SysWiz Database, the online database from the Cambridge Cell Networks Ltd. (CCNet) tailored for the purpose of FP7 Syscilia project with a systems biology approach to studying cilia, has integrated manually curated and interpreted information from public domain (scientific literature) related to ciliary functions and diseases - list of protein (gene) interactions as well as list of ciliopathies and associated genes – around 3000 of them, involved in different ciliary diseases, curated and interpreted from the literature (PubMed) by CCNet. Furthermore, some preliminary legacy data from different partners within the FP7 Syscilia project with systems biology approach to studying cilia, such as lists of ciliopathies (syndromes) with associated genes. SysWiz database/software tool provides you with information on what proteins/genes/chemicals are associated with specific ciliary diseases, with a number of supporting literature references beside each molecule and hyperlinks to abstracts on PubMed. SysWiz offers visualized relationships between the molecules, associated with specific ciliopathy, as well as related chemicals from assay of partner with supporting literature references by clicking on the connector lines and hyperlinks to abstracts on PubMed. By using the SysWiz integrated system, one can obtain an in-depth understanding of possible mechanism of action as well as to extrapolate data and observed effects from other species into humans.


Acanthaluteres vittiger, Scobinichthys granulatus), reef  or sand habitats (Nelusetta ayraudi). Predatory fish that consume molluscs, crustaceans and cephalopods were dominant with evidence of habitat generalisation in reef species to cope with local disturbances by wave action. Niche separation within major genera, and a sub-regional faunal break, indicate future zootone mapping should recognise both cross-shelf and longshore environmental gradients.Distributions of mobile animals have been shown to be heavily influenced by habitat and climate. We address the historical and contemporary context of fish habitats within a major zootone: the Recherche Archipelago, southern western Australia. Baited remote underwater video systems were set in nine habitat types within three regions to determine the species diversity and relative abundance of bony fishes, sharks and rays. Constrained ordinations and multivariate prediction and regression trees were used to examine the effects of gradients in longitude, depth, distance from islands and coast, and epibenthic habitat on fish assemblage composition. A total of 90 species from 43 families were recorded from a wide range of functional groups. Ordination accounted for 19% of the variation in the assemblage composition when constrained by spatial and epibenthic covariates, and identified redundancy in the use of distance from the nearest emergent island as a predictor. A spatial hierarchy of fourteen fish assemblages was identified using multivariate prediction and regression trees, with the primary split between assemblages on macroalgal reefs, and those on bare or sandy habitats supporting seagrass beds. The characterisation of indicator species for assemblages within the hierarchy revealed important faunal break in fish assemblages at 122.30 East at Cape Le Grand and subtle niche partitioning amongst species within the labrids and monacanthids. For example, some species of monacanthids were habitat specialists and predominantly found on seagrass ( BioregiFrom a global perspective, Australia’s southwest marine region is characterised by low levels of nutrients, an unusually deep photic zone, dominance offshore by carbonate sediments, disturbance driven by wind and waves, and a high species diversity and endemism . The bioOffshore of the Recherche Archipelago, the Leeuwin Current moves eastward along the edge of the continental shelf and interacts with the Great Australian Bight flow moving westward onshore in the eastern islands of the archipelago . The LeeDespite a large body of research linking the composition of fish assemblages to the structure of algal, coral and seagrass habitats at fine scales , fewUnderstanding how various structural components of habitats influences the structure of fish assemblages across a broad range of depths, at a bioregional scale, will be an important component of spatially explicit conservation and fisheries management in the future . In compMore recently, Chatfield et al.  used a cWe examine the same BRUVs dataset used by Chatfield et al. , but focWe aim to examine how patterns in the spatial distribution of demersal fish in the temperate coastal waters (3-85m) of the Recherche Archipelago, south-western Australia are constrained by the benthic habitat characteristics and the spatial location of sampling along the longitudinal gradient of the archipelago.No permits, or ethics approvals were required for surveys of this nature (video observations of fish in situ) in these locations, at the time of this study (2002).2, excluding reefs and islands, extending over 470 km of coastline and over 2 degrees of longitude in an approximately west-east direction (Dns.Algae), (2) reef with medium macroalgae (Med.Algae), (3) sand inundated reef with sparse macroalgae (Sprs.Algae), 4) vegetated sand (Veg), (5) bare sand (Snd), (6) dense seagrass (Dns.Sgrs), (7) medium seagrass (Med.Sgrs), (8) sparse seagrass (Sprs.Sgrs) and (9) rhodolith beds (Rdlths). Sites for fish sampling were selected from towed video tracks from three regions  to provide approximately equal representation of all habitat categories in all regions. However, there ended up being an uneven representation of the nine habitat categories amongst the three sampling regions, with more seagrass sites sampled off Esperance, more reef habitats close to islands sampled off Duke of Orleans Bay, and more deep sites sampled far from shore off Cape Arid . Stereo or single camera BRUVs were deployed on sites selected from previous towed video surveys. This BRUVs approach supersedes the tethered, single-camera, downward facing technique .Between 26th May and 13th June 2002, 219 BRUVs deployments were conducted during daylight hours at pre-determined waypoints within each of the nine habitat categories throughout Esperance Bay, Duke of Orleans Bay and Cape Arid . Each reSardinops neopilchardus sagax). Video was analysed, for “juvenile” and “adult” categorisation of each species, by counting the maximum number of individuals seen together in any one frame across the whole 60 minutes of tape , distance (km) to the nearest coastline (land.km) and distance to the nearest emergent island (rock.km).The BRUVs shown in  were depN; sensu ,27). DatMaxN) of the observed species were analysed in two ways. Firstly, repeated ordinations were performed by constraining the site scores to display only the variation among sites and species that could be explained by the environmental explanatory variables. Redundancy analysis was used, employing the RDA function in the “vegan” library of R-2.7.2  showed that N. parilus occupying reefs had similar diets to those individuals in seagrass beds, and suggested that individuals forage in a similar niche in both habitats or regularly move between the two. Cheilodactylid morwongs  are known to feed by “suck and sort” on infaunal molluscs, small crustaceans and echinoderms of interstitial sediments and algal turfs ).Pelsartia humeralis to the west and the cool temperate velvet leatherjacket Meuschenia scaber on the eastern side. The tree also identified an important faunal break in fish assemblages on sandy seafloors and seagrass beds at 122.3° East in the vicinity of Cape Le Grand. This was somewhat surprising given the present focus on eastward transport of sub-tropical fauna by the Leeuwin Current in biogeographic studies (see ). Cape LSphyraena, Trachurus, Arripis) are pelagic and can move widely [Pictilabrus and Dotalabrus are not known to venture far from sheltered habitats [The existence of the spatial break in assemblages near Cape Le Grand was detected even though the Leeuwin Current was running eastward across the whole width of the shelf, almost at its winter peak velocity (see ) at the e widely , but othhabitats ,52. The existence of a further long-shore subdivision within the Esperance Zootone might represent a “soft barrier” to allopatric speciation, around which natural selection can maintain adaptations in local populations despite ongoing gene flow . This coConversely, predictions of fish assemblages at large spatial scales using biogeographic models only, that do not account for habitat type or availability, can also be misleading. Such predictions are common in relation to poleward shifts in the ranges and composition of temperate reef faunas under scenarios of ocean warming . This implies that adding spatial predictors of sampling location to cover the faunal break at Cape Le Grand would not have increased the amount of variation accounted for by Chatfield et al.’s [Meuschenia) from each of nine genera. The combination of these approaches refines the basis for marine bioregional planning for both resource use and conservation in the Recherche Archipelago, and suggest a re-analysis of species distributions of other groups within the zootone should recognise both cross-shelf and longshore environmental gradients. Our study informs the models of fish-habitat associations published from the Recherche dataset by Chatfield et al.  in two met al.’s  species The use of bait in the BRUVs technique is often challenged as a bias toward predators and scavengers, and away from herbivores and prey species. However, all sampling techniques are biased to some degree, and the BRUVs offer a key benefit unavailable to all other techniques. This advantage is threefold. Firstly, operators skilled in fish taxonomy and survey techniques are not required for the deployment of the gear. Secondly, a permanent visual record of both the fish and seafloor habitat in the field of view is available for all stakeholders immediately. Finally, the technique is non-destructive and fish can be accurately measured (with stereo-BRUVs) to calculate biomass. The first two advantages allow “citizen science” to become an essential part of marine field research and planning, and for all stakeholders to visualise fish-habitat associations, fish size and abundance, and fish behaviour, with no need for translation by scientists. The engagement of the human users of coastal resources in the planning and management process is now seen as the critical gap to fill in the failures of previous attempts at an ecosystem approach to fisheries (e.g. ) and imp


