used to define cases of MCL and controls. The patients were selectedbased on the compilation of clinical, epidemiological and parasitological criteria inonly three studies. A common error observed in six papers was the inclusion of a PCRtest to determine the inclusion and allocation criteria. Of the remaining studies, threeused parasitological criteria, one used clinical criteria and one did not report thediagnostic criteria used.One paper clearly stated the calculation of a sample size considering only the expected sensitivity of the tested diagnostic methods. Seven papersused a case-control design, whereas the other one-half of the papers used across-sectional/cohort design for the recruitment and allocation .s and biopsies and seven used tissue samples collected bybiopsy. The data on the positivity and characteristics of the tests are detailed inWith respect to the type of samples analysed, three used blood samples, one used urinesamples, one used lesion scrapings, one used lesion aspirates, one used nasalswabWith respect to the properties of the diagnostic tests, specificity tended to be thehighest. Ten papers had a specificity of 100% and two reported a specificity of lessthan 90%. The level of sensitivity reported in most of the papers was between 60-90%.Two papers reported sensitivities below 50% and one paper reported a sensitivity of100%.Critical analysis of the selected papers - The analysis was performedusing the QUADAS tool , Bracho et al. (2007) and Thomaz-Soccol et al. (2011). It was possible to comparethe results in these studies to clinical research previously performed by this group;however, this comparison was restricted to tissue samples .The joint estimates of sensitivity and specificity in the univariate and bivariatemodels are presented in Some authors have reported that systematic reviews on diagnostic accuracy testing tendto result in studies of differing quality compared with reviews that examine clinicaltrials . Additionally, papersregarding diagnostic accuracy have considerable methodological heterogeneity comparedwith that of intervention studies. For this reason, it is not always possible tocomplete a meta-analysis . The full methodological procedures arefrequently not described within the papers and to understand these procedures, one mustconduct a detailed reading of one or more papers cited by the authors.Definition of cases and controls (the use of a composite referencestandard) - The definition of cases and controls exerts a fundamentalinfluence on the results of accuracy diagnostic studies. Variations in these criteriawere one of the most frequent points of heterogeneity among the papers (e papers . Recent e papers . L. (V.)braziliensis is known for its low density of parasites and severe localinflammation . We evaluated the procedures used to define cases of MCL andcontrols . These results confirm previousreports that consider PCR to be the most accurate method for the diagnosis of MCL .Limitations - One of the most important limitations of this study isthat we excluded studies with fewer than eight cases of MCL. This decision aimed todefine a minimal relevance of studies because of an initial intention to includenon-controlled studies and to use only simpler univariate methods of aggregation. Thisprocedure was based on existing recommendations for sample size calculation indiagnostic test studies. As an example, a sample size of eight patients would only besufficient if a low confidence interval inferior limit were set in association with anexpected sensitivity level greater than 95%, which is not realistic for the diagnosis ofMCL  . Because we constructed a simplified tool thatcovered these domains and the domains related to molecular biology procedures , we deciThe heterogeneous application of the composite reference standard in the selected papersensures that it is difficult to separate the patients with CL or MCL. The simultaneousinclusion of these two forms of ATL was identified in nine studies, which may haveincreased the risk of bias during the extraction of the data from the studies. Afterconstructing the 2 x 2 table and calculating the sensitivity, specificity, predictivevalues and accuracy, the authors of previously selected papers were contacted by emailto retrieve the incomplete data and confirm the accuracy of the data. This approachaimed to reduce possible discrepancies between the accomplishments of the study and thepossible interpretations of the scientific paper.Recommendations - This systematic literature review analyses theavailable data on the PCR techniques used in the diagnosis of MCL. The significantmethodological heterogeneity makes comparisons between studies more difficult.Leishmaniaexhibited better sensitivity than other sequences (Based on these results, it is necessary to generate a consensus and protocols thatrecommend optimised practices for PCR in MCL . It is pequences . Additio


Obsessive–compulsive disorder (OCD) is characterized by persistent anxious thoughts (obsessions) and repeated rituals (compulsion) , 2. The n-back task. Although both groups demonstrated increased activation of CSTC circuits with increased memory load, the OCD group exhibited hyperactivation of the parietal lobe, mid frontal gyrus, dorsal prefrontal cortex, and dACC at both low (1-Back) and high (2-Back) levels of memory load compared to that of HC. This memory load-related hyperactivation has been proposed as an intermediate phenotype for OCD (The study by Diwadkar and colleagues  represen for OCD . Psychop for OCD . In keep for OCD , a revisRegardless, the findings in this study are consistent with earlier research on pediatric patients which found elevated dACC connectivity during performance monitoring . It alsoThe study by Diwadkar et al. represents one of the few attempts to investigate direct connectivity in OCD. The majority of brain connectivity studies have focused on undirected functional connectivity that refers to temporal correlation between the time series of different brain regions . The PPIElucidating the neural basis of OCD is of great importance to the treatment of this disorder. As more evidence accumulates to support the involvement of the CSTC circuits in the pathophysiology of OCD, researchers have started to develop treatments that target regions of the CSTC circuitry. For patients with OCD who do not respond effectively to traditional pharmacotherapy or cognitive–behavioral therapy, it has been shown that deep-brain stimulation could be another treatment alternative. In patients with refractory OCD, the stimulation of the nucleus accumbens effectively reduced the severity of OCD . RepetitAll authors listed have made substantial, direct, and intellectual contribution to the work and approved it for publication.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.


