Research has shown that mHealth initiatives, or health programs enhanced by mobile phone technologies, can foster women’s empowerment. Yet, there is growing concern that mobile-based programs geared towards women may exacerbate gender inequalities.A systematic literature review was conducted to examine the empirical evidence of changes in men and women’s interactions as a result of mHealth interventions. To be eligible, studies had to have been published in English from 2002 to 2012, conducted in a developing country, included an evaluation of a mobile health intervention, and presented findings on resultant dynamics between women and men. The search strategy comprised four electronic bibliographic databases in addition to a manual review of the reference lists of relevant articles and a review of organizational websites and journals with recent mHealth publications. The methodological rigor of selected studies was appraised by two independent reviewers who also abstracted data on the study’s characteristics. Iterative thematic analyses were used to synthesize findings relating to gender-transformative and non-transformative experiences.Out of the 173 articles retrieved for review, seven articles met the inclusion criteria and were retained in the final analysis. Most mHealth interventions were SMS-based and conducted in sub-Saharan Africa on topics relating to HIV/AIDS, sexual and reproductive health, health-based microenterprise, and non-communicable diseases. Several methodological limitations were identified among eligible quantitative and qualitative studies. The current literature suggests that mobile phone programs can influence gender relations in meaningfully positive ways by providing new modes for couple’s health communication and cooperation and by enabling greater male participation in health areas typically targeted towards women. MHealth initiatives also increased women’s decision-making, social status, and access to health resources. However, programmatic experiences by design may inadvertently reinforce the digital divide, and perpetuate existing gender-based power imbalances. Domestic disputes and lack of spousal approval additionally hampered women’s participation.Efforts to scale-up health interventions enhanced by mobile technologies should consider the implementation and evaluation imperative of ensuring that mHealth programs transform rather than reinforce gender inequalities. The evidence base on the effect of mHealth interventions on gender relations is weak, and rigorous research is urgently needed. The gender divide in access to and use of mobile phone technologies is well known -5. StratHowever, despite evidence on the positive effects of mHealth interventions on women’s health and care-seeking, there is growing concern that mobile-based programs geared towards women may exacerbate gender inequalities. Particularly in settings where men have historically limited women’s autonomy and decision-making, little is known regarding the full impact of mHealth programs on the relational experiences of men and women ,7.Evidence suggests that while mHealth programs hold the potential to shift gender roles by empowering women through improvements in knowledge, decision-making, and economic gain ,9, some appropriation, or gendered access and ownership of technological resources, with less attention to incorporation or the influences of technology on gender power relations [The term, gender relations, refers to “varying roles and relations between women and men which are influenced by socio-cultural, political, economic, religious, and environmental factors” . Recent elations . This reelations ,2,10,18.elations ,16.Research studies that met the following criteria were included: (i) the study evaluated a mobile phone health intervention or intervention aiming to improve women’s mobile phone ownership and use; (ii) the study was conducted in a developing country, defined on the basis of the World Bank categories for low-income, lower-middle income, or upper-middle income economies ; (iii) oA preliminary literature search was conducted to identify relevant search terms and guide the development of study appraisal documents. The search strategy included an electronic and manual search. The electronic search was the primary means of identifying relevant studies and comprised of four electronic bibliographic databases of peer-reviewed literature: MEDLINE/PubMed, PsycINFO, SciVerse Scopus, and Excerpta Medica Database (EMBASE). These databases were selected to cover a broad range of disciplines, including medical and social science research. The search terms included Boolean-paired key word sets of synonyms and spelling variations (where applicable) relating to mobile phones, maternal and child health-related interventions, and gender relations Table .To obtain non-peer reviewed or gray literature, a manual review of nine websites of key organizations within the mHealth area was conducted: GSMA mWomen, Mobile Active, mHealth Alliance, Knowledge for Health, International Center for Research on Women, Women for Women International, Mobiles for Education Alliance, mHealth Info, and Health Unbound. The manual search also included a review of articles published from 2010 to 2012 in eight priority journals relating to mHealth or among which mHealth-related articles had recently been published. These included: Telematics and Informatics; Journal of Telemedicine and Telecare; Technology and Health Care; Gender; Technology and Development; BMC Pregnancy and Childbirth; Reproductive Health; AIDS and Behavior; and Contraception. The tables of content prior to 2010 of the priority journals were not reviewed given the relatively recent implementation of mHealth interventions and based on the limited number of eligible studies published before 2010 as identified in the electronic search.Figure All final selected studies underwent a systematic appraisal by the two reviewers Table . Data weAs part of the study appraisal, the methodological rigor was assessed for each article using an 11-item quality assessment checklist for quantitative studies and a 10-item quality assessment checklist for qualitative studies Table . Mixed mThe checklist for qualitative studies used 10 items to evaluate the study’s methodological quality. The rigor items used were: prolonged engagement in study setting; justification for design and methods selected; sampling strategy justified; analytical methods clearly described; use of verification methods; reflexivity of account provided; detailed report of findings; balanced and fair representation; conclusions supported and confirmed by the data; and report of intervention implementation detail sufficient for replication. The 10 items were scored similarly as the quantitative index with less than or equal to 4 points representing a weak rating, 5 to 7 points representing a moderate rating, and 8 to 10 points representing a strong rating. For mixed methods studies, separate quality ratings were calculated for the qualitative and quantitative methods presented in the article. Non-applicable assignments were not allowed for items in either of the quality indexes. Similar to the appraisal process, the quality scores were determined independently by both reviewers and then compared. Score discrepancies were resolved through discussion. In most cases, the reviewers agreed on study appraisal and quality assessment determinations.transformative influences on gender relations, representing positive relational changes which empower women as well as negative relational changes brought by gender-based tensions [non-transformative influences on gender relations, representing ways in which participation in mobile health interventions perpetuate rather than challenge gendered-based inequalities [Findings and implications related to the influence of mHealth interventions on gender relations were synthesized using a thematic approach. This is commonly used to summarize themes identified in systematic literature reviews of qualitative and quantitative studies -30. Simitensions ,13,16,33ualities ,12,16,34A total 173 full-text publications were retrieved for review from 11,948 potentially relevant citations based on the publication’s title and abstract (Figure et al.[et al.[et al.[et al.[et al.[et al.[Seven studies were retained in the final group of articles: Akinfaderin-Agarau et al., Balasubl.[et al., Chib etl.[et al., Corker l.[et al., L’Englel.[et al., Misraghl.[et al., and Odil.[et al.. The majTable The most common strengths of the quantitative studies were longitudinal follow-up of users over time with high response rates and descriptive intervention detail. Common strengths of qualitative studies were justification for selected methods and confirmable findings based on detailed presentations of narratives and quotes. Common weaknesses of qualitative studies related to information on how study participants were sampled and how narrative data were analyzed and verified. A comparison group, randomization, power calculations, or index of variability was often omitted in quantitative studies.Two of the selected studies included gender relations from the outset as part of the evaluation aim. For the remaining five articles, findings relating to gender relations emerged over the course of the program or during the evaluation. Methods to examine influences on gender relations included focus group discussions, surveys, case studies, and secondary analyses of mobile phone queries and quiz responses. With the exception of mobile usage analyses, all studies examined influences of the mHealth interventions on gender relations through direct reports from women. No assessments included direct perspectives from male spousal or sexual partners. The majority of studies reported short-term findings relating to gender dynamics within mHealth interventions, rather than examining changes over time.et al.[The current mHealth literature described several positive transformations in the interaction of men and women. One finding was that the provision of mobile-based health information empowered couples to discuss health matters that were traditionally addressed in women-only clinical settings. Using post-intervention mobile queries, L’Engle et al. suggesteet al.. L’Engleet al. also attet al.[The literature also showed that mHealth interventions can increase women’s autonomy in seeking health information and services. Using post-intervention interviews, Odigie et al. noted thet al.[et al.[A third finding suggests that mHealth projects that supply women with mobile products, skills, or information valued by men can shift control of household resources and elevate the status of women. In rural India, Balasubramanian et al. found thet al.. Women eet al.. Also inl.[et al. found aml.[et al..et al.[et al.[Other findings demonstrated the potential of mHealth interventions to aggravate existing household dynamics. Balasubramanian et al. found thl.[et al. additionet al.[et al.[The evidence pointed likewise to mHealth program effects which reinforced prior relational practices, including women’s dependence on men for approval, technical, or financial support. In Nigeria, Odigie et al. found thet al.. In somel.