The article reviews the use of robotic technology for head and neck tumours. The authors discuss the development of transoral robotic surgery (TORS), the current status of the technology, and the set-up in the operating room. The article provides a review of the literature, highlighting the applications, advantages, functional outcomes, and disadvantages of TORS for each anatomic subsite . New challenges related to reconstruction are also presented. Overall early functional and oncologic outcome data are promising; further long-term prospective trials are still needed to confirm the oncological safety of TORS. Robotic-assisted surgery has its roots in 1972, when the National Aeronautics and Space Administration began to investigate a method to provide surgical care to orbiting astronauts through telepresence surgery [After the first laparoscopic splenectomy performed in 1997 , roboticet al with a case report of a supraglottic laryngectomy in a canine model and by MacLeod and Melder [Transoral robotic surgery (TORS) was first introduced in  by Weinsd Melder , who repIn 2006 and 2007, preclinical and clinical studies by a team at the University of Pennsylvania demonstrated  the feasBecause of the possibility of obtaining superior visualisation and complete resection of tumours with wide margins, TORS seems to represent an alternative to open or endoscopic/microscopic approaches in oral and pharyngolaryngeal oncology—particularly with 5-mm instruments—that allows improved vision, greater ease of use, and a shorter operating time .The Da Vinci Surgical System consists of three components: a surgeon’s console, a patient-side robotic cart equipped with four arms, and a high-definition three-dimensional vision cart. Articulating surgical instruments are mounted on the robotic arms, which are introduced into the upper aerodigestive tract through the mouth of the patient and manipulated remotely with master robot manipulators from the surgeon’s console.As far as head and neck surgery is concerned, usually only three of the four arms are employed: one to handle a 12-mm stereoscopic endoscope at an angle of 0° or 30° and the other two equipped with 5-mm endo wrist instruments .Both the endoscope and the robotic instruments are introduced transorally and allow the surgeon to perform procedures equivalent to traditional surgery, with the advantages of enhanced three-dimensional HD visualisation, wide range of motion with seven degrees of freedom, reduction of hand tremors, possibility of navigating around corners through angled scopes, reduction of fatigue, proper hand– eye coordination, and the possibility of telesurgery and teaching opportunities with more favourable learning curves , 11–14.When compared with open surgical approaches, TORS may avoid disfiguring mandibulotomy; it reduces the need for adjuvant radio and/or chemotherapy and for tracheostomy/gastrostomy, improves the return to normal speech and swallowing, and reduces blood loss and postoperative pain , 15–17. TORS may be applied for benign and malignant lesions of the palate, the palatine tonsils, the base of the tongue, the posterior and lateral pharyngeal wall, the parapharyngeal space, the larynx, and the hypopharynx; main contraindications are reduced mouth opening, incomplete lesion visualisation, mandible involvement, tumours involving >50% of the base of the tongue or of the posterior pharyngeal wall, internal carotid artery, or prevertebral fascia involvement .TORS is defined as the surgery performed through the oral cavity that uses a minimum of three robotic arms and allows bimanual manipulation of tissues. The surgeon’s cart should be located at the end of the operating room, allowing free space to manoeuver the surgical cart that is placed on the left side of the patient, opposite to the surgeon . The assAll of the authors stress the importance of the correct positioning of the machine, to allow complete exposition of the lesion and free, unobstructed movements of the robotic arms , 11–14.Tongue baseet al reported a prospective clinical trial evaluating the use of TORS in three patients with tongue base cancer. They reported an excellent visualisation and tumuor removal possibility. The use of the FK retractor is described to be essential for proper exposure and for instrument manoeuverability. Complete resection with negative surgical margins was achieved in all three cases with an excellent control of bleeding; no intraoperative or postoperative complications were encountered [In 2006, O’Malley ountered .et al reported a retrospective study on ten patients with unknown primary tumours of the head and neck. All patients underwent a cervical biopsy, positron-emission tomography/computed tomography, formal endoscopy, bilateral tonsillectomy, and transoral robotic base of tongue resection. Robot-assisted base of tongue resection identified primary tumours in 90% patients with minimal morbidity [The use of Da Vinci robot has also been reported for tongue base biopsy in the evaluation of unknown primary tumours of the head and neck . Metha eorbidity .Reconstruction should be considered particularly for large defects, to maintain a balance between restoration of bulk and maintaining a sensate mucosal surface, so as not to impair the pharyngeal phase of swallowing and to avoid aspiration . The radTonsillar regionet al, TORS seems to represent a valid alternative to transmandibular approaches with free-flap reconstruction. All the patients underwent TORS radical tonsillectomy for invasive squamous cell carcinoma (SCC) of the tonsillar region, staged neck dissection, and adjuvant therapy. Major tumour-related contraindications for TORS radical tonsillectomy were: unresectability of involved neck nodes, mandibular invasion, tongue base invasion requiring a resection of >50% of the tongue base, pharyngeal wall involvement necessitating resection of >50% of the posterior pharyngeal wall, radiological confirmation of carotid artery involvement, and fixation of tumour to prevertebral fascia. Neck dissection was performed one to three weeks following TORS radical tonsillectomy, to avoid the risk of creating a connection between the pharynx and the neck and to avoid additional laryngopharyngeal swelling that might require a tracheotomy. No free-flap reconstruction was needed and the mucosal defect at the end of surgery was allowed to heal by secondary intention. The mean operative time to perform TORS was 1 h and 43 min including a mean of 9 min for exposure and robotic positioning. Complete resection with negative surgical margins was achieved in 93% of the cases. The surgical complication rate was 19%, most cases resolving without significant sequelae: one mucosal haemorrhage requiring a return to the operating room, one tracheostomy for OSA exacerbation, two cases of trismus, and one of hypernasality requiring an outpatient procedure for correction. No mortality occurred and no cases of pneumonia or fistula were observed. Twenty patients were extubated at the end of the surgical procedure, the remaining six patients remained intubated for laryngopharyngeal swelling, treated with steroids for one to three days and then extubated after an average of 2.7 days postoperatively. One patient required unplanned tracheostomy for his sleep aponea exacerbation. All the patients underwent percutaneous gastrostomy and 96% of them recovered a proper swallowing function at the follow-up [TORS radical tonsillectomy has widened the indications for transoral resection, because TORS allows excellent visualisation in all directions, concurrent tongue base resection, and the possibility of better identifying small and large vessels. In the series of 27 patients presented by Weinstein For the majority of the patients, no reconstruction is required if the resection is limited to the tonsillar region; free tissue transfer should be considered in patients predisposed to poor wound healing, or if the carotid artery is exposed in the parapharyngeal space . When thet al reported a prospective human clinical trial evaluating the use of TORS in three cases of supraglottic partial laryngectomy for supraglottic carcinoma. An excellent surgical exposure with complete tumour resection was achieved. No intraoperative or postoperative complications were reported. The median overall operation time was 120 min including 18 min for exposure and robotic positioning. Robotic-assisted supraglottic laryngectomy is reported to be technically feasible and relatively safe, representing an alternative to open approaches and conventional transoral supraglottic partial laryngectomy [Weinstein 2 laser robotic-assisted supraglottic laryngectomy. The FK laryngo-pharyngoscope was reported to provide excellent visualisation in only one patient, and the procedure was completed successfully. In the other two cases, adequate exposure could not be achieved and more traditional techniques were performed [Solares and Strome reported three cases of COerformed .et al [Park et al  reportedAlthough hypopharyngeal SCC represents a clinically distinct and less frequent entity among other cancers of the head and neck, early experiences using TORS for hypopharyngectomy for I- and II-staged cancers seem to be promising.et al reported a series of ten patients with T1 or T2 pyriform sinus and posterior pharyngeal wall cancer successfully treated with TORS. The mean operation time was 62.4 min with an average of 17.5 min for the robot setup. No significant perioperative complications were reported. A return to normal swallowing function was observed in all patients within 8.3 days average and decannulation within 6.3 days after surgery. The authors concluded that transoral robotic hypopharyngectomy is feasible and safe for the treatment of early hypopharyngeal tumours [Park  tumours .TORS used in skull base surgery was first assessed in  on animaIn 2010, the same authors assessed the outcomes of ten patients undergoing parapharyngeal space resection using the TORS approach . The suret al [McCool et al  reportedet al [In cadaveric dissections, Hanna et al  obtainedet al [In skull base surgery, robotic techniques can be considered as the natural evolution of traditional endoscopic techniques  and theiet al  reportedAs the application of TORS for the treatment of head and neck cancer increases, robotically assisted reconstruction, whether using free flaps, local flaps, or primary closure, holds the potential of expanding TORS applications, keeping the aim to provide patients with less morbid procedures. The introduction of vascularised tissue into an oropharyngeal defect can provide improved functional recovery. The flexibility of the robotic arms allows suture placement transorally in areas of decreased visibility using traditional open techniques. Even microvascular anastomosis has proved faster and more effective . In roboSeveral case series demonstrated the clinically applicable use of the robot for reconstruction of head and neck.et al [Mukhija et al  describeet al [Selber reported robotic-assisted reconstruction in five patients with oropharyngeal tumours: reconstruction included both local and free flaps, depending on the size of the defect, prior radiation, and the presence or absence of a pharyngotomy. The authors reported the first case of robotic anastomosis, with the advantage of tremor elimination, motion scaling up to 5:1, and an enhanced ability to work precisely in confined spaces. There were no oropharyngeal fistulas. Only one postoperative complication was reported; one patient accidentally bit through his pedicle but without resulting flap failure . Genden et al  reportedet al .et al performed 20 robot-assisted