The role of physical violence during pregnancy on receipt of prenatal care is poorly understood, particularly for South Asian countries that have high levels of both fertility and domestic violence. Data from the 1998/1999 Indian National Family Health Survey and a 2002/2003 follow-up survey that re-interviewed women in four states were analyzed, examining the association between physical violence during pregnancy and the uptake of prenatal care. Women who experienced physical violence during pregnancy were less likely to receive prenatal care, less likely to receive a home-visit from a health worker for a prenatal check-up, less likely to receive at least three prenatal care visits, and less likely to initiate prenatal care early in the pregnancy. This study highlighted the constraining effect that the experience of physical domestic violence during pregnancy had on the uptake of prenatal care for women in rural India. Maternal health services must recognize the unique needs of women experiencing violence from their intimate partners. The prevalence of domestic violence varies widely, with approximately 15-71% of women worldwide experiencing some form of violence at the hands of their husbands or male partners -6. The mA large body of literature describes factors associa-ted with and determinants of domestic violence and the intersection of such violence with negative reproductive health outcomes ,8-15. HoWomen may experience violence at any point in their lives. Although there is no conclusive evidence that the risk of domestic violence escalates during pregnancy -23, it iWomen who experience domestic violence are at an increased risk of many reproductive disorders, such as chronic pelvic pain and sexually transmitted infections ,25. TheiOne possible mechanism by which violence during pregnancy could be associated with negative pregnancy outcomes is through a constraining effect on women's use of preventative or curative health services during pregnancy ,36. StudResults of studies also indicate that women who experience physical violence from an intimate partner are likely to delay the initiation of prenatal care ,19,36-38Although rates of domestic violence and fertility are high in South Asia, very little information is available to quantify the impact of domestic violence during pregnancy on maternal healthcare-seeking behaviours. This analysis examined the association between experience of physical domestic violence during pregnancy and the uptake of prenatal healthcare in four culturally-contrasting Indian states: Bihar, Jharkhand, Maharashtra, and Tamil Nadu. Standards of living, health indicators, and the status of women vary widely among the four states. Indicators of female autonomy, such as rates of female education, are substantially better in Tamil Nadu (78%) and Maharashtra (76%) than in Bihar (38%) and Jharkhand (41%) . DevelopThis study assessed the effect of physical domestic violence on prenatal care-seeking behaviours in these four states using data collected from the two surveys.Data for this analysis were drawn from a prospective follow-up survey of women who responded to the Indian National Family Health Survey (NFHS) 2 conducted in 1998/1999.The NFHS 2 sample covered 99% of India's popu-lation residing in all of its states and ultimately included 89,199 women of reproductive age . The surData for current analyses were drawn from a pros-pective follow-up survey of original NFHS 2 res-pondents conducted by the International Institute for Population Sciences (IIPS) and the Johns Hopkins Bloomberg School of Public Health in 2002/2003. The sampling frame for the follow-up survey consisted of all respondents interviewed in the original NFHS 2 survey in four Indian states: Bihar, Jharkhand, Maharashtra, and Tamil Nadu. These states were selected to represent differing demographic and socioeconomic contexts in India. The follow-up sample was restricted to rural married women aged 15-39 years at the time of the NFHS 2 interview and who were usual residents of the household at that time. This sample was selected to facilitate the research interests of the survey organizers, which included the relationship between quality of family-planning service and subsequent contraceptive-use and the predictive validity of stated fertility intentions. The follow-up sample included 6,243 women. Re-interview rates were high in all the four states, ranging from 76% in Maharashtra to 94% in Tamil Nadu. A team of 63 female interviewers who had graduate degrees collected data for the follow-up survey. Extensive interview training and field practice were carried out in each state.The sample used in this analysis was further restricted to women who had at least one birth during the period between the 1998/1999 NFHS 2 survey and the 2002/2003 follow-up survey. This sample included 2,877 women aged 19-43 years.The survey instrument included questions pertaining to the respondent's background characteristics, reproductive behaviour and intentions, quality of family-planning care, use of family-planning methods and services, an event calendar covering the intervening months between the baseline (NFHS 2) and the follow-up survey , prenatal care and immunization, women's status, premarital pregnancyplanning, and domestic violence.The section of questions on domestic violence explored the respondent's lifetime and recent experience of domestic violence. Following the ethical recommendations of the World Health Organization that only one family member per household be interviewed , the youFour outcomes characterizing the respondent's maternal healthcare-seeking behaviour during her most recent pregnancy were examined in relation to her experience of domestic violence. The four outcomes included: (a) receipt of any prenatal care as indicated by the respondent's answer to a question asking whether or not she went for a prenatal check-up during her most recent pregnancy; (b) receipt of a home-visit from a health worker for a prenatal check-up; (c) receipt of three or more prenatal care visits throughout the duration of the most recent pregnancy as recommended by the Indian Reproductive and Child Health Programme; and (d) the trimester in which prenatal care was initiated. Receipt of prenatal care was modelled for the full sample of 2,877 women while the remaining three outcomes were modelled for a subsample of 1,340 women who received any measure of prenatal care during their most recent pregnancy.The exposure variable of interest for this analysis was the report of physical violence during the most recent pregnancy. All women who responded to the follow-up survey were asked to estimate the number of violent episodes that occurred during their most recent pregnancy. However, the number of women who reported more than one episode of violence was small enough to prevent the estimation of an odds ratio based on count data. Therefore, the exposure variable used in this analysis is binary and coded as positive for women who experienced any violent act asked about on the survey on at least one occasion during her most recent pregnancy.Statistical models were fitted for each of the four outcomes. Logistic regression models were fitted to the three binary outcomes of interest . A multi-nomial regression model was fitted to the categorical outcome . Each model controlled for demographic and socioeconomic characteristics known to be associated with receipt of prenatal care and thought to be potentially confounding in the relationship between violence and prenatal care: age, educational attainment, religious affiliation, ethnicity, employment status of respondents, household standard of living, and parity. Control variables were selected based upon their independent associations with experience of domestic violence and/or receipt of prenatal care. The authors also conducted appropriate tests for interactions among the variables and tests for confounding relationships, none of which proved to be significant. All analyses were conducted using the Stata statistical software (version 9.0).The ethical review committees at the International Institute for Population Sciences and the Johns Hopkins Bloomberg School of Public Health reviewed and approved the follow-up survey protocol and all the survey instruments.Women who experienced physical violence during their most recent pregnancy were less likely to receive any measure of prenatal care , less likely to receive a home-based prenatal check-up from a trained