The influence of lateral gene transfer on gene origins and biology in eukaryotes is poorly understood compared with those of prokaryotes. A number of independent investigations focusing on specific genes, individual genomes, or specific functional categories from various eukaryotes have indicated that lateral gene transfer does indeed affect eukaryotic genomes. However, the lack of common methodology and criteria in these studies makes it difficult to assess the general importance and influence of lateral gene transfer on eukaryotic genome evolution.We used a phylogenomic approach to systematically investigate lateral gene transfer affecting the proteomes of thirteen, mainly parasitic, microbial eukaryotes, representing four of the six eukaryotic super-groups. All of the genomes investigated have been significantly affected by prokaryote-to-eukaryote lateral gene transfers, dramatically affecting the enzymes of core pathways, particularly amino acid and sugar metabolism, but also providing new genes of potential adaptive significance in the life of parasites. A broad range of prokaryotic donors is involved in such transfers, but there is clear and significant enrichment for bacterial groups that share the same habitats, including the human microbiota, as the parasites investigated.Our data show that ecology and lifestyle strongly influence gene origins and opportunities for gene transfer and reveal that, although the outlines of the core eukaryotic metabolism are conserved among lineages, the genes making up those pathways can have very different origins in different eukaryotes. Thus, from the perspective of the effects of lateral gene transfer on individual gene ancestries in different lineages, eukaryotic metabolism appears to be chimeric. New govations . LGT is ovations ,4. Althoovations -7. Thus,ovations ,9. Theseovations  or resulovations ,12. For ovations , and genovations -16. Althovations . On a glovations .Dictyostelium discoideum [Entamoeba histolytica, which lives in soil. Some of the parasites we investigated, including species of Leishmania and Trypanosoma, are closely related to each other, providing comparative insight into LGT over shorter timescales. Our systematic analyses provide a detailed insight into the dynamics, role, and potential importance of LGT in the evolution of a sample of parasitic microbial eukaryotes, but also have general implications for understanding how eukaryotic genomes and metabolic pathways have evolved.A range of different methods have been used to detect LGTs, with varying degrees of agreement between methods . Detailescoideum , a free-The majority 96%) of protein trees in the primary screen  with the T. brucei and T. cruzi genomes identified only a single LGT affecting the Leishmania lineage [Giardia lamblia [Toxoplasma gondii and Plasmodium falciparum [Cryptosporidium parvum [D. discoideum, E. histolytica, and L. major had the highest proportion of LGTs in relation to the size of their annotated proteome  with LGTs for the five insect-transmitted blood parasites  rejected the null hypothesis  that the functional categories of LGTs were distributed similarly across the two groups  for the same functional distribution of LGTs for these two amoebozoan species  in the types of LGTs detected between the gut-dependent apicomplexans (C. parvum and T. gondii) and the three insect-transmitted Plasmodium spp.  code for hypothetical or poorly characterized proteins Table . Using pT. vaginalis provide enzymes capable of the degradation of host glycans  malic enzyme (TN183) and tryptophanase (TN224), see Additional file Trichomonas, degrades tryptophan to ammonia, pyruvate, and indole. Pyruvate can be metabolized further to eventually contribute to ATP production by substrate-level phosphorylation in the cytosol of Entamoeba or the hydrogenosomes of Trichomonas [Several of the parasites have lost the pathway for oxidative phosphorylation, and therefore cannot make ATP by that route. In these species, energy is generated in other ways, including glycolysis, fermentation, and substrate-level phosphorylation . Both T. glucose -44. In Echomonas .Leishmania lineage, and two additional LGTs occurred in the common ancestor of T. brucei and T. cruzi. We also infer that T. brucei and T. cruzi each have gained additional LGTs, and both have independently lost some LGTs that were probably present in the common ancestor of the group  to those of the five insect-transmitted blood parasites (Plasmodium spp. and Trypanosoma spp.) strongly rejects the null hypothesis (P < 0.001) that the taxonomic distribution of the major prokaryotic donors are the same for the two sets of parasites , Treponema denticola (Spirochaetes), T. vaginalis  and E. histolytica (Amoebozoa). A number of candidate LGTs were also identified among microbial eukaryotes living on mucosal surfaces  of protein-coding genes per genome, with an average contribution across the 13 genomes of 1 LGT per 357 protein-coding genes  and thiol-peroxidase tree TN225); see Additional file ; see Addnia spp. , may pronia spp. . T. vagiembranes -57. Nineof mucus  and α-mao growth . The actE. histolytica, G. lamblia and T. vaginalis, which between them are responsible for over 500 million new infections annually [E. histolytica, G. lamblia and T. vaginalis for LGTs from donors related to Bacteroidetes and Firmicutes, the dominant lineages in the gut microbiota of humans and other vertebrates [E. histolytica and its free-living relative D. discoideum also supports this distinction.The taxonomy of some of the LGT donors was sufficiently well resolved to identify them as belonging to particular taxonomic groups and this allowed us to compare patterns of gene flow affecting specific parasites. Thus, several of the investigated parasites share a habitat with the complex and abundant prokaryotic community that lives in the gut of vertebrates  and on oannually , are samtebrates . CompariPlasmodium mosquito vectors were recently shown to have a gut microbiota that is highly enriched in proteobacteria [T. brucei harbors a bacterial flora enriched in Firmicutes [Beyond its importance for understanding how the mucosal microbial community, which is vital for human health , evolvesbacteria . Howeverrmicutes  comparedrmicutes .Our analyses complement existing studies, which show that EGTs from the prokaryotic endosymbionts ,12,41 thOur data strongly suggest that LGT from diverse prokaryotes has had a major effect on the origins of genes that make up metabolic pathways in contemporary eukaryotes. Thus, although the number of LGTs we detected for individual eukaryotic genomes was typically less than 1% of the genes analyzed, the significance of LGTs for eukaryotic metabolism can be better appreciated when the LGTs from all 13 genomes are shown together on a single metabolic map Figure . All 11 Protein sequences from 13 completed microbial eukaryote genomes were collected from public databases  the identity with the query protein seemed to be due entirely to repeats, for example, as in the leucine-rich repeats of TvBspA [Based on our previous experience in identifying LGTs in the genome of parasite ) to alloparasite  to detecequences ). The HSf TvBspA . These pCandidate LGTs passing the initial screen were subjected to phylogenetic analysis using maximum likelihood distances and Bayesian inference. We first used automated MrBayes  analysesLGTs were mapped onto the KEGG  metaboliFisher's exact test was used to test the hypothesis that functional annotation of LGTs or the taxonomy of the candidate donor lineage in well-resolved phylogenies was distributed equally between sets of contrasted taxa.x number of protein sequences from a given taxonomic group as LGTs, given a process of sampling without replacement from the whole dataset used to search for homologs. The probability of observing x number of a particular donor lineage is described as:Over-representation or under-representation of LGTs from a given taxonomic group Figure  was deteet al. [where N  represents the total number of prokaryotic protein sequences in the whole dataset used as the search space for this study, m (163) is the total number of sequences from identified prokaryotic donor lineages defined as the adjacent  prokaryobs, that it can be found in a randomly selected genome, and that the presence or absence of the enzyme is independent between genomes. Under this assumption, the number of genomes that must be sampled in order for the enzyme to be observed in the collection of pooled genes has a geometric distribution with parameter pobs, and the probability that the enzyme is observed in k genomes is 1-(1-pobs)k. We additionally assumed that the probability pobs is the same for all KEGG enzymes and that presence or absence of an enzyme in a genome is independent of all other KEGG enzymes. Using the empirical value pobs = 328/1,806  including the number of genes retained at each step of the analysis for the 13 analyzed genomes.Click here for fileProkaryote-to-eukaryote lateral gene transfers (LGTs). Table with the accession numbers and annotations of proteins for prokaryote-to-eukaryote LGTs supported in the Bayesian consensus trees by at least one node. For legends to the table, see Additional file Click here for fileEukaryote-to-eukaryote lateral gene transfers (LGTs). Table with the accession numbers and annotations of proteins for eukaryote-to-eukaryote LGTs supported in the Bayesian consensus trees by at least one node. For legends to the table, see Additional file Click here for fileEukaryote-to-prokaryote lateral gene transfers (LGTs). Table with the accession numbers and annotations of proteins for eukaryote-to-prokaryote LGTs supported in the Bayesian consensus trees by at least