Spatial scan statistic has been shown as a useful tool to investigate spatial patterns and detecting the spatial clusters of cancer. This study conducted to study spatial analysis of breast cancer and its late-stage cases, one of the most common women cancers in Iran and the world.We used space-time and purely spatial scan statistic implemented in SaTScan software to detect clusters of breast cancer and late-stage cases, at city level by applying Poisson and Bernoulli distribution. Data on 40017 of breast cancer cases that reported to the Ministry of Health and Medical Education (MOHME) during 2005 to 2010 were included.Purely spatial and spatiotemporal high rates significant clusters of breast cancer and its late-stage cases with Poisson distribution were in the same geographical area including southwest, north, and northeast.Significant clusters areas have probably differences with other areas in terms of delay in diagnosis and access to appropriate health services because late-stage breast cancer cases had the greatest impact on formation of clusters. However, more studies are essential to be conducted in different areas of country to explain more precisely clusters detected areas and detecting reasonable justification for existence of significant clusters. Breast cancer with more than one million cases yearly is the most common cancer in women and is responsible for one-fifth of women cancers worldwide . IndustrSurveillance of routinely collected data for unusual clusters of disease in time and space is a key issue  and clusScan statistic developed by Kulldorff has been shown as a useful tool to study geographical patterns and detect the spatial clusters of cancer . HoweverThus, the aim of this study was to detect clusters with high and low rates of breast cancer and its late-stage cases using discrete Poisson distribution and finally investigate spatial distribution of the late-stage breast cancer cases with Bernoulli distribution. Since, the last-grade cases known as a good proxy of screening performance and access to health services.All data of 40017 women diagnosed with breast cancer between 2005 and 2010 were obtained from the Ministry of Health and Medical Education (MOHME). Available data for each case was age, province, city of residence, date of diagnosis, and grade of cancer. City location was selected for analysis as aggregation unit. However, 10.9% of the cases (4396 cases) despite provincial information had not been assigned to a particular city.Therefore, mentioned cases in each province were distributed randomly throughout city by proportion of women population in each city. SaTScan software ver.9.3.1 spatial Where C is the total number of cases, c is the observed number of cases within the window and E[c] is the covariate-adjusted expected number of cases within the window under the null-hypothesis. Since the analysis is conditioned on the total number of cases observed, C-E[c] is the expected number of cases outside the window.As well to explore the spatial and spatiotemporal clusters with high and low rates of late-stage breast cancer cases Bernoulli distribution was used (late-stage cases=case and other = control) in this case the likelihood ratio calculated based on following formula:Where c and C are defined as above, n is the total number of cases and controls within the window, while N is the combined total number of cases and controls in the data set.P value less than 0.05(α) as statistically significant. The simulation process was run 999 times.Then, to understand better of the late-stage cases distribution 65.31 percent of breast cancer cases (26136 cases) discrete Poisson distribution was used and analysis was adjusted for age. In order to build files needed for methods, cancer registry data and population data of Iran's cities was used. Population data were obtained from the Statistical Center of Iran , for theSpatial scan statistic with discrete Poisson distribution adjusted for age and grade of cancer detected three primary purely spatial clusters of breast cancer in study areas . Tow purPoisson distribution of the late-stage breast cancer cases adjusted for age detected five primary purely spatial clusters with high and low rates in study areas . ClusterIn addition, detected cluster with low rates had composed of a city . ClusterThe center coordinates, radius, number of the observed count, expected count, relative risk, log likelihood, and p-value for each cluster are shown in The space-time scan statistic detected six primary clusters with high and low rates of breast cancer in study areas . ClusterPoisson distribution of last-stage breast cancer adjusted for age detected six primary clusters with high and low rates in the study areas . ClusterSpatial scan statistic with Bernoulli distribution detected 15 purely spatial clusters with high and low rates of late-stage breast cancer cases in study areas . Purely Space-time scan statistic whit Bernoulli distribution detected two clusters with high and low rates of late-stage breast cancer cases in study areas . High raWe found several significant clusters for both breast cancer and its last-stage cases in study areas. Poisson model in total detected 18 primary space-time and purely spatial significant clusters with high and low rates of breast cancer and its late-stage cases. Space-time and purely spatial clusters with high rates of last-stage breast cancer cases were similar with high rates space-time clusters of breast cancer cases . HoweverIn order to detect the late-stage breast cancer cases used discrete Poisson distribution instead of the Bernoulli distribution, which does not allow covariates adjustment . PoissonThe relationship of late-stage breast cancer diagnosis was studied with access to health services in Illinois and showed that less access to health services associated with later diagnosis of breast cancer . AlthougOne of the main limitations of our study was lack of access to socio-economic factors, areas differences in terms of access to appropriate health services and other affecting factors that may affect our findings. Another limitation was continuous changes in number of city in some province so that over years of study we have had changes in more than ten provinces therefor was need to carefully study of any changes in order to true assignment of cases to provinces cites. Despite current study is the first national survey on breast cancer and its late-stage cases using spatial scan statistic.Significant clusters areas have different from other areas in terms of delay in diagnosis and health services coverage because late-stage breast cancer cases had the greatest impact on formation of clusters; however, more studies are essential to be conducted in different areas of country to explain more precisely clusters detected areas and detecting reasonable justification for existence of significant clusters.Ethical issues  have been completely observed by the authors.


This review summarizes the role of melatonin (MLT) in defense against toxic-free radicals and its novel effects in the development of the nervous system, and the effect of endogenously produced and exogenously administered MLT in reducing the degree of tissue and nerve injuries. MLT was recently reported to be an effective free radical scavenger and antioxidant. Since endogenous MLT levels fall significantly in senility, these findings imply that the loss of this antioxidant could contribute to the incidence or severity of some age-related neurodegenerative diseases. Considering the high efficacy of MLT in overcoming much of the injury not only to the peripheral nerve but also to other organs, clinical trials for this purpose should be seriously considered. Melatonin (MLT), N-acetyl-5-methoxytryptamine, is a secretory product synthesized nocturnally by the pineal gland. Its useful effects include modulation of pituitary hormones, stimulation of the immune system, and photoperiod adaptation.Peripheral nerve injury (PNI) can result in demyelination, axonal degeneration, or both. Peripheral nerve injuries can cause motor and sensory function losses. Depending on the severity and degree of nerve injury, function recovers with remyelination and with axonal regeneration and reinnervation of the sensory receptors or motor end plates. Seddon classified nerve injury degree according to severity.The central nervous system (CNS), composed of the brain and spinal cord, integrates received information and coordinates the activities of all parts of the body. Some classifications of the CNS additionally include the retina and cranial nerves. In conjunction with the peripheral nervous system (PNS), it is important in controlling behaviors.The pineal gland or epiphysis cerebri is an endocrine, pine cone–shaped organ located in the center of the brain, posterior to third ventricle, just above superior colliculi . MLT, aDespite numerous exploratory studies and clinical observations, there is still no clear treatment strategy for improving peripheral nerve recovery. Also, the role of MLT in nerve degeneration and regeneration is not completely understood. Specific understanding of peripheral nerve science is crucial for comprehending nerve degeneration and recovery. In the clinical setting, the capacity to control nerve biology at the cell level greatly improves the chances of nerve recovery. Various factors such as ischemia and neuroma formation can alter the outcomes of clinical practice.Nevertheless, some studies have begun to reveal that the pineal neurohormone MLT is neuroprotective and antioxidative. It can reduce oxidative stress by stimulating antioxidative enzymes such as superoxide dismutase (SOD), catalase (Ct), peroxidase, and ascorbate peroxidase.Wallerian degeneration, also known as anterograde or orthograde degeneration, occurs after axonal injury in both the PNS and the CNS. Axonal degeneration is followed by degradation of the myelin sheath . ActivaFurthermore, some studies have shown the effect of MLT via surgical removal of the pineal gland, called pinealectomy (Px).In 2006, a research team of the senior author (Mehmet Turgut) of this article investigated the effects of neonatal Px on peripheral nerve ultrastructure in chickens.One of our coauthors studied the alterations in offspring rat cerebellum induced by maternal exposure to carmustine- (BCNU) and investigated the effects of exogenous MLT on cerebellar BCNU-induced cortical dysplasia, using histological and biochemical analyses.MLT administration reduced vascular endothelial growth factor (VEGF) and nitric oxide (NO) levels as well as the leakage of rhodamine isothiocyanate, and reduced hypoxia-associated injury, in the developing hippocampus.In some recent studies using the sciatic functional index for nerve recovery, MLT application was shown to be a promising approach for the treatment of peripheral nerve crush injuries.1ΔgO2) is an extremely reactive form of oxygen that can be produced by living cells and is a probable cause of cytotoxicity. MLT has been reported to possess potent antioxidant activity and to be capable of scavenging1ΔgO2. Cagnoli et al investigated whether it can reduce the neurotoxic action of1ΔgO2.1ΔgO2.Singlet oxygen  activity can diminish the harmful effects of reactive oxygen.Shokouhi et al investigated the neuroprotective effects of MLT on neural fiber injury and lipid peroxidation after blunt sciatic nerve trauma; they found that a low dose reduces trauma-induced myelin breakdown and axonal changes in the sciatic nerve.Erol et al observed that both MLT and octreotide gave benefits in an spinal cord injury (SCI) model, and MLT had the more pronounced beneficial effect.I/R produces free radicals leading to lipid peroxidation and nervous tissue injury. The free radical scavenging and antioxidant effects of MLT have been shown to diminish I/R injury in many tissues.L-arginine and the opiate antagonist naloxone on those effects.L-arginine and naloxone, at doses that produced no effect on their own, partially reversed the anti-hyperalgesic effect of MLT.L-arginine–NO pathway and opioidergic system are involved in its anti-hyperalgesic effect in nerve-injured mice.Data from the literature, together with our studies using a different kind of experimental injury model, showed that MLT has positive effects on the number of axons and the thickness of the myelin sheath by inhibiting collagen accumulation and neuroma formation following traumatic events to peripheral nerves, and on the myelination of a developing peripheral nerve after intrauterine ethanol exposure.Recently, the protective effects of MLT have been supported from many perspectives. The interaction between the vagus nerve and MLT was studied and the protective effect of MLT was demonstrated.It has been shown that MLT affects the nervous system via free radical scavenging and antioxidant properties. Notwithstanding these studies, there is no obvious procedure for using MLT in clinical applications. Nevertheless, we believe that research on MLT can standardize its use. Almost every month new research is being published and giving a new impulse to the field, but further experiments and randomized controlled clinical studies are needed to standardize the clinical use of MLT. The future search for novel drug treatment for PNI is critical. Despite some use of MLT pills, deployment of MLT as a neuroprotective agent is still not close to clinical practice, but should become possible in future, as safe and effective procedures are discovered and developed.


