Improving access to delivery services does not guarantee access to quality obstetric care and better survival, and therefore, concerns for quality of maternal and newborn care in low- and middle-income countries have been raised. Our study explored characteristics associated with the quality of initial assessment, intrapartum, and immediate postpartum and newborn care, and further assessed the relationships along the continuum of care.The 2010 Service Provision Assessment data of Kenya for 627 routine deliveries of women aged 15–49 were used. Quality of care measures were assessed using recently validated quality of care measures during initial assessment, intrapartum, and postpartum periods. Data were analyzed with negative binomial regression and structural equation modeling technique.β = 0.71, p < 0.001), which in turn was positively associated with the quality of newborn and immediate postpartum care .The negative binomial regression results identified a number of determinants of quality, such as the level of health facilities, managing authority, presence of delivery fee, central electricity supply and clinical guideline for maternal and neonatal care. Our structural equation modeling (SEM) further demonstrated that facility characteristics were important determinants of quality for initial assessment and postpartum care, while characteristics at the provider level became more important in shaping the quality of intrapartum care. Furthermore we also noted that quality of initial assessment had a positive association with quality of intrapartum care (A continued focus on quality of care along the continuum of maternity care is important not only to mothers but also their newborns. Policymakers should therefore ensure that required resources, as well as adequate supervision and emphasis on the quality of obstetric care, are available. Maternal survival has been one of the most important developments and global health priorities in the past decades, exemplified by its adoption as the fifth Millennium Development Goals (MDG) ,2 and suHowever, improving access to delivery services does not always guarantee access to quality obstetric care and better survival. For instance, the Government of India launched in 2005 one of the largest conditional cash transfer programs in the world, Janani Suraksha Yojana (JSY), to encourage expectant mothers to obtain quality obstetric services in public or accredited private facilities . DespiteThere are several critical challenges before effective interventions to improve quality of maternity care can become available. First and foremost is the lack of clarity on the definition of quality of maternity care ,18–20. QYet, development of programs that would enable improvement in the quality of care in LMICs still requires a thorough understanding of its determinants. This is especially important in LMICs where resources for quality improvement are rather limited given other competing needs. In addition to the challenge of defining quality measures, measuring quality along the continuum of care presents another challenge which increases the complexity in evaluating the quality of care. The term continuum of care has been used differently in various fields such as health-service administration, palliative care, biomedical care, mental health, public health/health promotion, and maternal, newborn and child health care, but it has generally been used to reflect the continuity between components of care –30. In tThe 2010 SPA dataset of Kenya was used to explore our objectives. The SPA is a nationally representative health facility cross-sectional survey, and its complete details can be found elsewhere . The surThe validated and recommended signal functions and tracers of quality of intrapartum, newborn and postpartum care–suggested by experts in SSA  and listThe determinants of quality of care were categorized into three groups: facility, provider, and region. The facility indicators include: the level of health facility, including primary care level , secondary and tertiary care levels , and private hospitals ; managing authority (government versus non-government), which could be different than its ownership since some private hospitals were managed and supported by the government, and vice versa; delivery capacity (as indicated by the number of delivery couches); number of deliveries in the past 12 months; whether a delivery fee was administered; availability of piped water; and, availability of central electric supply. The government operated hospitals included most of the health centers, sub-district hospitals, district hospitals, provincial hospitals, and the national hospitals.Provider characteristics variables include six indicators: age, gender, years of experience, qualification , whether obstetrics and gynecologist (OB/GYN) are available for night duty, and whether providers received financial or non-financial incentives . Furthermore, region characteristics included eight provinces  and 96 districts to account for any remaining influences from locality-specific factors.n = 290). Chi-squared and general linear regression were used to test the differences across different types of facilities for categorical and continuous variables, respectively. A p-value of less than .05 was considered statistically significant.We explored characteristics associated with quality of maternity care in three phases–descriptive statistics, negative binomial regression analyses, and finally, structural equation modeling (SEM). For the descriptive statistics, we presented the average performance on quality indicators across the maternity care continuum at different levels of health facility for observations with complete information  to adjust for the sampling design (see n = 627) were used at this stage after imputing missing values.In the third and final phase of our analysis, we used SEM technique to determine, in addition to determinants of quality, the interrelationship among quality of care in different phases along the care continuum. SEM assessed the latent variables, for example, quality of intrapartum care, using observables measures, such as the seven dichotomized intrapartum care indicators, and it allowed us to examine the determinants of quality and the influences of the quality in an earlier phase on a later phase, all at the same time  and Missing Completely at Random (MCAR) assumptions, i.e. the Full Information Maximum Likelihood (FIML) method, was employed in LISREL 8.80 to estimate the relationships along the continuum of care for quality maternity care . One benp < 0.01 in all the measures of ‘initial assessment and examination’, except for the indicators “washed hand before examination” and “wear sterile gloves for vaginal exam”. Similarly, all measures of ‘newborn and immediate postpartum care’ are statistically at p < 0.05, except for the indicator “assisted mother to initiate breastfeeding within 1 hour”. In contrast, the three categories of health facilities are not statistically different at p < 0.05 in most of the indicators for ‘intrapartum care’ except “prepared newborn resuscitation equipment” and “assessed integrity of placenta/membranes”.Meanwhile, the three categories of health facilities differ significantly across geographical distribution and all facility characteristics—from infrastructure (e.g. such water supply), capacity (e.g. number of delivery couches and delivery volume in the past 12 months), to presence of clinical guideline of maternity care, providing evidence to support our categorization of health facilities. Across different types of facilities, providers are not too dissimilar in their age distribution, but their distributions in qualification, experience, and availability for night duty do differ significantly.p < 0.05. Across provider characteristics, the availability of OB/GYN for night duty have a positive impact on quality across all three phases of care. The age and years of experience are also associated with higher rates of quality intrapartum care. Finally, almost all the provinces have lower rates of quality delivery care than Central province across the three phases, except for Nairobi, which has higher rates in the quality of ‘intrapartum care’  and ‘newborn and immediate postpartum care’ .p < 0.05. Likewise, facilities with maternal and neonatal clinical guideline still remain significantly higher rates of quality during ‘initial assessment and examination’  and ‘newborn and immediate postpartum care’  at p < 0.05 than hospitals without such guidelines. However, the association between provider characteristics and ‘intrapartum care’ is only seen in the years of experience , and between age and ‘newborn and immediate postpartum care’ . Regional differences are mainly seen in the quality of ‘initial assessment and examination’ with almost all the provinces being at a lower rate of quality of care than Central province. Only Coast province is still statistically significant lower in quality across all three phases of obstetric care.After adjusting for all the variables, national/provincial hospitals still have higher rates of quality care during initial assessment and examination at IRR = 1.54  and IRR = 1.36 , respectively, than district/sub-districts hospitals . The prip < 0.05, except for wear sterile gloves for vaginal exam , correctly administered uterotonic , and palpated uterus 15 minutes after delivery   .β = 0.09, p = 0.046), and to newborn and immediate postpartum care latent  are positive and statistically significant  is positive and statistically significant at p < 0.05. The regional characteristics latent (REGION) has statistically significant associations with quality during assessment and examination  and intrapartum care . Lastly, along the continuum of care, quality of care in the initial assessment have a positive and statistically significant association with quality of intrapartum care , which in turn is positively associated with the quality of newborn and immediate postpartum care .nificant . On the The quality of maternity care is critical in improving health and life chances of both mothers and their newborns. Despite of the challenges in measuring quality of care due to its multi-dimensional nature, previous studies have repeatedly demonstrated that there is indeed much to be desired in the obstetric services in LMICs ,36. HoweTraditional analytic approaches on quality of maternity care frequently treat quality of care as either a uni-dimensional notion by using a summary score to indicate the level of quality performance, or a concept with multiple mutually independent dimensions by analyzing the determinants of quality for different categories of activities in separate regression models . The forInvestigating quality of different phases of delivery care with separate analytical models, as we have demonstrated with negative binomial regression analyses in this study, unfortunately only partially addresses the issue. Different phases of delivery care do not have the same set of inputs but nevertheless are provided by the same team of health professionals in the same facility and therefore are highly correlated. Indeed, our SEM models shows that quality of care in one phase of delivery care is positively associated with the quality in the next phase. Failing to account for such correlation of error terms across regressions would lead to consistent but inefficient estimates .The puzzling mismatch between high coverage of essential interventions of maternity care and poor maternal health outcomes underscore the importance of quality in addition to quantity . Yet, asWorth noting, however, is the strong positive relationship from one stage of delivery care to another, that is–the quality of initial assessment is related with the quality of intrapartum care which is subsequently related with quality of newborn and immediate postpartum care. This is important, especially in LMICs where quality of initial assessment may not necessarily mean quality of post-delivery care. A healthy woman may die within hours not because of the poor initial assessment but because of severe bleeding after delivery if she is unattended. Moreover, infection after childbirth may not be eliminated if the quality of care is compromised. A continued focus on quality of care along the continuum of delivery care is therefore important not only to saving the life of mothers but also to giving the newborn a healthy start in life. Policymakers should therefore consider availing necessary resources and also ensure adequate supervision and emphasis on the quality of delivery care.To our knowledge, this study is one of the first that empirically applies the expert-validated quality index for delivery developed by Tripathi and colleagues . This neDespite the above limitations, our study points out the importance of studying quality of care of maternity services, and perhaps in general, as a continuum of different sets of activities requiring different inputs, instead of collapsing the multi-dimensional quality performance measures into one summary score. This is particularly important in studying the determinants of quality in LMICs where health systems are frequently resource-constrained on multiple fronts, which needs to be distinctively examined. Quality of care in low and middle income countries is an important and yet have unfortunately been an under-studied issue. Future studies similar to our efforts hereof that investigate the distribution of quality in maternity care are urgently needed to accelerate health gains for millions of mothers and children around the world.S1 File(PDF)Click here for additional data file.