[et al. noted thl.[et al..et al.[Although not a direct measure of influences on gender relations, several articles also discussed the unexpected finding relating to men’s predominant uptake of mHealth interventions which were targeted towards women. Chib et al. and Corket al. noted thet al.. And, inet al.. The intet al.[In addition, expectations regarding the appropriate behavior of women shaped how and whether women participated in the mHealth project. In this sense, the literature suggested that mobile initiatives did little to impact gender relations, but reflected them instead. In Nigeria, Akinfaderin-Agarau et al. attributet al.. In focuTo our knowledge, this review is the first to-date to examine the current evidence on the effect of women’s participation in mHealth interventions on gender relations in developing countries. Findings showed that while the gender disparities in access to and use of mobile technologies are well known, the rapidly growing literature on mHealth interventions provides little information on the extent to which such efforts have positively or negatively impacted gender relations.However, despite the limited available evidence, several key findings emerged. The current literature suggests that mobile phone programs can influence the interactions of men and women in meaningfully positive ways by providing new modes for couple’s health communication and cooperation and by enabling greater male participation in health areas typically targeted towards women. The review found as well that mobile health programs can increase women’s autonomy in seeking health information and services, and when coupled with economic-strengthening activities can also elevate women’s status and resource control. We did not find strong evidence of specific adverse events such as domestic violence, mobile stalking, privacy invasions, or distrust by male partners and community members. However, the limited number of accounts in the available data may reflect lack of inquiry or reporting of such cases. In contrast, the review clearly demonstrated that mobile-based programs may inadvertently reinforce the digital divide, particularly in terms of access to information. The technology also has the potential to reflect the existing gendered context, rather than enabling a new dynamic, with little to no influence on gender relations. In some cases, it was unclear if changes in men’s engagement translated into positive and equitable outcomes for women, or represented new means for men to expand control over women. Other instances of limited influences on gender relations were women’s dependency on men’s approval or assistance to use mobile devices. Some unfavorable changes were also described such as tensions between couples regarding who ultimately owned the mobile phone and how it would be used.This points to an important recognition that while mHealth interventions can significantly improve women’s health and well-being, the expectation that mobile health programs will drastically alter gender inequities within relationships deserves some scrutiny. Unless there is a conscientious effort to design mHealth initiatives that promote equitable relationships between men and women, the scale-up of some current programs may prove harmful to women. At the same time, the literature on the influence of mHealth interventions on gender relations is relatively weak. While we identified positive and negative outcomes, to some extent the evidence remains inconclusive. Some selected studies reported that determining the full extent of whether women’s involvement in the intervention impacted gender structures was beyond the scope of study, and only two articles purposed from the outset of the evaluation to examine gender-based dynamics. In addition, the majority of studies used a single group post-test design which was unable to differentiate between direct effects of the intervention, such as autonomy or empowerment, on gender relations versus the added value of mobile technology itself. Thus, when coupled with the overall insufficient quality of the evidence base, we found that there was a scarcity of research purposefully investigating this topic. Rigorous research that examines gender relations either as a stand-alone study or embedded within existing experimental mHealth trials is urgently needed.Nonetheless, the commonality of findings across various settings can assist in the development of appropriately empowering and gender-transformative mobile health programs. Experience has shown that current gender inequalities have weakened attempts to scale-up health and development interventions . This reThe findings of this review were subject to limitations. Our analysis did not apply a tiered system to synthesize results by rigor category given the small number of identified studies. In addition, the quality ratings often reflected the methodological designs adopted for the primary outcome of interest, rather than peripheral findings related to gender relations. Given the role that socio-cultural factors play in defining relations between men and women, the interpretation of findings is also highly context-specific and may not be generalizable to other settings. Finally, it is possible that some studies were overlooked given that the search was limited to articles published in English and those which were available online. As a result, the findings do not represent experiences drawn from unpublished and non-English texts. However, among electronically accessible English-language studies, we applied a considerably thorough and robust search strategy.The scarcity and low quality of the literature on the effect of mHealth interventions on gender relations urgently necessitates more rigorous research. Current findings suggest that mobile interventions can beneficially influence gender relations, while at the same time strain and reinforce existing power imbalances. Given the increasing number of health and development interventions delivered by mobile technologies, more care should be taken to implement and evaluate mHealth program that promote, rather than hinder gender equality.AIDS: Acquired immune deficiency syndrome; HIV: Human immunodeficiency virus; SMS: Short message service.The authors declare that they have no competing interests.LJ designed the scope of the review and the search strategy. LJ and LG jointly conducted the search, screened citations, read and appraised the literature, and summarized findings. LJ led the content analysis and wrote the first draft of the manuscript. LG edited subsequent drafts and constructed the figures and tables. LJ and LG jointly revised the present manuscript version. Both authors read and approved the final manuscript.


During the evolution of the eukaryotic cell, plastids, and mitochondria arose from an endosymbiotic process, which determined the presence of three genetic compartments into the incipient plant cell. After that, these three genetic materials from host and symbiont suffered several rearrangements, bringing on a complex interaction between nuclear and organellar gene products. Nowadays, plastids harbor a small genome with ∼130 genes in a 100–220 kb sequence in higher plants. Plastid genes are mostly highly conserved between plant species, being useful for phylogenetic analysis in higher taxa. However, intergenic spacers have a relatively higher mutation rate and are important markers to phylogeographical and plant population genetics analyses. The predominant uniparental inheritance of plastids is like a highly desirable feature for phylogeny studies. Moreover, the gene content and genome rearrangements are efficient tools to capture and understand evolutionary events between different plant species. Currently, genetic engineering of the plastid genome (plastome) offers a number of attractive advantages as high-level of foreign protein expression, marker gene excision, gene expression in operon and transgene containment because of maternal inheritance of plastid genome in most crops. Therefore, plastid genome can be used for adding new characteristics related to synthesis of metabolic compounds, biopharmaceutical, and tolerance to biotic and abiotic stresses. Here, we describe the importance and applications of plastid genome as tools for genetic and evolutionary studies, and plastid transformation focusing on increasing the performance of horticultural species in the field. The existence of plastids represents one of the principal features that distinguish plant from other eukaryotic cells. Except for some gametic cells, plastids are assumed to be present as one of several different types in all living cells of higher plants, which show its essentiality for cell viability . These dMirabilis jalapa and Pelargonium zonale was proposed, suggesting the plastids would contain their own genome , encoding 120–130 genes. The plastome is commonly mapped as a single circular molecule, however, it shows a high dynamic structure  and ploydy level in each chloroplast  plays a crucial role in the plant cell controlling the entire metabolism. Moreover, organellar and nuclear genomes constitute a tightly integrated functional unit that co-evolves. This integration between cellular genomes  is involved in speciation processes where the lack of functional interaction between genomes results in reproductive barriers between populations . Fail inPlastid genomes, unlike most nuclear chromosomes, are typically uniparentally inherited. For sexually reproducing species with male and female gametes, maternal plastid inheritance is the norm , althougEffective genetic population size is a parameter influenced by the mode of inheritance. The haploid nature of chloroplast genome is related to its reduced genetic variation. Since the effective population size of a haploid genome is 1/4 in dioecious plants and 1/2 in monoecious plants of the nuclear genome, coalescence times and time to fixation of chloroplast DNA haplotypes within a population are shorter than in diploid genomes . MoreoverbcL gene was widely sequenced from many plant taxa, generating a suitable database for plant phylogenetic studies at family level and higher taxa  and Lactuca (Asteraceae) has resulted in the discovery of fast-evolving DNA sequences for use in species-level phylogenetics , began to be used for evolution , phylogeFigure 1). This marker became a widely used plastid marker, known as chloroplast simple sequence repeats (cpSSRs), consisting of repetitive DNA sequences in tandemly repeated motifs of six base pairs (bp) or less, which have aroused considerable interest due to their ability to generate highly informative DNA markers  bean germplasm by comparing local accessions with commercial and Americas varieties . It contains 115 genes, 79 protein-encoding genes and 35 encoding stable RNA species , photosystem II (PSII), the cytochrome b6/f complex and the ATP synthase. The second group includes the genes required for the genetic system of plastids – subunits of an RNA polymerase, rRNAs, tRNAs, and ribosomal