health worker , and less likely to receive three or more prenatal care visits  . CompareDomestic violence represents a significant public-health problem in resource-poor countries. Although progress has been made in documenting the prevalence of domestic violence and examining its contextual determinants, the mechanisms by which such violence affects maternal and child health are not well-understood. Domestic violence may lead to increased perinatal or neonatal morbidity and mortality directly through physical trauma or indirectly through increased stress on the mother during pregnancy ,33,34. AThe reported prevalence (23%) of physical violence during pregnancy in this sample is substantially higher than estimates of exposure to physical violence during pregnancy in other parts of the world -44. HoweThe results of this analysis indicate a strong relationship between the experience of physical violence during pregnancy and constrained maternal healthcare-seeking behaviour. Compared to women who did not experience violence, women in this analysis, who experienced at least one violent episode during their most recent pregnancy were 20% less likely to receive prenatal care and nearly 60% less likely to receive a home-based prenatal check-up from a trained health professional. They were also less likely to receive three or more prenatal care visits and more likely to begin prenatal care late in pregnancy. Decreased access to and/or use of maternal health services during pregnancy may prohibit women from obtaining necessary preventive or curative treatment that could improve their health and the health of their children.Among the outcomes examined in this analysis, the greatest disparity between women who experienced physical domestic violence during pregnancy and those who did not was observed in the receipt of home-based prenatal check-ups from health workers. Only 26% of women who experienced violence during pregnancy received a prenatal care visit from a health worker at their home compared to 50% of women who did not report violence. There are a number of possible explanations for this discrepancy. Lack of mobility due to controlling behaviour from a partner may limit the involvement of a woman in the community, thereby decreasing the likelihood that local health workers would be aware of her pregnancy. Even if the pregnancy were recognized, a partner's controlling behaviour may limit the ability of a health worker to visit the woman at home. Although domestic violence is recognized as a criminal offence in India, this widespread problem is largely tolerated. Reporting violence, or discussing it with a health worker, may lead to more violence. Finally, uneducated women and women belonging to scheduled tribes were especially unlikely to receive a prenatal check-up at home from a health worker, indicating that social structures and community-level factors may also affect service-provision patterns.Despite this difference in type of service, women who experienced violence during pregnancy received prenatal care at a rate similar to women who did not report violence. Forty-four percent of women who reported violence received some measure of prenatal care as did 50% of women who did not report violence. This suggests that women who experience violence during pregnancy do not abandon maternal healthcare altogether but may seek or receive care from alternate sources. For example, women who experience domestic violence may be more likely to seek prenatal care from untrained providers, such as traditional birth attendants or family members. Additional research is needed to better understand how women who experience violence during pregnancy seek prenatal care.Many studies have focused on the inclusion of violence screening during provision of maternal health services ,48. The Two potential limitations of this study should be noted. The first limitation of this analysis is our inability to know the exact temporal relationship between violence and prenatal care during pregnancy. From these data, we are unable to determine whether the violence occurred before or after prenatal care described. However, this study represents an improvement over previous work as we know that the violence and prenatal care reported were occurring within the same pregnancy. The second limitation concerns our reliance upon self-reports of domestic violence. The high level of social acceptance and limited repercussions for perpetrators of domestic violence in this setting  lead us Given the undeniable impact of domestic violence as a public-health problem in this setting, understanding the relationship between experience of violence and negative health outcomes is critical for the development of appropriate prevention strategies and maternal health services that are responsive to the needs of women experiencing violence. Levels of maternal and child morbidity and mortality remain high in India despite decades of programmatic efforts to improve the health of these populations. This analysis provides support for continued efforts to reduce levels of domestic violence through channels such as public education, legal reform, and community action, as a means to reducing morbidity and mortality among both these groups.The study was funded by the National Institute of Child Health and Human Development (Grant No. R01HD039405).


Despite well-articulated benefits, the introduction of Nurse Practitioners (NPs) in Australia has been slow. Poorly defined nomenclature relating to advanced practice roles in nursing and variations in such roles both across Australia and worldwide have resulted in confusion and uncertainty regarding the functions and roles of NPs. Qualitative studies focussing on the perceived impact on the care settings into which NPs are introduced are scarce, but are valuable in providing a complete contextual account of NPs in care delivery settings. This study aimed to investigate the perceived impact of the NP on the delivery of care in the ED by senior doctors, nurses, and NPs. Results will facilitate adoption and best use of this human resource innovation.A cross-sectional qualitative study was undertaken in the Emergency Departments (EDs) of two large Australian metropolitan public teaching hospitals. Semi-structured, in-depth interviews were conducted with five nurse practitioners, four senior doctors  and five senior nurses. Transcribed interviews were analysed using a grounded theory approach to develop themes in relation to the conceptualisation of the impact of the NP role on the ED. Member checking of results was conducted by revisiting the sites to clarify findings with participants and further explore emergent themes.The impact of the NP role was perceived differently by different groups of participants. Whilst NPs were observed to deliver few quantitative improvements to ED functioning from the perspective of ED directors, NPs believed that they assisted doctors in managing the increasing subacute presentations to the contemporary ED. NPs also believed they embraced a preventative paradigm of care which addressed the long term priorities of chronic disease prevention and cost containment in the broader healthcare environment. The ambiguous position of the NP role, which crosses the gap between nursing and medicine, emerged and resulted in a duality of NP governance.Interpretation of the NPs’ role occurred through different frames of reference. This has implications for the development of the NP role in the ED. Collaboration and dialogue between various stakeholders, such as ED doctors and senior nursing management is required. Originating in the 1960s in the United States, Nurse Practitioners (NPs) are advanced practice nurses who have completed additional training beyond that of a registered nurse . The NP Qualitative studies focussing on clinician perceptions and understandings of the NP role, as well as the perceived impact on the care settings into which they are introduced, are scarce. These types of studies are necessary because they add information beyond identifying and quantifying the prevalence of a particular view. One qualitative study which entailed interviews with nine key stakeholders undertaken by Tye  in a LonThere are grounds for believing that different professional perspectives are indicators of distinguishable frames of reference. A frame of reference is “a built-up repertoire of tacit knowledge that is used to impose structure upon and impart meaning to otherwise ambiguous