The aim of the present investigation was to systematically analyse the literature on the facial bone reconstruction defect using marine collagen or not and to evaluate a predictable treatment for their clinical management. The revision has been performed by searched MEDLINE and EMBASE databases from 2007 to 2017. Clinical trials and animal in vitro studies that had reported the application of bone substitutes or not for bone reconstruction defect and using marine collagen or other bone substitute material were recorded following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The first selection involved 1201 citations. After screening and evaluation of suitability, 39 articles were added at the revision process. Numerous discrepancies among the papers about bone defects morphology, surgical protocols, and selection of biomaterials were found. All selected manuscripts considered the final clinical success after the facial bone reconstruction applying bone substitutes. However, the scientific evidence regarding the vantage of the appliance of a biomaterial versus autologous bone still remains debated. Marine collagen seems to favor the dimensional stability of the graft and it could be an excellent carrier for growth factors. The management of large facial bone defects is a current challenge for clinicians and surgeons. Treatment success is frequently related to the size of the defect, the quality of the soft tissue covering the defect, the decision of reconstructive method and the choice of the grafted material ,2,3.Numerous bone grafts’ regenerative procedures are currently available for having complete regenerative processes after bone trauma, or for favoring healing between two bones across a diseased joint, and also for obtaining new clinical function or aesthetic on site affected by disease, infection, or resection ,3,4,5.Facial bone augmentation procedure using autologous bone is a reliable technique, as confirmed by several studies; however, this treatment choice has integration advantages associated with several disadvantages. Autogenous bone harvested from the patient’s extra oral or intra oral sites even considered the gold standard, at the same time is related with surgical intra and post operative complications, biological cost, and patient morbidity, pain and discomfort at the bone grafting area ,4,5,6,7.Recently, great interest has been directed towards the application of synthetic three-dimensional biomaterials scaffolds as bone substitutes used for facial large bone defect regeneration in order to have a substantial quantity of material and to avoid a second surgery site. Those synthetic bone substitutes materials should be non-toxic, compatible with the biological systems, and bio absorbable. The biomaterial has to be a macroscopic structure that is easy for surgeons to handle. Its microstructure should be able to promote cell adhesion, proliferation and new bone formation ,5,6,7,8.Nowadays, the tissue engineering approaches to the facial bone regeneration are connected with biomaterial matrices/scaffold that favorably interact with cells. The potential benefits of using recent tissue engineering findings is fundamental today in order to limit donor site morbidity, reducing operative time, and replacing the anatomical microstructure in an attempt to restore physiological craniofacial functions ,9,10,11.Recently, the use of bone substitutes obtained from marine origins is being considered high attractive by the industry as an alternative source. In this specific field, the marine collagen can be obtained from numerous sources. Type I collagen is obtained predominantly from skin, tendon, bone and muscle (epimysium), which is the most abundant type of collagen. Marine fish collagens find applications in numerous biomedical fields. Besides its mechanical elastic properties, marine collagen exhibited good absorption characteristics with interconnectivity between pores, which allowed human Mesenchymal Stem Cells (hMSCs) to adhere and proliferate, being a good base for osteogenic differentiation ,7,12.The aim of this review is to screen recent papers about biomaterials applied for facial bone reconstruction in order to give the clinicians’ valuable suggestions about the possibility of replacing autologous bone graft for large reconstruction defects.This systematic review also aimed to evaluate the potential of reconstructive marine biomaterials uses like scaffolds for growth factor in order to provide better results in comparison to others.A protocol including the investigation methods and the inclusion criteria for the current revision was submitted in advance and documented on the Center for Review and Dissemination (CRD) York website PROSPERO, an international prospective register of systematic reviews. The parameters and the analytic structure of the present work can be visualized relating the CRD id and code: Application number: CRD 74603.The data of this systematic investigation observed the Preferred Reporting Items for Systematic Review accordingly with the (PRISMA) statement .What are the overall treatment outcomes of reconstructive procedures using bone substitutes in the place of autologous bone?As an alternative focused question, does marine collagene use provide beneficial clinical outcomes applied as scaffolds for growth factors?The next spotlight questions processed the following guidelines, parameters, and possible aims of the Patient Intervetion Control Outcome (PICO) study design: The investigation method followed the examinations of electronic databases and searches by hand. A search of five electronic databases, including Ovid MEDLINE, PubMed, EMBASE, and Dentistry and Oral Sciences Source, and Biomaterials, for relevant studies published in the English language from February 2010 to September 2017 was carried out. Digital and searches by hand were then performed in facial bone reconstruction, biomaterials and bone graft scaffold journals from February 2010 to September 2017, including the following: (1) Journal of Craniofacial Surgery; (2) Journal Biomed. Mater. Research A; (3) International Journal of Oral and Maxillofacial Implants; (4) Clinical Oral Implants Research; (5) Implant Dentistry; (6) International Journal of Oral and Maxillofacial Surgery; (7) Journal of Oral and Maxillofacial Surgery; (8) Journal of Dental Research; (9) Biomed. Research International; (10) International Journal of Prosthodontics; (11) Acta Biomaterial.; (12) Journal of Clinical Periodontology; (13) Clinical Implant Dentistry and Related Research; (14) European Journal of Oral Implantology; (15) Facial Plastic Surgery; (16) Materials; (17) Marine Drugs; (18) Biomaterials; (19) Br. J. Oral Maxillofacial Surgery; (20) Aesthetic Plastic Surgery; (21) Ophthal. Plast. Reconstr. Surg.; (22) J. Craniomaxillofacial Surg.; (23) Arch Facial Plast Surg.; (24) Head and Face Medicine; (25) Talanta; (26) Eur. Cell Materials; (27) Mater. Sci. Eng. C Mater. Biol. Appl.; (28) Int. J. Biol. Macromol.; (29) Adv. Food Nutr. Res.; and (30) Macromol. Bioscience. The search was limited to English language articles. In-depth research of the reference lists in the recorded manuscripts was performed in order to add significant studies and to increase the sensitivity of the revision.The Medical Subject Headings (MeSH) was applied for finding the keywords used in the present revision. The selected key words: “facial” or “face” and “bone” or “bone graft” and “reconstruction” or “biomaterial” or “biomaterials” and “marine” and “collagen” were recorded for collecting the data. Two independent reviewers of two different universities (Messina and Naples) singularly analyzed the obtained papers in order to select inclusion and exclusion criteria as follows. Reviewers correlated their evaluations and analyzed differences through comparing the manuscripts and consulting a third experienced senor independent reviewer (Loma Linda University) when consensus could not be reached. For the stage of the full-text articles revision, a complete independent dual analysis was performed.The manuscripts selected in the analysis involved experimental and clinical research on humans and animals published in the English language. Letters, editorials, case reports, and PhD theses were excluded.The method of classification included all human prospective and retrospective clinical studies, split mouth cohort studies, case-control papers, and case series manuscripts, animal investigations and literature review published between February 2010 and September 2017, on biomaterial used for facial bone reconstruction.The sentence case of “facial bone defect reconstructive graft” was searched over each selected papers; moreover, authors investigated if there was a documented bone reconstructive surgery and a biomaterial graft placed in situ ,7,8,9,10Investigated surgical bone regenerative procedures in patients with vertical and horizontal defect of the jaws.Studies involving animals in which the created bone defects were vertical and horizontal.Clinical human prospective or retrospective follow-up research and trials, cohort studies, case-control investigations, and case series papers with at least six months follow-upAnimal or in vitro studiesThe full texts of all studies related to the main revision topics were obtained for comparing the inclusion parameters:Research treating patients with general specific diseases, heart disease, bloody pressure disease, virus infected patients, osteoporosis, immunologic disorders, uncontrolled diabetes mellitus, or other surgical risk related systemic conditions;Not enough information regarding the selected topic;Articles published prior to 1 February 2010;No access to the title and abstract number in the English language.The following exclusion parameters for manuscripts were decided as follows:After the first literature analysis, the entire manuscript titles list was highlighted to exclude irrelevant publications, case reports and the non-English language publications. Then, research was not selected based on data obtained from screening just the abstracts. The final selection was performed reading the full texts of the papers in order to approve each study’s eligibility, based on the inclusion and exclusion criteria.The results and conclusions of the selected full text papers were used for assembling the data, according to the aims and themes of the present revision, as listed onwards.The following parameters were used as a method for assembling the data and then organized following the schemes:“Author (Year)”—revealed the first author and the year of publication;“Type of study”—indicated the method of the research;“Sample size”—described the number of patients, animals or models examined;“Bone substitute/membrane”—described types of bone grafts and membranes used for regeneration;“Follow-up”—yes/no described the duration of the observed outcomes;“Bone graft histology”—yes/no described the presence of the graft at 6–9 months follow-up control.The grade of bias risk was independently considered, and in duplicate by the two independent reviewers at the moment of data extraction process. According to Moher and Higgins, this revision followed the Cochrane Collaboration’s two-part tool for assessing risk of bias and PRISMA statement ,15.Selection bias;Performance bias and detection bias;Attrition bias;Reporting bias;Examiner blinding, examiner calibration, standardized follow-up description, standardized residual graft