one node. For legends to the table, see Additional file Click here for filePhylogenetic trees supporting prokaryote-to-eukaryote lateral gene transfers (LGTs). Figure illustrating the phylogenies for the candidate LGTs from prokaryotes to eukaryotes supported by at least one well-supported node in the phylogenetic tree.Click here for filePhylogenetic trees supporting eukaryote-to-eukaryote lateral gene transfers (LGTs). Figure illustrating the phylogenetic trees for the candidate LGTs from eukaryotes to prokaryotes supported by at least one well-supported node in the phylogenetic tree.Click here for filePhylogenetic trees supporting eukaryote-to-prokaryote lateral gene transfers (LGTs). Figure illustrating the phylogenetic trees for the candidate LGTs from eukaryotes to prokaryotes supported by at least one well-supported node in the phylogenetic tree.Click here for fileComparison of lateral gene transfers (LGTs) detected in this and previous studies for individual taxa. Number of LGTs from this study contrasted with previously published LGTs cases for the target taxa. For all legends to the table, see Additional file Click here for fileRelative numbers of lateral gene transfers (LGTs) to proteome size. Figure and table of the relationship between the number of identified LGTs and the number of annotated genes in each respective genome.Click here for fileParalog counts for lateral gene transfers (LGTs). Estimated number of paralogs for each LGT listed in Supplementary Tables 1 to 3. For all legends to the table, see Additional file Click here for fileTaxonomy of donors of lateral gene transfers (LGTs). Table with the counts for specific comparisons between selected target taxa for the functional categories of LGTs or the taxonomy of LGT donor lineages supported by a least one node. For all legends to the table, see Additional file Click here for fileTaxonomy of donor lineages for candidate lateral gene transfer (LGT) between specific subsets of protists, with extended versions and additional comparison. Diagrams presenting comparisons of donor lineages for candidate LGTs between different groups of protists.Click here for fileTaxonomic counts of donors of lateral gene transfer (LGTs). Table with the counts of the taxonomy of the potential prokaryotic donor lineages for LGTs supported by at least one node  annotations. Table with the number of proteins annotated in KEGG for all the 13 target genomes analyzed in this study and the corresponding diversity of KEGG entries for annotated enzymes. For all legends to the table, see Additional file Click here for fileLateral gene transfer (LGTs) affecting KEGG secondary metabolites and regulatory pathways. Figure illustrating the LGTs mapped onto the KEGG secondary metabolite and regulatory pathways.Click here for fileKyoto Encyclopedia of Genes and Genomes (KEGG) pathway for the degradation of gangliosides. Figure illustrating a schematic overview of the KEGG pathway for the degradation of gangliosides.Click here for fileTable legends. Legends for tables in additional files Click here for file


Ulex europaeus. This study was carried out in southwest France in the context of water and nutrient stresses (mainly phosphorus limitation) due to the presence of nutrient-poor sandy soils. We analysed the regeneration of the species from the germination of seeds and emergence of new seedlings until the seedlings reached young shrub size. Our design included a P fertilisation treatment. We also investigated microsite characteristics (micro-topography and vegetation development) as they can interact with meteorological conditions and determine water availability for seeds and seedlings. We found that P availability controlled seedling growth and the time necessary to reach young shrub size. Water availability appeared to impact the species germination and seedlings survival. We also found that P and water availability depended on the interactions between microsite characteristics and climatic variations. Finally we found evidence that P and water availability are important ecological factors shaping the regeneration niche of the species, but we found weak evidence that any microsite would be appropriate for the regeneration of the species in the long term. Future studies regarding regeneration niches need to distinguish more clearly the ecological factors important for regeneration (the regeneration niche per se) and the physical world where the seedlings appear and develop (the regeneration habitat).The identification of an ecological niche specific to the regeneration phase has mobilised significant attention. However, the importance of the regeneration niche concept remains unclear. Our main objective was to study the existence of such a regeneration niche for a leguminous shrub,  The regeneration phase is of prime importance in the life history of woody plants. It determines species population dynamics, and in turn plant community assemblages. Following the pioneer work of Grubb , the idein situ the existence of such a regeneration niche for a woody species, Ulex europaeus L. (hereafter referred to as gorse). We made this choice because gorse is spontaneously present in a one million hectare area of south-western France, the Landes de Gascogne forest, which is characterized by acidic sandy soils )rubs see .2 placed within the stand, giving 24 quadrats per block. In each block, the 4 combinations of the treatments received 6 quadrats. Distribution of the quadrats within the different combinations was semi-systematic to ensure the presence of quadrats throughout the whole stand surface. At this scale, the main responses of the model species recorded were: the number of new seedlings that emerged , the proportion of dead seedlings (between 0 and 1), and the proportion of seedlings successfully recruited .Seedling emergence, survival, growth and recruitment success were monitored for two years every 50 ± 5 days, except during winter, with no survey from the beginning of December to the end of March, thus giving a total of 12 censuses. This monitoring was done at two different scales: the coarse-grained scale consisted of 72 quadrats of 1 m2. Each cell (with sides of 10 cm) had two coordinates, x and y, from 1 to 10, the cells  from CS615 probes (Campbell Scientific) in two sites close-by, under conditions similar to the experimental stand (i.e. young pine stands with low vegetation development and the same sandy soil texture). Data from the closest site (3 km) were only available for 2011, so we preferred to use data from a site farther away (30 km) after verifying that the daily soil water content measured at both sites in 2011 were highly correlated  based on visual vegetation cover . The vegetation development index was calculated as the sum of the 9 scores which ranged from 0 to 18. In addition, for each year of the study, after the end of vegetative growth, aerial biomass of the vegetation was harvested from four areas of 20 cm1-9t is the raw vegetation index at observation t; Biomjt is the aerial biomass of quadrat j weighed in the year corresponding to observation t; max (Biom)t is the maximum of aerial biomass weighed for the 72 quadrats in the corresponding year. Finally we grouped microsites based on three vegetation development classes of equal size , respecting the distribution of the tertiles of the vegetation development index.Σ COVERThe dry biomass harvested around each quadrat was used as an indicator of vegetation development at the coarse-grained scale.1) which individuals were dead and why? and 2) among the survivors, what were the factors or variables that influenced growth ?The response of a seedling depends largely on its date of emergence. Thus, we focused specifically on the response of different cohorts of seedlings (i.e. groups of seedlings whose presence was first recorded at the same census). With regard to seedling emergence, the effect of the sowing treatment was obvious. Sown and unsown areas were consequently analysed separately. Concerning seedling development, mortality and growth are two dependant processes. A low growth rate may indicate a plant that is not vigorous and healthy, which may lead ultimately to death. When the growth of a cohort of seedlings is analysed for a given lapse of time, some individuals present at the beginning of the interval are dead and absent by the end of the period. This 'not at random' loss of a part of the sample, preferential to seedlings with low growth rates, may lead to the spurious interpretation of statistical models . Thus de2 quadrat scale) were made by using variables characteristic to the quadrats .Emergence of new seedlings and mortality were first analysed at the microsite scales, and over the interval of time between two censuses (approx. 