Hematology-related diseases, such as anemia, malaria, sickle cell disease (SCD), and blood cancers, have differing rates of survival between high-income and low- and middle-income countries (LMICs). Nurses in LMICs have an unmet need for specialty training and education to address hematology and hemato-oncology disorders. A gap in the literature exists about hematology nurse education and clinical service demands in LMICs. This community case study documents a collaborative hematology and basic hemato-oncology education program to sustainably strengthen nurse capacity at a national referral hospital and university in Tanzania. The goal of the intervention was to provide culturally competent nurse training in pediatric and adult hematology. A certified pediatric nurse practitioner with hematology and oncology experience provided culturally competent training and staff development to nurses over two weeks to meet this goal. Prior to development of a training schedule, nurses confidentially identified five of their top learning needs. Main hematology and basic oncology educational needs identified by nurses were the management of anemia, safe handling of cytotoxic agents, and treatment of SCD. The format of the education varied from bedside teaching to formal presentations to one-on-one individual discussions. Overall, nurses expressed satisfaction with the education and verbalized appreciation for teaching and training activities tailored to meet their needs. Specialized training in hematology and hemato-oncology has the potential to increase nurses’ confidence, respect, and participation in interprofessional team decision-making. Lessons learned from the impact of collaborative nurse education and partnership in Tanzania can be generalized to other LMICs. This community case study highlights the importance of specialty nurse education, interprofessional development, and global partnerships needed to improve patient outcomes. Nurses play an important role in sustainably improving patient outcomes in low- and middle-income countries (LMICs). Nurse education in LMIC tends to focus on primary care topics. However, there is a growing need to manage chronic disease and reduce the burden of hematology-related diseases globally and improve public health. Nurses in LMICs have an unmet need for specialty training and education to address hematology and hemato-oncology disorders. Nurses with adequate levels of specialty hematology nursing education will better meet the health-care needs of patients. The purpose of this community case study is to document a collaborative hematology and basic hemato-oncology education program to sustainably strengthen nurse capacity at a national referral hospital in Tanzania.Hematology-related diseases such as anemia, malaria, sickle cell disease (SCD), and blood cancers have differing rates of survival between high-income and LMICs . GloballGlobally, nurses comprise the largest group of health-care providers. In almost all countries, nursing and midwifery services are estimated to comprise over 80% of the health-care services . About 4The strain of the nursing shortage on health-care systems is a worldwide concern. The need for specialty nurses is often overlooked in the face of this public health challenge. There is a gap in the literature about clinical service demands in relation to nursing and hematology in LMICs. It has yet to be demonstrated how nursing will evolve to meet public health demands. The lack of specialty training for nurses is being overlooked by the largest group of health-care providers. There are challenges associated with inadequately prepared nurses needed to care for the population suffering from hematology-related problems. Education and interprofessional collaboration should be used to meet the evolving service demands of specialty nursing in LMICs.The goal of the educational intervention was to provide hematology and basic hemato-oncology training and staff development to nurses with Muhimbili National Hospital (MNH) and nursing students at Muhimbili University of Health and Allied Sciences (MUHAS) in the largest city in Tanzania, Dar es Salaam. The nurse educator observed inpatient pediatric and adult nurses had little training in how to care for patients with hematological and hemato-oncological disorders and recognized a definite need for improved nursing care. The hematology and basic hemato-oncology training and staff development for nurses was developed based on the self-identified needs of the nurses and by the nurse educator through observation of patient care.MUHAS  aims to The organization fostering inclusive partnerships in this community case study is Health Volunteers Overseas (HVO). They are a United States-based non-profit organization dedicated to improving the availability and quality of health care through the education, training, and professional development of the health workforce in resource-scarce countries . At HVO,The American Society of Hematology (ASH) partners with HVO to bring consultation and training to hospitals in the developing world managing hematology patient cohorts with a wide range of disorders. Training takes the form of rounds in the clinics, bedside consultations, lectures in the classrooms, training in the laboratories, and more. The objective of the sponsorship is sustainable improvement of the management of hematology patients in the developing world .The format of the education at MNH varied from bedside teaching to formal presentations to one-on-one individual discussions. Flexibility was key to meeting the scheduling demands of approximately 50 Tanzanian nurses caring for pediatric and adult hematology patients in both in- and outpatient settings. Group lectures were presented more than once to reach a wide audience. At MUHAS, lectures were presented to both undergraduate and postgraduate nursing students.Education sessions were delivered by a certified pediatric nurse practitioner with over 10 years’ experience working in the fields of hematology and oncology along with clinical instruction at a large teaching hospital in the United States. The HVO nurse partner also has extensive experience working in LMICs with a major international medical humanitarian organization. The courses were delivered in English because nursing school, as with most tertiary education in Tanzania, is taught in English. At the national hospital, the HVO nurse partner participated in hematology department grand rounds, pediatric and adult hematology clinical rounds, outpatient pediatric and adult sickle cell clinics, as well as the new patient screening clinic and anti-coagulation clinic. Table Prior to the development of a training schedule, Tanzanian nurses were asked to confidentially prioritized five of their top learning needs related to hematology and basic oncology. Results of the prioritization survey were incorporated into the training schedule. The main educational needs identified by nurses were the management of anemia, safe handling of cytotoxic agents, and treatment of SCD. Specific goals of the nurse education program reached using the prioritization process are detailed in Table A 2-week collaborative educational program was developed to provide hematology and basic hemato-oncology education to nurses in Tanzania. The education program included three main themes: (a) overview of hematologic and hemato-oncologic disorders; (b) safe chemotherapy administration; and (c) supportive care. The education sessions included four components: (1) basic hematology and hemato-oncology group lectures; (2) individual instruction on self-identified needs; 3) direct observation of patient care in pediatric and adult inpatient wards and hematology outpatient clinics; and (4) group lectures to graduate and postgraduate nursing students. Table  direct oAt MUHAS School of Nursing, at the request of nursing faculty, 56 undergraduate students received one 2-h presentation including an overview of hematologic disorders, blood product administration, and how to recognize blood transfusion reactions. Another 2-h presentation was given to nine graduate nursing students on the recognition and treatment of hematologic and basic oncologic emergencies such as neutropenic fever and unexplained bleeding.A summary of educational topics covered at MNH and MUHAS is presented in Table At the end of the hematology nurse education program, participants were asked in an informal survey to confidentially write the three things they liked most about the education sessions. They were also asked to verbally evaluate their experience during informal small group discussions on the final day of training. Nurses were asked to describe the potential outcomes of the educational program and to comment on any potential nursing practice outcomes after collaborating in the educational program. No quantitative data were collected as part of the evaluation.The US-based HVO nurse partner used Leininger’s  transculThe teaching framework used by the HVO nurse partner followed the approach outlined in “Educating Health Professionals in Low-Resource Countries: A Global Approach” . Three cI am so glad you came to talk to us. Nobody ever pays attention to us nurses. Only the doctors get educated over and over again.I learned a lot about giving chemotherapy that I didn’t know before. Now, I am not so scared to give treatment as I used be.The presentations were very helpful.Thanks for listening to our concerns and teaching about what’s important for us to know.This community case study documents the collaborative hematology and basic hemato-oncology education intervention to sustainably strengthen nurse capacity at a national referral hospital in Tanzania. Overall, using informal qualitative surveys, nurses in the hematology and hemato-oncology areas expressed satisfaction with the education after the intervention was complete. The nurses ranked the following as what they liked most about the program: (1) opportunity for continuing education; (2) cross-cultural discussions; and (3) group lectures. The informal verbal feedback from participants following the educational intervention was extremely positive. Nurses verbalized appreciation that teaching and training activities were tailored to meet their needs. Some of the comments reflecting the nurses’ evaluation of the training included:It’s so nice to listen to international perspectives about nursing. We like to hear from experts in different subject areas. The best was about how to make sure blood types are compatible.I will remember to talk to my patients about getting good nutrition for healing if they have cancer of the blood.My best take home message is that sickle cell disease can stay in one family and hydroxyurea is a good medicine for those patients to take.Students in the School of Nursing at MUHAS also reported satisfaction with the presentations given by the HVO nurse partner. After class, students were each asked to write three of their top take-home messages from the education intervention. Narrative comments from the nursing students included:Specialized training in hematology and hemato-oncology has the potential to increase nurses’ confidence, respect, and participation in interprofessional team decision-making. The WHO and its partners recognize interprofessional collaboration in education and practice as an innovative strategy playing an important role in mitigating the global health workforce crisis . InterprWhile there is little information regarding hematology nurse education programs in LMICs, there are a couple of programs reporting results of oncology nurse education. Recognizing oncology nurses in LMICs have limited access to specialized education and clinical training, the International Outreach Nursing Program at St. Jude Children’s Research Hospital created the Latin