social and situational information to facilitate understanding” . Frames What do senior doctors, nurses, and NPs perceive to be the impact of NPs on the delivery of care in the ED?A qualitative study using in-depth semi-structured interviews of NPs, senior doctors and senior nurses from Emergency Departments in two large Australian metropolitan public teaching hospitals was undertaken Table . QualitaFourteen semi-structured interviews Table  were undInterviews undertaken were semi-structured with no pre-coded response categories. The interview questions were designed to introduce a broad theme for exploration and discussion with the participant. Questions were phrased differently to take account of the different clinical roles of those being interviewed , howeverA document outlining the study, its voluntary nature, confidentiality of results and participants, and a consent form were witnessed and signed by participants. An opportunity to raise queries related to the study was also presented at this time. Participants were recruited via email and approached personally in the department when email contact failed. Interviews with senior doctors and nurses regarding their understanding of the NP role were triangulated with data from NPs.A grounded theory approach using thematic content analysis was employed to derive themes. Grounded theory refers to the process of inductively developing theory from systematically gathered and analysed data . InductiNPs, senior doctors and senior nurses perceived a range of changes to the overall functioning of the ED following the introduction of NPs Table . Nurse UED directors at both sites expressed a significantly different view to that of NPs. ED directors perceived that the number of NPs employed in the ED was statistically insufficient to effect any real improvement to patient flow. Further, whilst their contribution to primary care was acknowledged, one Director questioned the cost-effectiveness of NPs in the time-sensitive ED environment where he perceived NPs could not match the patient throughput achieved by a junior doctor despite the greater cost of such positions. ED directors also observed on occasions the non-clinical aspect of the NP role preventing NPs from taking a “frontline” approach to care. Specifically, directors reported that NPs may spend considerable time in an office when the ED floor is especially busy. Directors identified this as a governance issue as they were not administratively responsible for the NPs and were excluded from negotiating the mix of NP responsibilities which were under the governance of the Director of Nursing. However, it was conceded that whilst junior doctors were largely transient, NPs contributed to increasing the pool of permanent staff in the ED. Further, Directors at both sites questioned the future of NPs in metropolitan EDs in the advent of an anticipated influx of medical graduates in Australia.Senior doctors and nurses agreed that the NP role had changed the task mix of doctors in relieving their subacute workload Table . NPs andSenior doctors, nurses and NPs agreed that NPs embraced a more holistic model of patient care Table . Senior NPs felt that they were part of a prominent shift in clinical decision-making from the clinician to the patient and an increased emphasis on preventative health and health promotion, advocating patient education and self care. Additionally, NPs reported that they were more facilitative of patient involvement in care-based decision-making and a team-based approach to care that is traditionally dominated by the perspective of a single doctor. NPs expressed frustration at what they felt was a consistent judgement of their practice against doctor-provided, or “gold standard” of care. They argued that the NP model of care rather complemented doctors’ practices to address changes in consumer demands and the nature of care delivered in the contemporary metropolitan ED. One ED Director stressed the importance of adherence to established scopes of practice to recognise that the NP was an independent practitioner who was nevertheless part of a multidisciplinary team.Our study found that senior doctors and nurses, and NPs expressed differing views on the impact of NPs on care delivery. NUMs were positive about NPs’ effects on ED functioning, believing that they improved patient throughput and contributed to alleviation of patient waiting times. NPs felt that they were ideal candidates for addressing the shifting nature of the ED from a purely acute care setting to an increasingly subacute treatment source. In contrast, ED directors questioned the ability of a very small number of NPs to deliver efficiencies which resulted in tangible improvements. Further, ED directors reported observing NPs prioritising office-based, non-clinical tasks over frontline care delivery during busy shifts.A shift in the subacute workload from doctors to NPs was observed by NPs, senior doctors and nurses. Nurses and NPs reported a positive NP influence on their nursing peers in the form of empowerment, education and role modelling for advanced practice career pathways. All respondents agreed that NPs adhered to a more holistic care paradigm whilst NPs challenged the validity of doctor-provided care as the established “gold standard” of medicine over the merits of consumer empowerment and a preventative care paradigm.Studies have quantified clinician perceptions and understandings of the NP role when evaluating NP implementation and service delivery through structured surveys ,26. WhilAdopting a macro view in their assessment, physician ED directors questioned the measurable impact of NPs as they are such a small portion of a large total ED workforce. Another concern they had was the cost-effectiveness and validity of the relatively more time-consuming preventative model of care adopted by NPs in a highly time-sensitive care setting where focus was on expedient patient movement through the department. However, drawing from a front-line perspective, senior nurses perceived NPs as pivotal in maintaining consistent patient flow through the department and relieving extensive wait times for the increasing numbers of low-acuity ED presentations. A number of studies have shown that NPs and doctors have similar levels of health outcomes and resource use ,27-36, aNPs perceived the contribution of NP practice lay in its accommodation of both the changing nature of consumer demand on the contemporary ED, as well as a general shift in care paradigm within the broader healthcare environment. In addition to the traditional role of providing urgent and life-saving treatment, the emergency care system now provides primary care services to an increasing number of patients who cannot access alternative services . ChangesED directors from both sites observed that, at times during periods of peak patient flow, NPs were removed from front-line clinical work by the non-clinical aspect of their role. Whilst NPs practised autonomous management of presentations within specific scopes of practice and were clinically responsible to the ED director, the Director of Nursing retained administrative governance over the NP position and determined task mix. Duality of NP governance appears reflective of the ambiguous position of the NP’s role between nursing and medicine. These ambiguities are best addressed through dialogue and collaboration between relevant medical and nursing representatives, as conflicting demands and priorities from multiple sources of management can create problems .Discrepancies in the role and function of NPs across sites and States limit generalisability of results beyond the study sites. The small sample of NPs is also reflective of the still limited availability of NPs. As our intention was to undertake in-depth interviews, the total number of interviews was modest. A larger sample of staff working with NPs in a future study would be important in validating our findings.The impact of the NP role in the ED was perceived differently by different groups of participants. The results demonstrate a misalignment of frames with implications for further development of the NP role. Reconciliation of perceptions of the role of the NP is essential to ensure that they achieve their desired goal of improving patient outcomes and efficiencies within the ED.The authors declare that they have no competing interests.JL, JW, JC and AG contributed to the conceptualisation and design of the study. JL undertook data collection, analysis, and drafting of the manuscript. JW, JC, AG and JB contributed to results interpretation and critical revision of the manuscript. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1472-6963/13/356/prepub