oropharyngeal reconstructions, including six anterolateral thigh flaps, five radial forearm flaps, two ulnar artery perforator flaps, two FAMM flaps, five buccal or pharyngeal transposition flaps. Robotic microvascular anastomosis was performed in four of these cases. No flap losses were described [Longfield escribed .et al reported a case series of five patients who underwent robotic free-flap reconstruction  after TORS for oropharynx tumours. In one case, the microanastomosis was performed using the robotic arms. No major complications were encountered, including flap failure, haematoma, or wound dehiscence [Song hiscence .et al provided an algorithmic approach to determine the need of reconstruction after robotic excision of head and neck tumours. TORS is not routinely necessary for tumours within the oral cavity, which usually offer a good manual transoral access. Retromolar trigone represents the only exception and, because of its anatomical features, tumours of this region may benefit from TORS resection and reconstruction: in these cases, local flaps are usually sufficient for reconstruction. Tumours of the oropharynx  are an ideal indication for TORS resection: complicated excisions  with resulting large defect may benefit from microvascular reconstruction. For supraglottic larynx, Longfield et al [Longfield ld et al  considerEarly TORS data support impressive functional outcomes with low rates of gastrostomy dependency, prompt decannulation, and resumption of normal oral intake .et al [et al reported that 83% patients were tolerating an oral diet within 14 days, while 17% required a feeding tube at 12-month follow-up, and 5.6% demonstrated signs or symptoms of aspiration [et al reported that 82% of the patients were tolerating oral diet by the first postoperative visit, whereas 17% required a feeding tube, and none required assistance with feeding at one-year follow-up [et al reported that 100% of the patients were able to return to oral diet on the day of surgery and 20% of them required feeding tubes mainly for adjuvant therapy [Genden et al  reportedpiration . Moore eollow-up . Hurtuk  therapy .The majority of the authors reported a low rate of tracheotomy for patients undergoing TORS , the authors reported no local or regional recurrence, though two patients had distant recurrences. In the HPV-negative group, there were no local recurrence, one patient had both regional and distant recurrences. Survival rates showed no statistically significant differences between the two groups of patients, with 81% in HPV-positive group and 80% in the HPV-negative group [Cohen ve group .et al in a prospective case study of 89 patients with head and neck SCC of all stages and subsites treated with TORS, reported at a median follow-up period of 26 months three patients with local recurrence, seven with regional recurrence , and one patient with distant recurrence; seven patients were treated with TORS for recurrent disease. Of the patients who underwent TORS as primary treatment, 63% underwent adjuvant radiotherapy and 48% had chemotherapy either before or after surgery; 8% underwent salvage TORS after primary chemoradiotherapy. At the last follow-up visit, 82 patients had no evidence of disease, one died of the disease, two died of other diseases, and four were alive with disease. The overall two-year recurrence free survival rate was 86.3% [White as 86.3% .et al in a prospective case-control study of 30 patients with head and neck SCC of all stages and subsites treated with TORS and adjuvant therapy, reported 24 patients alive with no recurrent disease at last follow-up visit. Two patients had local recurrence, two developed distant recurrence, and one developed a second primary tumour. The 18-month locoregional control, distant control, disease-free survival, and overall survival reported rates of 91%, 93%, 78%, and 90%, respectively [Genden ectively .et al reported a return to normal swallowing function and diet one year after surgery in 38 patients with oropharyngeal SCC treated with TORS, while the speech domain was significantly reduced even one year after surgery. They reported that patients who had TORS followed by chemoradiation had significantly lower swallowing scores compared with those without [Even if the most important outcome for cancer patients is overall survival, in patients with head and neck cancer, QOL, and functional outcome may really be affected by psychological impact of loss of function and physical disfigurement. This has led to a shift to not only organ-preservation treatments, but also function-preservation treatments. Frequent problems include difficulty with speech, respiration, and eating . Leonhar without .et al found that patients treated with TORS had significantly better short-term swallowing and eating ability and diet compared with patients treated with primary chemoradiation. While TORS patients had a return to baseline in all domains  at 12 months, patients who had chemoradiotherapy did not have a return to baseline in the diet domain [The case control study on 30 patients with head and neck SCC reported by Genden t domain .et al observed the resumption of normal oral intake in all but one patient, with no patients who needed tracheostomy. Although in all of the patients, the self-administered QOL questionnaire underlined a postoperative decreasing in all of the values, at the one-year follow-up the major part of them returned back to high domains, with the exception of eating function and attitude. QOL scores differed significantly among patients who underwent TORS for malignant diseases compared with those who had a robotic resection for benign lesions; similarly, QOL scores were significantly lower for those patients who underwent adjuvant radio- or chemotherapy and in those affected by tonsillar region cancer [In a cohort of 64 patients who underwent TORS for benign and malignant lesions of the head and neck region, Hurtuk n cancer .et al, all the 35 patients were discharged from the hospital within six days [et al, the mean hospital stay reported was 2.6 days [et al, it was between five and seven days [The overall hospital stay is reported to be shorter for TORS patients than for those who would have otherwise undergone an open approach. In the case series of Moore six days ; in the 2.6 days , whereasven days , 45.Development of TORS has greatly facilitated the minimally invasive surgical approach for head and neck carcinoma, circumventing many of the technical limitations commonly associated with transoral laser microsurgical techniques, such as line of sight and two-handed surgery.en bloc complete tumour resection. Technical feasibility, efficacy, and safety have been largely demonstrated by many studies. In patients undergoing TORS, shorter operative time and decreased hospital stay have been observed; excellent oncological and functional outcomes have been also reported [TORS provides superb three-dimensional visualisation and magnification in all directions, with tremor filtration, greater freedom of instrument movement facilitating delicate dissection, minimally invasive and less morbid access, and the ability of two surgeons to operate within the field. The excellent ability of bleeding control facilitates reported . Faster reported , affordiNot all the patients are good candidates for TORS because some of them may present some limiting factors, mostly affecting proper surgical exposure, such as trismus, narrow arched mandible, full dentition, and retrognathia . Access The bigger limitation of robotic technology seems to be represented by the absence of sensory tactile feedback, which may give significant drawback in a number of situations . The iniIn terms of the teachability of TORS, training programs have already yielded successes . As for In conclusion, TORS has proven to be a safe and feasible treatment for tumours of the upper aerodigestive tract, and its continuing use and development is encouraged; the results of the published articles are still not sufficient to validate the oncological safety of TORS and further long-term prospective trials are still needed to confirm those results.


Fragile states are home to a sixth of the world's population, and their populations are particularly vulnerable to infectious disease outbreaks. Timely surveillance and control are essential to minimise the impact of these outbreaks, but little evidence is published about the effectiveness of existing surveillance systems. We did a systematic review of the circumstances (mode) of detection of outbreaks occurring in 22 fragile states in the decade 2000-2010 , as well as time lags from onset to detection of these outbreaks, and from detection to further events in their timeline. The aim of this review was to enhance the evidence base for implementing infectious disease surveillance in these complex, resource-constrained settings, and to assess the relative importance of different routes whereby outbreak detection occurs.We identified 61 reports concerning 38 outbreaks. Twenty of these were detected by existing surveillance systems, but 10 detections occurred following formal notifications by participating health facilities rather than data analysis. A further 15 outbreaks were detected by informal notifications, including rumours.There were long delays from onset to detection (median 29 days) and from detection to further events . Existing surveillance systems yielded the shortest detection delays when linked to reduced barriers to health care and frequent analysis and reporting of incidence data.Epidemic surveillance and control appear to be insufficiently timely in fragile states, and need to be strengthened. Greater reliance on formal and informal notifications is warranted. Outbreak reports should be more standardised and enable monitoring of surveillance systems' effectiveness. The World Bank describes a fragile state as a country 'facing particularly severe development challenges such as weak institutional capacity, poor governance, political instability, and frequently ongoing violence or the legacy effects of past severe conflict' .In 2009, 29 countries were considered fragile, comprising a sixth of the world's population . FragileDetection and early containment of outbreaks in these settings is also challenging, as highlighted by the Global Polio Eradication Initiative's recent setbacks in several fragile states, where genetic analysis has demonstrated previously undetected poliovirus transmission of one year or more duration . Given tThe importance of epidemic surveillance is recognised, but there is a scarcity of evidence on optimal ways to detect outbreaks in the unique situations of fragile states, where routine health information systems are weak, diagnostic tools limited and resources for structured surveillance, such as training, sample transport and data transmission, very constrained. It has been suggested, at least for early warning systems in humanitarian emergencies, that emphasis should be placed on detecting alerts from health facilities or other informal sources (e.g. community informants and the media), rather than on analysis of weekly or other surveillance