50 days). The microsite variables (classes of micro-topography and of vegetation development at this time) were used for these analyses as well as treatments applied to the stand (P fertilisation and sowing). Events that occurred in the interval between two censuses were also compared to the SWAI corresponding to the same lapse of time. As the responses at the microsite scale were measured repeatedly at different censuses, we also performed longitudinal analyses for the evolution of new seedling emergence, mortality and growth of seedlings during the course of the study in different kinds of microsites. Coarse-grained analyses , we used general linear modelling with logit link function (i.e. logistic regression) for analysis. We used general linear modelling with log link function for Poisson distributed count data (e.g. number of new seedlings per quadrat).Regarding the probability of seedling emergence between two censuses, we used mixed models with random intercepts to take into account the dependence of the microsites of the same quadrat (lme4 package in R). Concerning seedling mortality between two censuses, since we often had only one seedling per cohort and per quadrat, we could not fit mixed models with a random intercept for each quadrat . Instead, we fitted conventional general linear models, and checked the significance of all model parameters using ordinary non parametric bootstraps with 2000 permutations (bootstrap package in R). Regarding longitudinal analysis, new seedlings emerged at each census. Thus we analysed the evolution of the proportion of different kinds of microsites without any seedling emergence during the course of the study with Cox proportional hazard models. The same kinds of models were used for survival analysis per cohort of seedlings in different kinds of microsites. We used mixed Cox models (library coxme in R) with a random intercept for each quadrat. As for growth, seedling size was normalised with logarithmic transformation. Then, we used mixed linear modelling with a continuous random effect for repeated measures of the size for the same individuals (library lme4 in R).Analysis of deviance tables were made for general linear models regarding the number of emerged seedlings and recruits per quadrat on a yearly basis. The proportions of dead and recruited seedlings were analysed in the same way.Important seasonal climatic variations occurred during our experiment . The mosMortality was also high in winter 2010–2011. We observed that the period immediately following emergence formed a critical stage for seedling survival. Indeed 151 of the 328 deaths (i.e. 46%) recorded during the survey were recorded following emergence. Periods of recruitment, when the plant size threshold was reached , extendeDespite emergence in contrasting climatic conditions and within a more or less developed vegetation cover Fig  and 1b, P fertilisation did not influence seedling emergence. Instead, its main effects were on seedling survival and seedling growth. During the dry summer 2010 (low SWAI), survival of seedlings that had just appeared was lower in fertilised areas, whereas in early spring 2011 (higher SWAI), their survival was lower in unfertilised areas . The lonRegarding growth, at the fine-grained scale, for seedlings that survived until the end of the study, P fertilisation was the main explanatory variable that enhanced growth, indicating that the size threshold for successful recruitment was reached faster in fertilised plots (result not shown). In fertilised areas, for early emergent seedlings (first cohort), the observed growth was higher where vegetation development was also higher over the whole study . For mos2 fixation rate (%Ndfa) in the gorse seedlings in fertilised areas in 2010. Conversely, the fixation rate was 10% lower in fertilised than in control areas , mortality of seedlings that had just appeared was lower when vegetation development was high .The most obvious effect of P fertilisation treatments on gorse regeneration was an improvement of seedling growth, which led ultimately to a higher number of successfully recruited seedlings in fertilised areas. This is consistent with other studies which found that P-availability limits legume growth . MoreoveIn P fertilised areas, we found an even higher growth for early emergent seedlings in microsites with higher vegetation development . This redfa., In addition, in 2010 we found a marginally significant positive effect of fertilisation on the rate of biological nitrogen fixation %Ndfa., . FertiliResults in relation to seedling survival in response to P fertilisation are better explained by taking into consideration the importance of water availability. Indeed, plants in fertilised areas have less developed and/or more superficial root systems which are concentrated in soil layers of high nutrient availability (e.g. ). ConseqWater availability was not measured directly in our experimental stand. Thus our interpretations regarding water availability presented here have to be considered with care. On the other hand, it is important to note that variations of our seasonal water availability index (SWAI) were totally consistent with the meteorological variations observed during the course of the study, which suggests that the use of our index is fairly justified.The general observation of seasonal variations of gorse regeneration  highlighUlex parviflorus seedling emergence has also been shown [The variation of emergence frequency in micro-pits with seasonal water availability suggests the specific role of local soil moisture around seeds. The increase in local soil moisture of micro-topographic pits is well described in farming systems where ridges and furrows are created during soil preparation ,42. Thusen shown . In thatThe decrease in mortality just after emergence in the presence of important vegetation development during dry episodes .Ulex parviflorus [The strategy of regeneration that appeared in our results—the importance of the early emergence after a disturbance, sensitivity to water availability and the importance of the facilitation by nurse plants during dry episodes—is totally consistent with former results regarding the Mediterranean gorse, viflorus ,39. As tviflorus .Moreover, many significant and contrasting effects were detectable during the fine-grained analysis, whereas only two results emerged at the coarse-grained scale: 1) the number of new seedlings increased with micro-topographic heterogeneity in the quadrats, certainly due to the higher frequency of micro-pits; and 2) recruitment was enhanced in fertilised areas, related to the improvement of seedling growth. No explanatory variable could be identified at the coarse scale regarding seedling mortality. In the context of our study, habitats with marked micro-topography in fertilised areas appeared more favourable for the recruitment of the species. In these habitats, appropriate soil moisture for germination may be found more frequently in micro-pits, and phosphorus availability for seedlings development was certainly higher there. Yet the generalisation and assignation of these habitats to the species regeneration niche remains questionable for two reasons.Firstly, it is important to take the high variability observed during the fine-grained analysis into consideration. P and water availability depended on the interaction between microsite characteristics and stochastic climatic variations. For instance, the increase in phosphorus availability removed a major limitation on growth but, on another hand, survival decreased in fertilised areas for some cohorts during dry periods. Thus, the effect of fertilisation on recruitment of new plants was contrasted, as reported in former studies (e.g. ). This cUlex species in the Mediterranean region [Secondly, the role of micro-topography that was observed at the coarse-grained scale is totally consistent with results found for the first cohort of seedlings, which accounts for 46% of recruited individuals. The difference in proportion of micro-pits where new seedlings appeared, compared with the rest of the micro-topographic classes at the end of the study, is almost totally determined by the initial difference that occurred when the first cohort appeared . Thus, tn region . ResultsIn his early definition, Grubb stated that the regeneration niche ‘includes elements of both address and profession’ and is partly composed of the 'habitat niche' or 'the physical and chemical limits tolerated by the mature plant in nature'. One migIn field studies, probably influenced by the ‘habitat niche’ definition of Grubb, the characterisation of regeneration niches has frequently been made on the basis of distinct habitats or micro-habitats distributed along a transect between the centre and the periphery of a gap, along a topographic gradient, or on different substrates  and the physical world where the seedlings appear and develop.This S1 File(DOCX)Click here for additional data file.S2 File(DOCX)Click here for additional data file.S3 File(DOCX)Click here for additional data file.


Acute dyspnea is a common symptom in the emergency department and several studies have investigated the usefulness of Lung Ultrasound (LUS) in the approach to the patient with dyspnea with different results.On the basis of the literature, we performed a prospective observational study, aiming to assess the accuracy of LUS for the diagnosis of cardiogenic dyspnea in patients presenting at the emergency department with acute dyspnea.70 patients presenting with acute dyspnea have been enrolled.On admission every patient underwent to LUS and chest X-ray (CXR). Ultrasound findings of Interstitial Alveolar Syndrome (IAS), which correlate with an increase in interstitial lung water, were reported. On the results of LUS, the patients were attributed to 2 different diagnostic groups: Group 1: patients with cardiogenic dyspnea, Group 2: patients with respiratory dyspnea. CXR was performed as gold standard exam to discriminate the respiratory and cardiogenic origin of the dyspnea. At the discharge from the hospital, two investigators blind to the results of the LUS exam, revised all the clinical charts and attributedevery patient to a definitive diagnostic group. On the basis of the results, it was possible to calculate Sensitivity, Specificity, Positive Predictive Value, Negative Predictive Value of LUS and CXR for the diagnosis of cardiogenic dyspnea.LUS showed a sensitivity of 92%, Specificity 93%, PPV 88%, NPV 95%; while CXR showed Sensitivity 79%, Specificity 74%, PPV 61%, NPV 87%. Differences between Specificity and PPV were significant .LUS can be more effective than CXR for the diagnosis of cardiogenic dyspnea.