The Galeazzi fracture-dislocation was originally described by Sir Astley Cooper in 1822 but was named after Italian surgeon Ricardo Galeazzi in 1934. It is an injury classified as a radial shaft fracture with associated dislocation of the distal radioulnar joint and disruption of the forearm axis joint. The associated distal radioulnar joint injury may be purely ligamentous in nature, tearing the triangular fibrocartilaginous complex, or involve bony tissue  or both. We report this case because of the rare association of posterior dislocation of the elbow along with Galeazzi fracture-dislocation. To the best of our knowledge, this has not been previously reported in the English literature.A 26-year-old Caucasian man presented to our department after a fall from a motorbike. He sustained a closed, isolated Galeazzi fracture-dislocation of the right forearm and no associated elbow injuries, and this necessitated open reduction and internal fixation of the radius. Post-operative radiographs films were satisfactory. However, clinical and radiological evidence of ipsilateral elbow dislocation was noted at a five-week follow-up, subsequently requiring open reduction of the joint and collateral ligament repair. Our patient was noted to have full elbow and forearm function at three months.Although the Galeazzi fracture-dislocation has been classically described as involving only the distal radioulnar joint, traumatic forces can be transmitted to the elbow via the interosseous membrane of the forearm. This can lead to instability of the elbow joint. Therefore, we recommend that, in every case of forearm fracture, both elbow and wrist joints be assessed clinically as well as radiologically for subluxation or dislocation. Fractures of the distal third of the radius which are associated with acute distal radioulnar joint (DRUJ) dislocations are known as Galeazzi fracture-dislocation . OriginaA 26-year-old Caucasian man presented to our department with an isolated right forearm injury, which he sustained after falling off his motorbike. His main complaint was of a painful and clinically deformed right forearm. A clinical examination revealed a closed and neurovascularly intact injury with bony tenderness and inability to move the right forearm. Radiographs showed a comminuted fracture of the right shaft of the radius  with an associated DRUJ dislocation but no evidence of elbow dislocation Figure .Our patient underwent open reduction and anatomic fixation of the distal radius fracture with a compression plate via a standard volar Henry approach. His elbow range of movement was checked immediately after fixation, and radiographs confirmed the elbow to be in joint. His elbow had been asymptomatic before the operation and so was not formally tested for instability. After the operation, the limb was rested in a long arm cast with the elbow in 90° of flexion and the forearm in a mid-prone position. The wound was checked at two weeks and was noted to be healing satisfactorily.The splint was removed at five-week follow-up, and the elbow joint was clinically and radiologically noted to be posteriorly dislocated Figure . Our patFractures of the distal third of the radius usually are associated with dislocation or instability of the DRUJ or both and commonly are referred to as Galeazzi fracture-dislocation. The usual mechanism of injury is a fall on an outstretched hand with a pronated forearm at the time of injury. The radius and ulna are parallel bones that are tightly constrained both proximally and distally. As a result, any disturbance in the length of either bone must affect the proximal or distal radioulnar joints or the stability of the elbow joint. The fracture-dislocation injury pattern is dictated largely by the magnitude of the deforming forces imparted and also the position of the upper limb at the time of injury .Although Galeazzi fracture-dislocation historically has been considered a combination of distal radius fracture and DRUJ dislocation, other associated injuries have been described in the literature. Soon and colleagues  1995) d d5]  that can spontaneously reduce. Stage 2 includes further disruption resulting in an incomplete posterolateral elbow dislocation with X-rays demonstrating the coronoid process 'perched' on the humeral trochlea. This can be reduced with minimal force. Stage 3 is subdivided into two components. In stage 3A, the posterior part of the medial collateral ligament and all of the soft tissues around it are disrupted whereas the anterior portion, or bundle, is spared. This bundle forms the pivot around which the elbow dislocates posteriorly by way of a posterolateral rotatory mechanism. Stage 3B features complete disruption of all components of the medial collateral ligament complex of the elbow .We speculate that the initial injury in our case not only caused a fracture of the radius but also damaged various capsulo-ligamentous stabilizers of the ipsilateral elbow joint and resulted in posterolateral instability. Although initial radiographs and intraoperative fluoroscopy failed to reveal any elbow instability, we feel that, after fracture fixation and resolution of any soft tissue swelling, the elbow joint dislocated posteriorly.The patho-mechanics producing both Galeazzi fracture-dislocation and posterior dislocation of the ipsilateral elbow are strongly correlated. The capsulo-ligamentous structures of both elbow and radioulnar joints are often adversely affected in these types of injuries. We conclude by emphasizing the importance of regular clinical and radiological examinations of both radioulnar and elbow joints in isolated Galeazzi-type fractures.DRUJ: distal radioulnar joint.Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.The authors declare that they have no competing interests.AR prepared the manuscript. SS performed clinical follow-up of the patient and edited the manuscript. JH conducted the surgical management of the patient. All authors read and approved the final manuscript.


Burkitt lymphoma (BL) and diffuse large B cell lymphoma (DLBCL) are aggressive forms of lymphoma in adults and demonstrate overlapping morphology, immunophenotype and clinical behavior. The risk of developing these tumors increases ten to hundred-fold in the setting of HIV infection. The genetic causes and the role of specific mutations, especially in the setting of HIV, are largely unknown.The decoding of the human genome and the advent of high-throughput sequencing have provided rich opportunities for the comprehensive identification of the genetic causes of cancer. In order to comprehensively identify genes that are recurrently mutated in immune-competent DLBCL and BL, we obtained a total of 92 cases of DLBCLs and 40 cases of BL. These cases were compared to a set of 5 DLBCLs and BL tumors derived from patients with HIV. The DLBCL cases were divided into a discovery set (N=34) and a prevalence set (N=61). The Burkitt cases were also divided into discovery and prevalence sets . For each of the discovery set cases we also obtained paired normal tissue. We performed whole-exome sequencing for all of these using the Agilent solution-based system of exon capture, which uses RNA baits to target all protein coding genes (CCDS database), as well as ~700 human miRNAs from miRBase (v13). In all, we generated over 6 GB of sequencing data using high throughput sequencing on the Illumina platform.We identified a total of 432 genes that were recurrently mutated in DLBCL and BL. We found that each tumor had an average of 20 gene alterations, which is fewer than most other solid tumors sequenced to date. Commonly implicated biological processes comprising these genes included signal transduction , immune response  and chromatin modification . We found that lymphomas that arose in the setting of HIV had fewer mutations overall and had a paucity of mutations related to immune response.These data implicate the depressed immune response by HIV as a contributing risk factor for the development of lymphomas and suggest that HIV lymphomas are genetically less complex than their immune competent counterparts. This study represents one of the largest applications of exome sequencing in cancer, and provides early clues to the genetic causes of HIV-lymphomas.