American Center for Pediatric Oncology Nursing Education in Santiago, Chile to provide education, resources, and support to local nurse educators . In turnRecognizing there is no existing pediatric oncology nursing curriculum written specifically for LMICs, the International Society of Pediatric Oncology (SIOP) Pediatric Oncology in Developing Countries (PODC) conducted a survey of LMIC nurses in 2012 . A crossA team of Australian nursing and midwifery educators delivered evidence-based education in Tanzania and found with appropriate levels of cultural competence, international health professionals can be effective at providing ongoing professional development to colleagues in developing countries . ResearcSustainable development calls for concerted efforts toward building an inclusive, sustainable, and resilient future for people and planet . Goal 17Urgent action is needed to educate nurses caring for patients with hematologic disorders such as anemia, SCD, blood cancers, and more in Tanzania and other LMICs. Nurses play an important role in achieving optimal care of patients with hematology-related problems yet there are large numbers of patients being cared for by nurses with no training in hematology. The work of HVO, in partnership with ASH, to improve the quality of health care in Tanzania through the education, training, and professional development of nurses in hematology is commendable. There is a definite need to advocate for other educational partnerships to increase the quality and supply of specialized nurses in LMICs.Quality education is the foundation for developing competent health workers who are equipped with the knowledge, attitudes, and skills necessary to deliver quality care . In futuThe interdisciplinary collaboration barrier identified by nurses should not be ignored by team members in Tanzania. A great deal of effort should be focused on building a “collaborative practice-ready” health workplace at Muhimbili and at other nurse education sites. Collaborative practice strengthens health systems and improves health outcomes . CollaboThe case study was time-limited because teaching strategies and cultural exposure took place over a period of two weeks. A longer period of immersion in the setting and culture would allow time for formal curriculum development and training to benefit nurses providing care to patients with hematology-related problems in LMICs. Follow-up education sessions would allow for the reinforcement of material as would be creating sound or video recordings of sessions. Another limitation is some of the nurses expressed a lack of time to attend educational sessions. In the future, efforts should be made to schedule dedicated time to learn without the responsibility of providing patient care. Of course, this will be a challenge as the nursing workforce far too often experiences high patient to nurse staffing ratios. However, with proper advanced planning, a greater number of nurses should be able to benefit from training initiatives.A limitation of the community case study is that it is written from only one side of the cultural exchange. Several unsuccessful attempts were made to contact lead nurses in the hematology department at MNH. The case study would no doubt be strengthened with the active input of Tanzanian participants in the writing process.Future studies should evaluate the effect of hematologic and hemato-oncologic nurse education in LMICs. Recommendations for future research in LMICs would be to examine the effects of educating nurses in hematology and whether there is an associated improvement in patient outcomes. Another recommendation would be to examine the costs associated with educating nurses. Eventual research should investigate the cost-effectiveness of nursing education and impact on patient outcomes. The incorporation of a systematic evaluation process including both qualitative and quantitative measures would add richness and inform future collaborative efforts.Lessons learned from the community case study experience in Tanzania can be generalized to other LMICs. Nurse educators and HVO nurse partners providing training in other settings must implement their programs with a willingness to provide culturally appropriate interventions in diverse settings. The education of hematology nurses should be scaled up in Tanzania and other LMICs settings. This community case study is the first one to document a hematology education intervention to sustainably strengthen nurse capacity in an LMIC and highlights the importance of specialty nurse education, interprofessional development, and global partnerships needed to improve patient outcomes.JB, the sole author, made substantial contributions to the conception, design, and drafting of the work including final approval of the version to be published.This work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Using the distal molar of a minipig as a model, we studied changes in the microstructural characteristics of apatite crystallites during enamel maturation , and their effects upon the mechanical properties of the enamel coat. The slow rate of tooth development in a pig model enabled us to reveal essential heterochronies in particular components of the maturation process. The maturation changes began along the enamel-dentine junction (EDJ) of the trigonid, spreading subsequently to the outer layers of the enamel coat to appear at the surface zone with a 2-month delay. Correspondingly, at the distal part of the tooth the timing of maturation processes is delayed by 3-5 month compared to the mesial part of the tooth. The early stage of enamel maturation (16-20 months), when the enamel coat is composed almost exclusively of radial prismatic enamel, is characterized by a gradual increase in crystallite thickness (by a mean monthly increment of 3.8 nm); and an increase in the prism width and thickness of crystals composed of elementary crystallites. The late stage of maturation (the last two months prior to tooth eruption), marked with the rapid appearance of the interprismatic matrix (IPM) during which the crystals densely infill spaces between prisms, is characterized by an abrupt decrease in microstrain and abrupt changes in the micromechanical properties of the enamel: a rapid increase in its ability to resist long-term load and its considerable hardening. The results suggest that in terms of crystallization dynamics the processes characterizing the early and late stage of mammalian enamel maturation represent distinct entities. In regards to common features with enamel formation in the tribosphenic molar we argue that the separation of these processes could be a common apomorphy of mammalian amelogenetic dynamics in general. Tooth development is a highly organized and complex process of interactions between neural crest-derived ectomesenchyme and oral epithelium  proceediAmelogenesis, or enamel formation, is often reported to proceed in two distinct steps, the secretory and maturation stages, differing in the types of enamel-matrix proteins involved and the overall density of the mineral composition –21. The During the maturation stage, the partially split matrix proteins are almost completely removed by KLK4 protease providing the space yielded by the lost proteins for CaP crystal growth . RobinsoIn any case, however, much less is known about how the particular processes contributing to enamel formation are orchestrated to produce the complex patterns of enamel microarchitecture characterizing particular clades of mammals, and how the distribution of particular enamel patterns over the particular loci of a tooth is controlled. Detailed comparative information on developmental mechanisms modifying the enamel patterns of particular mammalian clades is largely missing. The questions of which of them present true synapomorphies of all mammals and which were stepping stones in the evolution of mammalian amelogenesis  remain tDetailed developmental information is available for a few model taxa, mainly for mouse, rat and human. Unfortunately, in dental respects, including enamel microarchitecture, these taxa—muroid rodents and anthropoid primates—are extremely derived, showing a large set of phylogenetic rearrangements from the basic mammalian dental type. It can be expected that this might also concern some of the amelogenetic processes observed in them. Information on enamel formation in taxa retaining the ancestral form of mammalian dentition is urgently required. First of all, this refers to those taxa bearing the tribosphenic molar, the ancestral form of molar teeth and a key apomorphy of mammalian dentition –40. TribTo examine aspects of these processes in detail, we analyzed the crystallographic characteristics of enamel at different stages of pre-eruptional development using the lower distal molar (m3) of the miniature laboratory pig as a model  result in a broadening of the peak shape. These dislocations have the effect of dividing the original crystals into much smaller domains. These domains scatter incoherently with respect to one another and thus behave like very small crystals; they are usually described as crystallites. Finally, the extent of the dislocations that cause the subdivision of the original larger crystal into domains is referred to as microstrain .Statistical analyses were performed in Microsoft Excel and STATISTICA 8.0 software. The Gauss error function CIT, all crystallographic variables were significantly age-dependent and most of them showed clear mutual correlations , and 56 and 70 nm in length . We found no significant difference between adult and subadult m3 in the length of crystallites  of HIT and EIT, yet, adult teeth (>23 months) HIT values for the outer enamel zone were significantly higher than those for the inner zone .The SEM images of the completely mature enamel show a compactly packed radial prismatic pattern with a dense interprismatic matrix (IPM) uniformly dispersed across the overall enamel area. The radial organization of the enamel coat is further accompanied by distinct macroscopically visible radial strips of multiserial Hunter-Schreger bands (HSB) Figs  and 7. Iμm with a gradual increase from EDJ to the crown surface both at the mesial and distal parts of the tooth. The respective trend was present both in immature and mature enamel  was significantly smaller than in 24 month old individuals (2.6-5.3 μm). Corresponding trends were observed also with the mean thickness of the core crystals of the radial prisms, elementary structural units visible in the SEM images  was restricted to long fibers of radial enamel rods (covered by well-defined sheets) showing a considerable spatial divergence toward the crown surface . Only a  months wThe very thick layer of loose prisms of embryonic enamel was split into irregular spatial blocks (supposedly due to the continuous growth of tooth size during the pre-eruption period) separated by deep fissures initially lacking any mineralized infill. CaP mineralization of these between-block spaces began from the EDJ. In the deeper part of the enamel coat it took the form of prismatic crystallization producing the HSB pattern . In the All the above-mentioned changes associated with enamel maturation began in the zone of the EDJ. The term of enamel maturation specifically denotes the stage when the final thickness of the enamel layer is already achieved and amelogenetic processes are predominantly oriented to the removal of water and organic materials, mineralization, and promoting enamel mechanical properties . When thDuring the maturation stage, ameloblasts lose their Tomes processes and their secretory activity takes the form of a mass pumping of calcium ions into the space of maturating enamel, together with some calcium-binding proteins that do not appear during the secretory stage . This