proteins. The tobacco plastid genome, for example, consists of 155,943 bp and contains a pair of inverted repeat regions (IRA and IRB) separated by a small (SSC) and a large (LSC) single copy region  and Elaeis guineensis (monocotyledon), and two gymnosperms: Picea abies (conifer Clade I) and Taxus mairei . Although plastid genome shows a high conservative gene content, small changes may occur according to the species, such as complete gene losses, or presence of pseudogenes.In order to unify in a single table a list of genes category, group, and names commonly identified in plant plastid genomes, we arbitrarily choose four representative horticultural species from very distant taxa, two angiosperms: Nicotiana tabacum . In this review, we highlight species of high interest to horticulture, as tomato , Magnolia kwangsiensis  to simultaneously sequence multiple plastid genomes using the Illumina Genome Analyzer . The use of the PCR-based methods to amplify overlapping fragments from conserved gene loci in plastid genomes is time consuming and can be more difficult to implement considering that gene organization differs among plants  of Solanaceae  is the species transformed with the highest efficiency, commercial use of this technology for cultivar improvement is totally dependent on spread of the technology to plant species of agriculture and horticultural interest. Probably, the wide spread of plastid technology to several horticultural crops is dependent on the development of a highly efficient tissue culture system (via organogenesis or somatic embryogenesis), which is observed in tobacco as model species for plastid transformation  and observed an increase up to 50% in provitamin A content in tomato fruits , which changed the color from red to orange due to the conversion of lycopene into β-carotene. Another example in tomato chloroplasts and chromoplasts was the increase of tocochromanol, which provides tocopherols and tocotrienols (vitamin E), in a complex and successful transcription and translation strategy of a multigene operon containing three genes related to tocochromanol biosynthesis , however, it was a limited method due to the low transformation frequencies and low transgene expression in tubers of potato transplastomic plants. Later, by optimizing of the selection/regeneration procedure, using of new transformation vectors and new regulatory sequences for transgene expression in leaves and tubers, Potato contains edible tubers, which have amyloplasts, plastids related to starch accumulation as the plant energetic reserve. Potato is by far the most important non-cereal source of starch and carbohydrates for human nutrition and is the most consumed species in many countries around the world. The first transplastomic events in potato were obtained by aadA, and the reporter gene, uidA. The study demonstrated a transformation efficiency ranging from 2.7 to 3.3% and a successful accumulation of β-glucuronidase protein in transformed cabbage between 3.2 and 5.2% of total soluble protein. After the development of an efficient plastid transformation in this species, cry1Ab gene targeting to the resistance to Plutella xylostella in two cabbage varieties. The cry1Ab gene codifies Bacillus thuringiensis Cry1Ab delta-endotoxin . However, the limited number of plastid genome sequences for some species, families and genera restrings the quality and efficacy of this kind of analyses. Nowadays, the increasing number of whole plastid genomes are being used for phylogenetic analyses and have proven to be effective tools to resolve evolutionary relationships and genetic diversity or divergence in plant populations, especially at lower taxonomic levels, which limited sequence variation is available. Plastid genome is also an important tool to analyze genetic distance and plant speciation given that it is possible to relate plastid haplotypes with morphological characteristics in natural population as observed in the Oenothera genus.Plastid genomes are highly conserved with very low rates of substitutions when compared to nuclear genomes. Plastid genes, non-coding regions, RFLP and SSR markers have been frequently used to measure the evolutionary distance at many plant taxonomy levels. This markers are also very helpful for phylogeographical and plant population genetics analyses, as seed and pollen flow studies to the characterize population structure, population differentiation and cytoplasmic diversity . The rapidly growing number of plastid genomes available in the organelle genome resource database can be used to generate high efficient plastid transformation vectors, since sequences of genes, intergenic regions and regulatory elements are crucial information for design of efficient plastid transformation strategies.The interesting features of plastid compartment and genome, the exceptional advantages of plastid genome engineering and crescent necessity of horticultural crops for human consumption as food, raw material for industry and cost reduction for production of biopharmaceutical compounds, makes the plastid transformation a potential tool to manipulate different species for industry and food purposes . This gain of knowledge in last three decades, from the first plastid genome sequenced to present day, makes the plastid genome the best studied genetic compartment of the plant cell. The improvement of chloroplast isolation and the evolution of technology of genome sequencing will make plastid genome sequencing routine in many laboratories and will certainly contribute to unveil several unknown questions about plant cell genetic of families/species that no information about plastid genome is available.Finally, plastid genome sequencing is an essential tool for several applications related to plant science. The first knowledge about plastid genome was the starting point to elucidate many processes related to plastid gene function, expression machinery, evolution and transfer of genes to other genetic cellular compartments as mitochondria and the nucleus (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.


Systems biology is a field within biology, aiming at understanding biological processes at the systems level and emerging from dynamic interactions of individual components that operate at multiple spatiotemporal scales. It is now an established and fundamental interdisciplinary research field. Systems biology studies biological systems by systematically perturbing them ; monitoring the gene, protein, metabolite, and informational pathway responses; integrating these data; ultimately formulating mathematical models that describe the structure of the system and predict its response to individual perturbations. Integrated “omics”  approaches have created exciting opportunities for systems biology and other biological researches thanks to the rapid advancement of high throughput biotechnologies. Computational methods such as data preprocessing, representation, modeling, measurement, interpretation, prediction, visualisation, and simulation have been well applied to understand biological processes and biological systems.We organised this special issue to provide an international forum to discuss the most recent developments in the field regarding integrated data analysis approaches in systems biology research such as pattern recognition and prediction, modeling and simulation, and data representation and visualisation. This special issue featured “integrated approach” and “complex biological system” themes. We are interested in both new theories and tools in this area as well as their applications in systems biology. The potential topics include (i) large-scale or cross-species data integration for the reconstruction of networks and pathways; (ii) genomic data analysis using systems biology approaches; (iii) quantitative understanding of the dynamics of regulatory, signaling, interaction, and metabolic networks through modeling and simulation techniques; (iv) prediction of protein/RNA structure and biological network-based interactions; (v) data integration and knowledge-driven approach in biomarker identification and drug discovery; (vi) enhancement and enablement of knowledge discovery in functional genomics of disease and other phenotypes through integrated omics approach; (vii) semantic webs and ontology-driven biological data integration methods; (viii) development of integrated systems biology visualisation and analysis tools; (ix) development of integrated systems biology visualisation and analysis tools; (x) integrating approaches in transitional bioinformatics and personalized medicine.Eight manuscripts were submitted in response to this special issue and six were finally accepted for publication, ranging from mathematical model, computational pipeline, and engineering design to computational models, with the applications at molecular, neuronal, protein, gene regulatory network, and gene ontology levels.The comparison on biology sequences is one of the most important tasks in analyzing similarities of function and properties. W. Deng and Y. Luan integrated the dual-vector curve (DV-curve) and the detailed hydrophobic-hydrophilic (HP) model of amino acids, in the representation and visualization of protein sequences. Although the information might be lost in the representation, their results showed that the proposed method is efficient and feasible when focusing on the important part of the sequences.L. Pasotti and S. Zucca reviewed the recent advances and computational tools in biological engineering design on which predictability issues in promoters, ribosome binding sites, coding sequences, transcriptional terminators, and plasmids were specifically discussed. The authors suggested that bottom-up approaches are urgently needed in order to refine and exploit the full potential of synthetic biology and a mixture of prediction tools could rapidly boost the efficiency of biological engineering by providing a smaller search space than fully random-based approaches.A pipeline for neuron reconstruction based on spatial sliding volume filter seeding,” D. Sui et al. proposed a pipeline with a new seeding method for the construction of neuron structures from three-dimensional microscopy images stacks, which will be beneficial to three- dimensional neuron reconstruction and detection.In “Gene regulatory networks consist of interactions between large number of genes and their regulators and are involved in every biological process. L. P. Tian et al. designed a state observer to estimate the states of genetic regulatory networks with time delays from available measurements. Furthermore, based on linear matrix inequality approach, a gene repressillatory network was employed to illustrate the effectiveness of the proposed design approach.Effects of maximal sodium and potassium conductance on the stability of Hodgkin-Huxley model,” Y. Zhang et al. applied stability theory in the model design to investigate the importance of maximal sodium conductance and maximal potassium conductance. The study could help in researches relevant to diseases caused by maximal conductance anomaly.In “Correlating information contents of gene ontology terms to infer semantic similarity of gene products,” the author proposed a new semantic gene ontology similarity measurement. A gene product was represented as a vector that is composed of information contents of gene ontology terms annotated for the gene product, and the pairwise similarity between two gene products was viewed as the relatedness of their corresponding vectors using three measures: Pearson's correlation coefficient, cosine similarity, and Jaccard index.In “