Synovial sarcoma is a rare malignant neoplasm of soft tissue that typically arising near large joints of the upper and lower extremities in young adult males. Only 3% of these neoplasms have been found to arise in the head and neck region. To our knowledge, there are limited reports in the literature of this neoplasm in the cervical spine.A case of biphasic synovial sarcoma of the cervical spine is reviewed. A 29 year-old male presented with pain on the left side of the cervical spine. Physical examination revealed a global loss of cervical motion and large, palpable mass in the left paravertebral area. The long-delayed Magnetic Resonance (MR) scan revealed a soft tissue mass measuring 8.3 centimeters (cm) × 5.7 cm that was surgically removed. A malignant biphasic synovial sarcoma was diagnosed on pathologic examination.The clinical and imaging findings of an atypically located synovial sarcoma are reviewed. This case report emphasizes the consequences of a limited differential diagnosis, prolonged treatment and the failure to perform timely diagnostic imaging in the presence of a paraspinal mass. Synovial sarcoma is a seldom encountered, aggressive malignant neoplasm of soft tissue that typically arises near large joints of the upper and lower extremities in young adults. Synovial sarcomas account for 7-10% of all soft-tissue sarcomas  and justThis paper describes the clinical, radiological and pathological findings of a synovial sarcoma that was located in the lower cervical paravertebral space. Although the radiological and clinical features of a typically located synovial sarcoma are documented in the literature, our review of the literature reveals limited reports of synovial sarcoma arising from the cervical spine .A 29 year-old male presented with muscle discomfort and pain in the posterior left cervical spine, especially after weight lifting. There was no history of recent trauma. Five years prior to presentation, the patient had sustained cervical injuries from a motor vehicle accident. The patient's motor vehicle related cervical spine complaints resolved with manipulation and physical therapy shortly after the accident. The patient recently returned to care and a regional orthopedic and neurological examination was performed with findings of "myofascial trigger points on the left levator scapulae muscle". The patient was diagnosed with "myofascial pain syndrome of the left levator scapulae" and was placed on a course of care that consisted of manipulation, post-isometric relaxation, stretching and "post-facilitated stretching once the trigger points are resolved." No initial imaging studies were performed. The presenting size of the paravertebral "trigger point" was not documented in the record.The patient underwent a course of chiropractic care, which totaled 24 treatments over a 13-month period. The clinical record noted both positive and negative subjective responses to the conservative care. Multiple comments in the chart notes indicated the "trigger point" and "swelling" were worsening during the course of care, but these observations of an enlarging mass were not accompanied by any change in treatment, re-evaluation or additional investigation with any form of diagnostic imaging. The patient eventually discontinued care as the paravertebral mass had steadily grown and was now clearly visible on visual inspection of the area. The subsequent treating clinician ordered a MR scan.MR images with pre and post gadolinium axial and coronal T1 weighted images revealed a complicated mass extending from the C3-C4 level to the T1-T2 level. The coronal MR revealed a septated kidney bean shaped mass with a large portion demonstrating elevated signal intensity on T1 weighted images . One cell type was spindle and the other was epithelial. The spindle cells were similar to fibrosarcoma. The epithelial cells presented as focal glandular formations with clusters and trebeculae. Calcification and ossification, often seen on CT imaging of these tumors, were noted in the pathological study but were never visualized in the imaging studies. The final pathological diagnosis was "synovial sarcoma, biphasic type, intracystic."The prevailing therapeutic approach to high-grade soft tissue sarcomas is wide surgical resection followed by radiation, chemotherapy or both . The patSynovial sarcoma is a malignant neoplasm of soft tissue that typically arises near large joints of the upper and lower extremities in the young adult male, particularly the knee; however, they do not arise from synovial tissue ,8,9 but Presenting clinical symptoms vary according to the size and location of the tumor. Those tumors arising in an extremity may present initially with swelling, pain or tenderness. Limitation in motion may be noted if the tumor is located near a joint. The non-specific nature of the symptoms may initially be interpreted as more commonly encountered soft tissue entities such as bursitis and myositis. The increasing size of the tumor also has the ability to compress nerves and result in the gradual onset of neurological deficits. A high degree of clinical suspicion, along with the observation of gradually developing mass should prompt the use of diagnostic imaging even in the absence of a history of trauma.Synovial sarcoma of the spine is quite uncommon and early diagnosis may be difficult without advanced imaging. The tumor may cause a variety of symptoms, again depending on the size and location of the mass. Neurological compromise is also possible with tumors located near the spine. A case of paravertebral synovial sarcoma in the lumbar spine was noted to produce a grade III weakness in dorsiflexion in the right great toe and decreased sensation of the L4-5 dermatome . A palpaSynovial sarcoma occurs in 2 histological subtypes: the biphasic form contains elements of both epithelial and spindle cells and the monophasic type contain only spindle cells .Synovial sarcomas may aggressively grow and imaging studies have shown they vary in size between 2 and 9 cm ,12. DeteSynovial sarcomas are usually treated aggressively with wide excision with negative margins, often including removal of adjacent muscle groups and even total amputation ,13. LimiThis case demonstrates the ever-present potential for an uncommon condition to present in an atypical location in the ambulatory outpatient setting. This patient would have benefitted from earlier diagnostic imaging and consultation with other practitioners when the patient began to develop a paraspinal mass. Although rare, synovial sarcomas and other forms of soft tissue tumor should be included in the differential diagnosis of paraspinal masses in patients, irrespective of their response to conservative care.Written informed consent was obtained from the patient for publication of this Case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.The authors declare they have no competing interests. SMF was involved in this case as a consultant for the patient after the tumor had been resected.SMF conducted the initial review of the case and prepared the first draft of the manuscript. MJS participated in the conception of the report, the revision and coordination of the final manuscript. Both authors read and approved of the final manuscript.


This article looks at the steady flow of Micropolar fluid over a stretching surface with heat transfer in the presence of Newtonian heating. The relevant partial differential equations have been reduced to ordinary differential equations. The reduced ordinary differential equation system has been numerically solved by Runge-Kutta-Fehlberg fourth-fifth order method. Influence of different involved parameters on dimensionless velocity, microrotation and temperature is examined. An excellent agreement is found between the present and previous limiting results. Understanding the flow of non-Newtonian fluids is a problem of great interest of researchers and practical importance. There are several natural and industrial applications of such fluids, for instance volcanic lava, molten polymers, drilling mud, oils, certain paints, poly crystal melts, fluid suspensions, cosmetic and food products and many others. The flow dynamics of non-Newtonian fluids can be described by non-linear relationships between the shear stress and shear rate. Further these fluids have shear dependent viscosity. In literature there exist many mathematical models with different constitutive equations involving different set of empirical parameters. The micropolar fluid model is adequate for exocitic lubricants, animal blood, liquid crystals with rigid molecules, certain biological fluids and colloidal or suspensions solutions. The micromotion of fluid elements, spin inertia and the effects of the couple stresses are very important in micropolar fluids During the past few decades, several researchers have concentrated on the boundary layer flows over a continuously stretching surface. This is because of their in several processes including thermal and moisture treatments of materials in metallurgy, in the manufacture of glass sheets, in textile industries in polymer processing of chemical engineering plants. Further the stretching flow with heat transfer is quite important in polymer extrusion, cable coating etc. The boundary layer flow of a viscous fluid over a stretching sheet was initially studied by Crane To the best of authors’ knowledge, the flow of micropolar fluid over a stretching sheet with heat transfer in the presence of Newtonian heating has not been addressed so far. The resulting problems are solved numerically and solutions obtained are compared with the existing results. It is found that the present results are in a very good agreement. Variations of several pertinent physical parameters are also analyzed in detail by plotting graphs.We consider the steady boundary layer flow of an incompressible Micropolar fluid induced by a stretching surface. The sheet is stretched with a velocity The boundary conditions of the present problem are Here Introducing above Eqs. (6) into Eqs. (1)–(5) one hasThe skin friction coefficient Now using Eqs. (6) and (14) into Eq. (13) we haveThis section the effects of different parameters on the velocity, microrotation and temperature profiles , and 6. The present study describes the boundary layer flow of Micropolar fluid with Newtonian heating. The main observations of this study are:Velocity and momentum boundary layer thickness are increasing functions of vortex viscosity parameter Microrotation profile has a parabolic distribution when The effect of vortex viscosity parameter Temperature and thermal boundary layer thickness are decreasing functions of vortex viscosity parameter An increase in the value of Prandtl number The present results in a limiting case An appreciable increase in the magnitude of The temperature profiles are also increased by increasing