caIn this paper, we present the results of a crystallographic study of enamel maturation using a minipig m3 as a model. While focusing on sampling techniques designed to prevent methodological bias in the estimations of crystallographic variables , we founIn regards to general aspects of mammalian enamel maturation, our results deserve some further comment, particularly with respect to differences from the standard mouse model of enamel maturation. (i) First, we should stress the difference in size of the core structural units visualized by SEM imaging and of the elementary CaP crystallites revealed with the aid of X-ray powder diffraction. It suggests that in porcine enamel, in contrast to enamel of the mouse incisor but similarly as in enamel of tribosphenic molars , the cor(ii) The comparison of particular ontogenetic stages undertaken in this study demonstrated a fluent gradual increase in the thickness of individual crystallites composing the prisms (with a monthly increment of ca 3.8 nm). This suggests that the continuous absorption of calcium phosphate onto the lateral faces of nuclear CaP crystallites is the key factor in their maturation. Such a view is consistent with numerous studies on the embryonic growth of CaP crystallites employing high-resolution transmission electron microscopy , 58, 61,CIT, differed substantially: for the inner enamel it exhibited no significant correlation with any other variable except for the CIT of the outer enamel. This variable, which quantifies the capacity to respond to long-term load, exhibited a rapid decline between postnatal months 17 and 18. This preceded the changes in other variables, including the CIT of the outer enamel, which correlated significantly with other micromechanical variables  The abrupt decrease in microstrain observed during the last stages of the maturation process (more than 50% compared to that in 120 DoC) is, to our knowledge, reported here for the first time. Microstrain values can serve as a quantitative measure of lattice defects in the crystal structure, which can induce significant variations in its physical and mechanical properties . A high ariables . This me(v) Consequently, in terms of crystallization dynamics, enamel formation seems to include two (or three) distinct processes: (a) the early appearance of a radial prismatic scaffold preforming the total thickness of the enamel coat, which simultaneously allows the further enlargement and reshaping of the immature tooth, and (b) delayed mineralization of the interprismatic matrix postponed to the late stage of maturation, which terminates with (c) the appearance of surface aprismatic enamel prior to the eruption of the finally shaped tooth crown. The respective processes seem to differ not only in their timing and functional effects, but, as mentioned above, also in the dynamics of crystallite growth and presumably the amount of lattice disorder. The heterochrony of these processes has been proposed as an essential factor in the developmental dynamics of the tribosphenic molar, a key apomorphy of mammalian dentition . With th(vi) The respective processes  undoubtedly differ in the regulation of crystallite growth and crystallization dynamics, likely through differences in the composition of the crystallization environment. The restriction of amelotin to the surface zone and its secretion at the late stage of enamel maturation in mammals , suggest(vii) The most detailed data on enamel formation provided by studies on incisors of muroid rodents, including high resolution TEM images of the earliest stages of crystallite formation (comp. ), suggesμm in mouse), to extraordinary mechanical requirements. Obviously, during the extremely shortened developmental period of muroid rodents, such complex enamel organization could hardly be produced without radical rearrangements of the amelogenetic dynamics, shifts in the timing of particular processes and their spatial domains and/or modifications of enamel matrix proteins (note the quite derived structure of rodent amelogenin [(viii) The contradiction between observations on muroid rodents that show prismatic and interprismatic enamel to be produced simultaneously  and our elogenin ). Which The prolonged calcification of the minipig distal molar (510-540 days until tooth eruption) enabled us to trace the particular stages of enamel maturation in great detail. Our results revealed that: (a) both crystallization and maturation processes start along the EDJ; (b) the pattern and mechanism of enamel formation in the early and late maturation periods differ significantly: the former is associated with the establishment of enamel prisms and the subsequent growth of their crystallites, the latter is marked by the rapid appearance of the interprismatic matrix and a shift in micromechanical properties by which, about a month prior to tooth eruption, the enamel achieves the hardeness values characterizing the adult tooth crown; (c) a rapid decrease in crystallite microstrain at the latter stage suggests that the initial organization of prismatic enamel might produce a considerable amount of structural defects that are either repaired by the subsequent growth of crystallites and/or entirely compensated by the interprismatic matrix, crystallizing at that time; and (d) early maturation producing radial prismatic enamel and late maturation associated with the appearance of IPM and resulting in adult enamel qualities should be looked upon as quite distinct processes. Their separation seems to be an essential component of mammalian amelogenetic dynamics.S1 TableEdEc—expected duration of enamel calcification.(PDF)Click here for additional data file.S2 Table(PDF)Click here for additional data file.S3 Table(PDF)Click here for additional data file.S4 Table(PDF)Click here for additional data file.S5 Table(PDF)Click here for additional data file.S1 Fig(TIF)Click here for additional data file.S2 Fig(TIF)Click here for additional data file.S3 Fignote the enamel surface with no aprismatic enamel cover.(TIF)Click here for additional data file.S4 Fig(TIF)Click here for additional data file.


Coarctation of aorta in adulthood is usually complicated by other cardiovascular anomalies, posing great technical challenge for intervention.Here, we report an extremely rare case of aortic arch coarctation combined with a poststenotic biloculated calcified aneurysm and hypoplastic left subclavian artery.First, an extra-anatomic bypass was established, along with narrowing of aorta just proximal and distal to the aneurysm. While the bypass graft significantly relieved trans-coarctation gradient, the latter procedure decreased intra-aneurysm pressure and created landing zones for aneurysm occlusion. Six months later, 2 muscular ventricular septal defect occluders were deployed at the proximal and distal orifice of the aneurysm.Follow-up computed tomography angiography confirmed the absence of contrast leakage into aneurysm.A 2-stage hybrid approach described here appears to be feasible, safe, and associated with favorable clinical outcomes in the treatment of complicated aortic coarctation and poststenotic aneurysm. Sometimes, coarctation in adulthood is accompanied by congenital and acquired vascular pathology that may require surgical intervention. The management of an adult patient with aortic coarctation and other vascular anomalies poses a great technical challenge. We hereby present a rare case with the combination of aortic anomalies including an aortic arch coarctation, a poststenotic biloculated calcified aneurysm, and a hypoplastic left subclavian artery (LSA), which was successfully treated with a 2-stage hybrid approach.2Informed consent was obtained from the individual participant in the study.A 35-year-old man (body weight: 100 kg) was admitted to our center complaining of headache and chest discomfort. Physical examination revealed high blood pressure (184/88 mm Hg) in the right arm and weak lower extremity and left arm pulses. Echocardiography and computed tomography (CT) angiography demonstrated an aortic arch coarctation with a minimal diameter of 5 mm. The coarctation was located between the left common carotid artery and the LSA, with a large collateral circulation and a large biloculated calcified aneurysm just distal to the coarctation. The LSA arose from the upper locule of the aneurysm with an upper-to-lower flow direction . The patient was discharged 8 days after the operation in good condition.Six months later, the patient was readmitted for transluminal occlusion of the aneurysmal orifice. Preoperative CT aortography showed persistent flow of contrast into the aneurysm sac Fig. C and D. 3 Aneurysm may develop distal to the coarctation in patients without any intervention and is associated with significant risk of aortic rupture. Inflammation of the aortic wall, congenital weakness of the aortic arterial wall, or asymmetric and enhanced shear stress may play a significant role in the development of aneurysm formation.,2 In the present case, the formation of the calcified biloculated aneurysm just distal to the coarctation may be associated with the relatively advanced age and the bifurcate structure composed of LSA and descending aorta. We believe that the upper portion of the aneurysm is the dilated LSA and the lower portion is the dilated descending aorta.Coarctation of the aorta may occur anywhere along the descending aorta and more than 95% of the cases; it is located below the origin of the LSA and may involve the origin of this vessel.The management of patients presenting with complex aortic coarctation necessitates consultation of a multidisciplinary team including vascular and cardiac surgeons, interventional congenital cardiologist, and interventional radiologist. Variables that could influence treatment strategy include the degree of residual coarctation; location of the aneurysm relative to the coarctation; the shape, size, and degree of calcification of the aneurysm; suitability of landing zones for percutaneous devices deployment; patient age; and presence of collateral flow if LSA exclusion is required. Endovascular approach such as percutaneous balloon dilatation and stent implantation is not suitable in cases with extensive calcification and is associated with a high procedural risk of aortic rupture. In this setting, bypass grafting between the ascending and descending aorta, instead of aortic arch reconstruction, is also effective in relieving trans-coarctation gradient and improving systemic blood perfusion. We ligated the origin of the LSA without causing cerebral ischemia or cerebral infarction because of the upper to lower flow direction. However, the aneurysm can hardly be occluded by surgical ligation. So, we intentionally constricted the proximal and distal segment of the aneurysm in order to decrease the blood flow and the pressure of the aneurysm and provide landing zones for VSD occluders, which are preconditions for the subsequent endovascular procedure of aneurysmal orifice occlusion.In this case, the aortic arch aneurysm was located at the greater curvature where the LSA arose from, and was complicated by aortic arch coarctation. Conventional anatomical aortoplasty, which requires cardiopulmonary bypass or deep hypothermic circulatory arrest, would be complicated and carries a high mortality and morbidity risk.4In conclusion, the use of a 2-stage hybrid approach integrating open and endovascular repair for the treatment of a complex aortic coarctation appears feasible, safe, versatile, and effective during short-term follow-up. Besides, such a hybrid approach also offers several advantages over isolated conventional surgical repair or endovascular repair.The authors thank the patient participating in the present study who provided written permission for publication of this case report.