measurement, standardized radiographic assessment.Potential causes of bias were investigated: In this way, the possible random sequence generation, the possible allocation concealment, the possibility of blinding of participants and personnel, the possible presence of having incomplete outcome data and other biases were all considered and evaluated.This method applied by the two reviewers was valuable for giving to each study a level of bias. Then, the selected papers were classified with low, moderate, high and unclear risk.n = 4), weak methods or being way off-topic (n = 5). Manuscript revision and recording data process followed the PRISMA flow diagram . The iniAutlogous Bone: Thirteen studies ,26,27,28Homologous Bone: Five studies ,31,32,33Xenograft or Allograft material and bone derived from animal or synthetic origin: Ten studies ,41,42,43Marine collagen material: Eleven studies ,53,54,55After the study selection, a new division related to the kind of bone graft has been performed:Evaluation on the total risk of bias for each selected paper, and the majority of the manuscripts were allocated as unclear risk ,34,35,36Numerous limitations have arisen from the present revision. Current analysis of the data extracted from studies written in English only could introduce a publication bias. The main limitation of the revision is related to the different kinds of biomaterials used for the same final objective, having a bone graft material able to be predictable and safe in the reconstructive and regenerative bone tissue procedures. Regarding the bias, some selected papers have a relatively short follow-up period and, when in clinical study, included relatively small numbers of treated patients. Moreover, the presented data underlined high heterogeneity and several differences in each study method, selections of the cases, and final treatment results.It is also important to note that choice of biomaterial for doing reconstruction surgery of the facial bones is a convoluted technique and its success is related to numerous parameters, comprehending patients’ general health conditions, oral hygiene habits, bone defect size, surgical procedures, operator skill, and various other factors that are not possible to fit within the frames of systematic literature. Autogenous bone graft is still considered the “gold” standard graft by the international community. The selected papers underlined the autogenous bone graft osteoinductivity properity and its good integration in the treated bone defect; however, its limited availability due to the donnor site has been underlined.n = 32) and compared with costochondral grafts (n = 28) in the condylar reconstruction in case of temporomandibular joint (TMJ) ankylosis. The clinical outcomes in both groups were satisfactory and comparable concluding how the autogenous coronoid process grafting may therefore be a good alternative for condylar reconstruction in patients with ankylosis of the TMJ [Janner et al. demonstrated how the addition of autogenous bone chips and the presence of the collagen membrane increased bone formation. Wound protection from mechanical noxa during early healing may be critical for bone formation within the grafted area, but the presence of the chips guaranteed the cells osteoinduction . The pre the TMJ . Nkenke  the TMJ . Cicciù  the TMJ . Nary Fi the TMJ . Koerdt  the TMJ . Pereiraafts n =  in the cAllogeneic bone graft used for facial reconstruction has been considered as a good alternative option in the place of autogenous bone. However, a short number of investigations recorded long-term clinical success and totally safe procedures for the treated patients.Krasny et al. recently demonstrated how the fresh, frozen, radiation sterilized, allogeneic bone blocks constitute good and durable bone-replacement material allowing effective and long-lasting reconstruction of the atrophied alveolar ridge to support durable, implant-based, prosthetic restoration . Schlee The bone grafts derived from animal or by synthetic production can be classified as biomaterials with osteoconductivity properties and currently have been used for being scaffolds for growth factor application in the bone defects. Scheyer et al. just published a randomized controlled multicenter clinical trial in which different biomaterials for the preservation of the bone volume after tooth extraction were tested. Authors stated how, at six months follow up, the xenograft collagen and autologous bone graft can give no significant difference on the socket modifications after extraction . Le et aYou et al. evaluated the effects of the bilayer bone augmentation technique for the treatment of dehiscence-type defects around implants and evaluated the role as a membrane of the xenogeneic bone using a histological method for evaluating the new bone formation. The results of this study showed the osteogenic effect of autogenous bone and the effect of mechanical support for prolonged space maintenance of xenogeneic collagen membrane applied for the treatment of dehiscence-type bone defects around implants . De Oliveira et al. studied the regenerative results of the addition of bone marrow aspirate concentrate, using a single or double centrifugation protocol, to a xenogeneic bone graft in sinus floor elevation. This pilot study indicates that the clinical use of bone marrow aspirate concentrate, obtained by either a single or double centrifugation process, combined with a xenograft result in more adequate bone repair when used in the bone regenerative surgery . GhanaatThe in vivo results analyzing the data extracted from the inflammatory infiltrates revealed that the grade of inflammation is not severe, particularly in terms of collagen production and formation of fibrous capsule . Kim et al. investigated the efficacy of the alveolar ridge preservation technique using collagen sponge and xenograft after extraction. The results indicated that, in the ridge preservation using collagen sponge and xenograft, xenograft prevents the horizontal resorption of the alveolar ridge, and the upper collagen sponge blocks the infiltration of soft tissues to the lower area, and thus it has the advantage of the enhancement of bone fill .Marine collagen and marine derived bone substitutes as an alternative to autologous bone are quickly advancing, especially since the service of tissue engineering is researching biomaterial with low cost and high availability. Marine collagen should be a true alternative source of collagen. Marine species present a distinct advantage as a lower known risk of transmission to humans of infection-causing agents and are thought to be far less associated with cultural and religious concerns regarding the human use of marine derived products. Moreover, a clarification of the marine collagen origin is important in order to underline the microscopical features of the final material used for bone defect repairing. Not only marine invertebrate collagen sources, but also marine vertebrate ones reflect several similarity with human collagens . Fish woRecently, Lin et al. developed a novel scaffold, derived from fish scales, as an alternative functional material with sufficient mechanical strength for medical regenerative applications. Fish scales, which are usually considered marine wastes, were acellularized, decalcified and fabricated into collagen scaffolds. The scanning electron microscope (SEM) was used for imaging the microstructure of the scaffold. The highly centrally-oriented micropatterned structure of the scaffold was beneficial for efficient nutrient and oxygen supply to the cells cultured in the three-dimensional matrices, and therefore it is useful for high-density cell seeding and spreading . HayashiRaffery et al. tried to determine if the incorporation of chitosan into collagen scaffolds could improve the mechanical and biological properties of the scaffold. In addition, the study assessed if collagen, derived from salmon skin (marine), can provide an alternative to collagen derived from bovine tendon  for tissue engineering applications. The data results underlined how the collagen–chitosan composites showed similar results to the bovine one. Moreover, a clear support to stem cell differentiation towards both bone and cartilage tissue was demonstrated. The collagen obtained from the bovine bone resulted in a versatile scaffold incorporating the marine biomaterial chitosan and showing great potential as appropriate platforms for promoting orthopaedic tissue repair while the use of salmon skin-derived collagen may be more suitable in the repair of soft tissues such as skin . Coelho et al. performed an investigation in which collagen has been isolated from the skins of the squids using acid-based and pepsin-based protocols, with the higher yield being obtained from I. The produced collagen was selected for evaluating its biomedical potential, exploring its incorporation on poly-ε-caprolactone (PCL) 3D printed scaffolds for the development of hybrid scaffolds for tissue engineering, exhibiting hierarchical features .Nowadays, the autologous bone is considered to be the “gold standard” by the scientific community, as its use is a predictable practice. As widely described above, it increases the formation of new bone near defects. The main advantage, moreover, is to have an osteoinductive power, and to offer increased resistance to infections due to its biological activity and the revascularization of the graft, so this is a biological active tissue. In any case, in the case of autologous bone regenerations, the patient’s morbidity should be considered, due to the donor site, such as the inability to access large amounts of bone tissue ,26,27,28Furthermore, Rahman published a paper just recently that demonstrated the potential for marine calcifiers to generate new drugs. Among the different sources of polysaccharides, algal polysaccharides such as chitin and collagen could play an important role in future development of tissue engineering, bone regeneration, and much more. In light of these emerging findings, in the near future, established techniques might also be potentially useful for isolating skeletal proteins from similar marine calcifiers for drug discovery . MoreoveEven if a comprehensive and complete investigation of the effects of surgical therapies had been performed, there were some limitations to this systematic review. Our findings could not provide the ideal material for the bone reconstruction technique of the face. The choice of the materials depend on the size of the defect, the skill of the surgeons and the donor host in the case of autogenous bone. Moreover, there could be potential language bias in this systematic review, as we only considered literature written in English.The first aim of this revision is to highlight the evolving role of biomaterial used like bone graft in the place of autologous bone during craniofacial bone reconstruction and regenerative procedures. Discussion highlighted how the ideal biomaterial scaffold is still far from being realized because of it it still being hard to reproduce the design, the micro shapes and the chemical features of the autologous bone. While human clinical applications are limited to date, great promise seems to start from scaffolds originating from the lab or obtained from the sea. Specifically, marine collagen replacing the human bone features can be optimally used for being a safe scaffold on large bone reconstruction defects of the facial area.