This study analyzed cost of implementing computer-assisted Clinical Decision Support System (CDSS) in selected health care centres in Ghana.A descriptive cross sectional study was conducted in the Kassena-Nankana district (KND). CDSS was deployed in selected health centres in KND as an intervention to manage patients attending antenatal clinics and the labour ward. The CDSS users were mainly nurses who were trained. Activities and associated costs involved in the implementation of CDSS (pre-intervention and intervention) were collected for the period between 2009–2013 from the provider perspective. The ingredients approach was used for the cost analysis. Costs were grouped into personnel, trainings, overheads (recurrent costs) and equipment costs . We calculated cost without annualizing capital cost to represent financial cost and cost with annualizing capital costs to represent economic cost.Twenty-two trained CDSS users  participated in the study. Between April 2012 and March 2013, users managed 5,595 antenatal clients and 872 labour clients using the CDSS. We observed a decrease in the proportion of complications during delivery (pre-intervention 10.74% versus post-intervention 9.64%) and a reduction in the number of maternal deaths (pre-intervention 4 deaths versus post-intervention 1 death). The overall financial cost of CDSS implementation was US$23,316, approximately US$1,060 per CDSS user trained. Of the total cost of implementation, 48%  was pre-intervention cost and intervention cost was 52% . Equipment costs accounted for the largest proportion of financial cost: 34% . When economic cost was considered, total cost of implementation was US$17,128–lower than the financial cost by 26.5%.The study provides useful information in the implementation of CDSS at health facilities to enhance health workers' adherence to practice guidelines and taking accurate decisions to improve maternal health care. The widely used approach to improve the skills of health workers and the quality of health service provision is the use of clinical decision support systems In the light of this, most African countries adopted the WHO guidelines on Pregnancy, Childbirth, Postpartum and Newborn Care (PCPNC) th Framework programme of the European Union. Computer-assisted CDSS has been successfully implemented in developed countries and applying it in developing countries is promising In Kassena-Nankana District of Northern Ghana (KND), the paper based WHO PCPNC guideline is poorly used and followed by health workers In addition, a computer-assisted CDSS can support clinicians in reducing medical errors and costs The QUALMAT computer-assisted CDSS is designed based on locally adapted WHO PCPNC Despite the advantages associated with the use of computer-assisted CDSS, the costs of implementing such a system for ANC and delivery services in primary care facilities in developing countries is unknown. This study describes the activities and the cost  of a computer-assisted CDSS implementation in the Kassena-Nakana district of northern Ghana to provide estimates that may be useful in guiding other initiatives for computer-assisted CDSS implementation.The study was approved by the ethics committee of the University of Heidelberg (S-173/2008) and the Institutional Review Board of the Navrongo Health Research Centre in Ghana (NHRCIRB 085).The study was done in the Kassena-Nankana District of northern Ghana. The district is located in the northeastern corner of the country bordering Burkina Faso, and occupies an area of about 1,675 square kilometres. As in many parts of the savanna zone of Ghana, poverty is endemic in this district. Due to the erratic nature of rainfall and deteriorating soil quality, harvests are often poor and seasonal food shortages are not unusual. The KND has a population of 150,000 with females constituting 53% The district has a district hospital located in Navrongo that serves as a referral point for the Kassena-Nankana district, the Builsa district and neighboring towns in Burkina Faso. There are six main health centers, and two community clinics jointly run by the Catholic Diocesan Development Office and the District Health Administration that provide services to the communities. There is one private clinic and 27 functional Community-based Health Planning and Services (CHPS) compounds with resident Community Health Officers (CHOs) offering doorstep services A descriptive cross sectional study was conducted in the Kassena-Nankana district. The study captured data from October 2009 to March 2013. Costs were collected from the programme/provider perspective. All information on activities involved in the implementation of the computer-assisted CDSS and associated costs were collected. These activities included training of computer-assisted CDSS users, buying equipment such as laptops and monitoring and supervision of computer-assisted CDSS users. Computer-assisted CDSS software development costs were not collected and therefore not included in the analysis. The study is part of a wider project assessing the quality of maternal and prenatal care  using a computer-assisted CDSS. The QUALMAT research project started in 2009 as collaboration between six partners- Centre de Recherche en Santé de Nouna (Burkina Faso), Ghent University (Belgium), Heidelberg University (Germany), Karolinska Institute (Sweden), Muhimbili University of Health and Allied Sciences (Tanzania), and Navrongo Health Research Centre .The computer-assisted CDSS is being tested in the six health care centres in the Kassena-Nankana district. Each health centre has at least a nurse, a midwife, and a medical assistant and provides outpatient services and normal deliveries. With regards to maternal health care, the Ghana health service policy stipulates that all health facilities are to use the reproductive health guideline “ National Safe Motherhood Service Protocol (2008)” The selected health centres have basic infrastructure such as utilities (electricity and water) equipment and medical supplies Future users (midwives), medical experts and Information Technology (IT) specialists jointly developed the computer-assisted Clinical Decision Support System (CDSS) within the project and the system was subsequently adapted to the country specifics of Tanzania, Burkina Faso and Ghana. The Ghana computer-assisted CDSS is based on Ghana's reproductive health guideline “ National Safe Motherhood Service Protocol (2008)” Two software release candidates were piloted and feedback incorporated to produce a final version that was then used for implementation. The final version of the computer-assisted CDSS software was implemented and authorized for use in patient care in the six health centres in April 2012.A form was designed for the project coordinator to document all activities and associated costs (quantities and unit costs) that occurred during the CDSS implementation. In addition, the project had a financial manager who kept records on all expenditure made on the project. Information on the activities and costs were therefore retrieved from both the project coordinator and the financial manager. We collated information on trainings, meetings, management, monitoring and supervision as well as logistics and transportation involved in the computer-assisted CDSS implementation . Data onFor the effects of the CDSS, we collected pre-intervention data to capture 12 months (April 2011 to March 2012) of information on maternal health routine services before computer-assisted CDSS implementation and the post-intervention captured 12 months (April 2012 to March 2013) of data after computer-assisted CDSS implementation. The health centres have books that there record maternal health services provided. We therefore reviewed these books or registers at the health centres and collected data on the number of antenatal consultations, labour cases, deliveries, referrals (due to complications) during ANC visits as well as labour referrals (due to complications). We also collected information on maternal mortality that occurred at the study health centres during the study period.The data were entered, cleaned and analyzed using excel. An ingredients approach where quantities of the resources are multiplied by their unit prices was used to calculate costs. Costs were categorized into personnel, trainings, overheads costs (representing recurrent costs) and equipment costs .Costs of implementation were further grouped into two phases. The first phase was referred to as the pre-intervention phase. This first phase was defined as all activities and associated costs that occurred before computer-assisted CDSS was commenced for patient care (October 2009 to March 2012 period). The second phase was referred to as the intervention phase and included all the activities and associated costs incurred during the 12 months period of actual use of computer-assisted CDSS for patient care (April 2012 to March 2013). The cost of implementation was calculated by adding the pre-intervention costs and intervention costs.We calculated cost without annualizing capital cost to represent financial cost of the implementation and cost with annualizing capital costs to allow differential timing of capital costs to represent economic cost. Capital costs (resources with lifespan greater than 1 year) such as equipment  were annualized using discount rate of 3% and a useful life of 5 years, consistent with economic evaluation guidelines Personnel costs were calculated by summing the cost incurred on staff involved in the computer-assisted CDSS intervention during the 12 months period of actual use of computer-assisted CDSS for patient care. The two main staff that were involved were a technical Officer and computer-assisted CDSS users. A technical officer with knowledge in information technology (IT) provided trainings and technical support to the computer-assisted CDSS users. The officer visited the computer-assisted CDSS users fortnightly to monitor and supervise them. The technical officer also downloaded data captured in the computer-assisted CDSS and updated antivirus during the monitoring visits. In addition, whenever a computer-assisted CDSS user moves , the officer trains a new user to continue the use of the computer-assisted CDSS. Based on the time spent monitoring, supervising and training the computer-assisted CDSS users (45% of time spent on CDSS activities) and the monthly pay for staff in technical officer category , an agreed amount of US$250 was paid per month to the technical officer. The total cost of the technical officer was therefore calculated by multiplying number of months worked by the monthly allowance.Not all staff at the health centres were trained to use