Human papilloma viruses (HPVs) cause a variety of clinical manifestations in children including skin warts, laryngeal papillomas, and condyloma acuminatum. Whereas the mode of transmission is well understood and management of HPV infection is clearly defined by guidelines in adults, less is known about the mode of transmission, natural history of disease, and appropriate management of high-risk anogenital HPV infections in children. The patient is a previously healthy 6-year-old female who presented with multiple vaginal lesions causing pain and discomfort and was diagnosed with HPV 18 positive CIN I. Children infected with high-risk HPV subtypes remain a vulnerable patient population, and there is minimal literature on the natural history of disease and effects of overtreatment. Based on a literature review, conservative management, HPV vaccination, and consideration of the cervical cancer screening guidelines for adolescent females are an appropriate treatment course until more studies are reported on cervical cancer screening in survivors of child sexual abuse. Human papilloma viruses (HPVs) are a family of small double-stranded DNA viruses, of which 30–40 genotypes infect the genital tract. The virus infects epithelial cells through abrasion of the skin or mucosa and can exist as a latent infection . Low-risLittle is known about the natural progression of high-risk HPV infection in children. It has been suggested that young children may be monitored for malignancy in a similar manner to adolescent females , 2. PrevThe patient is a premenarchal, 6-year-old female who presented to the emergency department (ED) with her mother because of mild discomfort with urination and “pimples” causing pain in the vaginal area. The patient was previously healthy and denied increased urinary frequency or urgency, vaginal bleeding, vaginal discharge, malaise, and fever. The patient and her mother denied inappropriate contact or touching. On physical examination, the patient was comfortable, smiling, and playful. The external pelvic examination was notable for multiple raised lesions on the labia minora and erythema of the external genitalia. No vesicles or vaginal discharge were observed. At the ED, a clinical diagnosis of genital warts was made.Social Work and the Department of Child Protection and Permanency were contacted. The patient and her mother were referred to a state-designated child protection center that provides crisis intervention and child abuse assessments. At the state-designated child protection center, a team of trained professionals conducted an evaluation and was able to ascertain a history of abuse from the patient by an adult, male family member living in the household. The center conducted a thorough physical examination and infection screening.Two months after initial presentation and evaluation at the child protection center, the patient's symptoms worsened secondary to an increase in the size of the lesion. The patient was able to urinate but unable to sleep at night secondary to pain and irritation caused by rubbing. On examination, the patient had warts in the vestibule that carpeted the space between the labia minora and fourchette, obliterated the vaginal introitus, and appeared to obscure the urethra.The patient then underwent an exam under anesthesia (EUA) and excision of vaginal lesions, as seen in At the postoperative follow-up visit, the mother and patient reported a smooth recovery with minimal pain. Exam of the surgical site in the supine frog-leg position showed that it was well healed with minimal residual disease. The patient was instructed to follow up with gynecology every 6 months and with pediatric surgery as needed. Given this patient falls outside CDC guidelines for vaccination and her pathology results, we plan to recommend HPV vaccination at the patient's next visit , 4.The detection of a sexually transmitted infection (STI) in a child should raise suspicion for sexual abuse. Genital or anal condyloma acuminatum appearing for the first time in a child older than 5 years is likely to be the result of sexual transmission . A retroWhile little is known about the epidemiology of HPV in children, one study demonstrated that 16% (5/31 girls) of child sex abuse victims are infected with HPV . FactorsHPV infections behave differently in adolescent and young women when compared to older adult women . Two expThe Papanicolaou (Pap) test is a screening tool for cervical cancer and has reduced the mortality rates of cervical cancer in the United States . The BetThese guidelines were based on studies of HPV in young women, which can provide insight regarding the management of this 6-year-old female since the natural progression of HPV in victims of child sexual abuse is not known. Although adolescent and young women have higher rates of HPV infection than older adult women, they are also more likely to clear the infection. One study noted that 65–75% of adolescent and young women were found to test negative for HPV DNA by 30 months. The same study suggested chronic HPV infection might be correlated with oncogenic, high-risk HPV viral types, indicating that high-risk viral types may more effectively evade the immune system . AdditioVictims of child sex abuse are an especially vulnerable population for several reasons. Often, as in this case, the sexual abuse begins prior to the age at which HPV vaccinations are routinely given; the FDA has approved HPV vaccination starting at the age of 9 in females. This patient endured sexual abuse at a young age, placing a longer time period between the time of initial infection with HPV and onset of routine cervical cancer screening at the age of 21 . MoreoveThis case of a 6-year-old female victim of child sexual abuse infected with high-risk HPV highlights a vulnerable patient population where there is minimal understanding of the natural course of HPV infection and appropriate management. Further study is needed to ascertain the optimal management and appropriate time to perform a Pap smear . In this


A hallmark of cardiovascular disease is cardiac autonomic dysregulation. The phenotype of impaired parasympathetic responsiveness and sympathetic hyperactivity in experimental animal models is also well documented in large scale human studies in the setting of heart failure and myocardial infarction, and is predictive of morbidity and mortality. Despite advances in emergency revascularisation strategies for myocardial infarction, device therapy for heart failure and secondary prevention pharmacotherapies, mortality from malignant ventricular arrhythmia remains high. Patients at highest risk or those with haemodynamically significant ventricular arrhythmia can be treated with catheter ablation and implantable cardioverter defibrillators, but the morbidity and reduction in quality of life due to the burden of ventricular arrhythmia and shock therapy persists. Therefore, future therapies must aim to target the underlying pathophysiology that contributes to the generation of ventricular arrhythmia. This review explores recent advances in mechanistic research in both limbs of the autonomic nervous system and potential avenues for translation into clinical therapy. In addition, we also discuss the relationship of these findings in the context of the reported efficacy of current neuromodulatory strategies in the management of ventricular arrhythmia. •We review advances in mechanistic research in the cardiac autonomic nervous system.•This is discussed in relation to neuromodulatory therapy for ventricular arrhythmia.•Neuromodulation therapies can influence both neurotransmitters and co-transmitters.•This may therefore improve on conventional medical treatment. The phe2The autonomic nervous system functions to tightly regulate cardiac excitability and contractile function . The intIn the setting of cardiovascular disease or cardiac injury such as myocardial infarction, neurophysiological changes take place at distinct levels in the neural circuitry . EffectsUnderstanding of this complex cardiac neural-axis has led to targeted autonomic modulation therapies for heart failure and arrhythmia aimed at the cervical cardiac vagus and sympathetic nervous system respectively . This re3An understanding of the mechanisms responsible for the initiation and maintenance of ventricular arrhythmia is critical if effective treatment strategies are to be investigated and developed. The principle contributing factor to the onset of arrhythmia is re-entry. Fibrillation occurs when an electrical wave-break induces re-entry and leads to a sequence of new wave-breaks . Wave-br4Contemporary research has led to a spectrum of neuro-axial therapies in the setting of patients at high risk of malignant ventricular arrhythmia. This has been based on mechanistic evidence from models of sympathetic hyperactivity at the level of the organ in animals , and morKs distribution, potentially influencing the vulnerability to arrhythmia. The ability of local changes in sympathetic activity to trigger ventricular arrhythmias is well established . Heart failure is also associated with changes in other inflammatory and neurohumoural pathways including a range of growth factors and cytokines. Candidate molecules include leukemia inhibitory factor (LIF) and members of the interleukin (IL-6) family . These m6Efferent vagal innervation of the heart is classically thought to be only concentrated in the sinoatrial, atrial and atrioventricular nodal regions. Advances in anatomical techniques have however challenged the historical perspective that this innervation is restricted to the atria and structures in the conduction system . Immunohanti-fibrillatory effect of the vagus was first described in 1859  coupled to inhibitory G proteins , with subsequent decrease in the hyperpolarisation-activated current, If, and PKA dependent phosphorylation of the L-type calcium current, ICaL, thereby reducing diastolic depolarisation and heart rate  and downstream coupling to Gi, eNOS and Gk signalling cascades. Gi inhibits adenylyl cyclase and thereby reduces cAMP dependent stimulation of L-type Ca2 + current (LTCC) and phosholamban. M2 dependent stimulation of eNOS activity has also been proposed as a mechanism for accentuated antagonism of β-receptor stimulation when cAMP levels are already elevated , and this was prevented by mecamylamine, a specific inhibitor of the nicotinic AChR demonstrating that the source of NO was neuronal.In the innervated, rabbit heart preparation described above, the  for NOS . This su for NOS  demonstr for NOS  suggesti for NOS . Using aTherefore, observations in the rat are in keeping with the observations in the rabbit that nNOS derived NO is a key component of the anti-arrhythmic effect of cholinergic signalling. However, in the rat the anti-fibrillatory effect is abolished by atropine in keeping with the established autocrine role of NO . FurtherNotwithstanding the above observations, these data must also be considered within the limitations of the model systems studied. Sensory fibres make up to 70% of the cervical vagus  and theyanti-arrhythmic role of NO in mediating vagal protection is supported by studies across multiple domains, and future studies will need to further delineate the sites of action and optimum strategies to exploit this effect therapeutically. Speculatively, a nicotinic receptor based NO mediated mechanism that converges on the muscarinic receptor is conceivably amenable to a more targeted approach with gene therapy or a pharmacological treatment strategy. Percutaneous cardiac gene transfer of nNOS increases vagal neurotransmission and bradycardia   was a sm8The potential of the vagus nerve as a therapeutic target in heart failure continues to be the subject of clinical trials, but challenges remain in delivering effective device therapy. Historically, pharmacological approaches such as cholinesterase inhibition  have als9Other approaches to reducing cardiac sympathetic drive include targeting higher centres via deep brain stimulation (DBS). DBS of the periaqueductal grey is a treatment for chronic pain can also lead to increases or decreases in blood pressure depending on the location of the electrode and alter102 + handling, thereby potentially influencing arrhythmogenesis. Neuromodulation therapies may not only remove the source of the principal neurotransmitter, but also influence the local release of co-transmitters providing increased efficacy over conventional medical therapies. The functional significance of these pathways and potential therapeutics avenues in disease states is yet to be established.Although neuromodulation therapies offer promise in terms of treatment of ventricular arrhythmias, it is interesting to note that most to date have been trialed in patients already taking the maximally tolerated doses of β-blockers . The mecNone.