Most breast cancers are driven by a transcription factor called oestrogen receptor(ER). Understanding the mechanisms of ER activity in breast cancer has been a majorresearch interest and recent genomic advances have revealed extraordinary insightsinto how ER mediates gene transcription and what occurs during endocrine resistance.This review discusses our current understanding on ER activity, with an emphasis onseveral evolving, but important areas of ER biology. Dr Jason Carroll was born in Australia and completed his PhD degree inSydney at the Garvan Institute. He then did postdoctoral work with Prof Myles Brown atDana-Farber Cancer Institute at Harvard Medical School. Dr Carroll joined CancerResearch UK, University of Cambridge as a group leader in 2006 and is currently a seniorgroup leader and a Fellow at Clare College, University of Cambridge. His main researchinterest is in understanding how oestrogen receptor (ER) regulates gene expression inbreast cancer and recently has been focussing on delineating the hormonal cross-talkthat exists between ER and other hormonal nuclear receptor pathways.Oestrogen receptor (ER) is a transcription factor that regulates gene expression eventsthat culminate in cell division, an important property that contributes to its criticalrole in mammary gland development. ER is a member of the nuclear receptor superfamily,which comprises 48 proteins  that hav+ and these women as candidates for specific treatments that block ERactivity. One of the first targeted agents in the treatment of cancer was the selectiveoestrogen receptor modulator (SERM) tamoxifen, which is an effective treatment forER+ breast cancers and a class of compounds termed aromatase inhibitors (AIs). Fulvestrant binds to the LBDof ER, but unlike tamoxifen, it induces degradation of the ER protein, and this drug hasbeen an effective treatment in tamoxifen-resistant contexts  (source: Cancer Research UK) arecharacterized by the presence of ER. These cancers are therefore defined asER cancers . Ithas contexts . In pre-+ disease will benefit from targeted drugs thatblock the ER pathway, but one-third of women will develop drug resistance (+ breast cancers (ESR1) and thesemutations occur in predictable amino acid residues in the LBD of ER, decreasing thedependence on oestrogen and the response to targeted treatments  .Once ont cancer , 22. Thet cancer , 23, andThe study of a small number of ER target genes revealed insight into how ER caninteract with DNA and regulate transcription , 25, butGiven that most (~95%) ER binding sites are not at promoter proximal regionsand instead occur at distal enhancers ,a chall+ breast cancer, and was also shown to berequired for ER binding and growth of endocrine-resistant breast cancer cell linemodels  is commonly mutated in the metastatic context, but itis rarely mutated in primary tumours within the breast. FOXA1 and GATA3 on the otherhand are mutated in primary breast cancer , 57, 58.g domain . GATA3 m protein . Whether+ breast cancer research field is hampered by the scarcity ofmodels. A limited number of ER+ PR+ cell lines that areresponsive to endocrine drug treatment exists. The ‘workhorse’ in thefield is the MCF-7 breast cancer cell line, which has helped to resolve a substantialamount of information around ER function. This included the discovery of the mostrobust oestrogen-regulated genes  tumours, which providenumerous additional models for the investigation of ER+ disease, althoughthe primary tumours that typically engraft in mice, such as PDX tumours, tend to bethe more aggressive ER+ cancers  does not accurately reflect the physiological situations.Recent findings have shown a substantial degree of nuclear receptor crosstalk inER+ breast cancer, with both PR and AR converging on the ER pathway will contribute to this and, importantly, our ability and motivation to studydrug resistance by analysing metastatic material and using models of metastasis is ofparamount importance, as evidenced by the recent observation that ER itself isfrequently mutated in metastases, something that was largely overlooked for decades. Thesubstantial parallels between different hormonal cancers mean that insights generatedfrom one system (such as breast cancer) will inform our understanding of other diseases(such as prostate and ovarian cancers), and the tools, technologies and biologicalobservations need to be translated and exploited in diseases with common underlyingpathological properties.The research community has studied the ER pathway for decades and the findings haverevealed a complex picture, where ER associates with hundreds of proteins, interactswith thousands of regions in the genome and can regulate a multitude of target genes andnon-coding RNAs, many of which are only now being identified. The findings from thestudy of this pathway have identified the mechanisms of drug resistance and novel waysof targeting this disease, which has translated to improved survival rates in women withthis disease. The advent of immunotherapy in combination with existing and noveltargeted agents is likely to improve the survival rates even more, but women withERI declare that I do not have any conflict of interest.Funding was received from Cancer Research UK and the funding code is ‘corefunding’.