data, which often feature low completeness and timeliness, or high background noise due to non-specific case definitions . So as tst December 1999, within a predefined list of fragile states. The list of fragile states was created using the World Bank's quantitative definition, taking into account both the eligibility of a country to receive an interest-free International Development Association loan and a nation's Country Policy and Institutional Assessment score [A systematic review of the published literature was performed to identify reports describing infectious disease outbreaks which began after 31nt score . Countrint score ,12-15. Tth July 2010 and 23rd August 2010, a combined OVID SP search of the MEDLINE, EMBASE and Global Health databases was done. OVID SP is a search engine that taps into various literature databases relevant for global health. MEDLINE is a database of life sciences and biomedical journals. EMBASE is similar to MEDLINE but focuses on drug therapeutic studies. Global Health focuses on public health and medical science and includes conference abstracts, thesis reports, electronic information and other hard to find material. The basic search concepts were '(fragile state of interest) AND (epidemic-prone event) AND (detection)'. Each concept was expanded and variations of terms, including contemporary and historic, French and Spanish were included  formal notification if the initial alert was raised by health workers as part of an ongoing surveillance system; and (iii) informal notification if the alert was raised through mechanisms other than an existing surveillance system, either by health workers or other community members. Both authors made this classification independently and came to a consensus decision on any discrepant choices.For each eligible outbreak, the mode of detection was categorised into (i) Whenever available, we also calculated time lags from detection or onset to further events in the outbreak timeline, as per the definitions in Table Vibrio cholerae (2), Plasmodium falciparum malaria (3), Neisseria meningitidis (2), measles virus (3), hepatitis E virus (2), Shigella dysenteriae type 1 (1), Leishmania donovani (1), yellow fever virus (7), dengue virus (1), Ebola virus (3), unspecified viral haemorrhagic fever (1), scurvy (1), Marburg virus (1), Escherichia coli (1), influenza virus (1), Yersinia pestis (1), Tunga penetrans (1), Gnathostoma spinigerum (1), monkeypox virus (1), Rift Valley fever virus (1), West Nile virus, Salmonella typhi (1), and Borrelia spp. (1).Of the 2634 abstracts produced by the search strategy, 58 reports describing 38 separate outbreaks were found eligible Figure , of whicOf the 58 reports included in the review, 20 were primarily authored by the World Health Organization; 14 by Médecins Sans Frontières; six by journalists; five by international research institutes; three by national research institutes; three by the United States Centers for Disease Control and Prevention; two by overseas governments; two by other NGOs; two by UNICEF; and one by the national government.Salmonella typhi in central Myanmar, September 2000 [Borrelia spp. relapsing fever in Southern Sudan, 2000 [Among the 35 outbreaks for which mode of detection information was available, 20 (57.1%) were detected through existing surveillance systems, with 10 detected by data analysis Table . For thrber 2000 ; Borrelian, 2000 ), the moReports suggested that data analysis proved successful when there was frequent reporting and analysis of data, and with the provision of a free and dependable supply of medication . Poor reporting practices delayed detection (outbreak 9). In two instances failures were compensated for by informal notifications after substantial delays .For both data analysis and formal notifications, limited access to and distrust of health services delayed detection . In two instances, warnings provided by a geographic information system and detection of an outbreak amongst local wildlife led to enhanced surveillance and eventually detection .Informal notifications originated from a local non-governmental organisation (NGO) (outbreak 27), a research institute (outbreak 26), an embassy (outbreak 30), a UN radio operator (outbreak 21), a rumour received by the WHO (outbreak 33), international NGOs , national hospital staff . Again, treatment charges and limited access to health facilities delayed detection . Four outbreaks occurring within isolated rural communities were associated with late detections .Overall, the median lag time from onset to detection was 29 days (range 7-80) in 16 outbreaks for which this information was available. In two cases, investigation also unveiled previously undetected and undiagnosed outbreaks due to the same agent. Outbreaks detected through informal notifications appeared to feature the longest detection delays  delays were 7 days 0-30) to investigation, 23 (5-42) to confirmation, 30 (15-50) to declaration and 55 (26-154) to start of control (reactive vaccination). Numbers were small and no obvious pattern emerged according to the aetiologic agent's route of transmission  to investigation in nine outbreaks for which both time to detection and time from detection to investigation were available; 53  to confirmation; 56  to declaration; and 80  to control.Early warning alert and response network (EWARN) systems set up in southern Sudan and Darfur in 2000 and 2004 respectively, were involved in six Sudanese outbreaks. These outbreaks generally featured the shortest times from onset through to confirmation .Cooperation by communities was greatly hampered by fear and distrust of control teams and biomedical interventions during investigations of Ebola virus and Marburg virus outbreaks . Other obstacles to investigation included poor road conditions and insecurity . On two occasions, misconceptions by authorities and subsequently late investigations significantly delayed confirmation of causative agents .This review suggests that over the last decade surveillance systems have played a considerable role in early outbreak detection in the 22 fragile states included in the review. However, on the whole data analysis seemed to lead to a minority of outbreak detections, with both formal and informal notifications of alerts playing a more prominent, though less timely role. Certain elements of the system played an important role in sensitivity and timeliness, including reduced barriers to health facility utilisation and frequent data analysis. Combining knowledge of the seasonal outbreak risks particular to each area with predictive tools such as geographic information systems could be used to improve the effectiveness of such systems. More importantly, surveillance systems in fragile states should enhance the detection of alerts outside routine data analysis, by focussing more efforts on building both formal and informal networks of informants, particularly where acute emergency conditions or remoteness prevent sophisticated data collection and analysis.Our review suggested that timeliness of detection, investigation and response is poor for most outbreaks occurring in fragile states, with up to five months elapsing until the start of meaningful control. These delays negate most of the advantages of surveillance and make containment extremely difficult.Our review is limited by our search strategy, which did not capture outbreaks described in the grey literature. Furthermore, findings may not apply to other states that met fragility criteria for only some of the years within the review's timeframe. Publication bias is likely to influence our findings, but its direction is difficult to gauge: while large outbreaks that were intensively investigated and controlled are more likely to be the subject of publications, small outbreaks that were detected early and contained are probably under-reported. We noted that the vast majority of reports included were authored by institutions based outside the affected countries, with only one report coming from the national ministry of health. This suggests a need to strengthen capacity by fragile states to communicate outbreak surveillance findings, so as to promote ownership of surveillance and outbreak control, and raise the profile of outbreaks and epidemic-prone diseases that international counterparts would not otherwise respond to.During data abstraction, the considerable heterogeneity of formats and variables included in outbreak reports was apparent. We recommend that a more standardised format be introduced for papers reporting outbreaks, particularly affecting vulnerable populations; and that key meta-data such as the dates of salient events in the outbreak timeline and the circumstances of detection always be reported, so as to enable ongoing global monitoring of the effectiveness of surveillance systems and outbreak control interventions.DRC: Democratic Republic of Congo; EWARN: Early Warning Alert and Response Network; WHO: World Health Organization; MSF: Médecins Sans Frontières; NGO: Non-governmental organization.The authors declare that they have no competing interests.CB designed the search strategy, carried out the review and co-wrote the paper. FC designed the search strategy and co-wrote the paper. All authors read and approved the final manuscript.Appendix containing details on the selection of countries included in the review and on the search strategy used.Click here for file


Systematic evaluation of outcomes is essential for clinical trial research, yet outcomes often neglect the voice of the child and parent, particularly within paediatric orphan diseases.While guidance for the development and validation of Patient Reported Outcomes (PROs) and Observer Reported Outcomes (ObsRO) measures are available from EMA and FDA , little attention has focused on paediatric and orphan disease PRO/ObsRO development methods,2.We summarize considerations for the development, validation and use of paediatric measures and provide examples of their successful use.Table Concept elicitation  and psychometric validation require samples sizes within narrow age bands , but also need to consider rates of development within the context of the condition being studied. From 0-5 years, parents are asked about child behaviours they observe that are indicative of symptoms or impact. For 6-11 years, the child and parent should be asked though simple questions, with images attached to responses, should be used for the child. For 12-17 years, more adult language (without jargon) can be used. Pooling data across ages can only be considered if different age versions are shown to be conceptually equivalent.PROs have been used to aid decision making for regulatory approval (as in the case of Icatibant for the treatment of Heriditary Angioedema)-5 and reStrong paediatric PRO/ObsRO research is needed to ensure ‘fit for purpose’ outcomes are used in paediatric trials to collect robust evidence regarding the safety and efficacy of drugs for children who have orphan diseases. When successfully implemented, all stakeholders benefit: regulators, payers, doctors, parents and most importantly, the children themselves.