Recently, autism-related research has focused on the identification of various genes and disturbed pathways causing the genetically heterogeneous group of autism spectrum disorders (ASD). The list of autism-related genes has significantly increased due to better awareness with advances in genetic technology and expanding searchable genomic databases. We compiled a master list of known and clinically relevant autism spectrum disorder genes identified with supporting evidence from peer-reviewed medical literature sources by searching key words related to autism and genetics and from authoritative autism-related public access websites, such as the Simons Foundation Autism Research Institute autism genomic database dedicated to gene discovery and characterization. Our list consists of 792 genes arranged in alphabetical order in tabular form with gene symbols placed on high-resolution human chromosome ideograms, thereby enabling clinical and laboratory geneticists and genetic counsellors to access convenient visual images of the location and distribution of ASD genes. Meaningful correlations of the observed phenotype in patients with suspected/confirmed ASD gene(s) at the chromosome region or breakpoint band site can be made to inform diagnosis and gene-based personalized care and provide genetic counselling for families. Classical autism or autistic disorder is common, with developmental difficulties noted by three years of age. It belongs to a group of heterogeneous conditions known as autism spectrum disorders (ASDs) with significant impairments in verbal and non-verbal communication and social interactions with restricted repetitive behaviors, specifically in movements and interests ,2,3. OthPTEN tumor suppressor gene mutations [CHD8) can also lead to macrocephaly and autism [Autism was first used as a term by Kanner in 1943 when describing a group of children lacking the ability to establish interpersonal contact and communication ,11. Whenutations , while ad autism .i.e., translocations at chromosome breakpoints or deletions  indicating the location or loss of specific genes) in individuals with ASD along with overlapping linkage and functional data related to the clinical presentation, with certain chromosome regions identified by genetic linkage using DNA markers that co-inherit with the specific phenotype [PTEN gene).Autism is due to a wide range of genetic abnormalities, as well as non-genetic causes, including the environment, environmental and gene interaction (epigenetics) and metabolic disturbances , with the recurrence risk dependent on the family history and presence or absence of dysmorphic features. Candidate genes for ASD are identified by different means, including cytogenetic abnormalities  were implicated in axonal guidance with lower gene expression levels in brain specimens from individuals with ASD [For idiopathic or non-syndromic autism, the empirical risk for siblings to be similarly affected is between 2% and 8% with an average of 4% . In mult in 2006  using 60 in 2006 ,35,36,37with ASD , reviewewith ASD . Since twith ASD ,51,52,53The ability to identify an increased number of SNPs with advanced genetic platforms and extensive approaches using bioinformatics have led to improved access and a more thorough analysis. This has led to comparing genotyping data from GWAS and DNA copy number variants (CNVs) with the identification of structural genetic defects, such as submicroscopic deletions or duplications of the genome, which was not possible a few years ago. Separate studies using array comparative genomic hybridization or microarray analysis to investigate those individuals with ASD continue to yield useful data in identifying candidate genes for ASD in affected individuals ,21,54. TAutism is frequent in single-gene conditions, such as fragile X syndrome, tuberous sclerosis, Rett syndrome or neurofibromatosis, but single-gene disorders as a whole account for less than 20% of all cases; therefore, most individuals with ASD are non-syndromic. The heritability of ASD, which takes into consideration the extent of genetic factors contributing to autism, is estimated to be as high as 90% ; hence tA current list of clinically relevant and known candidate genes for ASD is needed for diagnostic testing and genetic counselling purposes in the clinical setting. Historically, a previous list of known or candidate genes showing an association with ASD was reported in 2011 by Holt and Monaco  with theThe diagnostic approach for an individual with ASD should include a clinical genetics evaluation with interviews of parents and health caregivers for the collection and overview of historical problems, a three-generation family pedigree, recording of developmental milestones and description of atypical behaviors along with medical and surgical procedures and a current list of medications and ongoing treatments. Laboratory tests should include lead, thyroid function, lactate and pyruvate levels in order to assess metabolic and mitochondrial functions that may be impacted by an underlying genetic disturbance along with cholesterol and urine collection for organic acid levels. Brain imaging and electroencephalogram patterns should be reviewed, if available. In addition, the ADI-R and ADOS instruments are used to test the diagnosis of ASD.et al. [PTEN gene mutation screening would be indicated in those patients with extreme macrocephaly (head size > 2 SD) [To further increase the diagnostic yield in individuals with ASD presenting for genetic service, Schaefer et al.  proposedet al. . Exome s > 2 SD) , if not  > 2 SD)  if the a > 2 SD) , and a d > 2 SD) ,21,54.Advances made in genetic technology and bioinformatics have led to vastly improved genetic testing options for application in the clinical setting in patients presenting for genetic services . SignifiNext generation exome DNA sequencing and RNA sequencing allows for discoveries of disease-causing genes and regulatory sequences required for normal function. Identifying and characterizing molecular signatures for novel or disturbed gene or exon expression and disease-specific profiles and patterns with expression heat maps have led to the recognition of interconnected disturbed gene pathways in many diseases, including a growing body of genetic evidence for autism and other psychiatric or aberrant behavioral disorders .The position for each known or candidate gene for ASD susceptibility is plotted on high-resolution chromosome ideograms (850 band level), as shown in https://www.ncbi.nlm.nih.gov/pubmed) to search key words for genetics and autism. This included the integrated catalogue of human genetic studies related to autism found at the Simons Foundation Autism Research Initiative (SFARI) website (https://gene.sfari.org), which currently lists 667 genes reported as of 25 February 2015. This public access initiative is an ongoing curated collection of clinically proven ASD genes supported by clinical and autism experts, medical geneticists and laboratory specialists in the study of autism. This site includes gene description and evidence of support for causation with cited literature reports. We examined peer-reviewed articles found in the medical literature following our search for genetic evidence  and the involvement of genetics playing a role in autism. Sources included whole-genome sequencing of ASD families randomly selected with at least one unaffected sibling [www.OMIM.org). We then compiled the list of genes from these major sources for a total of 792 genes, whereby at least one mechanism was involved for each gene that could lead to ASD, a heterogeneous condition involving many genes; as our report is focused on the compilation of ASD genes from peer-reviewed research articles and authoritative computer website genomic databases for autism and not necessarily related to causal relationships between the individual gene and ASD. Those genes recognized, to date, as playing a role in ASD susceptibility and causation generally appear to impact chromatin remodeling, metabolism, mRNA translation, cell adhesion and synaptic function [We used computer-based internet websites and PubMed  at https://www.ncbi.nlm.nih.gov/gap, the Online Inheritance in Man (OMIM) at www.omim.org or Genecards at https://www.genecards.org.SFARI is a publicly available manually curated web-based searchable site of human genes with links to ASD and includes genes in catalogue form based on five categories—genetic association, syndromic, rare single-gene variant and functional and multi-genetic copy number variation—supported by cited research publications for each. Additional literature sources in our study consisted of both primary research articles and reviews summarizing genetic evidence. Many of the listed genes were identified in multiple research studies and widely reported in literature reviews, data repositories and/or computer genomic-based websites for autism . A large number of genes showed a varied relationship to autism and neurodevelopment, but the mass of the literature surveyed limits the reliability of our relative strength estimates for the ASD and gene associations. The gene would be included if cited and recognized in peer-reviewed publications  with supportive genetic evidence . Other supporting genetic evidence can be found at Simons Foundation Autism Research Initiative (SFARI) at Readily available tissue sources, such as peripheral blood, established lymphoblastoid cell lines and saliva, hold promise for more advances in ASD by enabling the identification of new genes and a better understanding of the causation and disease mechanisms to further stimulate research with the hope to discover new treatment modalities impacted by the recognition of known disease-causing or candidate genes for ASD. We illustrated the master list of clinically relevant and known ASD genes in our summary by plotting individual genes on high-resolution chromosome ideograms and generated a tabular form to increase the awareness required for genetic testing and counselling purposes for family members presenting for genetic services. Creating a master list of genes related to ASD is a complicated process; new genes are continually identified, but not all genes are equally important or certain to be causative. Additional research is needed to further investigate the causal relationships between the specific gene and ASD. The authors encourage the use of this collection of known and clinically relevant candidate genes for ASD in their evaluation of patients and families presenting for genetic testing options and for accurate genetic counselling.