Although a previous study found high risk of breast cancer in mothers of children with soft tissue sarcomas, breast cancer risks in mothers of sufferers of other childhood cancers largely remain unknown. The aetiology is not fully understood. The present study explored this excess by varying type of childhood solid cancer and formulated a hypothesis.Mothers of 2668 children with solid tumours included in the Manchester Children’s Tumour Registry, 1954–96, were traced and followed up to 31 December 2000 through the UK National Health Service Central Register. Standardized incidence ratio (SIR), p-values and 95% confidence intervals were calculated from age and calendar-year-specific female breast cancer incidence rates for England and Wales.There was a significant excess of breast cancer in mothers overall  mainly due to mothers of children with rhabdomyosarcoma (RMS) , skin cancer  and central nervous system tumours . Maternal breast cancer risk was associated with late age at birth of the index child, and male sex and young age at diagnosis in the index child. Risk was highest in the ten years, following the birth of the index. The pattern was seen most strongly in mothers of children with embryonal RMS.There are excesses of breast cancer in mothers of children with solid tumours in general and specifically in RMS, skin and central nervous system (CNS). There appears to be a temporal relationship between certain tumours in children and breast cancer in their mothers, suggesting an origin of their respective pregnancy. We propose a mother–foetal interaction mechanism to explain this association. Since a twofold increased risk of breast cancers among first degree relatives of children with soft tissue sarcomas was reported , 2, it hThe mothers of 2668 children with histologically confirmed solid tumours diagnosed younger than 15 years of age, who were included in the Manchester Children’s Tumour Registry (MCTR) between 1 January 1954 and 31 December 1996 were eligible. The ascertainment procedure and the follow-up procedure have been described in detail elsewhere , 12 and Expected numbers of breast cancers were calculated from serial age-specific female breast cancer incidence for England and Wales, from 1971 onwards, applied to the similarly defined arrays of person-years at risk generated by the data. National rates were used rather than north-west England regional rates to allow for migration of families out of the region during the lengthy follow-up period. All population data were supplied by the Office for National Statistics, London, UK. For earlier years at risk, the incidence rates for 1971 were used to calculate expected numbers. To calculate the risk of carcinoma of the breast, mothers entered the person-years at risk on the date of birth in the index child and left the person-years at risk on the date of diagnosis of carcinoma of the breast, date last known to be alive, date of embarkation from the UK, date of death, or the closing date of the study, whichever was the earlier. Two-sided p-values and 95% confidence intervals (CI) of standardized incidence ratios (SIRs) were computed on the assumption the observed numbers followed a Poisson distribution. All analyses have been carried out using Stata .Separate analyses were initially performed for groups of mothers defined by diagnostic group in the index child. In those groups, showing a statistically  significantly elevated SIR, the excesses were explored in more detail by comparing sub-groups defined by characteristics in the children and their mothers according to the following rationale. Germline mutations may lead to earlier ages of cancer onset. We hypothesized that early age of diagnosis in the index child may be a marker for breast cancer risk in the mothers. We therefore analysed breast cancer risks in selected sub-groups of mothers whose children were below the population median age for diagnosis of their respective tumours. Similarly, we conducted analyses of breast cancers by age at diagnosis in the mothers. Factors that may indicate mother–foetal interaction in pregnancy include differences in breast cancer risks in mothers of boys compared with girls  and a teThe mothers of 2345 (88%) were successfully traced and flagged at NHSCR. The reasons for non-trace were due to lack of name/date of birth, adoption, emigration, in prison and in the armed forces.There was no significant excess risk of carcinoma of the breast in mothers of children with osteosarcoma and chondrosarcoma. Therefore, previous findings based on an earlier series from the MCTR were not substantiated in this extended series .In view of our previous findings, mothers of children with embryonal RMS (eRMS) were analysed separately and showed a significant excess of breast cancer .The following diagnostic groups were selected for sub-group analyses of maternal breast cancer risk: eRMS, skin cancer and CNS tumours .For the individual diagnostic group of eRMS in the index, there were significant excesses of carcinoma of the breast in mothers of boys , breast cancer diagnosed under 50 years old , breast cancer in the ten years following birth of the index , and in mothers above 35 years old at birth of the index . In addition analyses by age at diagnosis in the index child showed that mothers of children under median age at diagnosis had a much higher SIR of 7.3  than mothers of children at the median age and above (SIR=0). This was due to mothers of children in the first age quartile at diagnosis . For skin cancer in the index child, there were significant excesses among mothers in all sub-groups. However, markedly higher SIRs were observed for mothers in the first ten years, following the birth of the index and aged 35 years or more at the birth of the index. The population median age at diagnosis of skin cancer is above 60 years. Therefore, no analyses by age of the index case were carried out since all index cases were exceptionally young and located at the extreme lower end of the age distribution. When melanoma and non-melanoma skin cancers were analysed separately, a similar pattern of results was obtained for both groups. For individual diagnostic group of CNS tumours in the index, non-significant SIRs above 1.5 were found for mothers of boys, mothers in the ten years following birth of the index, and mothers above 35 years old at birth of the index. PNET was the only CNS tumour sub-group with a population median age below 15. Analyses of breast cancer in mothers of children with PNET diagnosed below the median age of nine years showed O 8, SIR 1.9 and 95%CI 0.8–3.8.The study indicates that the excess risk of carcinoma of the breast among mothers of children with solid tumours is not uniform across all groups, but is associated with a small number of tumour types and patient characteristics.The observed pattern is seen most strongly in eRMS. There are higher risks in mothers of children with eRMS diagnosed at very young ages, mothers of boys and in the ten years following birth of the index, suggesting an origin of the respective pregnancy. A biologically feasible interpretation would be hormonal mother–foetal interaction in pregnancy in genetically susceptible individuals .This is suggested by higher risks of developing carcinoma of the breast in mothers in the first few years after birth of the index and higher risk in mothers of boys. It is likely that in these children the eRMS originates before birth. It is known that the foetus itself is actively involved in the production and regulation of oestrogen, a hormone that is an established aetiological factor in breast cancer.Risk factors for breast cancer, identified in population-based studies, include early menarche, late menopause, late first full-term pregnancy, and use of exogenous oestrogens. All these factors increase the amount of oestrogen to which the breast epithelium is exposed . To meetThe foetal adrenal cortex also undergoes a process of maturation involving apoptosis (programmed cell death), a basic process in tissue remodelling, to eventually produce the mature adrenal cortex. Apoptosis starts in the 14th week, increases with advancing gestation and is maximal during the first postnatal month .We hypothesize that a germline defect in the foetus in a gene involved in cell-cycle control, apoptosis and tissue development, results in abnormal levels of steroid hormones via aberrant functioning of the foetal adrenal cortex, due to failure of the normal process of apoptosis and maturation.This would explain the observed temporal relationship between pregnancy, birth of the index child, development of tumour in the child and development of breast cancer in the mother. One such gene is TP53.The differences in risks between mothers of boys and girls with eRMS might suggest that the relevant cancer-associated genes in male foetuses are more important in maintaining