It is sometimes difficult for some patients to optimally flex their hips and knees making traditional position for induction of spinal anaesthesia difficult to achieve. The ease of induction of spinal anaesthesia was compared with patients in sitting position with legs remaining on the table (new sitting method) versus legs placed on the side stool .One hundred eligible elderly patients, aged between 65 and 80 years, scheduled for open prostactectomy, were prospectively randomized to 2 groups, LS and LT. Patients in (LS group) had their spinal anaesthesia induced in sitting position with their legs placed on the stool while patients in (LT group) had their spinal anaesthesia induced in sitting position with their legs remaning on the operating table. The primary endpoint was correct needle placement. Numbers of attempts, needle redirections and patients' comfort were determined to compare outcome in the two groups.More patients in LS group (78%) than those in the LT group (64%) had successful placement of spinal needle at first attempt . Needle redirections were similar at first attempt . The groups were equivalent with respect to 100% overall success rate (P = 1.000). It took longer time to induce spinal anaesthesia in patients in LS group . Patients in LT were more comfotable.The 100% overall success rate was comparable. However, patients were generally more comfortable with their legs placed on the table. Generally, reduced lumbar lordosis during induction of spinal anaesthesia is a product of good positioning prior to the procedure . AnecdotThis prospective randomized study was carried out at the Ekiti State University Teaching Hospital, Ado-Ekiti, Nigeria. After institutional approval and informed written consent, one hundred elderly patients in the age group 65-80 years, belonging to the American Association of Anaesthesiologists (ASA) physical status score I or II, scheduled for elective prostatectomy, were included in the study. Patients with anatomical spinal deformity, inability to flex the knees, body mass index (BMI) > 30 kg/m2, neurological disease, coagulation disorders, local infection and unstable haemodynamics were excluded from the study. Preoperative assessment of the patients was carried out in the wards the day before surgery. This of a clinical history and physical examination. Mallampati and ASA Scores as well as the degree of flexion at knees and hip joints were determined. Laboratory investigations included a full blood count, serum electrolytes, urea and creatinine and urinalysis. In the pre-anaesthetic review on the day before surgery, patients were briefed about the proposed position for the procedure according to group allocation. All patients were fasted overnight and premedicated with oral diazepam 10mg a day before surgery. In the operating theatre, spinal pack was made available. Routine anaesthetic equipment check was carried out and anaesthetic machine with appropriate sizes of endotracheal tubes and laryngoscopes were made on stand-by. Baseline vital signs were recorded including systolic, diastolic, mean arterial blood pressures, oxygen saturation and continuous electrocardiographic monitoring, using electronic multiparameter monitor. Intravenous line was established for all the patients using a 18 gauge cannula and Ringers Lactate infusion was started. Spinal anaesthesia was performed either in the sitting position with the two legs on a stool beside the operating table or in the sitting position with the two legs maitained straight on the operating table. Patients were randomized into two groups of 50 patients each based on a computer-generated randomization system: in Group LT, patients were put in sitting position with the two legs placed straight on the operating table and in Group LS, patients were put in sitting position with legs placed on the side stool.In the operating theatre, patients were preloaded with 12ml/kg Ringers Lactate and patients were positioned for subarachnoid block. Patients in Group LS were placed in a sitting position with the legs placed on a stool at the edge of the table with one pillow hugged around the chest. The patients in group LT were placed in sitting position with their two legs placed in a straight state on the operating table with one pillow hugged around the chest. The patients in the two groups were made to be in flex posture by bending the hip joints and flexing the neck towards knee as far as possible (forehead to knee position). An anaesthesia assistant helped each patient to obtain and maintain the best possible flexed posture by holding the patients at their occipital region and knees. Block was performed in any of the two positions. Patients in LS group sat on the table with their legs hanging from the edge of the table with the support of a stool under their feet. The height of the stool was adjusted to achieve flexion of the back.All patients were asked to bend forward and arch out their back maximally. Arms were rested over a pillow which was kept on the lap. This prevented the patient from slumping to either side. Under aseptic conditions and following standard techniques of spinal anaesthesia, the second anaesthetist performed the blocks with a 25 G Quincke spinal needle. Using the iliac crest on both sides as the landmark, the anaesthetist had option of using any of the spaces for his first and the second preferred intervertebral space out of L2-L3, L3-L4 and L4-L5. In performing induction of spinal anaesthesia, the first attempt was achieved by introducing the spinal needle into first preferred interspinous space untill tactile sensation was felt. At this stage, no needle re-direction except for bony contacts. Correct placement of spinal needle into the subarachnoid space was judged by appearance of cerebrospinal fluid (CSF) in the hub of the needle. Appearance of free flow of CSF confirmed a successful needle insertion. In case there was either no CSF or there was scanty CSF, the following adjustments were carried out in order to achieve correct placement of the spinal needle. The needle would be rotated clockwise 90° and waited for 10s; another sequence of 900 rotation would be done if CSF was still not observed untill a total of four-quadrant rotations of 90° was achieved, amounting to 360° clockwise rotation, with an allowance of interval of 10s between each rotation. Inspite of these maneuvers, if there was no free flow of CSF, the anaesthetist would further advance the spinal needle untill another tactile sensation was felt. Also at this stage no needle re-direction except for bony contacts. A free flow of CSF confirmed correct placement otherwise the above outlined 3600 clockwise maneuver would be carried out. Inability to achieve free flow of CSF following second advancement, even after these maneuvers, would result in the needle being withrawn to a level just beneath the skin for re-direction cephalad, horizontally or caudally.A maximum of three re-directions was allowed for each attempt. Following each re-direction and feeling of tactile sensation a free flow of CSF confirmed correct placement of spinal needle, otherwise, the above-mention 3600 maneuver was observed. Inability to observe flow of CSF at the hub of the spinal needle, despite three re-directions and three needle advancement coupled with 3600 maneuver, was followed by completely withdrawal of the spinal needle from the skin and this was considered as failed first attempt. Also whenever there were persistent bony contacts (more than three-times) despite cephalad, horizontal or caudal angulation of the needle, then the needle would be withdrawn completely from the skin. This was also termed failed first attempt.The number of times for needle re-directions and bony contacts was documented. Following completely removal of the needle after failed first attempt, a reassessment of the midline and the second most preferred interspinous space was located. Second attempt was carried out by re-introducing the spinal needle to the second most preferred intervertebral space untill another tactile sensation was felt. Its correct placement was confirmed by free flow of CSF otherwise the second advancement of needle or needle re-directions coupled with 3600 maneuvers were carried out step-by-step as outlined for first attempt.Following the above-mentioned maneuvers, if there was no free flow of CSF then the needle would be withddrawn completely from the skin and this was considered as failed second attempt. Also whenever there were persistent bony contacts (more than three-times) despite cephalad or caudal angulation of the needle, then the needle would be withdrawn completely from the skin. This was also termed failed second attempt. The number of times for needle re-directions and bony contacts was documented. Following failed second attempt, the third and the final attempt was considered in first or second preferred space. Another reassessement was carried out in order to facilitate correct placement. In order to establish third attempt at spinal anaesthesia, the spinal needle was advanced into either of the first or second most preferred interspinous space to look out for free flow of CSF at the hub of the needle. A free flow of CSF confirmed correct placement. Lack of free flow of CSF prompted the anaesthetist to carry out the second advancement of needle or needle re-directions coupled with 3600 maneuvers step-by-step as outlined for first attempt.Following the above-mentioned maneuvers, second advancement and needle re-direction coupled with 3600 maneuver of the needle, if there was no free flow of CSF then the needle would be withdrawn completely from the skin and this was considered as failed third and final attempt. Also whenever there were persistent bony contacts (more than three-times) despite cephalad or caudal angulation of the needle then the needle would be withdrawn completely from the skin. This was also termed failed third attempt. The number of times for needle re-directions and bony contacts was documented. Thus, considering all the above-mentioned manipulations, each attempt was considered as a failed attempt if: (i) there was no CSF in the hub, despite advancement, three re-directions coupled with 3600 maneuver of the needle (ii) when the needle could not be negotiated because of three repeated bony contacts. Following intrathecal administration of 3ml of hyperbaric bupivacaine, patients were returned into supine position. Maximum sensory block height was assessed at every two minutes untill T6 was achieved, using loss of sensation to cold and gentle pin prick test. A minimum sensory block height of T6 was the minimum desired level for commencement of surgery. Also documented was time to induce spinal which was the time from completion of preload until patient was returned into supine position.Overall onset time which was the time from when the spinal needle was introduced until T6 analgesia was achieved. The following parameters were recorded: overall success, attempts required, number of patients requiring manipulation of needle and the type of manipulations. Complications such as hypotension, headache and backache were noted by the anaesthetist during and after the operation. Primary outcome measure was the number of attempts during correct needle placement. Each attempt was considered as a failed attempt if: (i) there was no CSF in the hub, despite advancement, three needle re-directions coupled with 3600 maneuver of the needle (ii) when the needle failed to advance because of three repeated bony contacts. Additional data including onset of sensory block, side effects and patients' comfortability was assessed  and documented. 10cm denoted maximal comfort while 0cm denoted minimal comfort. These primary and secondary outcomes were compared in the two groups.Statistical analysis: Normally distributed numerical variables among the two groups were analyzed with unpaired Student's t-test. Proportions and median were analyzed respectively with Chi-square or Fisher's exact tests and Mann-Whitney test respectively. In all calculations, P < 0.05 is the level of significance. The primary objective of the study was to decrease the incidence of bony contacts from 50%  while uAs shown in According to this present study, correct placement of spinal needle is possible in the elderly in sitting position with the two legs placed on the operating table. Although, more patients in group with legs placed on the stool 78%) than those in whose legs were placed on the table 64%) had successful placement of spinal needle at first attempt; the overall success rate was hundred percent and comparable among the two groups. Our study also demonstrated that onset of analgesia was faster in patients whose legs were placed on the table than in patients whose legs were placed on the side stool. It significantly took a longer time to institute spinal block in patients whose legs were placed on the side stool. However, patients in whose legs were placed on the table significantly consumed more ephedrine in the first 15 minutes following injection of bupivacaine. Most anaesthetists in our centre preferred to place the legs of their patients on the table because they believe that it reduces time to place spinal anesthesia especially in fetal distress [8% than t4% had suResearchers observed that putting the legs on the table helped in the reversal of lumbar lordosis by increasing hamstring tension, tilting the pelvis, and reducing lumbar curvatures ,13. In cCorrect placement of spinal needle is possible in the elderly in sitting position with the two legs placed on the operating table. Although, more patients in group with legs placed on the stool than those in whose legs were placed on the table had successful placement of spinal needle at first attempt; the overall success rate of hundred percent was comparable among the two groups.Traditional method of putting the two legs on side stool during induction of spinal anaesthesia is excellent;There is high succes rate following this position.Induction of spinal anaesthesia, with patient's legs placed on theatre table, also yields excellent result;High success rate in this new position is also observed, however, patients are more comfortable with their two legs placed on the theatre tables;Time to establish spinal anaesthesia is faster in this new position.The authors declare no competing interests.