Rare disease patient organisations have a tendency to be deeply involved in research development and infrastructures, and are practiced at founding strategic alliances with clinical and research networks . In builRD Connect collaborates closely with two related research projects EURenOmics (rare kidney disease) and Neuromics (rare neuromuscular/neurodegenerative disease) both of which utilise genomic technologies to improve care and therapies for specific disease groups. A workshop of 45 clinicians, scientists and patients/advocates from RD Connect, EURenOmics and Neuromics, identified two areas of concern. The first were procedural, around the inclusion of patients in governance including: on-going dialogue between researchers and patients; mutual education; and reporting and dissemination. The second set were contemporary ethical, legal and social issues (ELSI), around privacy, informed consent, data sharing, return of results and incidental findings. A review of the literature found that rare disease patients’ views on these contemporary issues are rarely documented.To explore these two areas we have parallel initiatives designed to include patients through membership of boards and committees at the highest levels and via a specific research strand investigating ELSI. Through including patients in governance, RD Connect fulfils the top level of Arnstein’s ladder of participation, that of citizen control, whereby those who the governance structure serves are represented in decision making . Among oIn our research strand we are exploring patient hopes, expectations, concerns and fears for the creation of an integrated platform for rare disease databases, registries and biobanks in a series of focus groups and a Delphi exercise. Using the notion of communities of practice, which encourage collective learning through shared endeavour, we aim to use the findings from this research to inform discussion and education activities which will enable patient perspectives to be embedded into the work of RD Connect, EURenOmics and Neuromics . Bearing


In recent years, remote sensing, morphometric analysis, and other computational concepts and tools have invigorated the field of geomorphological mapping. Automated interpretation of digital terrain data based on impartial rules holds substantial promise for large dataset processing and objective landscape classification. However, the geomorphological realm presents tremendous complexity and challenges in the translation of qualitative descriptions into geomorphometric semantics. Here, the simple, conventional distinction of V-shaped fluvial and U-shaped glacial valleys was analyzed quantitatively using multi-scale curvature and a novel morphometric variable termed Difference of Minimum Curvature (DMC). We used this automated terrain analysis approach to produce a raster map at a scale of 1:6,000,000 showing the distribution of glaciated valleys across Europe and western Asia. The data set has a cell size of 3 arc seconds and consists of more than 40 billion grid cells. Glaciated U-shaped valleys commonly associated with erosion by warm-based glaciers are abundant in the alpine regions of mid Europe and western Asia but also occur at the margins of mountain ice sheets in Scandinavia. The high-level correspondence with field mapping and the fully transferable semantics validate this approach for automated analysis of yet unexplored terrain around the globe and qualify for potential applications on other planetary bodies like Mars. Agassiz  recognizSince the advent of GIS-assisted mapping in the 1990s, a large variety of tools have been developed to extract geometric properties from digital elevation models to support geomorphological mapping  automated geomorphological mapping promises two substantial advantages over conventional methods: time-efficient analysis of large areas, and objective landscape classification. In this study, we tried to achieve both, based on simple morphometric semantics. We automatically mapped areas dominated by glacially incised valleys in Europe and western Asia using an algorithm introduced by Prasicek, Otto, Montgomery, and Schrott . The cruhttp://hydrosheds.cr.usgs.gov) with a resolution of 3 arc seconds (80 m), derived from the Shuttle Radar Topography Mission (SRTM) of the United States Geological Survey (USGS). Therefore, terrain north of the 60th parallel is not included in this survey. Besides our automated mapping results, elevation from the SRTM data and field mapping of glacial extent during the LGM are displayed on the map for validation. The field mapped data are part of a global dataset, compiled by Ehlers and Gibbard (6 km2 and has a WGS 84 / World Mercator projection (EPSG 3395).A raster map of areas with valleys incised by warm-based alpine glaciation is the result of this work. The map covers major parts of Europe, as well as Armenia, Azerbaijan, Georgia, Turkey and fractions of Iran, Iraq and Syria. This extension of the study area across European Borders allows analysis of the Caucasus and adjacent mountain ranges. The input data are hydrologically conditioned terrain models . Curvature is calculated as the change of slope in radians per 100 m. To account for differences in object size, the cumulative change of slope is given – a dimensionless ratio providing similar values for similar shapes independent of scale. Prasicek et al.  can highlight divergent and convergent parts of the landscape and has important implications for surface processes , and only cells forming the drainage line of a valley  holding the majority of thalweg cells for quadrangles of 180 × 180 cells . The quadrangles have to meet two criteria: they have to be large enough to hold a representative number of thalweg cells (no empty quadrangles); and they should be small enough to take into account small areas like single massifs where distinctive glacial valleys have developed.Generalization plays a major role in visualizing our results on a map. It is needed because: (i) only thalweg cells, a limited part of the DTM that cannot be displayed on a small-scale map, are used for classification; (ii) as the theoretical framework is based on idealized valley cross sections, single cells may not be representative due to the heterogeneity of valley morphology; and (iii) the surrounding terrain most likely belongs to the same class as the thalweg cells. For this, we classify all thalweg cells by applying our DMC threshold and then determine the class . We then calculated multi-scale curvature for these tiles.In addition, upstream drainage area had to be calculated per cell to apply the drainage area cutoff. This regional LSP is computed in two steps: calculation of flow direction, specified by the steepest gradient in a 3 × 3 neighborhood ; and ca3. et al., glacial. However, this would lead to similar results for fluvial valleys. Hence our preference was to use ‘no data’ cell values and consistently interpret the sea surface as ‘terrain of unknown morphology’.The DMC threshold required to distinguish between fluvially and glacially incised valleys was derived empirically from eight fluvial and eight glacial sample sites. The results are shown in et al. , which consequently affected curvature values. Nevertheless, DMC thresholds for various sample sites with the same drainage area cutoff and calculated from datasets with the same resolution seem to be similar.The general switch of probabilities for the 16 fluvial and glacial samples from all over Europe and western Asia at a DMC of −1.15 supports the hypothesis of a globally uniform DMC threshold, posited by Prasicek et al. . However  and numerous other regions with small-scale LGM-glaciations do not show development of morphologically distinctive glacial valleys. Therefore, these glaciations are not predicted by the automated mapping algorithm. In the Apennine Mountains (ii), as well as in the Cantabrian Mountains, the southern Balkan Mountains, and the eastern Pontic Mountains, isolated fluvial quadrangles are misclassified as glacial due to deep fluvial canyons with a lack of V-shape. Glaciation in eastern Turkey, mostly situated in the Pontic Mountains (iii) and in the Taurus Mountains, was quite extensive and glacial valleys were identified by our methodology. Nevertheless, the western part of the Pontic Mountains was not classified glacial, because Pleistocene ice cover was limited to summit regions and distinctive glacial valleys did not develop. Conversely, the deeply incised canyon of the Çoruh River in the eastern Pontic Mountains leads to a number of cells misclassified as glacial. In the Taurus Mountains, our results match the field mapping only partially, due to glaciated plateaus lacking distinctive valley development and adjacent deeply incised canyons. In the Tatra Mountains (iv) and the Transylvanian Mountains (v), as well as in the central Balkan Mountains, the Rhodope Mountains, and on Corsica, glacial valleys coincide with former local glaciations. In northern Europe, glacial valleys mostly occur in the Highlands of Scotland (vi), Wales, and Ireland, and in the Scandinavian Mountains. 4. 6 km2 in a short time. As hypothesized previously (Prasicek et al., We present a map of morphometrically classified areas with glacial valleys in Europe and western Asia. The methods applied for automated mapping are based on simple assumptions on the differences in cross-sectional shape between glacially and fluvially incised valleys and accordingly derived morphometric semantics. The validated results illustrate the advantages and the drawbacks of automated geomorphological mapping. Objective landscape classification and large dataset processing allow automated morphometric analysis at a continental scale and processing of about 10Automated mapping of U-shaped valleys, a conventional indicator for past glaciation, is a simple and novel example for the application of morphometric semantics and may be applied to identify terrain features with U-shaped or V-shaped cross sections in a regional manner on less well-explored terrain around the globe and on other planetary bodies like Mars, where evidence for glacial remains is extensively investigated yet controversial (Head, Mustard, Kreslavsky, Milliken, & Marchant, The geographic information system LandSerf Wood,  and partClick here for additional data file.