To the Editor: Recently, the novel and highly virulent variant of porcine reproductive and respiratory syndrome virus (PRRSV), which first emerged in the People’s Republic of China and Vietnam in 2006 , skin discoloration/reddening, high incidence of illness (50%–100%), and high proportion of deaths (20%–100%) in pigs of all ages. This new PRRS has spread throughout the swine industry in China, resulting in the culling of an estimated 20 million pigs annually in 2006–2007 in China , and some other point mutations, have occurred, which were markedly different from those found in any other previous virus isolate.After a surveillance study of the epidemic and an analysis of >300 novel highly pathogenic PRRSVs were conducted, the highly pathogenic PRRSV from China was considered to have gradually evolved from CH-1a, a local PRRSV isolate. The evolutionary path could be traced through intermediate PRRSV strains (,Highly pathogenic PRRSV first emerged in China and Vietnam almost simultaneously in 2006, and the epidemic focus was in the area between southern China and northern Vietnam (In addition, all highly pathogenic PRRSV isolates share high sequence identity and have the same deletions as the highly pathogenic PRRSV isolated from China or Vietnam. PRRSV can spread through a variety of routes, including direct contact between pigs, droplet contact through nasal secretions, direct contact with saliva and feces, and indirect contact.PRRS has spread rapidly around the world through pig sales, semen, and airborne transmission, including from airline passengers who carry the virus on their clothing, shoes, or equipment while traveling (


About one third of deaths in children less than 5 years of age are due to underlying undernutrition. According to an estimate, 19.4% of children <5 years of age in developing countries were underweight (weight-for-age Z score <-2) and about 29.9% were stunted in the year 2011 (height-for-age Z score <-2). It is well recognized that the period of 6-24 months of age is one of the most critical time for the growth of the infant.We included randomized, non-randomized trials and programs on the effect of complementary feeding (CF)  and education on CF on children less than 2 years of age in low and middle income countries (LMIC). Studies that delivered intervention for at least 6 months were included; however, studies in which intervention was given for supplementary and therapeutic purposes were excluded. Recommendations are made for input to the Lives Saved Tool (LiST) model by following standardized guidelines developed by Child Health Epidemiology Reference Group (CHERG).We included 16 studies in this review. Amongst these, 9 studies provided education on complementary feeding, 6 provided complementary feeding (with our without education) and 1 provided both as separate arms. Overall, education on CF alone significantly improved HAZ , WAZ , and significantly reduced the rates of stunting . While no significant impact were observed for height and weight gain. Based on the subgroup analysis; ten studies from food secure populations indicated education on CF had a significant impact on height gain, HAZ scores, and weight gain, however, stunting reduced non-significantly. In food insecure population, CF education alone significantly improved HAZ scores, WAZ scores and significantly reduced the rates of stunting, while CF provision with or without education improved HAZ and WAZ scores significantly.Complementary feeding interventions have a potential to improve the nutritional status of children in developing countries. However, large scale high quality randomized controlled trials are required to assess the actual impact of this intervention on growth and morbidity in children 6-24 months of age. Education should be combined with provision of complementary foods that are affordable, particularly for children in food insecure countries. About one third of deaths in children under 5 years of age are due to underlying undernutrition, which includes stunting, severe wasting, deficiencies of vitamin A and zinc, and suboptimum breastfeeding . ChildhoInfants from 6 to 18 months are especially vulnerable to developing malnutrition. In order to sustain the gains made by promoting exclusive breastfeeding for the first six months of life, interventions need to extend into the second half of infancy and beyond. This could be ensured by enabling caregivers to appropriately feed their children with safe and adequate complementary foods while maintaining frequent breastfeeding . It is wSeveral strategies have been employed to improve CF practices . These iOver the last five years, several reviews have been published on the impact of various CF interventions ,5,9. DewIn this review, we have assessed the impact of education on CF and provision of CF with or without education on growth and morbidity among children under 2 years of age in LMICs. We reviewed the available literature and evaluated the quality of included studies according to the Child Health Epidemiology Reference Group (CHERG) adaptation of Grading of Recommendations, Assessments, Development and Education (GRADE) criteria .To evaluate the impact of CF interventions on child growth, a search, following CHERG Systematic Review Guidelines, was conducted on PubMed, Cochrane Library, Google Scholar and WHO global database. We also reviewed the reference lists of identified articles, existing reviews and meta-analyses, and looked for studies that were not identified in the initial search. We included randomized  and non-randomized controlled trials and programs. The last date of search was October 01, 2012 and we did not apply any language restriction.Studies on education on CF and provision of CF  with or without education were included if those provided interventions for at least 6 months and were conducted in LMICs on children less than 2 years of age. Studies in which interventions were given for supplementary and therapeutic purposes were excluded. We also excluded studies in which fortified complementary foods were compared with non-fortified complementary foods.The developing countries were defined according to World Bank classification . StudiesFor the studies that met the final inclusion criteria, data was abstracted describing study identifiers and context, study design and limitations, intervention specifics and outcome effects into a standardized abstraction form as detailed in the CHERG Systematic Review Guidelines . Each st2 and I2, which can be interpreted as the percentage of the total variation between studies that is attributable to heterogeneity rather than to chance, a low p-value (less than 0.1) or a large chi-squared statistic relative to its degree of freedom and I2 values greater than 50% were taken as substantial and high heterogeneity. A subgroup analysis was also performed based on food security of the populations.We conducted meta-analyses for individual studies and pooled statistics was reported as the relative risk (RR) for categorical data and standard mean difference (SMD) for continuous data between the experimental and control groups with 95% confidence intervals (CIs). HAZ scores were further converted into stunting considering the standard deviation of 1.4 for stunting in the population [We summarized the evidence by outcome, including qualitative assessments of study quality and quantitative measures, according to the standard guidelines. A grade of “high”, “moderate”, “low” and “very low” was used for grading the overall evidence indicating the strength of an effect on specific health outcome according to the CHERG Rules for Evidence Review. The stuWe found 701 titles on the initial search, of which 16 met the inclusion criteria and were finally included  Figure . While nThe combined pooled analysis indicated that provision of CF with or without education reduced the incidence of respiratory infections by 33%   on growth and morbidity in children less than 2 years of age in LMICs.Our review indicates that in food secure population, education on CF had a significant impact on linear growth as evident by significant increase in height gain and HAZ scores, and also significantly improved weight gain, however rates of stunting reduced non-significantly. Education in food insecure population also improved linear growth and weight gain as evident by significant increase in HAZ and WAZ scores and significant decrease in rates of stunting. We did not find any study on provision of complementary feeding (with or without education) from food secure population, however, from food insecure population the intervention improved HAZ and WAZ scores. Our review indicated that CF provision had no significant impacts on height or weight gain, while previous reviews ,9 suggesAs part of causal chain, it is well recognized that educational interventions improve feeding practices which then lead to improved growth outcomes. The educational messages should lay emphasis on the importance of appropriate home prepared foods, hygiene and high energy foods and it is important to assess the recall of the messages by mothers once the messages are delivered and our review suggest a significant 62% increase in compliance with the imparted messages, reinforcing the importance of such intervention. Considerable variations were observed in the types of educational messages delivered and an attempt to assess the quality of educational messages and delivery strategies was difficult, but in general most of the studies delivered educational interventions of reasonably good quality with the appropriate use of charts, posters and booklets. The two studies that had the most impact on linear growth ,21, alsoNutritional status has a strong and consistent relation to death from respiratory infections. Nutrition education and complementary feeding with or without education had a positive impact on reducing respiratory infections. A review by Rice et al.  reportedThere were a variety of complementary food(s) used as intervention in the included studies. Amongst these foods were maize, fortified fat based spread, food prepared from locally available raw ingredients, cereal and porridge. The scarcity of available studies and their heterogeneity as well as the variety in complementary feeding interventions makes it difficult to conclude one particular type of complementary feeding intervention as the most effective; moreover, the variation in the reported outcomes amongst studies makes it difficult to compare them.In future, further trials are needed particularly from food insecure population in which interventions are consistent and standardized in terms of study design and quality, complementary food chosen, duration of intervention and should report consistent outcomes for growth and morbidity. However, the available evidence is sufficient to recommend that in food insecure populations, education should be accompanied with provision of affordable yet effective complementary food. Accelerated and concerted actions are required to deliver and scale up nutrition education and CF provision interventions that are cost-effective, feasible and effective in improving the nutritional status of children.CF interventions have a high potential to improve the nutritional status of children in developing countries. Nutrition education interventions should be combined with provision of CF that are affordable, particularly in food insecure countries.Child Health Epidemiology Reference Group (CHERG); confidence interval (CI); Grading of Recommendations, Assessments, Development and Education (GRADE); Height-for-age Z score (HAZ); Low and middle income countries (LMICs); Randomized Controlled Trials (RCTs); Relative risk (RR); Standard deviation (SD); Standard mean difference (SMD); Weighted mean differences (WMD); Weight-for-age Z score (WAZ).We do not have any financial or non-financial competing interests for this review.Dr. ZAB was responsible for designing and co-ordinating the review. ZSL, GZ and JKD were responsible for: data collection, screening the search results, screening retrieved papers against inclusion criteria, appraising quality of papers, abstracting data from papers, entering data into RevMan, analysis and interpretation of data. ZSL, GZ, JKD and ZAB wrote the paper. ZAB and ZSL critically reviewed and modified the manuscript.Characteristics of studies on impact of education on complementary feeding.Click here for fileCharacteristics of studies on impact of provision of complementary feeding with or without education.Click here for file