the CDSS. At least two nurses were trained in each health centre. Each health centre had at least one midwife. All the midwives in the health centres were trained. In addition to the midwives (main CDSS users), some community health nurses (CHN) were trained to support the midwives. These additional nurses were selected in consultation with the in-charges of the study health centres. The basic criteria for selection of these additional nurses for the training were based on their involvement in the provision of antenatal care and delivery in the health centre. Whenever a midwife was transferred or on annual leave or left for further studies, a new person was trained on time for replacement. The staff that were not selected and trained to use the CDSS carried out their normal duties. CDSS users and non-users both abided by the normal work regulations (both start and close work same time). In order not to disrupt the normal duties of the selected CDSS users, training sessions were organized on days and times that were most convenient to the CDSS users.For the period, 22 computer-assisted CDSS users were trained . The government of Ghana pays on average US$626 per month to a midwife, and US$ 404 per month to a community health nurse. We did not include these salary costs in our personnel cost, since this cost was already incurred by the government and the focus was on additional costs. However, in order to motivate the computer-assisted CDSS users to use the system, a token  of US$31 was given per month to each CDSS user. Cost of computer-assisted CDSS users was therefore calculated by multiplying the number of months worked by the computer-assisted CDSS users by the monthly allowance.Training costs included all cost incurred during the various training sessions. For the period, a total of six major meetings/training sessions were held. The first meeting was a one day stakeholder meeting, in which the directors of health services, district public health nurses, midwives and other key stakeholders participated. During the meeting, the computer-assisted CDSS concept was discussed and approval and support by the stakeholders were established.Five training sessions for the computer-assisted CDSS users were held. Each training session lasted two days. The training sessions were facilitated by a technical officer and four support staff . The computer-assisted CDSS users were first introduced to basic computer training sessions, as most of them were using computers for the first time. Further specific trainings on computer-assisted CDSS usage (2 trainings: pre-intervention period) and refresher trainings (2 trainings: intervention period) took place. These training workshops aimed to help users understand the algorithm, the algorithm stages and the decision stages of the programme. During the training workshops, demonstrations and hands-on training took place. In addition, each participant was asked to enter an initial and follow- up visit using a simulated patient material. The computer-assisted CDSS users were also taught how to access and use technical support on the software. Participants of these trainings were each paid an allowance of US$11 per training day for their time. This is a standard amount paid by the Ghana Health Service to health workers who participate in trainings of this kind. The cost of training was calculated by summing all the allowances for participants, facilitator and support staff per training session and other expenditure made during the training sessions.Transportation costs were calculated as hired costs (US$0.45 per km) per vehicle rented for visiting the health centres for monitoring and supervision. The total cost for transportation was therefore calculated by multiplying the kilometre covered by the cost per kilometre.Equipment costs included all the equipment bought for the computer-assisted CDSS implementation and the associated costs. Six dell laptop computers  were purchased and the computer-assisted CDSS software was installed on each of them. These laptops were distributed to each of the six health centres. One additional laptop was bought and the software installed on it, and it served as a backup laptop. In addition, six computer tables and chairs were bought and distributed to the six computer-assisted CDSS health facilities to support computer-assisted CDSS users' work. The total equipment cost was calculated by multiplying the unit cost of items by the quantities. Further analysis was done where laptops, chairs, tables were categorized as capital cost and were annualized using discount rate of 3%, and a useful life of 5 years to determine the economic cost.Other costs (overheads) including stationary, repairs of computers and other costs incurred in the computer-assisted CDSS implementation were obtained and calculated by multiplying the unit cost of the items by their quantities.Average cost of training a computer-assisted CDSS user was calculated by dividing the total cost of computer-assisted CDSS implementation by the number of computer-assisted CDSS users trained during the entire study. Computer-assisted CDSS cost per woman managed was calculated by dividing the total cost of implementation by the total number of women managed using computer-assisted CDSS.One-way sensitivity analysis was conducted to determine whether changes in variables such as discount rate and life expectancy of equipment will change the economic costs of CDSS implementation significantly. Accordingly, we varied the discount rate from 3% to 5% and 10% as well as the life span for equipment from 5 years to 10 years.Given that the aim of this analysis was to provide the cost of the computer-assisted CDSS implementation, which would be of use to health providers/policy makers considering the use of computer-assisted CDSS within health centres, we did not include health centre specific costs such as actual salaries of computer-assisted CDSS users (midwives and CHNs), capital costs  in the analysis as these were already costs incurred by the health centres. Only additional costs not already borne by the health centres were included.In addition, cost of developing the CDSS software, research cost such as cost of conducting cross sectional surveys and qualitative studies and other costs not related to computer-assisted CDSS implementation were not included.Costs results are presented by: pre-intervention cost (cost from October 2009 to March 2012); intervention representing the cost incurred over the course of the one year intervention (from April 2012 to March 2013); and cost of implementation representing overall cost (pre-intervention plus intervention cost). Costs were also presented by health centres. The personnel, training, and overhead costs were allocating to the various health centres based on the number of staff trained per health centre. Transportation cost allocation was based on the distance from the research centre to the health centres. All costs were collected in local currency, Ghana cedis  on computer-assisted CDSS to manage antenatal and labour patients. The prime users were the midwives with the CHN providing assistance. Out of 22 nurses, about 80% (18) had no basic computer knowledge before they were introduced to computer-assisted CDSS. However, with the intensive training, all were able to attain the necessary skills to use the computer-assisted CDSS. Twelve months before the CDSS implementation (pre-intervention), the total number of ANC consultations was 12,343 . At the end of 12 months of CDSS implementation (April 2012 to March 2013), ANC consultations increased to 12, 854  . Of the It must be noted that not all clients were managed with the CDSS. There were occasions that the main CDSS user was not available during ANC consultations or/and delivery and for that matter clients were not managed using the CDSS. Out of the total ANC consultation patients, 5,595 (44%) were managed in line with guidelines by a midwife using the computer-assisted CDSS.During the 12 months pre-intervention period, the number of labour cases registered in the six health centres was 1,769 . Of the total labour cases, 10.74% (190) had complications during labour/delivery and were referred to a hospital for care. At the end of the twelve months CDSS intervention, the proportion of women who had complications during labour or delivery and were referred decreased to 9.6% (141), though the difference was not statistically significant . Comparing labour clients and deliveries, the proportion of deliveries attended by skilled midwives increased from 89% (pre-intervention) to 90% (post-intervention), though not statistically significant . Out of 1,463 labour patients recorded during the intervention period, 872 (60%) were managed using computer-assisted CDSS . This reThe average time spent by a midwife per antenatal consultation without the use of CDSS was about 10 minutes. Using the CDSS doubled the average time spent on an ANC client to about 20 minutes. Due to problems related to data collection, we were not able to estimate the time spent by midwives on labour clients before and during CDSS intervention.Of the total financial cost of implementation, equipment cost accounted for the largest proportion of expenditure (34%), followed by personnel (29%), while training and transportation costs accounted for 12% and 8.5% respectively. About 61%  of the equipment cost was spent on the purchase of the computer-assisted CDSS laptops. By disaggregating the costs, recurrent cost  was US$15,399 representing 66% of total cost.The distribution of economic cost is presented in Results from sensitivity analysis  showed tThis study analyzed cost for implementation of computer-assisted Clinical Decision Support System (CDSS) in six primary health centres in the Kassena-Nankana district of northern Ghana. The findings indicated that the total financial cost of implementing a computer-assisted CDSS was US$23,316 while the average financial cost per antenatal case using computer-assisted CDSS was $4.17 as well as the per labour case was $26.7. About US$1,060 was needed to train a nurse to use a computer-assisted CDSS. However, due to economies of scale the unit costs are likely to fall over time.In this study, it is important to note that the greatest proportion of the cost of the computer-assisted CDSS implementation was intervention phase costs. This is in the right direction as compared to other projects implementing new technologies such as computer-assisted CDSS, where most of the total costs were spent in the pre-intervention phase Equipment such as durable laptop computers are the core of the computer-assisted CDSS. We used laptop computers against desk tops because of unstable power supplies (frequent light offs) faced in the study district. Given that large data captured by computers slows down the system, it is desirable to use a computer with a reasonable space (hard drive) and memory (RAM). In our study, equipment costs accounted for the largest proportion of financial cost (34%). This is contrary to other studies in related areas, that rather found cost of personnel accounting for the entire cost of implementing a computer-assisted CDSS CDSS users were cautioned to take proper care of the laptops to avoid lost or theft. For study period, no computer was stolen. This corroborates with a similar study conducted in Ghana (MOTECH) in which mobile phones were provided to nurses to provide maternal health care and there was no reported loss of a mobile phone Training on the use of the computer-assisted CDSS was an essential component of the computer-assisted CDSS implementation. Though most of the computer-assisted CDSS users (midwives and CHNs) had no/limited computer knowledge, the study demonstrated that with substantial training and regular support, health workers in rural settings can acquire computer skills and apply it on computer-assisted CDSS for antenatal and delivery care. The need for substantial training of computer-assisted CDSS users has also been mentioned in similar studies In general, there is low computer knowledge among health workers in Ghana which limits computer usage in the various health facilities. However, in recent times, Information and Communications Technology (ICT) teachings in various schools, including health training schools in Ghana have been intensified. Also the Ghana Ministry of health has instituted strategies to improve ICT in the health facilities Computer-assisted CDSS allows nurses to follow thoroughly the algorithm and patient care guidelines and it provides checks which prompt nurses to complete the whole cycle of care at lower health facilities such as health centres. In our study, on average, one midwife was able to provide all the vital care on 44% of ANC clients and 60% of labour clients with the aid of computer-assisted CDSS. The findings of the study showed increase in the proportion of identified pregnancy complications during antenatal consultations. Considering that most maternal deaths are due to delays in recognizing early complications (danger signs) and immediate referrals Computer based is appropriate over the paper-based CDSS because with computer based, patient characteristics and clinical data are matched to a computerized clinical knowledge base and recommendations are then presented to the health provider to make a decision at the point of care Notwithstanding the numerous benefits of CDSS, there are few reported rejections. For instance, a study reported rejection of CDSS by nurses and physicians based primarily on ethical viewpoints Considering the activities involved and the cost distribution in the implementation of the computer-assisted CDSS, adopting the system and integrating it into the routine maternal health care delivery is feasible and it would require marginal additional costs. For instance, given that personnel costs accounted for a high proportion of total costs, if the system is integrated into the normal health care delivery, this cost component would be reduced or eliminated. Also, over time, transportation costs relating to frequent monitoring and supervision of computer-assisted CDSS users will reduce when users became adequately versed with the system. The additional costs that would therefore be required would be computer costs which would be relatively marginal especially considering economic costs.The costs presented are based on only one- year usage of the computer-assisted CDSS. However, there is the likelihood of additional costs for maintaining the system over time . Staff attrition is a possible additional cost. For instance, when trained computer-assisted CDSS users are transferred or leave for further studies, new users would have to be trained and supported. There is the possibility of declining willingness to use the system over time which can negatively affect the sustainability of the system. However, if the system is well integrated into routine maternal health care activities at the health centres, then it would be mandatory for the system to be used.This study provided a lower-bound estimate of the total cost of computer-assisted CDSS implementation as we did not include some costs components such as building costs and salaries of the CDSS users. When these costs are included, the total cost will increase substantially. For instance, given that the government pays on average US$626 per month to a midwife, if this cost is included, then the cost of salaries of midwives for the one year period will be US$45,072. When this is added to the total cost of CDSS implementation , the total cost will quadruple . Nevertheless, the study was based on the assumption that if CDSS is incorporated into routine maternal health care, these costs components that are already catered for by the government will not be additional costs to the health centres.There is no published study on cost of computer-assisted CDSS implementation in a developing country to compare our results. The few available studies on cost of computer-assisted CDSS were conducted in developed countries Though maternal mortality is preventable, these deaths continue to drain a nation of its human resources and Gross Domestic Product (GDP). This study revealed that using computer-assisted CDSS to manage antenatal and delivery clients by midwives in a rural setting is possible. The system can reduce complications during delivery and as a result can reduce maternal deaths. A financial cost of approximately US$1,060 is needed to train a nurse to use computer-assisted CDSS for a one year period. The study provides useful cost information in the implementation of computer-assisted CDSS to enhance health workers adherence to practice guidelines and taking accurate decisions to improve maternal and child health quality.


In this article, we have studied the flow and heat transfer in Sisko fluid with convective boundary condition over a non-isothermal stretching sheet. The flow is influenced by non-linearly stretching sheet in the presence of a uniform transverse magnetic field. The partial differential equations governing the problem have been reduced by similarity transformations into the ordinary differential equations. The transformed coupled ordinary differential equations are then solved analytically by using the homotopy analysis method (HAM) and numerically by the shooting method. Effects of different parameters like power-law index  Because of the occurrence in a variety of engineering operations the boundary layer flow and heat transfer over a stretching surface has gained much importance. A few applications in the field of chemical engineering and metallurgy include extrusion of polymers, production of paper and so forth. The final product's quality massively depends on heat transfer rate between the fluid and stretching surface during the operation of heating and/or cooling. Consequently, most suitable heating and/or cooling fluid must be chosen as it has immense influence on the heat transfer rate. The physical importance of heat transfer over a moving surface has compelled many researchers to report their findings on this topic et al.et al.et al.The convective heat transfer is of excessive significance in procedures in which high temperatures are involved. For instance, gas turbines, nuclear plants, storage of thermal energy etc. Referring to numerous industrial and engineering processes the convective boundary conditions are more practical including material drying, transpiration cooling process etc. Due to the practical importance of convective boundary conditions several researchers have studied and reported results on this topic for viscous fluid. Bataller et al.et al.et al.et al.et al.On the other hand, the study of non-Newtonian fluids including Generalized Newtonian Liquid (abbreviated as GNL) with heat transfer has gained extensive importance due to a number of industrial applications such as molten plastic, polymer solutions, pulp and foods etc. At the same time, heat transfer in non-Newtonian fluids with convective boundary conditions has been dealt by a few researchers. The three-dimensional flow of a Jeffrey fluid over a stretching surface with convective boundary conditions has been examined by Hayat However we can notice that the Sisko fluid with heat transfer analysis specially with an emphasis of convective boundary conditions is less explored. In the work under consideration we explored the flow and heat transfer in Sisko fluid over a nonlinearly stretching surface with convective boundary condition. It is hoped that present work serves as stimulus for the shear thinning and thickening fluid flows in the areas where high rate of heat transfer or rate of cooling is required such as extrusion processes, glass fiber and storage of thermal energy.Let us consider steady, laminar and incompressible flow of Sisko fluid over an isothermal flat sheet  is employed to solve non-linear Eqs. (8) and (16) subject to the boundary conditions (9) and (17) respectively. The analytic solutions are obtained for the velocity and temperature fields. The convergence of these solutions is ensured by taking the most suitable value of the auxiliary parameter As a special case of the problem for see ref. (22)(23)Now for see ref. (26)(27)In order to get definite perception of the physical problem, velocity profile Taking into account the obtained numerical solutions, In order to illustrate the influence of the magnetic parameter The variation of the generalized Prandtl number A, M, s, Pr and A, M and s. A, Pr, M for different values of the power-law index The numerical values of the skin friction coefficient In this study, we have investigated the heat transfer with convective boundary condition at the wall for Sisko fluid flow over a non-linearly stretching sheet in the presence of a transverse uniform magnetic field. The governing non-linear equations were formulated and solved analytically by the HAM and numerically by shooting method. Additionally, the exact analytical solutions have been determined for the power-law index For the power-law index Behavior of the material parameter Behavior of stretching parameter The influence of For the increasing power-law index It is expected that the present analysis serves as stimulus for the shear thinning and thickening fluid flows in the areas where high rate of heat transfer or rate of cooling is required such as extrusion processes, glass fiber and storage of thermal energy.