Animal models of osteoarthritis are extensively used for investigating disease pathways and for preclinical testing of novel therapies. Their predictive utility, however, has often been questioned, mainly because preclinical efficacy of novel therapeutics is poorly translated in clinical trials. In the current narrative review, we consider the preclinical models that were used to support undertaking clinical trials for disease-modifying osteoarthritis drugs, and compare outcomes between clinical and preclinical studies. We discuss this in light of the 1999 Food and Drug Administration draft guidelines for industry for use in the development of drugs, devices, and biological products intended for the treatment of osteoarthritis, which raised five considerations on the usefulness of osteoarthritis models. We systematically discuss what has been learnt regarding these five points since 1999, with emphasis on replicating distinct risk factors and subtypes of human osteoarthritis, and on comprehensive evaluation of the disease in animals, including pathology of all joint tissues, biomarker analysis, and assessment of pain and joint function. Finally, we discuss lessons learnt and propose some recommendations for how the evidence from preclinical research might be strengthened with a view to improving success in clinical translation. Despite this, a detailed analysis by one large pharmaceutical company of failures in their drug development pipeline showed that the most common reason (40 % versus 29 % for next most common) was inadequate linkage of the molecular/cellular target with the disease and no validated models [The current practice of translational biomedical research is failing its end-users, with as much as 90 % of ‘highly promising basic science discoveries failing to enter routine clinical use within 20 years’ . As a red models . Thus, wIn 1999, the US Food and Drug Administration (FDA) provided draft guidelines for industry for use in the development of drugs, devices, and biological products intended for the treatment of osteoarthritis (OA) . The briOA is no longer considered a single disorder; rather, it is a collection of different disease phenotypes that share certain clinical and pathological features . ConsequAge is one of the strongest risk factors for OA. Ageing causes changes in chondrocytes and articular cartilage, as well as in other joint tissues  and these age-related changes contribute to OA pathogenesis (reviewed in ). RadiogTrpv4−/− mice [Adamts5 or Mmp13. As suggested above with ageing, such studies would be of value in improving knowledge of the interaction of clinically important OA risk factors and improve the translational utility of data from preclinical models.While age remains perhaps the strongest predictor of OA development, overweight and obesity not only significantly increase the risk of incident hip and knee OA, particularly in women, but also its radiographic progression (reviewed in ). Studie−/− mice . To our Not only does diet-induced obesity increase OA joint pathology in a mouse model, but it also induces anxiety and hyperalgesia, and decreases muscle function and locomotor activity . These gDespite sex (in association with age and obesity) being a significant confounding factor for OA risk (reviewed in ), this hOA can be stratified according to affected tissues Fig. . For insIn knee OA, population studies support a substantial discordance between radiographic changes and knee pain . Many knAdamts5 or Mmp13 protects against cartilage damage and SCB sclerosis but not osteophyte formation after DMM [Ccr5 null mice develop less cartilage degeneration but show no differences in bone or synovial response to surgery [To date, the relationship between pain/disability and specific joint structural changes have not been extensively explored across different OA models and species. Yet, targeted pharmacological modulation of specific facets of OA pathology in experimental animals permits dissecting the contribution of different aspects of joint disease to pain. Such studies require measuring pain on the one hand, which can be approached using different assays, including evoked pain responses and spontaneous pain behaviors (reviewed in ), and jofter DMM , 85, whi surgery . This co surgery . In addi surgery , 89, cha surgery .The contribution of SCB to OA pain has been examined in some detail in preclinical models of OA treated with different bone-remodeling agents. In rat MIA, pre-emptive alendronate treatment preserved SCB trabecular microarchitecture, decreased bone turnover and had moderate effects on cartilage degradation. These structural effects were accompanied by a positive effect on weight-bearing asymmetry, an indicator of pain . In a caOsteoarthritis and Cartilage 2010, Supplement 3). Histology, however, does not allow for longitudinal assessment of the joint, and recent years have witnessed tremendous efforts to improve joint imaging in animals. In rodents, microCT, high-field MRI, and an array of contrast, luminescent and fluorescent bio-imaging methods have been developed  has published guidelines for histological assessment of OA joints in different species in an attempt to standardize the assessment and reporting of animal studies . DisOne of the great challenges of clinical trials in OA has been the slow progression of disease and a lack of biomarkers that are predictive of OA structural disease onset and progression, and associated pain and disability. Since the writing of the FDA guidelines, emphasis has shifted to diagnosis and treatment of patients with early  OA prior to significant/irreversible structural change and/or chronic pain where central sensitization may confound symptom modification . With reFor patients and clinicians, clearly the outcomes that matter are pain relief and preservation of joint function. In large animal models, for instance in dogs and horses, it has been a longstanding practice to assess joint function, mainly through evaluating gait. Increasingly in small animal models, methods to assess disease sequelae of OA, including pain, sensitization, locomotion, gait, and even anxiety or depression, are incorporated as outcomes . For insMany induced models of OA, particularly in rodents, are relatively rapidly progressive; thus, there may be a limited window for differentiating prophylactic from therapeutic effects. Progression of OA is generally slower in large animals, providing scope for evaluating timing of intervention, but they require more drug and are more expensive. The same OA induction method may have a very different time course and severity of disease in different species - for example, anterior cruciate ligament transection in sheep , goats , dogs , and mice  (reviewed in ). WithinSpontaneous OA develops not only with advanced ageing  but also precociously  in a number of animals . These spontaneous models are slowly progressive and amenable to evaluation of therapies for both prevention and structural arrest . This wMaking measured outcomes more clinically relevant by evaluating whole joint pathology (not just cartilage) and including measures of pain/disability in addition to structural pathology. Understanding how the outcomes measured in the animal model relate to the human disease may be improved through using clinically relevant imaging modalities in preclinical studies . ChanginIncreasing the rigor of preclinical science and its reporting, including use of ARRIVE or other guidelines  enablingEmbracing and making use of the One Health Initiative . The conDesign and use of animal models of OA can be deemed suboptimal, mainly with respect to OA phenotype, risk factors, and endpoints under evaluation. Suggestions for improvements that will enable translation in OA research are similar in other diseases  and inclRather than concluding that preclinical models are not useful in translational medical research , this re


The noted children’s human rights lawyer, Michael Freeman, posed the provocative question of whether the world viewed children as “beings or becomings?” Freeman, . This enAIDS Care, would support the needs of children as beings. The end of 2015 saw the end of the Millennium Development Goals (MDGs), and achievements inclusive of substantial reduction of mother-to-child transmission (MTCT) of HIV, prevention of HIV and decrease in HIV incidence as well as expansion of HIV treatment and care programmes globally, but in particular in the most-affected countries of Sub-Saharan Africa (SSA). Yet there are situations where outcomes for children are wanting. These include the unacceptably high 30% MTCT in the Democratic Republic of the Congo  children below the age of 15 years were living with HIV globally, nearly all of whom became infected through MTCT. The prevalence of HIV among pregnant women varies from less than 1% in resource-rich settings of Western Europe, America and Asia to over 40% in some areas of southern Africa UNAIDS, . AlthougBy March 2015, 15 million people had been initiated onto ART globally, nearly 11 million in SSA; it is unclear how many remain on treatment and how many of these are virally suppressed. About 40% of HIV-infected adults were estimated to have accessed ART, but only 32%, or even less, of children; in 2014 nearly three-quarters of pregnant women living with HIV had access to ART for the prevention of mother-to-child transmission (PMTCT) – again high numbers although universal access is not yet enjoyed everywhere. Elimination would require a complete cascade of programmatic provision to ensure universal and appropriately regular HIV testing of all pregnant women to ensure identification of HIV early in pregnancy, followed by comprehensive roll out of appropriate HIV care, ART and support. Better still, not only should HIV-negative pregnant women in high-prevalence areas be tested regularly, but also their households including their partners – this has been reported to halve HIV acquisition  and <4–5% at 18 months of age (depending on the duration of breastfeeding under the cover of ART); it is anticipated that with the further expansion of ART for treatment and prevention, rates at the end of breastfeeding will be below 2% – already <1% has been achieved in some of the busier clinics in the KwaZulu-Natal midlands of South Africa. Community support for pregnant women has also shown promise in improving PMTCT outcomes , the second cluster (second 90%) on linkage to care and treatment and the third cluster on adherence and viral suppression. The editors have also created a fourth category that the majority of papers talk to that encompasses the continuum of care incorporating the psychosocial aspects of HIV.n = 2 and children n = 3). The selection is not exhaustive and coverage not comprehensive, but this issue gives insight into current areas of research, concern, understanding and achievement from a wide geographical area. The majority of studies are carried out in SSA, reflecting the epicentre of child HIV burden, but papers from China, Haiti and Panama were also included to demonstrate and reflect the global challenges. Wei, Li, Harrison, Zhao, and Zhao (The chosen papers indicate various challenges for which interventions need to be developed or improved to ensure all HIV-affected children “survive, develop and reach their full potential without discrimination” UNICEF, . It gathand Zhao  examine and Zhao  use the and Zhao  explore and Zhao  note thaand Zhao  highlighand Zhao  explore and Zhao  exploresand Zhao  focus onand Zhao  summarisand Zhao  examine and Zhao  argue thand Zhao  assess sand Zhao  comment and Zhao , utiliziand Zhao  explore and Zhao  report oand Zhao  focus onand Zhao  write a and Zhao  comment and Zhao  focuses becomings – they are beings. Yet with their being underserved, mistreated and overlooked, they are becoming impatient. True progress can only be measured by the extent to which equity for children has been achieved universally. The UN fast track targets can be used as proxy measures to monitor equity being achieved as we head towards the 2020, 90-90-90 goals on the road to the 2030 goals of an AIDS-Free Generation.These papers feed into the Coalition on Children affected by HIV/AIDS meeting at Durban 2016, in a concerted effort to keep attention and energy focussed on the broad and ongoing needs of children. The challenges come from many directions. As gains in treatment and care are made, the spotlight needs to be on the updating of treatment guidelines, health policies, improving implementation and the review of these as well as health care system and community support systems strengthening. Improved linkages between health services and the community are required. Community-support programmes, in which psychosocial challenges in households of HIV-affected children are identified and addressed, have been shown to improve outcomes for children receiving ART and improve early childhood development outcomes (Fatti, Ngonzo et al.,