We assessed the knowledge and awareness of cervical cancer, HPV and HPV vaccine, and willingness and acceptability to vaccinate in sub-Saharan African (SSA) countries. We further identified countries that fulfill the two GAVI Alliance eligibility criteria to support nationwide HPV vaccination.We conducted a systematic review of peer-reviewed studies on the knowledge and awareness of cervical cancer, HPV and HPV vaccine, and willingness and acceptability to vaccinate. Trends in Diphtheria-tetanus-pertussis (DTP3) vaccine coverage in SSA countries from 1990–2011 were extracted from the World Health Organization database.The review revealed high levels of willingness and acceptability of HPV vaccine but low levels of knowledge and awareness of cervical cancer, HPV or HPV vaccine. We identified only six countries to have met the two GAVI Alliance requirements for supporting introduction of HPV vaccine: 1) the ability to deliver multi-dose vaccines for no less than 50% of the target vaccination cohort in an average size district, and 2) achieving over 70% coverage of DTP3 vaccine nationally. From 2008 through 2011 all SSA countries, with the exception of Mauritania and Nigeria, have reached or maintained DTP3 coverage at 70% or above.There is an urgent need for more education to inform the public about HPV, HPV vaccine, and cervical cancer, particularly to key demographics, , to leverage high levels of willingness and acceptability of HPV vaccine towards successful implementation of HPV vaccination programs. There is unpreparedness in most SSA countries to roll out national HPV vaccination as per the GAVI Alliance eligibility criteria for supporting introduction of the vaccine. In countries that have met 70% DTP3 coverage, pilot programs need to be rolled out to identify the best practice and strategies for delivering HPV vaccines to adolescents and also to qualify for GAVI Alliance support. The introduction of vaccines has been one of the most effective public health interventions for combating infectious diseases Worldwide, 15% of all cancer cases and nearly 26% of cancer cases in developing countries are attributable to infectious agents, particularly viruses Several recent developments have emphasized HPV vaccine as an important prevention strategy. The 2009 WHO position paper on HPV vaccines recommended they be included in routine national immunization programs as a public health priority http://www.gavialliance.org/support/nvs/human-papillomavirus-vaccine-support). GAVI Alliance also announced that in 2014 it will support the first nationwide introduction of HPV vaccine in Rwanda for girls of all eligible ages, as well as other HPV demonstration projects in Mozambique, Zimbabwe, Ghana, Madagascar, Malawi, Niger, Sierra Leone, and Tanzania .Currently, the GAVI Alliance uses two criteria to determine eligibility for vaccination support, including HPV vaccine: 1) a DTP3 threshold of 70% national coverage (WHO/UNICEF estimates) and 2) a pilot demonstration of the ability to deliver a complete multi-dose series of vaccines to at least 50% of the target vaccination cohort in an average sized district in a country These developments, coupled with SSA's recent success in reaching 70% coverage for other routine vaccines, namely measles, hepatitis B, Influenza, tuberculosis and polio since 1990 Nevertheless, introducing HPV vaccine in SSA offers unique challenges, especially due to limited awareness of cervical cancer, its relationship to HPV, concerns about safety and future fertility, and political factors In this study, we assessed the knowledge and awareness of cervical cancer, HPV and HPV vaccine, willingness and acceptability to vaccinate through a systematic review of peer-reviewed literature. We further identified the fulfillment of GAVI Alliance eligibility criteria among countries in SSA. To the best of our knowledge this is the first systematic review of the potential readiness for introduction of HPV vaccine in the sub-continent, which reveals further insight into some of the unique challenges that need to be addressed.Studies examining awareness, knowledge of cervical cancer, HPV and acceptability of HPV vaccines in SSA were identified by searching PubMed/MEDLINE (NCBI), Embase (Elsevier), African Index Medicus (AIM), and POPLINE  from their earliest dates through July 11, 2013. Bibliographies of relevant reviews and eligible studies were examined for additional sources. The search was performed by a librarian (PAB) using terms for papillomavirus vaccines and vaccination, acceptability or awareness, and the names of all SSA countries . The seaThe review was conducted using methodology reported in the National Health Service Centre for Reviews and Dissemination report, supplemented by Harden's recommendations for systematic reviews of qualitative studies Studies included in the review needed to meet the following criteria: 1) it occurred in a SSA country; 2) it was published in 2006 or later, after HPV vaccination was introduced; 3) it focused on one or more of the three key demographics ; and 4) it examined at least one or more of the following key themes: a) level of awareness of HPV and/or cervical cancer; b) level of knowledge of cervical cancer and/or awareness; c) willingness to vaccinate; d) and acceptability of HPV vaccine. Studies that conducted a pilot HPV vaccination program were automatically included in the review. Animal studies were excluded from the review.A systematic review of the identified studies was then performed summarizing key results. The authors' findings were treated as primary data and studies were synthesized using a framework approach. Data were extracted and organized by key information such as demographic, method and sample size, and key findings of the study about levels of knowledge, awareness, willingness and acceptability. Any strategies for vaccination or increasing awareness (whether recommended or implemented strategies) were also extracted along with factors influencing acceptability of HPV vaccine.Levels of awareness, knowledge, acceptability and willingness were broken down into these categories: 1) awareness of cervical cancer, HPV and/or HPV vaccine; 2) knowledge of cervical cancer, HPV and/or HPV vaccine; 3) acceptability of HPV vaccine ; and 4) willingness to vaccinate or get vaccinated. Willingness was broken down further into categories based on how each individual article defined it as seen in The literature search returned 142 unique records as summarized in the flow chart . Review Two qualitative studies were considered to be of good standard while one was considered moderate and one was considered poor. Nearly all of the surveys were well conducted and 17 of these had a sample size greater than 200 respondents. Sixteen of those had a response rate greater than 70%. The remaining studies varied in quality from moderately good to poor Fifteen studies examined awareness of cervical cancer, HPV and/or HPV vaccine among specific demographic groups. Levels of awareness were mixed with 11 studies demonstrating high awareness, nine studies demonstrating low awareness and two studies demonstrating moderate awareness. Levels of knowledge of cervical cancer and HPV were consistently low. Of the 16 studies examining knowledge of cervical cancer, HPV and HPV vaccine, all noted low levels of knowledge, three reported no knowledge, and two reported moderate knowledge. Only one study specified a moderately high level of knowledge of HPV vaccine.Categories of willingness varied across studies: willingness to recommend HPV vaccine (five studies); willingness to get vaccinated (four); willingness to get daughter vaccinated (four); willingness to participate in vaccine trials (one); “interest” in the vaccine for daughters (one); and “interest in learning more about the vaccine” (one). All studies reported high rates of willingness in their respective categories. Twelve studies examined acceptability levels of HPV vaccine and one study examined acceptability of cervical cancer screening . All 12 Of the 27 studies, 26 discussed strategies for vaccination and increasing awareness. Studies in the six countries in the review where HPV vaccination pilot programs were conducted discussed the implementation strategies used for vaccination while the remaining countries in this review discussed recommended strategies for implementation. Rwanda, South Africa Tanzania and Uganda used school-based strategies achieving 93.2%, 97.8%, 71.6% and 88.9% vaccine uptake, respectively Education for increasing awareness was a strong theme throughout the majority of studies. Recommended strategies to implement sensitization programs included community health education programs, continuing medical education for nurses, midwives, doctors and other healthcare workers, and health promotion and policy programs including awareness through social and mass media .Factors influencing acceptability also varied. Twelve studies addressed reasons for acceptability of HPV vaccine. Two studies in Nigeria Of the 13 countries included in this review, 12 have achieved 70% coverage or higher of the DTP3 vaccine since 2003, one of GAVI Alliance's criteria for vaccine support; the exception is Nigeria . Six of This review identified low levels of knowledge and mixed levels of awareness on cervical cancer, HPV and HPV vaccine, and high levels of acceptability of HPV vaccine among all key demographics. In particular, high acceptability of HPV vaccine despite the lack of knowledge about cervical cancer and HPV represents an opportunity for increased education and awareness strategies about cervical cancer, HPV and HPV vaccine. This is important to help key demographics understand the transmission of HPV, its characteristics and associated risks Engaging all key demographics through improved and increased education will elevate public trust, which is a critical component of successful implementation of widespread vaccine coverage. Incidences such as those seen in Japan, India and Rwanda Anti-vaccination groups frequently post inaccurate information about vaccine side effects on the web, which is publicized by both local and national media Tailored community-based interventions and sensitization programs are a viable means to achieve this for multiple reasons. They have the potential to curb concerns about safety and effectiveness of the vaccine while dispelling negative myths or controversies In addition to understanding levels of knowledge, awareness and acceptability, this review uncovered encouraging trends concerning SSA countries' eligibility for GAVI Alliance support. Only six countries have currently met the two criteria required by the GAVI Alliance to support introduction of the HPV vaccine at a lower cost of US$4.50 per dose Further, our analysis of national vaccine coverage for DTP3 in SSA shows rapid expansion from just one country reaching 80% in 1980 to 35 countries in 2010 Such consistently high DTP3 coverage levels among the majority of SSA countries indicates structural health system capabilities to deliver simple vaccines to the population As this review shows, engaging all stakeholders at multiple levels in countries that meet these requirements is necessary for successful HPV vaccine implementation. Governments should leverage the high levels of acceptability and willingness to vaccinate by increasing education for healthcare workers, women/girls and parents/guardians. Governments should also determine appropriate strategies for disseminating information and vaccine delivery by building upon current infrastructures, such as existing EPIs and school-based programs. This has been shown to be an effective approach because it relies on the involvement of multiple critical stakeholders from the government down to the community level, as seen in Rwanda, South Africa, Uganda and Tanzania The objective of this study was to provide a systematic review of knowledge and awareness of HPV vaccine, willingness to vaccinate, and acceptability of the vaccine, as well as fulfillment of GAVI Alliance's eligibility criteria for vaccine assistance in SSA. To the best of our knowledge, this is the first systematic review of the potential readiness for introduction of HPV vaccine in the sub-continent. Examining the region collectively offers insight into its readiness and ability to implement HPV vaccination on a broader scale while shedding light on the successes, challenges, and lessons of implementation.From this review, three important themes have emerged. (1) There are high levels of acceptability and willingness to vaccinate. These should be harnessed by national governments to establish and implement HPV vaccination strategies that build upon existing infrastructures. (2) Overall, six SSA countries qualify for GAVI Alliance assistance to introduce HPV vaccine at a national level. (3) Lastly, there is a need for increased education and awareness among all three key demographics about HPV, HPV vaccine and the burden of cervical cancer as a disease.The combination of required DTP3 coverage, high acceptability of HPV vaccine and high willingness to vaccinate, indicates the readiness and potential for SSA countries to introduce HPV vaccine to the population. Successfully doing so will depend on implementing tailored delivery strategies that fit each country's needs and engaging the government at all levels. Building upon the lessons learned from GAVI Alliance eligible SSA countries will pave the way for those SSA countries still working to meet the criteria. These countries should also take advantage of and benefit from the “decade of vaccines” and the GIVS when there is a re-dedication by donors to meet these goals There were some limitations in this review. The studies reviewed lacked consistency in regards to psychometric characteristics used. Not all of the studies used a theoretical framework, consistent labeling of themes examined, or rigorous testing and validation of the measures as previously outlined Figure S1Flow Chart Diagram.(TIFF)Click here for additional data file.Table S1Quality appraisal of qualitative studies.(DOCX)Click here for additional data file.Table S2Quality assessment of surveys.(DOCX)Click here for additional data file.Checklist S1PRISMA Checklist(DOC)Click here for additional data file.Appendix S1Search strategies for bibliographic databases.(DOCX)Click here for additional data file.