Borrelia burgdorferi, Lyme disease can affect the nervous system, joints and heart. No human vaccine is approved by the Food and Drug Administration. In addition to novel human vaccines, new strategies for prevention of Lyme disease consist of pest management interventions, vector-targeted vaccines and reservoir-targeted vaccines. However, even human vaccines can not prevent Lyme disease expansion into other geographical areas. The other strategies aim at reducing tick density and at disrupting the transmission of B. burgdorferi by targeting one or more key elements that maintain the enzootic cycle: the reservoir host and/or the tick vector. Here, I provide a brief overview of the application of an OspA-based wildlife reservoir targeted vaccine aimed at reducing transmission of B. burgdorferi and present it as a strategy for reducing Lyme disease risk to humans.Control strategies are especially challenging for microbial diseases caused by pathogens that persist in wildlife reservoirs and use arthropod vectors to cycle amongst those species. One of the most relevant illnesses that pose a direct human health risk is Lyme disease; in the US, the Centers for Disease Control and Prevention recently revised the probable number of cases by 10-fold, to 300,000 cases per year. Caused by  Given the unabated increase in Lyme disease in the US, public health officials are searching for effective and creative solutions to quell the epidemic. The immunization of animals as a means of preventing disease in humans and in domesticated animals of agricultural economic interest was comprehensively reviewed by Monath . The useB. burgdorferi sensu stricto (s.s.)   Young, .B. burgdorferi genome does not encode any known toxins or the machinery that would be required to secrete them   in modified commercial bait boxes was also effective in reducing nymphal and larval tick infestations as it reduced tick density , deer and the vector are measures generally accepted as effective in disrupting transmission of B. burgdorferi in the US is the white-footed mouse (Peromyscus leucopus)  and from the ticks that feed on them. In other words, the ultimate objective of RTV vaccination is to turn competent reservoir hosts into incompetent hosts while at the same time depleting B. burgdorferi from the vector without eradicating either (the vertebrate host or the tick) from the ecosystem  of acquiring Lyme disease. Implementation of a reservoir targeted vaccine (RTV) as part of integrated pest management interventions to block transmission of B. burgdorferi should consider deployment both in sylvatic as well as in suburban areas and broad distribution of such vaccines should take into account issues of toxicity to humans.Such decreases in the prevalence of infected B. burgdorferi) from the ecosystem while leaving all other living components of the enzootic cycle undisturbed  and long-term (5-year) field trials lead to reductions of tick infection prevalence ranging from 24 to 76%, respectively. Other reservoir targeted approaches reduced infection prevalence in the tick vector as well as cured infection in the reservoir host. A multi-pronged integrated pest management intervention combined with human vaccination maybe the most effective route to drastically reduce Lyme disease incidence. Lastly, eco-epidemiological factors should be studied to understand the relationship between the pathogen, the tick, the hosts, and its environs to be able to assess the long-term effects of any strategies that may affect the ecosystem.Reservoir targeted vaccines are under development for prevention of transmission of Maria Gomes-Solecki has a relevant patent and is a co-founder of US BIOLOGIC.


Ventricular arrhythmias are a leading cause of non-elegibility to competitive sport. The failure to detect a significant organic substrate in the initial stage of screening does not preclude the identification of structural pathologies in the follow-up by using advanced imaging techniques.Here we report the case of a senior athlete judged not elegible because an arrhythmia with the morphology consistent with the origin of the left ventricle, in which subsequent execution of a cardiac MR and a thoracic CT scan has allowed the identification of an unique association between an area of myocardial damage, probable site of origine of the arrhythma, and a rare aortic malformation. Ventricular arrhythmias are a leading cause of non-elegibility to competitive sport.  As in thA 60-year-old male high-level tennisplayer was referred at our outpatient sports cardiology clinic for palpitations after competition. 24-hour Holter ECG recordings revelead frequent and complex ventricular arrhythmias with dominant right bundle branch block morphology .A complete diagnostic work-up, including echocardiogram, stress test, ventriculography and coronary angiogram, failed to detect any organic substrate of the arrhythmia. No tachicardia was inducible by ventricular stimulation performed with an aggressive protocol. However the athlete was judged not eligible for competition due to the high weight of arrhytmic events and high heart rate of ventricular tachycardia (R-R cycle of less than 400 msec on ECG). In the follow-up period a cardiac MRI was performed showing normal left and right ventricular cavity dimensions and systolic function on cine images. At the level of the interventricular septum, pre- and post-contrast morphological images detected a focal area of fibrofatty replacement involving the inferior interventricular junction . The samSubsequently a thoracic CT scan demonstrated the absence of esophageal and/or tracheal compression, confirming the absence of a ligamentum arteriosum to complete the vascular ring .A left-dominant variant of arrhythmogenic cardiomyopathy (LDAC) has been recently described  and it i“Chronic” myocarditis is also a possible cause of apparently idiopathic arrythmia of the athletes.  Cardiac In the present case, detection on MRI of patchy myocardial fibrosis with subepicardial/midwall distribution, for lack of a medical history and of genetic or biopsy evidences, can not be attributed with certainty to the LDAC nor the myocarditis.ligamentus arteriosus also persists a complete vascular ring can be generated, with consequent compression of the esophagus and trachea and need of corrective surgery. [The Kommerell’s diverticulum  consistssurgery. In our case cardiovascular MRI and thoracic CT, in addition to three-dimensional visualization of the heart and its relationship with the thoracic structures, have allowed the identification of abnormalities of the aorta that had escaped the cardiac examinations, even invasive, previously performed.To our knowledge this is the first description of an association between left cardiomyopathy and Kommerell’s diverticulum. The etiological or pathophysiological link between the cardiovascular anomalies observed in this case appears unclear. However, the possibility that hemodynamic changes induced by vascular malformation might have favored the development of areas of myocardial tissue damage or predisposed to the the occurrence of myocarditis should not be excluded.The search for a structural heart disease is the primary task in the assessment of ventricular arrhythmia in athletes. However, the failure to detect a significant organic substrate in the initial stage of screening does not preclude the identification of structural pathologies in the follow-up by using advanced imaging techniques. In this way we were able to identify a unique combination of rare cardiovascular disease. Future observations and further investigations are required to elucidate their pathophysiologic link.