R>0.98) between added and pixel based calculated concentration of adulterant materials. This developed Raman imaging system thus, can be considered as a powerful analytical technique for the quality and authenticity analysis of food products.The potential adulteration of foodstuffs has led to increasing concern regarding food safety and security, in particular for powdered food products where cheap ground materials or hazardous chemicals can be added to increase the quantity of powder or to obtain the desired aesthetic quality. Due to the resulting potential health threat to consumers, the development of a fast, label-free, and non-invasive technique for the detection of adulteration over a wide range of food products is necessary. We therefore report the development of a rapid Raman hyperspectral imaging technique for the detection of food adulteration and for authenticity analysis. The Raman hyperspectral imaging system comprises of a custom designed laser illumination system, sensing module, and a software interface. Laser illumination system generates a 785 nm laser line of high power, and the Gaussian like intensity distribution of laser beam is shaped by incorporating an engineered diffuser. The sensing module utilize Rayleigh filters, imaging spectrometer, and detector for collection of the Raman scattering signals along the laser line. A custom-built software to acquire Raman hyperspectral images which also facilitate the real time visualization of Raman chemical images of scanned samples. The developed system was employed for the simultaneous detection of Sudan dye and Congo red dye adulteration in paprika powder, and benzoyl peroxide and alloxan monohydrate adulteration in wheat flour at six different concentrations (w/w) from 0.05 to 1%. The collected Raman imaging data of the adulterated samples were analyzed to visualize and detect the adulterant concentrations by generating a binary image for each individual adulterant material. The results obtained based on the Raman chemical images of adulterants showed a strong correlation ( Due to an increase in the number of food adulteration cases over the past decade, food safety has become a growing concern for both the food industry and for food safety organizations. In general, the major food commodities subjected to adulteration are spices, edible oils, honey, meat, and milk products . AlthougWheat flour is one of the main processed products of wheat and consumed worldwide. Therefore, the safety of wheat flour is of particular importance. However, several examples of wheat flour adulteration with hazardous chemicals such as benzoyl peroxide (BPO) and alloxan monohydrate have been documented in the literature –7. Such There is a long history of spice adulteration, particularly, paprika and chilli powders’ adulteration with various hazardous azo dyes such as; Sudan dye, Congo red, and Rhodamine B to obtain the desired aesthetic quality and make spices looks fresh ,10. The Spectroscopic techniques, such as near-infrared (NIR), mid-infrared (MIR), and Raman spectroscopy have been widely used as fast and sensitive analytical techniques for the authenticity analysis of a variety of powdered food products . HoweverThe early applications of Raman imaging for food quality analysis were performed using a confocal point-scan Raman imaging microscopic system, which allowed the simultaneous analysis of various chemical components in carrot root , in addiRecently, Qin et al.  developeTo advance the application of Raman imaging in food quality and authenticity analysis, we herein report the design of a Raman imaging instrument similar to that developed by Qin et al. ,21. HoweHerein, more specifically we aim to explore the potential of the RHSI technique for the authenticity analysis of two different globally used powdered food products, in addition to developing custom-built software for the RHSI system to allow image acquisition and analysis by the addition of image processing algorithms for different applications. Furthermore, we wish to develop fast and effective Raman spectral and image processing algorithms for the visualization of concentration maps of adulterant materials present in food powders. Finally, we expect that the developed system will enable the fast and high-throughput screening of powdered food samples for authenticity analysis, while mapping a large sample area along the laser direction, which can be further expanded by increasing the sample-to-camera distance or by making some minor alterations to the developed system while considering the required spatial resolution for any particular application.f = 200 mm). However, the use of a cylindrical lens produces a poorly illuminated line, and is limited by the non-uniform and Gaussian-like intensity distribution [The developed system consists of an optical assembly to ensure a uniform laser excitation and Raman signal collection, and was further coupled to a charge-coupled device (CCD) camera through the spectrometer to generate Raman images without interference from Rayleigh scattering. A schematic representation of the developed system is illustrated in ribution . An ideaThe laser line was then projected onto a 785 nm dichroic beamsplitter  and its path changed to a vertical orientation. The dichroic beam splitter (10 cm × 3.5 cm) was mounted on an xyz translation stage incident at 45° to reflect the laser beam to the image plane. The dichroic beamsplitter should reflect the majority of incident light while blocking the non-informative Rayleigh scattering generated during Raman data collection. The uniformity of the laser line on the sample surface was measured by scanning a Teflon sheet at two different vertical distances  from the center of the beamsplitter, giving line uniformities of ~10 and ~14 cm, respectively. The sensing module to collect the generated Raman signals is identical to Raman imaging system described in . A manuaCustom software for focus alignment, image acquisition, and RHSI system control was developed using MATLAB . This software also includes control of the RHSI camera and the sample stage. The display interface of the MATLAB code is shown in −1  and that it has an effective average spectral resolution of 3.5 cm−1. The spectral resolution at the full width at half maximum, which corresponds to the theoretical maximum resolution of the spectrograph, was tested according to the method reported in reference [−1. Spatial calibration was carried out using black and white striped paper. Under the desired settings, the calculated and measured image line lengths and spatial resolutions showed a perfect match.Spectral calibration is a basic and routine procedure in all spectroscopic and spectral-imaging techniques. The goal is to assign a wavelength to all pixels along the spectral dimension of the CCD. In this study, the system was spectrally calibrate using two standard materials . As shown in eference , and wasWheat flour and paprika powder samples were obtained from a local market in Korea, and four adulterant materials, namely BPO, alloxan monohydrate, Sudan-I, and Congo red dye (purity >95%) were purchased from Sigma-Aldrich . As quantification of the penetration depth of the laser line for the powdered food samples is important in food authentication applications to ensure all adulterant particles can be detected, the penetration depth was determined by placing the wheat flour and paprika powder samples at four different thicknesses over a 5 mm-thick layer of the adulterant material . In thisThe powdered food samples were then adulterated at six different concentrations, where the concentrations were selected based on previous reports ,26. Thus−1 using a CCD spatial binning of 2. The major signals corresponding to the adulterant materials used in this study were mainly observed in the spectra between 360 and 1800 cm−1. To correct the raw images, dark current images were acquired with the laser switched off and the camera lens covered with its opaque cap.Both the layered and mixed samples were scanned using the described RHSI system shown in The data acquired from Raman imaging instruments equipped with a CCD detector are usually characterized by occasional high intensity spikes, with fluorescence often being an issue. In this case, the collected Raman image data were first reorganized from a three-way array to a conventional two-way array (pixel × Raman shifts) and initially corrected by subtracting the dark current. To address the issue of unwanted fluorescence background signals, the adaptive iteratively reweighted Penalized Least Squares (airPLS) fluorescence correction method reported in literature  was applx and y) and one spectral dimension. Therefore, each band has an intensity image of the whole scanned sample. Since the Raman spectra of BPO and alloxan monohydrate present fine and well resolved peaks  materials were examined to estimate the effective penetration depth. ed peaks , and no Finally, the single band images of the wheat flour adulterants and the summation images of the paprika powder adulterants were subjected to image segmentation to isolate the adulterant pixels from the powdered food background by selecting a threshold value. The binary image of the individual adulterant of the same sample was then combined to form a chemical image of the two identified adulterants. The concentration of each individual adulterant in the wheat flour and paprika powder samples was then calculated using the number of pixels belonging to that particular adulterant material in the binary image. The detected pixels for each adulterant at all concentration levels for both powdered food samples were correlated with the adulterant concentrations in the samples. All image correction and analysis processes were programmed in MATLAB .As a demonstration of the developed RHSI system, we initially examined the layered powder samples. The penetration depth of the laser line through the wheat flour and paprika powder was measured following the method used in  to ensur−1 at a depth of 4 mm. Furthermore, the collected Raman image data for the layered paprika powder and Sudan dye samples were evaluated using the same method to ensure effective penetration depth determination. These results suggested that under the current laser powder and system setup, the maximum effective penetration depth of the line laser through the wheat flour and paprika powder samples is ~2 mm, and so this thickness will be employed for further (mixed sample) investigations.A gradual decrease in the average spectral peak intensity of adulterant can be observed with increasing sample depth . During −1  at the two unique Raman peaks of the two adulterants. However, for quantification of the adulterant pixels in paprika powder, the threshold value was determined based on the band summation image of each dye. Each pixel counted as either adulterant or food powder was evaluated to avoid false-positive and false-negative determination.The obtained threshold values were then applied to convert all pixels with intensities below the threshold value into background pixels, while identifying all pixels with intensities above the threshold as representing a particle of the adulterant