Eurosurveillance invites authors to submit papers in the categories, Research articles, Surveillance and Outbreak reports, Reviews and Perspectives for a special issue on advanced diagnostics to inform public health policy.The submission deadline has been extended to 13 May 2018.Recent advances in laboratory technology, including the application of qualitative and quantitative molecular diagnostics, proteomics (e.g. MALDI-TOF MS) and genomics, particularly whole genome microbial sequencing (WGS) and metagenomics are transforming the field of clinical and public health microbiology. The use of advanced methods enables unprecedented capability and capacity for rapid and comprehensive pathogen detection, quantitation and characterisation, when applied to clinical and environmental samples. Advanced diagnostics may therefore impact public health policy during specific incidents or on a wider scale.Topics of interest may include, but are not limited to:Focused reviews portraying pathogen- or disease-specific use of advanced diagnostics in public health microbiology or practical aspects of integrating new diagnostics in public health;Advanced laboratory tools for generating data that inform risk assessment and risk management;Possible role of rapid diagnostic testing in public health and cross-border health security;Moving to culture-independent public health microbiology;Policy and Regulatory aspects of harnessing new technologies for public health.our instructions for authors regarding article formats or contact the editorial team at eurosurveillance@ecdc.europa.eu.If you would like to submit a paper or ask for more information, please see


Mycobacterium tuberculosis—is estimated to be ~9 million new cases  per annum, causing 1.5–2 million deaths per annum and with an estimated 450,000 people developing multi-drug resistant tuberculosis each year); moreover, the WHO estimates that ~1/3rd of the World's population carries a latent M. tuberculosis infection, thus representing a huge reservoir of potential future TB cases. In the context of this Research Topic, it is also relevant that the burden of TB disease is very uneven globally, with certain countries in Africa having a much higher incidence than observed in the developed world—for example, in South Africa the national incidence of TB disease is around 1% of the population and a single city, Cape Town, reports more cases of TB annually than the whole of North America and Europe combined. Furthermore, roughly 21% of all deaths in South Africa are associated with TB disease today, despite proactive efforts at TB control since the beginning of the twentieth century and despite the TB control program in Cape Town achieving 75% case finding and 85% completion rates for smear positive disease. Similarly depressing statistics abound for numerous other infectious diseases in the developing world, with disease burden being driven by both microbial adaption (to drug resistance and to differing ecologies), as well as by the emergence of new, often zoonotic pathogens . According to the World Health Organization (WHO), infectious diseases today account for more than 70% of premature deaths across 22 African countries  disease—caused by infection with the pathogen ies Who, , with cointer alia virus, bacteria, fungi, and protozoa.During the last two decades, powerful high throughput research platforms—namely genomics, transcriptomics, and proteomics—have contributed significantly to our understanding of the life styles of pathogenic microbes, including important aspects of host interactions and infection . Their review starts by acknowledging early contributions of 2-DE gel approaches, and how this approach implicated novel proteins—such as peroxidoxin, outer membrane protein Rmp, and the 50S ribosomal proteins L7/L12—in the Neisseria gonorrhoeae acquired resistance to spectinomycin. They then highlight how the employment of recent quantitative proteomics  has illuminated the pathways utilized by N. gonorrhoeae to adapt to different lifestyles, including during host interaction itself. A similar trend, suggesting that progression in the field of proteomics strongly augments classical microbiological research on microbial pathogens, is also evident in several others reviews , as well as opinion articles, in this Research Topic (Soares and Blackburn).In this Research topic, we have particularly sought to highlight the powerful synergies that can be found between the fields of proteomics and microbiology, as exemplified by the review of Baarda and Sikora, which outlines the treasure hunt for counter-measures against old disease (Pérez-Llarena and Bou) and, following this lead, this Research Topic carries several original reports that employ proteomics based approaches to investigate different aspects of bacterial/fungi virulence, including biofilm formation , motility , virulence factors , altered virulence between strains , and determinants that mediate host interaction in Candida albicans . For example, Peters et al. used a combination of discovery and targeted liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based proteomics to compare the proteomes of six clinically relevant mycobacterial strains within the M. tuberculosis complex (MTBC) ; MTBC members show a high degree of genetic conservation (~99.9%), yet clinically they exhibit differing pathogenicity and virulence. Peters et al. identified an average of 3290 protein groups for each MTBC organism, corresponding to >80% coverage of the theoretical proteomes; thereafter, the authors identified quantitative differences between strains for specific proteins that could be linked to enhanced bacterial fitness in the more virulent W. Beijing lineage of M. tuberculosis .Elsewhere in this Research Topic, Perez-Llarena and Bou describe proteomics as a tool to study bacterial virulence ; ; (Soares and Blackburn) (Soufi and Soufi), providing evidence that proteomics has now evolved into a robust platform capable of generating comprehensive datasets comparable in size and utility to those described in genomic studies and enabling the application of mass spectrometry-based proteomics to genome reannotation and refinement , including 2810 ORFs previously annotated to a reference protein and 63 ORFs not previously annotated to any reference protein .This Research Topic also includes a number of manuscripts that explore novel applications of mass spectrometry within microbial research ; ; (Pérez -Llarena and Bou); (Soares and Blackburn); (Soufi and Soufi) and it will be interesting to see whether future investigation of bacterial PTMs provide a means to discover targets for novel therapies (Soufi and Soufi). In an Opinion article, we challenge researchers in the field to join efforts and to take advantage of recent advances in mass spectrometry instrumentation and in the development of targeted quantitative workflows that enable detection and accurate quantification of bacterial PTMs (Soares and Blackburn) since we believe that this represents a golden opportunity to access the dynamics of bacterial PTMs at sites of infection and that, through this, researchers will gain meaningful insights into the functional role of such PTMs during host-pathogen interactions.Finally, several papers in this Research Topic have described the enormous contribution of proteomics to the knowledge-based regarding bacterial protein post translation modifications (PTMs) and their intimate association with virulence proteomics to yield major breakthroughs in our understanding of host-pathogen interactions. Therefore, it seems reasonable to suppose that as proteomics-based experimentation is married ever more closely with biologically relevant models of human microbial disease, the analytical power of quantitative mass spectrometry will yield testable hypotheses about key molecular host-pathogen interactions and might identify new candidate drug or vaccine targets. However, in order to reach this Holy Grail, the burgeoning microbial proteomics field will need to not only infer but then experimentally validate true biological significance from amongst the vast datasets generated. Tighter integration and iteration between computational modeling of proteomic data and model-driven further experimentation, including use of cell biology, imaging and CRISPR technologies therefore seems likely to represent the future.NS and JB wrote the original draft of the paper, read and edited the final draft. GB critically discussed the content of the manuscript.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.


Chlamydia are Gram negative bacterial pathogens responsible for disease in humans and economically important domesticated animals. As obligate intracellular bacteria, they must gain entry into a host cell where they propagate within a parasitophorous organelle that serves as an interactive interface between the bacterium and the host. Nutrient acquisition, growth, and evasion of host defense mechanisms occur from this location. In addition to these cellular and bacterial dynamics, Chlamydia differentiate between two morphologically distinct forms, the elementary body and reticulate body, that are optimized for either extracellular or intracellular survival, respectively. The mechanisms regulating and mediating these diverse physiological events remain largely unknown. Reversible phosphorylation, including classical two-component signaling systems, partner switching mechanisms, and the more recently appreciated bacterial Ser/Thr/Tyr kinases and phosphatases, has gained increasing attention for its role in regulating important physiological processes in bacteria including metabolism, development, and virulence. Phosphorylation modulates these events via rapid and reversible modification of protein substrates leading to changes in enzyme activity, protein oligomerization, cell signaling, and protein localization. The characterization of several conserved chlamydial protein kinases and phosphatases along with phosphoproteome analysis suggest that Chlamydia are capable of global and growth stage-specific protein phosphorylation. This mini review will highlight the current knowledge of protein phosphorylation in Chlamydia and its potential role in chlamydial physiology and, consequently, virulence. Comparisons with other minimal genome intracellular bacterial pathogens also will be addressed with the aim of illustrating the importance of this understudied regulatory mechanism on pathogenesis and the principle questions that remain unanswered. Chlamydia are obligate intracellular bacteria that are responsible for diseases in humans and animals creating a significant burden on global health and national economies , and exhibit developmental stage-specific gene expression patterns corresponding to an early, middle, and late stage of infection  of which 41 have homologs in all sequenced Chlamydia . While EBs are metabolically inactive, proteome studies and axenic culturing conditions indicate that EBs contain, and can likely activate, the majority of enzymes involved in central and secondary metabolism suggesting that they are primed for metabolism upon entry into the host cell . To date, the phosphoproteomes of other obligate intracellular pathogens have not been examined. Coxiella, which encode multiple protein kinases and phosphatases  and PknD (inner membrane), and a putative pseudokinase, Pkn5 (T3SS effector) -type PSM, which has been extensively studied in Bacillus  and one putative sensor phosphatase , two anti-anti-sigma factors, RsbV1 and RsbV2, and an anti-sigma factor, RsbW , could not be dephosphorylated by RsbU. The current working PSM model suggests that it serves as a molecular throttle on metabolic activity and consequently growth rate. PSM mutant strains are currently being put through normal and “stress” conditions to further test the PSM model. Ligands controlling the sensor phosphatases, the roles of CT_589 and RsbV2, and whether other targets for RsbW and RsbV2 exist remain to be explored.In Two-component signaling systems (TCSS) enable adaptive responses to changing environmental conditions (Mitrophanov and Groisman, Chlamydia spp. possess a single complete TCSS along with an orphaned RR (Koo and Stephens, 54 regulated genes. CtcC-type activators promote transcription by binding DNA at enhancers, forming oligomers, and inducing ATPase activity that converts closed complexes to open complexes (Tucker and Sallai, 54 activators (Koo and Stephens, 54 RNA polymerase holoenzyme activation. While the physiological role of CtcB/CtcC is not yet known, this system is developmentally regulated as transcripts and protein levels are present during late development and are speculated to play a role in RB to EB differentiation. In addition to CtcB and CtcC, Chlamydia also encode ChxR, a response regulator that is homologous to the OmpR subfamily, but is atypical in that the receiver domain lacks the invariant Asp residue (Koo et al., Chlamydia can deliver proteins into both the inclusion lumen and host cytoplasm using the T3SS and a type 2 secretion system (Hsia et al., C. trachomatis species, and IncA indicate that phosphorylation of the homologs may not occur in all chlamydial species (Bannantine et al., Chlamydia and other obligate intracellular bacterial pathogens appear to encode a limited number of two-component signaling systems compared to most free-living bacteria (Table Chlamydia and Coxiella seem capable of Ser/Thr/Tyr protein phosphorylation, and Chlamydia is the lone species possessing a PSM. While limited in scope, the maintenance of these phosphorylation pathways by minimal genome organisms suggests that they are vital for bacterial survival and pathogenesis, and chlamydial mutagenesis and inhibitor studies are supportive of an integral role for phosphorylation in development and growth.Protein phosphorylation is a widely employed post-translational modification that mediates important processes in bacteria including cell signaling, enzyme activity, and protein-protein interactions contributing to bacterial growth and virulence. ia Table , which mChlamydia and other obligate intracellular pathogens. Despite the validation of chlamydial protein kinases, phosphatases, TCSSs, and the sole PSM, their roles in vivo remain unclear. In addition, the Ser/Thr/Tyr phosphoprotein network and an understanding of the functional consequences of substrate phosphorylation are far from complete. Fortunately, the burgeoning number of genetic methods now available for use with Chlamydia (Bastidas and Valdivia, More research is needed to elucidate the physiological role of protein phosphorylation in DF conceived of the topic and helped with writing and editing of the manuscript. JC and LM contributed ideas, wrote the manuscript, and helped with editing.Research reported in this publication was supported by the NIAID of the National Institutes of Health under Award Number 1R15AI109566-01A1 to DF. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.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.