The 2010 Dietary Guidelines for Americans (DGA) recommend that individuals age two years and older reduce intakes of solid fats (SoF) and added sugars . MyPlate illustrates the proportions of five major food groups to promote healthy eating .To assess if the foods currently consumed by Americans are in concordance with the DGA, food consumption data from What We Eat In America, National Health and Nutrition Examination Survey (WWEIA-NHANES) 2007–2008 (n = 8 527) was used to estimate the proportion of foods that contained SoFAS and to report them by food group. Weighted analysis was conducted to be nationally representative.The Dairy group contained the highest proportion (93%) of either SoF or AS, followed by Grains . Fruits contained the least SoFAS (7%).Results suggest that the high proportion of SoFAS in each recommended food group makes it challenging for Americans to reduce their intake of SoFAS. In the United States (US), people of all ages fail to meet federal dietary intake recommendations for a healthy diet; in particular, the consumption of fruits, vegetables, and whole grains is suboptimal . AlthougThe intent of the 2010 Dietary Guidelines for Americans (DGA) is to present a set of recommendations for consumers aged two years and older to encourage healthy eating. The DGA specifically recommends “Reduce the intake of calories from solid fats and added sugars” . These rBased on the definitions used to describe the food consumption by the American people, the following criteria to determine solid fats and added sugars are: “solid fats, any fat that is solid at room temperature , and added sugars, , are also known as “empty calories” as they provide little or no nutrients yet are high in calories” . While mSince the DGA and MyPlate recommendations are based on the total diet, not individual foods, no maximum amounts of solid fats and added sugars (SoFAS) for any given food are provided. Thus, consumers may choose to consume eat any combination of items from food groups, and - at least in theory - still achieve a healthy diet. Britten et al. modeled the effects on the total diet meeting the DGA when foods low in SoFAS were chosen instead of the usual American diet. They found that the guidelines can be met, but only with a large increase in the choice of low-fat, no added sugar foods . Other gThe NHANES protocol was approved by the National Center for Health Statistics Research Ethics Review Board and all participants provided informed consent.Data were obtained from the United States Department of Agriculture, Agricultural Research Service’s (USDA-ARS) 2007–2008 What We Eat in America (WWEIA) survey, which comprises the dietary intake component of the National Health and Nutrition Examination Survey (NHANES) 2007–2008. The WWEIA survey consists of two non-consecutive 24-hr recalls; the first completed in-person and the second by phone. For the purposes of this study, foods reported in the first recall by 8 528 individuals two years and older were included. Individuals age 12 and over reported their own diet and caregivers provided and assisted in recalls by children aged 2–12. Complete information on WWEIA can be found elsewhere . The totEach food description is linked to a 8-digit food code, where the first digit identifies one of the nine major food groups , the second digit indicates subgroups within each major food group and mixed foods, and the third and subsequent digits provide ever-more detailed discriminations until the level of individual food items. For this analysis, food codes were grouped by the primary level of coding to ascertain intake of the main MyPlate food groups, Vegetables, Grains, Protein Foods, Fruits and Dairy. Groups 2, 3, and 4 were combined into the Protein Foods group. Foods categorized as Fats, Oils and Salad Dressings and Sugars, Sweets, and Beverages group are not part of the MyPlate recommendations, but are of public health significance and were therefore presented separately. The Fats, Oils and Salad Dressing group includes fats that are solid at room temperature (SoF), including naturally-occurring fats, mostly from animal products, and hydrogenated vegetable oils. It also includes solid fats, such as butter and solid margarine that are added at the discretion of the consumer. Oils include naturally-occurring oils such as those nuts and seeds, non-hydrogenated vegetable oils, salad dressings, and soft margarines. The Sugars, Sweets and Beverage group includes candies, sweet desserts, sugar added at the table at the table, sugar-sweetened beverages, water, tea and coffee. Sugar from fruits is not included.As the DGA recommendations pertain to individuals aged two and over, baby foods, formula and breast milk were excluded, resulting in an analytical sample of 4 046 unique foods reported by 8 527 respondents a total of 135 934 times. All foods consumed by the sample population were categorized as containing SoF (=1), AS (=1) or both (=2). We also include a category of “either or both” as many foods contain both SoF and AS. Tertiles of SoF and AS in each category are presented to show an approximate range of values within food group categories. The amount of SoFAS in each food was not calculated as no specific maximum recommended amount of SoFAS in any given food has been established. For instance, a dairy food may have 10 grams of AS, which would be considered excessive for a person who consumes many other foods high in AS, but could be an appropriate addition to a healthy diet for a person consuming few other high-AS foods. Thus, in contrast to other studies examining the sources of SoFAS at the level of individual diet, this study provides an overview of food choice at the aggregate level. Sampling weights were used to adjust estimated results to maintain the nationally representative character of the data. Weighted proportions of the foods in each of the food groups and their SoF, AS, and SoFAS presence were calculated.Overall, 60% of foods consumed contained SoFAS, or empty calories, of those, 43% contained SoF and 39% contained AS, 22% contained both. Disaggregation of the foods consumed into MyPlate food groups are presented in Table Over two-thirds of the foods in the Vegetables group contained either SoF or AS compared to less than 10% of fruits, derived mostly from AS. Nearly three-fourths of the Grains, Protein, and Dairy groups contained SoF; including over 90% of Dairy foods. Half of the foods in the Grains group contained either or both SoFAS with roughly equal amounts contributed by SoF and AS. Half of the foods in the Fats and Oils group included AS and over two-thirds contained SoF. Although the Sugars, Sweets, and Beverages group might be expected to have large proportions of foods with SoFAS, the inclusion of non-sweetened water, tea, or coffee constituted over 50% of this group (data not shown); therefore, the foods consumed from this group had a relatively small proportion of foods containing SoFAS. Although there are no recommended amounts of SoFAS, tertiles of SoF (g/100 g) and AS (tsp) content of foods in each group are presented in Tables The majority of foods consumed within the MyPlate food grouping system contained SoFAS. Almost all of the foods in the Dairy group contain either SoF or AS, mostly in the form of SoF and over three-fourths of the foods in the Grains and Protein Foods groups contained either AS or SoF. Within the categories of foods containing either SoF or AS, tertiles of the amounts of either show that the frequency of consumption of foods in these groups often does not consist of foods that fall into the highest tertiles of SoF or AS content, highlighting the difficulty of choosing foods low in SoF or AS. However, no absolute value of the SoF or AS tertiles may be considered “good” or “bad” foods given the lack of specific cut-off amounts allowed in a healthy diet independent of energy needs.Although the amounts of SoFAS in the foods may vary, consumption of large numbers of foods containing these components predicts low diet quality and excess energy intake , althougLimitations of this study include that the analysis was based on self-reported dietary intake data. However, the major strength of this analysis was that the researchers did not impose any judgment based on questions such as the potential value of consuming foods despite the presence of SoFAS in the food. For instance, flavoured milk usually has added sugar and therefore might be considered a food that should be limited. However, one might argue against limiting flavoured milk intake because many people notoriously under-consume calcium-rich foods and might therefore benefit from the drinking flavoured milk - especially if the flavoured milk were to replace soda or sweetened fruit drinks/ades ,15. An aThe classification of foods into either having SoFAS or not, removed any potential bias towards certain foods within any of the five MyPlate food groups. Future research might include analysis in population sub-groups to establish population groups at highest risk for consuming foods with SoFAS. In addition, examination of the average amount of SoFAS in the foods within each MyPlate category might provide a venue for improved dietary guidance for the population.Diet patterns usually establish over time and reflect typical choices or food intake habits. While the use of mathematical modelling to create disease-specific prevention food plans or patterns, such as a diet plan to prevent cancer , might bThis analysis of nationally representative US food consumption data revealed a surprisingly high proportion of foods consumed with SoFAS, or empty calories. Establishing guidelines for maximum values of the SoF or AS content of a food, similar to the percent daily values, might be a venue to help people limit those two food components. The approach used here represents a new and critically important way of examining American’s adherence to federal dietary guidance. Similar analysis in assessing or planning population-based food consumption education could help policy makers and health professionals to target the foods with the highest potential to lead to a low quality diet.DGA: Dietary Guidelines for Americans; SoF: Solid fats; AS; together SoFAS: Added sugars; WWEIA-NHANES: What we eat in America, national health and nutrition examination survey; MPED 2.0: MyPyramid equivalents database for 2.0 for USDA survey foods, 2003–2004; USDA: United States Department of Agriculture; FNDDS: Food and nutrient database for dietary studies; SR: Standard reference.The authors declare that they have no competing interests.LJ and SK jointly conceived and designed the experiment, analysed the data, wrote the paper and critically reviewed it. Both authors read and approved the final manuscript.