development and normal functioning of fast growing organs, such as the foetal adrenal cortex than in females. Male foetuses grow faster and males have higher average birth weight but shorter gestations than girls , 20.The striking effects of maternal age at birth of the index child may suggest that timing of pregnancy in mothers is also important. In older women, there may be a greater chance that precancerous changes are present in the breast epithelium. In these circumstances, carrying a foetus with a cancer predisposing mutation may trigger the process of carcinogenesis, and thus accelerate the development of breast cancer, following the birth of the index child. The effect would be even more marked in mothers who carried the same mutation.A practical implication of our model is that the highest risks and earliest ages at onset would be seen in mothers of babies who were mutation carriers and who themselves also carried the mutation. These mothers are predisposed and are also subjected to abnormal exposure to steroids produced by the foetal adrenal cortex, which had failed to mature (apoptosis) in the normal way. Mothers of babies who were mutation carriers would also be at increased risk even though they themselves do not carry the mutation. We would predict that carrier mothers of non-carrier babies and non-parous carriers would have a later age of onset (though still young) than carrier mothers of carrier babies.In this series of eRMS, there was one known case with a germline TP53 mutation, whose mother was also a mutation carrier. In addition, this case had a sister, 15 months older, who carried the mutation. The mother’s breast cancer was diagnosed at age 27 years, 19 months after the birth of the child. Four children with other tumours, ACC, astrocytoma and PNET (2 cases) carried germline TP53 mutations. Their mothers, who were also confirmed mutation carriers, all developed breast cancer seven years or less after the birth of the respective children.The striking excesses of breast cancer in mothers of children with eRMS in the ten years following birth of the index are unlikely to be completely explained by a transient increase in risk of breast cancer following the first pregnancy in mothers. First pregnancy has been reported to be associated with increased risk of breast cancer in the 15 years or less after birth , 22. HowThe observed breast cancer excess is not explained by these potential confounders relevant to the first birth. The results need not be seen as contradictory to the previous findings of transient increase in risks of breast cancer in the first pregnancy since the present study shows that the pregnancy is a crucial period in the development of breast cancer in women. However for the mothers in the present study, the pregnancy with the child who subsequently develops cancer appears to be of greater importance in the development of breast cancer than that with the first child and the striking effects in the mothers observed in the present study might reflect a different aetiology from mothers of children without cancer. The mechanism proposed above, which relates breast cancer risk to peculiarities of adrenal cortex development, might explain the marked excess.Because of the nature of this cancer-registry-based study, retrospective direct measurement of oestrogen levels in pregnancy with the index is not possible. Similarly, access to birth records which may contain other relevant details would require individual written consent, which would be impractical since the births date back to 1939 and many index patients and their mothers have died. Furthermore, it is likely that many records will have been destroyed. However, data on birth weight are available for children with RMS as part of previous family studies. Oestrogens are known to stimulate cell proliferation and represent an important determinant of foetal growth . BirthweWe compared the birthweights of the children with RMS whose mothers developed breast cancer, and index children whose mothers did not, with that of live-born children in the general population. Mean birthweights of index children of mothers with breast cancer and mothers without are 257 and 54 g more than that of the general population, respectively, . Mean birthweights of boys with RMS whose mothers did or did not develop breast cancer are 114 and 27g more than that of male babies in the general population, respectively. Mean birthweights of girls with RMS whose mothers did or did not develop breast cancer are 658 and 75 g more than that in the general population, respectively. There is a trend of decreasing birthweight among index cases whose mothers had breast cancer, index cases whose mothers did not have breast cancer and children in the population. This is consistent with the role of oestrogen in foetal development, and with our hypothesis relating to failure of normal maturation of the foetal adrenal cortex.Interestingly, the present study reported an excess of carcinoma of the breast in mothers of children with skin cancer (melanoma and non-melanoma combined) with the highest excess in the first ten years, following birth of the index (SIR 23.5). Skin cancer is typically an adult-onset cancer and is very rare in children. The median age for sporadic melanoma is 67 and 35 years for familial melanoma. Therefore, all childhood cases are unusual and may be associated with genetic susceptibility. It is known that germline mutations in CDKN2A are the most common cause of inherited susceptibility to melanoma. CDKN2A encodes two proteins via alternate reading frames (ARFs). The p14ARF product, acting via the p53 pathway, can induce cell-cycle arrest or apoptosis. In multi-case melanoma families with mutations affecting p14ARF specifically there appears to be increased risk of breast cancer . This isIn mothers of children with CNS tumours, the present study showed borderline significant excesses among mothers of boys and mothers diagnosed in the ten years following the birth of the index. This might suggest roles of BRCA2 as well as TP53. Biallelic BRCA2 germline mutation carriers do develop childhood brain cancers as recently reported , 10, altIn contrast to an earlier study , we did Considering childhood cancers are rare events, the sample size in our study is relatively large and allows us to carry out stratified statistical analyses. However, non-statistically significant results in certain diagnostic groups in children cannot completely rule out the possibility of increased breast cancer risk due to the aforementioned mechanism. Among other diagnostic groups, the highest point estimate of SIR for breast cancer is in mothers of children with adrenocortical carcinoma (ACC) although statistically not significant due to the small number. Of 12 mothers of children with ACC, two mothers developed breast cancer following birth of the child, compared with an expected number of 0.3. It is thought that ACC originates in the foetal adrenal cortex, that is an abnormality in the process of cell proliferation and programmed cell death during adrenal development. Furthermore, germline mutations in TP53 have been found among the majority of ACC cases in a number of studies , 30.In this population-based study, a near complete ascertainment of children with solid tumours in a well-defined geographical area was achieved, and the case children included in the study were representative of all the case children in the corresponding population series. Therefore, the present study is unlikely to be subject to ascertainment bias due to notification of severely affected families or the knowledge of family history of cancer in surviving cases only. Neither can the excesses be explained by the bias due to the follow-up procedure, because the majority of mothers were successfully traced and there are no reasons to believe that the causes of non-trace are influenced by occurrence of breast cancer.The study is free of reporting bias because all data were obtained from population registries rather than self-reports, that is both breast cancer in mothers and childhood cancers were derived from population-based data. However, another possible bias worth mentioning is the ‘healthy mother effect’, by analogy with the healthy worker effect, that is mothers may experience a lower breast cancer risk than those non-parous women in the general population.Childbearing has been demonstrated to be associated with decreased breast cancer risk in human and animal studies due, in part, to the pregnancy-specific hormone, chorionic gonadotropin (hCG) . The conIn conclusion, the study confirms and extends the previous findings of a temporal relationship between embryonal RMS in children and breast cancer in their mothers. We propose a hypothesis to explain these observations and suggest a possible mechanism. This mechanism may also be operating in mothers of children with other types of cancers. The present study points to pregnancy as the critical period, when mothers and children are physiologically linked. Germline mutations to cancer-associated genes, inherited or de novo might play an important role. Germline mutations might commonly target the p53 pathway affecting tissue remodelling in the foetal adrenal cortex, not just a single gene within that pathway. The pathway may be disrupted by a germline mutation within the TP53 gene itself, as well as p14ARF, BRCA1 and BRCA2, etc. Further studies of aetiology of breast cancer in mothers of children with cancer incorporating genetic/molecular measurements including mutation screening of cancer-associated genes will be useful in exploring this hypothesis. This is feasible as tissue banks and appropriate genetic techniques become available. The study may help to define periods of highest risk to enable health interventions aimed at reducing mortality from breast cancer in susceptible women.