Risk assessment and early warning (RAEW) are essential components of any infectious disease surveillance system. In light of the International Health Regulations (IHR)(2005), this study compares the organisation of RAEW in China and the Netherlands. The respective approaches towards surveillance of arboviral disease and unexplained pneumonia were analysed to gain a better understanding of the RAEW mode of operation. This study may be used to explore options for further strengthening of global collaboration and timely detection and surveillance of infectious disease outbreaks.A qualitative study design was used, combining data retrieved from the literature and from semi-structured interviews with Chinese  and Dutch  experts.The results show that some differences exist such as in the use of automated electronic components of the early warning system in China (‘CIDARS’), compared to a more limited automated component in the Netherlands (‘barometer’). Moreover, RAEW units in the Netherlands focus exclusively on infectious diseases, while China has a broader ‘all hazard’ approach . In the Netherlands, veterinary specialists take part at the RAEW meetings, to enable a structured exchange/assessment of zoonotic signals.Despite these differences, the main conclusion is that for the two infections studied, the early warning system in China and the Netherlands are remarkably similar considering their large differences in infectious disease history, population size and geographical setting. Our main recommendations are continued emphasis on international corporation that requires insight into national infectious disease surveillance systems, the usage of a One Health approach in infectious disease surveillance, and further exploration/strengthening of a combined syndromic and laboratory surveillance system. In view of the complex and global spread of infectious diseases, the timely detection of outbreaks requires mechanisms to increase situational awareness and to initiate outbreak management. Outbreaks such as Zika 2015), Ebola (2014) and severe acute respiratory syndrome (SARS) 2003) have shown the necessity of effective infectious disease surveillance systems for early detection, to allow proper assessment, a fast response and collaboration at regional, national and global levels [5, Ebola  have shoTo strengthen infectious disease surveillance in the aftermath of the 2003 SARS outbreak and to control diseases at their source, the adjusted International Health Regulations (IHR) (2005) aimed for a syndrome-inclusive approach that encouraged surveillance of infectious diseases of both known and unknown origin. The IHR aims to enhance early warning systems for World Health Organization (WHO) Member States that contribute to global communication. To enable timely communication between WHO Member States and the WHO itself, National IHR Focal Points are set up. These Focal Point are responsible for notifying WHO on events that may constitute a Public Health Emergency of International Concern (PHEIC) .Early warning systems are also in place on a supranational and (sub-)national level. To our knowledge, there are no standard early warning protocols among countries, but many countries have established units to screen surveillance sources, in order to be able to assess and control infectious disease outbreaks. In this study, we refer to these units as Risk Assessment and Early Warning (RAEW) units, although we are aware this is not a standard term or universally applied concept. RAEW units usually organize recurring, fixed meetings among infectious disease experts to discuss observations from (inter)national surveillance systems, to inform public health professionals and the public and to initiate outbreak management. Information exchange mechanisms are often in place with supranational agencies such as the European Centre for Disease Prevention and Control (ECDC) to strengthen defences against infectious diseases.Although Chinese early warning systems have improved greatly since the SARS outbreak (2003) and the Netherlands expanded their early warning systems after their experience with a large Q fever outbreak (2007–2009) , 6, furtA qualitative study design was used through a literature search and semi-structured interviews to acquire in-depth knowledge on early warning systems in a global perspective, with a specific focus on arbovirus and unexplained pneumonia surveillance systems in China and the Netherlands. Scientific databases  were searched using keywords related to early warning. In the Netherlands, 5 experts from RIVM were interviewed. In China, 6 experts from the Chinese Centre for Disease Control and Prevention (China CDC) and 5 experts from the Beijing provincial CDC were interviewed. The interview questions were structured according to the guidelines for evaluating public health surveillance systems  and inclChina (population 1.3 billion) and the Netherlands (population 17 million) both operate multi-layered infectious disease surveillance systems. In China, infectious disease surveillance data is analysed by the China CDC at different levels: national, provincial, prefecture and county  Fig. . A PHS iAs China and the Netherlands are Member States of WHO, events that may constitute a PHEIC and certain diseases (e.g. polio and SARS) require international reporting under the IHR . In ChinIn China, 39 infectious diseases are notifiable by law and categorized as A, B or C diseases . CategorIn China, if a notifiable infectious disease is clinically diagnosed and/or laboratory confirmed according to the unified national diagnostic criteria issued by the NHFPC, cases must be reported to the national China CDC, which collects and analyses the acquired data. The health care provider enters the case information using a standard form into the Notifiable Infectious Diseases Reporting Information System (NIDRIS), a web-based system that enables all healthcare institutions to report cases of notifiable infectious diseases. Approximately 5 million infectious disease cases are reported annually  [In the Netherlands, if a notifiable infectious disease is suspected and/or laboratory tests confirms it, the case must be reported both by the attending physician and the laboratory to the regional PHS. The case information is collected and entered by the PHS into Osiris, a web-based database that transmits the data to RIVM for further analyses. In 2014, 13,863 notifiable disease cases were reported via Osiris to RIVM  [Timeliness is an important factor for an effective response . It requTo facilitate early warning at different China CDC levels, the China Infectious Disease Automated-alert and Response System (CIDARS) has been in place since 2008 . AlthougAlthough the Chinese early warning system is based on CIDARS, China CDC also organizes regular RAEW meetings among infectious disease experts Fig. . ImportaIn the Netherlands, the RIVM organizes regular RAEW meetings to discuss important signals and advise on or initiate an outbreak response Fig. . The sigTo better understand the workflow and to provide a detailed explanation of the surveillance systems focusing on a specific disease, in-depth studies were performed on arbovirus and unexplained pneumonia surveillance in China and the Netherlands.Although lower respiratory infections, including pneumonia, are one of the main causes of death worldwide , real-tiIn the year after the SARS outbreak in 2003, NHFPC developed a surveillance system for unexplained pneumonia to facilitate timely detection of airborne pathogens that form a severe threat to public health. Therefore, all Chinese health care facilities are required to report any patient who has a clinical diagnosis of pneumonia with an unknown causative pathogen and whose illness meets the following five criteria (2007 modified definition): (1) fever ≥38 °C; (2) radiologic characteristics consistent with pneumonia; (3) normal or reduced leukocyte count or low lymphocyte count in early clinical stage; (4) no improvement or worsening of the patient’s condition after first-line antibiotic treatment for 3–5 days; and (5) the pneumonia etiology cannot be attributed to an alternative laboratory or clinical diagnosis (clinicians are granted flexibility to determine how to interpret this criterion and specific tests are not specified) , 23. OncUnexplained pneumonia is not a notifiable condition in the Netherlands as it is in China. However, according to the Public Health Act (2008), each physician should notify a case or an unusual number of cases with an (unknown) infectious disease that forms a severe threat to public health. An example is the Q fever outbreak (2007); the unusual number of atypical pneumonia cases early in the outbreak were not detected by routine surveillance systems but by astute general practitioners (GPs) . Both DuThe current Zika outbreak (2015) shows how important an effective arbovirus surveillance system is, as the IHR requires countries to report unusual Zika-related cases .In China, dengue virus infection and Japanese encephalitis virus infection are to be reported (both category B) . JapanesIn the Netherlands, West Nile virus (WNV) infection, transmitted via endemic Culex mosquitoes, is currently the only notifiable arbovirus infection (category C) . Once a The results of the present study indicate that many similarities exist among infectious disease surveillance for early warning systems in China and the Netherlands. Both countries generally apply similar notifiable disease reporting systems and RAEW units. The infectious disease surveillance institutes have comparable aims and functionalities in China and the Netherlands, which reflects 100% IHR (2005) implementation.Some differences exist in early warning systems. In China, early warning is mainly based on the automatically generated and disseminated signals of CIDARS by means of fixed thresholds. In the Netherlands, the emphasis is on expert opinion based on epidemiological analysis and additional checking of raw data. The experts at RIVM decide whether or not to contact PHS for further investigation. Multiple factors need to be taken into account to understand why certain systems are in place. At first, the infectious disease outbreak history plays an important role. The Netherlands experienced Q fever outbreaks (2007–2009) , 29, leaThe concept of ‘One Health’ emphasized by the Dutch government recognizes that in such a densely populated country, the health of humans is interlinked with the health of animals and the environment and acknowledges the importance of intensive animal husbandry . China cUnexplained pneumonia and arbovirus surveillance in China relies more on laboratory confirmation than the Dutch surveillance system, where syndromic surveillance currently plays a larger role. Since China is a large country with multiple governmental levels, the spectrum of socio-economic conditions and facilities for laboratory testing vary widely among different regions . To incrThe infectious disease surveillance systems for the two diseases assessed in China and the Netherlands are remarkably similar in general structure considering the large differences in the two countries’ infectious disease history, population size and geographical setting. Routine procedures and (electronic) communication mechanisms are key components in the system, and help both countries to achieve situational awareness and to control infectious disease outbreaks.However, the systems differ on some details. The substantial demographic differences and recent history of emerging infectious disease outbreaks in both countries may have influenced the assessment and communication mechanisms in place. The main differences are the usage of thresholds and automatically top-down disseminated (SMS) signals in China for validation purposes, which might be more efficient and perhaps better accepted in a large country. This is in contrast to a more qualitative and exploratory approach in the Netherlands, probably due to its small size and short communication lines. Those surveillance differences must be addressed at the international reporting level, in order to convey national used baselines or syndrome counts in understandable terms. Continued emphasis is therefore needed on international cooperation to curb the global spread of infectious diseases, which requires an insight into the early warning and infectious disease surveillance systems of all countries to improve global assessment and response capabilities.The additional zoonotic RAEW in the Netherlands, initiated since a large Q-fever epidemic, improved zoonotic surveillance and assessment capacity. Therefore we recommend that infectious disease surveillance systems should consider using a One Health approach, to interlink the environment, human and animal health. While the Chinese ‘all hazard’ approach might improve the surveillance assessment quality due to early involvement of different stakeholders and experts, with shared public health responsibilities.Combining syndromic surveillance together with the outcomes of laboratory tests increases the probability of timely detection and proper assessment. Further strengthening a combined syndromic and laboratory surveillance system can be further explored by both countries.