Australia's Aboriginal and Torres Strait Islander (Indigenous) populations have disproportionately high rates of adverse perinatal outcomes relative to other Australians. Poorer access to good quality maternal health care is a key driver of this disparity. The aim of this study was to describe patterns of delivery of maternity care and service gaps in primary care services in Australian Indigenous communities.We undertook a cross-sectional baseline audit for a quality improvement intervention. Medical records of 535 women from 34 Indigenous community health centres in five regions  were audited. The main outcome measures included: adherence to recommended protocols and procedures in the antenatal and postnatal periods including: clinical, laboratory and ultrasound investigations; screening for gestational diabetes and Group B Streptococcus; brief intervention/advice on health-related behaviours and risks; and follow up of identified health problems.The proportion of women presenting for their first antenatal visit in the first trimester ranged from 34% to 49% between regions; consequently, documentation of care early in pregnancy was poor. Overall, documentation of routine antenatal investigations and brief interventions/advice regarding health behaviours varied, and generally indicated that these services were underutilised. For example, 46% of known smokers received smoking cessation advice/counselling; 52% of all women received antenatal education and 51% had investigation for gestational diabetes. Overall, there was relatively good documentation of follow up of identified problems related to hypertension or diabetes, with over 70% of identified women being referred to a GP/Obstetrician.Participating services had both strengths and weaknesses in the delivery of maternal health care. Increasing access to evidence-based screening and health information (most notably around smoking cessation) were consistently identified as opportunities for improvement across services. Approximately four percent of women giving birth in Australia are Aboriginal and/or Torres Strait Islander (Indigenous) . DispropProviding access to appropriate and quality care in the antenatal and postnatal period is a key part of closing the gap in Indigenous perinatal outcomes. It also offers an important opportunity to ameliorate disease in adult life, given the recognised link between early life influences and chronic disease .Antenatal care aims to provide appropriate screening, preventive or treatment interventions and health information to maximise the health of women and their infants . Almost The importance of achieving equity in access to antenatal care is recognised in several local and international development initiatives ,10. HoweRecognising the potential benefits of quality improvement principles in primary health care, the Australian Government launched the Healthy for Life program in 2005 . The proThe data presented here arise from baseline clinical audits undertaken in the ABCD Project. Of 56 participating primary health care centres in early 2009, 34 elected to audit their maternal health records. These centres were located in: a) remote communities in the Top End (13) and Central Australia (2) of the NT and in North Queensland (QLD) (4); and b) small regional towns in Far West New South Wales (NSW) (6) and Western Australia (WA) (9). Participating services were widely distributed across Australia and many of the remote health centres were located in sparsely populated areas in the northern part of Australia.Delivery of maternal health care was assessed by auditing a sample of clinical records from participating services. Records of women with an infant aged between 2-14 months and who were resident in the community for at least six months of that infant's gestation were eligible. From eligible records in each service, a random sample of up to 30 records was drawn using computer generated random numbers. Where there were fewer than 30 eligible records all were included for audit. In the ACBD project these sampling methods have been demonstrated to be sufficient to show meaningful differences between communities and trends over time.The audit was based on previous research , publishhttp://www.abcdproject.org.au >. A clinical service related to antenatal/postnatal care was assessed as "delivered" if there was a record of the service being delivered at specific periods in line with antenatal/postnatal care guidelines.The audits were conducted by trained members of the project team familiar with the auditing process and the maternal audit tool, in collaboration with local health staff. The audit form and protocol are available at: <We have previously published a short report on selected data from this study . Here weThe study was approved by the human research ethics committees in the Top End of the NT, Central Australia, Far West NSW, WA and Cairns and Townsville, and their Indigenous sub-committees where required.The records of 535 women  from the 34 participating services were audited (Table Across services the median age of women was 25.3 years range 14-48) . The first antenatal assessment was undertaken by a variety of providers; with the exception of WA and North QLD services, the most common provider was a midwife  prior to conception. In contrast, more than half of women in most services were prescribed iron during pregnancy. Over 80% of women had an antenatal care plan recorded in their file Table .The mean gestational age at birth was 38.6 weeks, and the majority of women had a vaginal birth (67%) Table . The proRecorded use of cigarettes at any time in the pregnancy was high across all services , followed by use of alcohol (22%) and illicit drugs (9%) , but improved for checks undertaken between 13-24 weeks gestation , and after 24 weeks gestation   Table , with thDocumentation of routine ultrasound varied between regions. Overall only 42% of women had a recorded ultrasound between 16-20 weeks gestation for fetal morphology (range 31-69% across regions)  in those communities. Importantly, Australia recently introduced a policy of mandatory fortification of certain foods with folic acid for additional protection against NTD.Uptake of fetal anomaly screening was low, which supports previous calls for the development of culturally safe resources around these tests . There iIn the postnatal period, only 55% of women received breastfeeding advice, and there was poor documentation of advice around smoking, hygiene, injury prevention and SIDS prevention. This is a significant area for improvement given the high prevalence of SIDS risk factors such as smoking, preterm birth and low birth-weight in these communities. Overall, this indicates there is great potential to improve the continuity of care throughout the antenatal and postnatal period. It should be noted that centres in this study do not provide birthing services; local policies currently require women in remote areas to be transferred into regional hospitals for birthing from 36 weeks gestation. Therefore, attempts to improve continuity in this setting will require better integration of services or a redesign of care to support community-based services across the spectrum of maternity care. This was acknowledged in the recent report of the Australian Maternity Services Review , which aThe findings of this study are subject to some limitations. Participating services have a history of involvement in quality improvement activities, expanded from a focus on chronic disease management to maternal, child and other aspects of health, which may limit the generalisability of findings. The maternal audit was undertaken to provide baseline data for individual services with an interest in improving delivery of maternal health care, as part of an on-going quality improvement study (the ABCD project). Not all services participating in this larger study elected to audit maternal records, which may also limit the generalisability of findings. Our audit data provide similar estimates of mean maternal age and smoking prevalence, but lower estimates of preterm birth and low birth weight than estimates reported in routine NT, WA, QLD and NSW Indigenous perinatal information . As suchThe measures of quality of care reported in this study provide important data for feedback to services at a local level. When aggregated, they provide a picture of regional patterns of maternity care which will be progressively more informative for broad scale policy and program purposes as increasing numbers of services become involved. Importantly, these measures provide information that is not currently available from routinely collected perinatal data .There is increasing activity in Australia and internationally around assessment of maternity care, with the completion several projects designed to facilitate benchmarking of services -35. The Supporting services to improve maternity care for Indigenous women is a recognised priority  given thABCD: Audit and Best practice for Chronic Disease; BMI: Body Mass Index; BP: Blood Pressure; FBE: Full Blood Examination; FHR: Fetal Heart Rate; GBS: Group B Streptococcus; GDM: Gestational diabetes mellitus; GP: General Practitioner; GTT: Glucose Tolerance Test; Hb: Haemoglobin; HBsAg: Hepatitis B Antigen; HIV: Human Immunodeficiency Virus; MSU: Midstream Urine; NSW: New South Wales; NT: Northern Territory; NTD: Neural Tube Defects; QLD: Queensland; Rh: Rhesus; SIDS: Sudden Infant Death Syndrome; WA: Western Australia; WBM: Women's Business Manual.The authors declare that they have no competing interests.ARR played a primary role in the interpretation of study results and preparation of the manuscript. RSB developed the study design, managed the implementation of the study, and played a primary role in the interpretation of study results and preparation of the manuscript. DS was responsible for data management and data analysis and contributed to preparation of the manuscript. MCD, RJC, LO, HEL, RKK, SCT, HPB, ADHB, TW, CMC provided expert advice in contextualising study findings, particularly in relation to each jurisdiction, and assisted with preparation and editing of the manuscript. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2393/11/16/prepub