of interest. At each concentration level, the binary images of the two adulterants were combined and the pixels of each component were color-coded by assigning a particular value while thresholding. The final color-coded images for all six adulterant concentrations and two replications for both wheat flour and paprika powder are shown in Figs Once the binary images have been generated for the adulterants, the mass concentration of each individual adulterant can be calculated by calculating the percentage of adulterant pixels in the binary image. Thus, the pixel concentration was calculated for each adulterant in all measured samples, and an average was calculated using the replicated samples. As expected, the number of detected pixels increased considerably with increasing mass concentration of the adulterants, with a linear trend being observed for all adulterants in both powder samples. However, the pixel concentrations in the binary images were lower than the corresponding mass concentrations of the adulterants. We believe that this is caused by the significant difference in density between the adulterants and the food powders, as the density ratios between BPO and wheat flour and between alloxan monohydrate and wheat flour are approximately 1.5 and 1.65, respectively, while those between Sudan dye and paprika powder and between Congo red and paprika powder were approximately 2.4 and 2.16, respectively. These higher adulterant densities decrease their particle volumes when the mixed samples are prepared using the weight-by-weight concentrations. Therefore, to convert the pixel concentration into a mass concentration, each pixel concentration was multiplied by the corresponding density ratio, and the results are presented in As the main objective of the present work was to develop and test the RHSI system for the authenticity analysis of powdered food, the result clearly demonstrates the capability of the RHSI technique to detect and spatially visualize the presence of adulterants in such samples. Although only two adulterants were investigated for each powdered food, we expect that the detection of multiple adulterants will be possible using a similar methodology or by adopting multivariate methods for data analysis when selective information from multiple spectral channels is not available.Compared with previous attempts regarding authenticity analysis of wheat flour using Raman imaging ,24, the R>0.98) was found between the mass concentration and the pixel-based detected concentration of adulterants in both wheat flour and paprika powder.We herein described the development and calibration of a rapid line-scan Raman hyperspectral imaging technique (RHSI) technique with custom-built software and its use in the detection of food adulteration and authenticity analysis of two different powdered food samples. Following the collection of Raman images for the layered samples to determine the effective penetration depth of the laser , mixed (adulterated) powder samples were examined. The quantification of individual adulterants in adulterated powder was possible through the application of a threshold value to the intensity value of the corrected band images or summation images  for the adulterant of interest. Indeed, a strong linear relationship (The obtained results therefore suggest that combination of this RHSI system with univariate and bivariate data analysis techniques is a rapid and effective tool for the detection of chemical adulteration in food powders. We expect that this study can easily be extended to simultaneously detect various adulterants in different kinds of food powders even on a large scale. In addition, the proposed methodology will provide a novel approach to the rapid determination of food authenticity and can also be considered for pharmaceutical quality analysis. We therefore expect that it exhibits potential for industrialization in the near future. Future studies will focus on the application of our system for the detection of multiple possible adulterants in adulteration-susceptible powdered foods, in addition to the quality analysis of dairy products, fruits, and vegetables.


Dr herring and his colleagues at the Texas Scottish Rite Hospital for Children have produced the latest edition of Tachdjian's Pediatric Orthopaedics combining a hard copy with an online versionThis is a two-volume book with the complete three-volume digital version available online. The online access via expertconsult.inkling.com requires a user name and password. The hard copy has 34 chapters. Chapters 35 to 43 are online and comprise neuromuscular and other orthopaedic disorders. Fifty-eight videos of operative procedures, scoliosis casting techniques and patients' clinical examination are available online.The videos include most of the major surgical procedures in paediatric orthopaedics such as the growing rod for scoliosis, open reduction for developmental dysplasia of the hip, pelvic osteotomies, surgical hip dislocation for slipped capital femoral epiphysis, triple arthrodesis of the foot and the 8-plate.The quality of some of the videos however, could be improved with further editing as the operative field was sometimes obstructed by the surgeon or too small to visualize.The videos on physical examinations show the clinical features of a child with asymmetric abdominal reflexes, an infant with femoral nerve palsy after using a Pavlik Harness and children with unilateral and bilateral developmental dysplasia of the hips.There are numerous computer-aided colour illustrations throughout the book including 44 operative procedures in the hard copy and another 33 procedures online. The illustrations provide excellent educational and aesthetic value to the book.The book does not have a CD-ROM and accessing the book online will need an internet connection.Overall, this is an excellent textbook on paediatric orthopaedics.


Shigella sonnei linked to the Orthodox Jewish Community (OJC). Ultimately, 52 cases of S. sonnei phage type (PT) P and PT7 were notified between November 2013 and July 2014. Whole-genome sequencing (WGS) was performed on a HiSeq 2500 platform (Illumina) on isolates of S. sonnei submitted to PHE during the investigation. Quality trimmed sequence reads were mapped to a reference genome using BWA-MEM, and single-nucleotide polymorphisms (SNPs) were identified using GATK2. Analysis of the core genome SNP positions  revealed that isolates linked to the outbreak could be categorized as members of distinct monophyletic clusters (MPCs) representing concurrent regional outbreaks occurring in the OJCs across the United Kingdom. A dated phylogeny predicted the date of the most recent common ancestor of the MPCs to be approximately 3.1 years previously . Isolates of S. sonnei from cases from the OJCs in Israel included in the phylogeny, branched from nodes basal to the UK OJC outbreak clusters, indicating they were ancestral to the UK OJC isolates, and that the UK isolates represented multiple importations of S. sonnei into the UK population from Israel. The level of discrimination exhibited by WGS facilitated the identification of clusters of isolates within the closely related bacterial populations circulating in the OJC that may be linked to a unique point sources or transmission routes, thus enabling a more appropriate public health response and targeted interventions.In December 2013, Public Health England (PHE) observed an increase in the number of cases of  The accession numbers are listed in Table S1 (available in the online version of this article).Short-read FASTQ sequences have been deposited in the NCBI Short Read Archive under the BioProject PRJN A248042  worldwide. Although all species of the genus Shigella contribute to the high burden of diarrhoeal disease in low-income regions, S. sonnei is the most commonly reported species in middle- and high-income countries . The household contacts in MPC1 were located on the same branch but those in MPC2 an MPC3 were not . In the S. sonnei circulating in England amongst the OJC between 2008 and 2014 were closely related to each other but distinct from contemporary S. sonnei isolates circulating outside of the OJC in England. Instead, they clustered more closely with S. sonnei isolated in Israel [S. sonnei isolates in neighbouring clusters .Placing the OJC outbreak clusters into a broader national and international phylogenetic context indicated that n Israel   and found that the majority of cases (92 %) self-identified as, had known links with, or had strong evidence to indicate that they belonged to the OJC. The WGS data enabled us to deduce that the increase in cases observed in the OJC in North London between November 2013 and July 2014 comprised distinct, contemporary outbreak clusters, each containing between 7 and 24 cases, focused around London and Greater Manchester. By reviewing the distribution of demographic characteristics, clinical features and exposures associated with cases within each WGS cluster, we found that MPCs were associated with different regions of England, different areas of London and specific households. This was only apparent following analysis of the WGS data and might reflect heterogeneity in terms of exposures between different groups within the OJC. Interventions could be further tailored to these communities by better understanding such heterogeneity.We investigated an outbreak of laboratory-confirmed cases of S. sonnei among the OJC support those from previous retrospective application of this typing approach for an outbreak amongst the same population in 2011 [Historically, attempting to find common epidemiological factors amongst OJC cases, that were erroneously linked or not linked by phage typing, hindered outbreak investigations by distorting any association between exposure and illness. Findings from this prospective application of WGS during an outbreak of  in 2011 . ResultsS. sonnei in the rest of the UK population, and clustered more closely with publicly available sequences from strains of S. sonnei isolated in Israel . The phn Israel . Global n Israel . The temn Israel . Despiteo Israel .S. sonnei were confounded by the lack of a robust typing scheme. With the advent of WGS, we now have access to a molecular typing method that has utility for outbreak detection and investigation. The level of discrimination exhibited by WGS facilitates the identification of clusters of isolates within closely related bacterial populations circulating in the OJC that may be linked to a unique point source or transmission route, thus enabling more appropriate public health response and targeted interventions. Furthermore, these data enable us to track the emergence and dissemination of specific lineages on a global scale. Sharing of such information could result in the timely reinforcement of direct public health messaging to travellers and high-risk domestic populations in the UK, in order to reduce the number of imported infections and mitigate the effects of imported infections and associated outbreaks.Prior to the implementation of WGS at PHE, public health management of outbreaks of Dallman TJ, Ashton PA, Jenkins C, Grant K. NCBI Short Read Archive PRJNA248042 (2015).