Canadian Inuit have often reported concerns about the quality of their municipal drinking water; research has also shown that some Inuit communities experience some of the highest incidence rates of self-reported acute gastrointestinal illness (AGI) in Canada and globally. The goal of this thesis research was to investigate drinking water perceptions and consumption patterns, as well as water contamination and potential associations with AGI in the Inuit community of Rigolet, Canada. Three census cross-sectional surveys captured data on AGI, drinking water, and water storage (2012–2014); additionally, bacterial contamination of household drinking water was assessed alongside the 2014 survey. Concerns regarding the taste, smell, and colour of tap water were associated with lower odds of consuming tap water. The use of transfer devices  was associated with household water contamination; while no water-related risk factors for AGI were identified, incidence of AGI was high compared with southern Canada. This thesis research provides a valuable contribution to the limited literature assessing drinking water and health in the Arctic. Ultimately, this work is intended to inform safe water management practices, as well as contextually appropriate drinking water interventions, risk assessments, and public health messaging in the Canadian Arctic.


Since 2013, the State Public Health Actions to Prevent and Control Diabetes, Heart Disease, Obesity and Associated Risk Factors and Promote School Health  program has been implemented to support and reinforce healthy choices and healthy behaviors among the US population. The Centers for Disease Control and Prevention’s Division of Population Health’s School Health Branch has been a critical component, ensuring that state health departments support schools in adopting nutrition standards and creating a supportive nutrition environment. The objective of this article was to describe early outcomes of the school nutrition strategies of State Public Health Actions.We examined the extent of progress for short-term performance measures and for school nutrition evaluation questions, using data secured from 51 grantees through the performance measures database and state evaluation reports.During the first 4 years of the cooperative agreement, grantees demonstrated significant progress compared with year 2 for school nutrition performance measures. Collectively, grantees provided professional development and technical assistance to staff in 7,672 local education agencies and reached more than 29 million students. Success was also noted for several nutrition practices in schools.These early outcomes suggest that State Public Health Actions has had a positive impact on the nutrition environment of US schools. Systematically addressing areas for improvement could further expand the reach of these efforts during the remainder of the cooperative agreement. State Public Health Actions to Prevent and Control Diabetes, Heart Disease, Obesity and Associated Risk Factors and Promote School Health  is a 5-year cooperative agreement that supports state health departments in the promotion of healthy choices and healthy behaviors among the US population . The CenMore than one-third of children and adolescents in the United States are overweight or obese . BecauseThis article describes the early outcomes of the school nutrition strategies, specifically changes in school-level nutrition practices, of State Public Health Actions.In June 2013, all 50 states and the District of Columbia were awarded funding under either the basic or enhanced component of State Public Health Actions , and appWe conducted a document review of annual progress reports and analyzed quantitative performance measure data using a mixed-methods design. These data represented performance from July 1, 2013, through January 31, 2017. Data were obtained from 51 grantees that reported on basic performance measures; 32 of those grantees also reported on enhanced performance measures for enhanced states. School Health Profiles (Profiles) was the primary data source for all school-level performance measures. Profiles is a system of surveys that assess school health policies and practices among secondary schools in states, territories, tribal jurisdictions, and large urban school districts . ProfileIn addition, we collected and analyzed year 3 state evaluation reports. These evaluation reports represented data collection from August 1, 2015, through July 31, 2016. Grantees submit annual evaluation reports that provide detailed findings derived from their state-level evaluation of interventions and strategies. All grantees submitted evaluation reports, of which 29 of the 32 enhanced grantees evaluated the implementation of the enhanced school nutrition strategy. Evaluation reports addressed core questions corresponding to level of implementation. Grantees self-identified as being in either the adoption or implementation phase for the school nutrition strategy. Grantees at the adoption stage reported findings in response to the following core questions: 1) “What state activities have been effective in promoting nutrition policy development and nutrition practice adoption among districts and schools?” and 2) “What are the major facilitators and barriers in helping districts and schools create a supportive nutrition environment, such as partnerships with the Department of Education? How were the barriers overcome?” Grantees at the implementation stage reported findings related to the following core questions: 1) “What critical factors or activities influence the successful implementation of nutrition policy and nutrition practice?” and 2) “To what extent has implementation of nutrition policies and nutrition practices increased access to healthier foods and beverages at school?” In their evaluation report, grantees provided summaries of the approach and strategies of the intervention, the facilitators and barriers to implementation of the strategies, the evaluation indicators, and the evaluation findings.P < .05), the average percentage change  was compared with zero by using one-sample t tests. Achievements of basic component short-term measures are also described.For analysis of the annual progress reports, year 2 and year 4 data for eligible states were aggregated. Reach estimates were calculated on the basis of the performance measure type . Measures reported as counts were summed as totals across eligible states. Measures reported as percentages were reported as means across eligible states. In addition, for each performance measure, the percentage change in the actual values reported from year 2 to year 4 were calculated. Next, to determine whether the percentage change for each measure was significant .Data from the basic component show that 7,672 LEAs received professional development and technical assistance on strategies to promote the adoption of nutrition standards, affecting 29.3 million students in these LEAs  and reprIn the areas of nutrition policy and school nutrition practices among the 32 enhanced grantees, 59.5% of LEAs reported adopting and implementing policies to establish standards (including for sodium) for all competitive foods available during the school day, compared with 50.4% in year 2 . AdditioFifty-one state evaluation reports containing results of interventions designed to create supportive nutrition environments were analyzed. Fifty-seven percent of grantees evaluated the strategy focused on creating healthy school nutrition environments (12 in the adoption phase and 17 in the implementation phase). More than half of the 29 grantees evaluating this strategy reported the facilitators and barriers to creating supportive nutrition environments. Among them, 67% identified strong leadership, committed staff, formal partnerships, and engaging champions for school nutrition as key facilitators. The availability of professional development and technical assistance to support staff in the development, implementation, and evaluation of school nutrition interventions also was beneficial. Collectively they provided more than 780 professional development and technical assistance opportunities; 11 grantees reached more than 4,200 state, district, and school administrators; food service staff; and teachers. Other facilitators included communicating about school nutrition, offering incentives, and disseminating resources. Forty-one percent of grantees also found these facilitators influential in the successful implementation of nutrition policy and practice. Sixty percent of grantees reported barriers to creating a supportive nutrition environment, including inadequate capacity , negative attitudes, perception of changing traditions , and lack of buy-in and support.Grantees also described many activities that contributed to the perceived increase in access to healthier foods and beverages. For 75% of grantees, the implementation of nutrition practices and policies to increase access to healthier foods and beverages in schools was largely accomplished by changing and adopting district-level nutrition policies and practices for competitive foods, healthy school celebrations, events, or fundraisers; food and beverage procurement; and meal preparation and service. Many of these policy changes were enacted to better align with state and national nutrition standards such as the new Smart Snack regulations, but some also aimed to improve the consistency and quality of how food is presented to students, availability of information about menu nutrition contents for parents and students, and access to healthier food options . Some of these policies also prohibited advertising and promotion of less nutritious foods and beverages on school property.As a result of these policy changes, 66.7% of grantees saw practice changes implemented in schools and districts, including increased use of locally grown food  and scratch cooking methods, thus improving the quality and nutritional value of school meals. Changes in local wellness policies also bolstered the development of school health improvement plans that targeted healthy eating habits; the consumption of