Since then, attention to older adult falls has gained significant momentum.Falls are the leading cause of older adult injuries and injury-related deaths. Until 2004, the growing public health issue of older adult falls received little national attention. To elevate and focus on the issue, the National Council on Aging launched the Falls FreeTo describe the steps taken to create the momentum around fall prevention and lessons learned that could be applied to supporting other older adult health-related issues.® Initiative took key steps to promote the older adult falls prevention movement, including initiating organized advocacy and supporting the development of state coalitions through increasing awareness of the issue, promoting evidence-based programs, instituting evaluation, implementing systems change, and providing tailored technical assistance.The Falls Free® Initiative and many partners, advocacy efforts have increased federal funding for fall prevention, the majority of states have fall prevention coalitions, and thousands of stakeholders are now engaged in fall prevention. Select lessons learned include leveraging compelling data, choosing passionate leaders for the movement, aligning the cause with partner missions, and being inclusive of all stakeholders.Through the support of the Falls FreeAlthough much progress has been made in the fall prevention movement, the issue is growing along with the aging population. Efforts must continue to gain support from all affected stakeholders to reduce older adult falls and fall-related injuries. In 2012, over 2.4 million older adults were treated in emergency departments for falls; more than 722,000 or 30% of these patients had to be hospitalized . With an® Initiative  Falls Freeitiative .® Initiative brought together national and state agencies to collaboratively address older adult falls with evidence-based solutions; the authors of this article were leaders in the effort. The Falls Free® Initiative has been particularly successful in advocacy at the national level and in supporting the creation and development of state fall prevention coalitions and local collaborative efforts across the country. The purpose of this paper is to describe the steps taken to create the momentum around fall prevention and lessons learned that could be applied to supporting other older adult health-related issues. Steps include creating a national initiative; initiating advocacy efforts; and developing and supporting coalitions to increase awareness of the issue, promote evidence-based programs, institute evaluation, and implement policy and systems change.Launched in 2005, the Falls FreeIn the early 2000s, the Archstone Foundation, a private grantmaking organization based in California, began funding local fall prevention initiatives in the state. The Archstone Foundation was pleased with the growth of statewide activities and the subsequent development of a state fall prevention plan. The Foundation approached the NCOA to design a similar initiative on a national level. NCOA, with funding from the Archstone Foundation and the Home Safety Council, seated an advisory group of leading fall prevention experts to begin planning and conducted an environmental scan of organizations that were or should be working on fall prevention to identify key national stakeholders.Concurrently, leading researchers were commissioned to develop review papers based on the best available evidence on fall prevention strategies targeted toward community-residing older adults. The review papers focused on the topics of physical mobility, medications management, home safety, environmental safety in the community, and additional cross-cutting areas for attention such as policy and advocacy.® Summit in Washington, DC, USA in December 2004. Fifty-eight national organizations, professional associations, federal agencies, and leading fall prevention experts were invited to participate in this landmark summit to review the evidence and design a national blueprint for reducing falls among older adults.With continued financial support from the Archstone Foundation and Home Safety Council, NCOA convened the national Falls Freehttp://www.ncoa.org/improve-health/center-for-healthy-aging/content-library/FallsFree_NationalActionPlan_Final.pdf) was created with 9 goals and 36 evidence-based strategies key to reducing older adult falls  Tool Kit for health care providers . In 2014® Initiative accelerated with the addition of the State Coalitions on Fall Prevention Workgroup. At that time, only four states had fall prevention coalitions. These states approached Falls Free® leadership and asked to join the effort. The State Coalitions on Fall Prevention Workgroup was formed and designed to facilitate collaboration between states working on similar issues. The State Coalition Workgroup members reported that developing a state or large regional coalition to address falls and fall-related injuries offered a common forum for multidisciplinary organizations to address falls, deter duplication of efforts, raise awareness, and facilitate necessary roles of resource coordination, policy development, and systems change at the state level ; CHA’s mission is to promote evidence-based health promotion and disease prevention programs. The CHA has been working with a variety of state and local grantees since 2003 to adopt and sustain programs making a difference in the health, independence, and quality of life of older adults. These programs provide measurable improvements in patient outcomes and build patient knowledge skills and confidence to manage problems.The Falls Free® Initiative is to increase access to quality programs and promote linkages and referrals from the health care community. A number of strategies within the State Policy Toolkit for Advancing Falls Prevention (discussed below) promote this effort to affect fall prevention.Since providers are increasingly being required by Centers for Medicare and Medicaid (CMS) to promote appropriate healthy behaviors, evidence-based programs can be a valuable asset for provider referrals. In alignment with this requirement, a key strategy of the Falls FreeCDC Compendium of Effective Fall Interventions: What Works for Community-Dwelling Older Adults, 2nd Edition represents a significant CDC investment in providing access to programs that can work in a variety of community and home settings and have been shown through randomized trials to reduce falls  added a subset of questions from the standard set of survey questions to their state Behavioral Risk Factor Surveillance System (BRFSS) survey. In 2012, 94 people from across the country attended a webinar to learn how to use the Evaluation Guidelines .® leadership in identifying, implementing, and advancing a full array of fall prevention policies to pursue.Through these various efforts, significant progress was made in the areas of increasing fall prevention awareness, creating multidisciplinary networks, and identifying evaluation measures. However, to achieve systems change and long-term sustainability, state fall prevention coalitions recognized that implementing policy change was necessary, and subsequently requested assistance from Falls Free® leadership developed and released the State Policy Toolkit for Advancing Falls Prevention, which incorporates the previously discussed Falls Free® Logic Model as a framework to advance policy change  panel of Review Editors. Because this Research Topic represents work closely associated with a nationwide evidence-based movement in the US, many of the authors and/or Review Editors may have worked together previously in some fashion. Review Editors were purposively selected based on their expertise with evaluation and/or evidence-based programming for older adults. Review Editors were independent of named authors on any given article published in this volume.


Progressive, incurable cancer is associated with increased fatigue, increased muscle weakness, and reduced physical functioning, all of which negatively impact quality of life. Physical activity has demonstrated benefits on cancer-related fatigue and physical functioning in early-stage cancer patients; however, its impact on these outcomes in end-stage cancer has not been established. The aim of this systematic review is to determine the potential benefits, harms, and effects of physical activity interventions on quality of life outcomes in advanced cancer patients.A systematic review of peer-reviewed literature on physical activity in advanced cancer patients will be undertaken. Empirical quantitative studies will be considered for inclusion if they present interventional or observational data on physical activity in advanced cancer patients. Searches will be conducted in the following electronic databases: CINAHL; CIRRIE Database of International Rehabilitation Research; Cochrane Database of Systematic Reviews (CDSR); Database of Abstracts of Reviews of Effects (DARE); Cochrane Central Register of Controlled Trials (CENTRAL); EMBASE; MEDLINE; PEDro: the Physiotherapy Evidence Database; PQDT; PsycInfo; PubMed; REHABDATA; Scopus; SPORTDiscus; and Web of Science, to identify relevant studies of interest. Additional strategies to identify relevant studies will include citation searches and evaluation of reference lists of included articles. Titles, abstracts, and keywords of identified studies from the search strategies will be screened for inclusion criteria. Two independent reviewers will conduct quality appraisal using the Effective Public Health Practice Project Quality Assessment Tool for Quantitative Studies (EPHPP) and the Cochrane risk of bias tool. A descriptive summary of included studies will describe the study designs, participant and activity characteristics, and objective and patient-reported outcomes.This systematic review will summarize the current evidence base on physical activity interventions in advanced cancer patients. The findings from this systematic review will identify gaps to be explored by future research studies and inform future practice guideline development of physical activity interventions in advanced cancer patients.CRD42015026281PROSPERO The online version of this article (doi:10.1186/s13643-016-0220-x) contains supplementary material, which is available to authorized users. Quality of life is a subjective, multidimensional construct encompassing several aspects of physical and psychosocial well-being . OptimizCancer is the leading life-threatening disease . It is eGiven the negative impact of fatigue and loss of physical functioning on quality of life in cancer patients, recent attention has been given to behavioral interventions to improve these outcomes . SystemaThree previous reviews have reported that there was insufficient evidence to determine the safety, feasibility, or efficacy of physical activity interventions in advanced cancer patients –16; an uThe aim of this systematic review is to evaluate the potential benefits, harms, and effects of physical activity interventions on quality of life outcomes in advanced cancer patients. The ultimate goal is to identify the gaps in the existing literature, to develop interventions that can be tested in clinical research, and to inform physical activity recommendations to improve quality of life for advanced cancer patients.The reporting of this systematic review protocol will adhere to the preferred reporting items for systematic reviews and meta-analyses protocol (PRISMA-P) checklist , OCLC PapersFirst, European Association of Palliative Care conference abstracts, Multinational Association of Supportive Care in Cancer symposium abstracts, and American College of Sports Medicine meeting abstracts.Adults aged 18 years and older will be included as study participants. Lack of consensus on defining the palliative cancer population is a well-recognized limitation in palliative care research; the definitions for “advanced cancer,” “palliative,” “end-stage cancer,” and “terminal illness” are not uniform across studies . For theAny health outcomes research examining physical activity in advanced cancer patients will be included. Physical activity will be defined as any bodily movement produced by the skeletal muscles that results in a substantial increase in energy expenditure over resting levels . For theThe comparison groups may be no intervention or standard of care.Included studies must examine at least one of the following primary outcomes: (1) patient-reported quality of life, (2) patient-reported physical function, or (3) patient-reported fatigue. Secondary outcomes of interest would include the following: (1) objective measures of physical fitness; (2) objective measures of physical function; (3) patient-reported symptoms including pain, depression, and dyspnea; and (4) other adverse outcomes. A preliminary scan of the available literature suggests that the body of evidence may be at risk of outcome reporting bias, which is defined as “the selection for publication of a subset of the original recorded outcome variables on the basis of the results” ; therefoRelevant studies will be searched from the following electronic databases : Cumulative Index to Nursing and Allied Health Literature (CINAHL); Center for International Rehabilitation Research Information and Exchange (CIRRIE) Database of International Rehabilitation Research; Cochrane Database of Systematic Reviews (CDSR); Database of Abstracts of Reviews of Effects (DARE); Cochrane Central Register of Controlled Trials (CENTRAL); Excerpta Medica Database (EMBASE); Medical Literature Analysis and Retrieval System Online (MEDLINE); PEDro: the Physiotherapy Evidence Database; Psychological Abstracts (PsycINFO); US National Library of Medicine Database (PubMed); National Rehabilitation Information Center Database (REHABDATA); Elsevier Bibliographic Database (Scopus); EBSCO Sports Medicine Database (SPORTDiscus); and Web of Science. Reference lists of all included articles will be hand-searched for additional studies. Additional studies meeting inclusion criteria will be located by assessing the reference lists of relevant reviews. Forward citations of the included articles will be identified. Further studies meeting inclusion criteria will be located in those databases which offer the “related/similar to” function. Searches will be conducted without a language filter, and subsequent analysis will be restricted to English-language articles, with a supplementary appendix list of citations to articles in languages other than English.The proposed MEDLINE search strategy , rating each of the following study components as strong, moderate, or weak: selection bias, study design, confounders, blinding, data collection methods, and withdrawals/dropouts . For ranStatistical meta-analysis will be done if studies are clinically homogenous and the data permit. In the event that meta-analysis is not possible, narrative synthesis of data will be conducted, following Popay et al.’s framework for narrative synthesis . Data frThis review is transparent in its adherence to validated methods and employs a systematic and replicable approach toward searching, screening, appraising, and extracting data from the current evidence base. There are clear inclusion and exclusion criteria, and the search strategy is comprehensive. Including information professionals with advanced search skills in the development of the search strategy will improve accuracy of the search methodology. The involvement of two reviewers in screening, data extraction, and quality appraisal will enhance the reliability of the review’s conclusions. With respect to limitations, reporting bias may be present given judgments made by the reviewers. There may be relevant studies which have non-English titles and abstracts and therefore will be excluded at initial screening.This systematic review will provide a comprehensive and rigorous evidence base from which future research directions for physical activity can be proposed. It can lead to the development of physical activity interventions and inform clinical recommendations regarding physical activity to improve the quality of life of advanced cancer patients. The findings from this systematic review will be disseminated by scientific peer-reviewed publication and conference presentations.


Women who become pregnant after recovery pose little risk for transmitting the virus to the baby or others. Many of the survivors of the 2014–2015 epidemic of Ebola virus disease (EVD) in West Africa were women of childbearing age. Limited clinical and laboratory data exist that describe these women’s pregnancies and outcomes. We report the case of an EVD survivor who became pregnant and delivered her child in the United States, and we discuss implications of this case for infection control practices in obstetric services. Hospitals in the United States must be prepared to care for EVD survivors. The 2014–2015 epidemic of Ebola virus disease (EVD), which was centered in West Africa, is the largest EVD epidemic in history. Vertical transmission of Ebola virus from mother to fetus can occur during acute Ebola infection, leading to intrauterine fetal death, stillbirth, or neonatal death  and isolated after results of an EBOV real-time reverse transcription PCR (rRT-PCR) were positive for EBOV RNA (cycle threshold unknown). According to the woman, she spent 13 days in the ETC, where she was treated with oral rehydration fluids, acetaminophen, and a second course of antimalarial medications. She was discharged from the ETC on August 16, after showing negative results on 2 EBOV rRT-PCRs. After her recovery, the woman noted some fatigue, anorexia, arthralgia, and alopecia; she did not report any sleep disturbances, headaches, or vision problems. Symptoms resolved 2–3 months later.Eight months before her EVD diagnosis, the patient had had a spontaneous abortion at 10 weeks’ gestation. In January 2015, twenty-two weeks after her last negative EBOV rRT-PCR, she became pregnant again. For this second pregnancy, the estimated date of delivery was established on the basis of an 11.5-week ultrasound that was consistent with the patient’s last menstrual period. The patient received routine prenatal care in West Africa, and at 25 weeks’ gestation, she traveled to Kern County, California, USA, and a detailed anatomy ultrasound was performed in Los Angeles County, California, and demonstrated normal fetal development.The hospital identified staff members who were willing to assist during labor and delivery for the patient, and at 40 weeks and 1 day of gestation, labor was induced to ensure that those staff members were present. The patient was given 2 vaginal doses of misoprostol, and oxytocin was administered, and labor progressed normally. The patient was given epidural anesthesia for pain control and had a normal vaginal delivery of a female neonate  with Apgar scores of 8 and 9 at 1 and 5 min of age, respectively. The patient had a second-degree perineal laceration, which was repaired.The patient and her neonate were discharged from the hospital at 36 h postpartum. They returned for routine follow-up 7 days postpartum and were monitored for 6 weeks following delivery, after which they traveled home to West Africa.Two weeks before the patient’s delivery date, her US obstetrician contacted the California Department of Public Health  and the Centers for Disease Control and Prevention  to determine if there were any special precautions needed for infection control; the California DPH notified the Los Angeles County DPH . Because the patient was healthy and had fully recovered from EVD ≈4 months before becoming pregnant, all public health agencies agreed that she presented an extremely low risk for transmission of Ebola virus. Nevertheless, it was deemed appropriate that public health officials play an active role assessing and guiding management of the patient. The Los Angeles County DPH and CDC collaborated with the hospital’s healthcare providers, nursing directors, laboratory director, environmental services staff, anesthesiologists, and hospital administration to address concerns and review the care plan, including plans for any complications, such as the need for cesarean delivery or the development of peripartum fever.Hospital infection control procedures were reviewed in person with hospital staff. In review of these policies, no additional precautions were recommended above the standard precautions and policies currently used for all deliveries at the hospital. Several hospital staff members not directly involved in patient care expressed discomfort about working while an EVD survivor was admitted. To reassure these staff members, the patient was kept in 1 room during labor and delivery and after delivery. No changes were made to the policies for environmental cleaning or waste disposal.Hospital staff raised concerns about the possibility of EBOV being harbored in immune-privileged sites  in EVD survivors and, thus, expressed their concerns about a theoretical risk for EBOV transmission , 2 durin>1:1600, IgM negative).One week before delivery, EBOV rRT-PCR testing was performed on the patient’s blood by the Los Angeles County DPH laboratory and the CDC Viral Special Pathogens Branch; both results were negative. As expected, Ebola serum antibodies were detected by ELISA , cord blood, placenta, umbilical cord, breast milk (colostrum collected 16 h after delivery), and oral and ear swab samples from the neonate. Cord blood, colostrum, amniotic fluid, and swab samples were kept refrigerated until processed or frozen on dry ice for shipment to CDC. A placental sample was frozen in a sterile specimen cup and samples of placenta and umbilical cord were placed in buffered formalin and shipped at room temperature to CDC. EBOV rRT-PCR testing was performed on all of these specimens at the Los Angeles County DPH and CDC laboratories by using assays specific for nucleoprotein and viral protein 40 genes.>1:1600. Amniotic fluid and colostrum were negative for IgM and IgG. The placenta and umbilical cord were histologically normal, and no Ebola virus antigen was detected by immunohistochemistry . At 6 weeks follow-up, before returning to West Africa, the mother and baby were doing well. Given that the mother did not exhibit any signs or symptoms of post-EVD sequelae during her pregnancy, we did not expect to find any EBOV by rRT-PCR in any specimens obtained, and none was detected. It is somewhat surprising that we did not detect Ebola IgG in the colostrum; however, studies of antibodies for other infections have found that levels of IgG and IgM in colostrum are much lower than in serum (Although we did not detect EBOV RNA in this patient during pregnancy, women who are pregnant during acute EBOV infection usually transmit virus to the fetus and may pose an infectious risk to healthcare providers and others during delivery or abortion (The immune effects of pregnancy in the context of EVD have not been well documented (16,The normal pregnancy for the patient described in this study and her delivery of a healthy neonate offer reassurance that women who become pregnant after recovery from EVD pose little risk for transmission of EBOV to the baby or others. Many more EVD survivors will become pregnant and deliver, and some may do so in the United States. Many other survivors will require routine medical care, including care for post-EVD syndrome. Lessons learned from this patient, specifically those addressing concerns about potential risks for virus transmission, may be applied to future patients. However, each survivor who seeks medical care will likely need to be assessed individually to determine possible risks for transmitting virus (