fruits, vegetables, and healthy snacks; and use of evidence-based and comprehensive health education curricula that align with national and state standards to promote healthy behaviors among students in districts.In addition, some districts and schools restricted food celebrations, marketing of unhealthy choices, and use of food and beverages as a reward. For example, one grantee reported that nutrition guidelines changed to require that healthy food options be made available at school celebrations, events, and/or fundraisers. Finally, grantees reported observing some improvements in the availability, quality, and selections of foods and beverages in food service lines and à la carte items among its targeted districts, and one grantee reported a 4% decline in the consumption of soda among high school students.State Public Health Actions’ school health strategies aim to provide a comprehensive approach to adopting nutrition standards and creating a supportive nutrition environment in schools through professional development and training of school staff, adoption and implementation of nutrition policies, and implementation of various evidence-based nutrition practices. The findings from this evaluation provide both a broad perspective and more details of school nutrition work in the United States. For example, significant progress has been made in reaching school nutrition and other school health professionals through professional development and technical assistance. This progress enables new knowledge, skills, and abilities among key stakeholders who are also often the implementers of school nutrition policies and strategies.Outcome data for most school-level nutrition performance measures were favorable. Grantees implemented practices such as placing fruits and vegetables near the cafeteria cashier, where they are easy to access, and prohibiting all forms of advertising and promotion for candy, fast-food restaurants, or soft drinks. These are just 2 examples of no-cost or low-cost strategies that schools can implement to create a supportive nutrition environment. Grantees also reported achieving significant increases in 2 evidence-based practices: not selling less-healthy foods and beverages  and providing information to students or families on the nutrition, caloric, and sodium content of foods available. Slight nonsignificant increases were observed in the percentage of local education agencies that adopted and implemented policies that prohibit all forms of advertising and promotion  of less-nutritious foods and beverages on school property, the percentage of schools that price nutritious foods and beverages at a lower cost while increasing the price of less nutritious foods and beverages, and the percentage of schools that offer fruits or nonfried vegetables when foods or beverages are offered at school celebrations. Surprisingly, decreases were observed in 2 evidence-based practices: allowing students to have access to drinking water and allowing students to purchase fruits and vegetables from vending machines or at the school store, canteen, snack bar, or as à la carte items. Although these decreases suggest an opportunity for improvement, these achievements collectively demonstrate the capacity of school nutrition nationwide .These data also show that more than half of all targeted LEAs have adopted nutrition standards. These standards require schools and school cafeterias to offer more fruits, vegetables, whole grains, and fat-free or low-fat dairy products and limit sodium, added sugar, calories and unhealthy fat in competitive foods found in à la carte, vending machines, and other venues ,17. The School nutrition policies, when implemented, support consistent and lasting change in schools. Although 56.9% of schools reported prohibiting all forms of advertising and promotion for candy, fast foods, or soft drinks, only 33.5% of LEAs adopted and implemented policies that prohibit all forms of advertising and promotion. This area is one that needs to be better understood. In practice, grantees are making progress in prohibiting advertising; however, ensuring that this practice is sustainable through the adoption of policy still needs to be improved.Furthermore, federal legislation such as the Healthy Hunger Free Kids Act of 2010 has been a leverage point for State Public Health Actions grantees, including local wellness policy requirements, Smart Snacks in School, and school meal standards . State PFinally, state evaluations have allowed for exploration of facilitators, barriers, and outcomes that enable both CDC and grantees to identify future training, technical assistance, and policy development needs among LEAs and schools. For example, from grantees’ evaluation reports, common facilitators have been identified, such as having strong leadership, committed staff, formal partnerships, and engaged champions. Other studies have found similar facilitators to those of grantees, suggesting that these elements support greater implementation of local wellness policies and environmental strategies to promote healthy food and beverages ,22. ThesAlthough results are encouraging, our study has limitations. Many of the findings were derived from performance data from 32 enhanced grantees who were awarded funding on a competitive basis. These data, although representative of the LEAs selected, may not be generalizable to all LEAs in the United States because grantees’ used their own criteria  to select LEAs. In addition, we used self-reported data that were not verified or corroborated by other data or observations. Furthermore, grantees who choose to evaluate the school nutrition strategy may represent more highly motivated grantees, so data from these reports should be interpreted cautiously. Despite these limitations, the data we used were collected by using quality surveillance and data collection systems.To date, close to 8,000 LEAs and more than 29 million students, representing 57% of US school districts and 59% of students, have been reached by State Public Health Actions . Our finFinally, as grantees enter the final year of the cooperative agreement, they are required to develop impact statements. These impact statements will highlight the accomplishments of their work during the past 5 years. These impact statements can be used by grantees and CDC to garner support from funders and key decision makers for continued work in the area of school nutrition.


The adoption of the 17 sustainable development goals (SDGs) listed in the 2030 Agenda for Sustainable Development by the United Nations urged the scientific community to generate information for planning and monitoring socioeconomic development and the underlying environmental compartments. SDGs 2, 3, 6, 11, 13, 14, and 15 have targets which commend direct consideration of soil resources. There are five groups of SDGs and assigned SDG indicators where soil plays a central role. Frameworks of soil-related sustainable development goals and related indicators which can be monitored in current monitoring schemes are proposed. In addition, soils play an important role in mitigating and adapting to climate change (SDG 13). Further, SDGs 7 and 12 will indirectly rely on the availability of healthy soil resources. Regarding the remaining SDGs, linkages can be found to the sustainable management of soils to some extent , under the 2030 Agenda for Sustainable Development, urged the scientific community to generate sound information with the aim of supporting planning and monitoring of socioeconomic development interlinking with environmental sustainability dimensions UN . SDGs 2,The recent 48th session of the UN Statistical Commission revised the list of the global SDG indicators UN . The tarexplicitly include productivity ,explicitly include soil degradation (15.3),name soil in the SDG although no soil-based indicator has been proposed (3.9),have direct relevance to soil resources with explicit reference to land resources but no reference to soil (11.3),have direct relevance of soil to SDG without naming soil in SDG nor including soil-related SDG indicator .The main question lies in what soil indicators should be considering and the monitoring methodologies behind. An analysis on the content of the SDGs and its indicators helps to clarify the level of integration of soils to these. There are five groups of SDGs and assigned indicators where soil plays a central role, namely:Productivity is the soil property considered in several SDGs and incorporated into a broader concept of “agricultural productivity” term . Nevertheless, while agricultural productivity defines various factors and might also include components like animal husbandry and other segments, the fundamental factor of agricultural productivity is based on soil fertility (and climatic conditions). In addition, soil productivity loss is a central concept of land degradation UNCCD . Land deTo achieve the SDGs, there is an urgent need to assess and monitor the soil properties that impact soil productivity and the soil threats, with an emphasis on soil hydraulic properties, nutrient status, pollution, soil biodiversity, and SOC changes. An option is through the assessment of soil properties in the minimum datasets (Doran and Parkin Efforts are being made for improving soil monitoring systems, such as the European Union’s work gathering information on soil bulk density and soil biodiversity (Fernández-Ugalde et al. The spatial extent of global and regional soil quality assets has to be considered and integrated into policies ranging from sustainable urbanization to agricultural development. Soil functions and degradation threats are manifold, and soil indicators are diverse. Monitoring soil and land changes for all these considerations is a challenge which needs to be addressed. The SDGs help to streamline the efforts of soil monitoring programs, which, combined with the new sources of soil information and extensive application of modern technological solutions can provide the needed data and information. Additionally, harmonization between different sampling and monitoring programs as well as between measurement standards and protocols (Nortcliff