Although some preliminary work has revealed the potential transcriptional regulatory function of the introns in eukaryotes, additional evidences are needed to support this conjecture. In this study, we perform systemic analyses of the sequence characteristics of human introns. The results show that the first introns are generally longer and C, G and their dinucleotide compositions are over-represented relative to other introns, which are consistent with the previous findings. In addition, some new phenomena concerned with transcriptional regulation are found: i) the first introns are enriched in CpG islands; and ii) the percentages of the first introns containing TATA, CAAT and GC boxes are relatively higher than other position introns. The similar features of introns are observed in tissue-specific genes. The results further support that the first introns of human genes are likely to be involved in transcriptional regulation, and give an insight into the transcriptional regulatory regions of genes. Protein coding genes in eukaryotes contain multiple introns that are cut off in RNA splicing process The characteristics of human introns have attracted considerable attention The CpG island is also known to be involved in transcriptional regulation of genes. Generally, unmethylated CpG islands are the binding sites of some important transcription factors (TFs), such as Sp1 Transcriptional regulatory elements in many genes consist of several essential motifs In this paper, we focus on investigating the intron features associated with transcriptional regulation in human genes. In order to systematically obtain the rational results, we analyze intron features not only in the entire sample genes, but also in introns of tissue-specific (TSP) genes, additionally. Firstly, we compare the intron length in various ways and find that the first introns are generally longer than other introns, consistent with the previous studies A C++ script was written to extract data from NCBI Genbank database (builder 36.2). Only genes with transcript and coding sequence (CDS) features were utilized. Intron lengths were inferred according to the mRNA location information. Since some genes have multiple transcripts , we only retained one transcript feature to avoid duplicate identification of introns for the identical genes. Thus a set of about 185,000 introns were obtained from 19770 intron-containing genes. In order to compare the intron features better, sampled introns were classified by two ways. The first classified pattern is ‘first introns’ which contain all the first introns and ‘non-first introns’ in which all other introns are classified into the same group. The second way is to classify introns based on their position specificity in genes .We retrieved the TSP genes from the HugeIndex database The characteristic length  between all sampled first introns and non-first introns were compared. For the genes containing two or more introns, we also compared the length of the first intron with the average intron length  of the same gene. Due to the large sample size and unknown distributions of the intron lengths, two-sample Kolmogorov-Smirnov (KS) tests were used to assess the significance of the length difference between the first introns and non-first introns.Nucleotide contents, especially high C+G and CG dinucleotide contents are usually thought to be related to transcriptional regulation of genes However, for large sample sizes, the exact computation may take too much time. Based on center limit theorem in statistics, the binomial distribution has an asymptotic standard normal distribution as Namely, Choosing significant level The similar method and significant level were used to examine the difference in occurrence frequency of dinucleotides between the first introns and non-first introns.We searched potential CpG island regions in introns using the method described by Gardiner-Garden and Frommer (1987) The frequencies of introns harboring potential TATA, CAAT and GC boxes were assessed, respectively. The corresponding consensus sequences for the three motifs were TATAWAW (W represents A or T), CCAAT and GGGCGG.The average intron lengths of the entire samples, HK genes and TSP genes are listed in About 2/3 of the first introns are longer than the expected length of the same gene. Except breast and colon-specific genes, the genes with the first introns longer than the expected length are more than the genes with the first introns shorter than the expected length . The rese longer . We can The contents of nucleotides and dinucleotides in introns are shown in  introns , the res overall . We founThe u -value analysis to investigate usages bias of nucleotides and dinucleotides in the first introns relative to position-specific non-first introns are located in the introns, we calculated the frequencies of introns that contain TATA, CAAT and GC boxes. The results show that, of all the first introns, 56.4% contain TATA boxes; 66.2% and 56.2% contain CAAT and GC boxes, respectively. However the percentages of the non-first introns that contain TATA, CAAT and GC boxes are 49.9%, 52.6% and 20.6%, respectively. This indicates that the three TFBSs occur more frequently in the first introns than in the non-first introns. In particular, the occurrence frequency of the GC box in the first introns is nearly 36% higher than that in the non-first introns, in accordance with previous finding that the first introns contain a larger degree of GC dinucleotide and CpG island than the non-first introns. The frequencies of TATA and CAAT boxes in the first introns are only 6.5% and 13.6% higher than those in the non-first introns. Nevertheless, since nucleotides A and T and their dinucleotide compositions and the CA dinucleotide are under-represented in the first introns, it is reasonable to think that the contents of TATA and CAAT boxes in the first introns are richer than those in the non-first introns.Similar results are also found in introns of the TSP genes . In all Our study also reveals that there are differences in frequencies of TATA, CAAT and GC boxes with respect to the intron position . The notIt is noted that, we determined the first intron of a gene only based on one transcript of the gene. However, most genes have alternative transcription start sites which maybe affect what is annotated as the ‘first’ intron and the characteristics of the first introns. To counter these problems, we random chose two groups of alternative transcripts from sampled genes and performed the similar analysis for the features of introns. Excitingly, the scores of intron features have no significant difference between two collections of transcripts (data not shown). For instance, the Using the introns derived from nearly 20000 intron-containing genes, we analyze the sequence features associated with transcriptional regulation. The various characteristics of the first introns within these genes suggest that the first introns are most likely to be involved in transcriptional regulation. Consistent with previous observations Another feature is that C, G and their dinucleotide compositions are over-represented in the first introns, whereas A, T and their dinucleotides are under-represented. In addition, nearly 70% of the first introns contain the CpG island, not only higher than the other introns but also higher than the estimated percentage in entire human genes (40∼50%) Obvious differences in the distributions of TATA, CAAT and GC boxes between the first introns and the non-first introns are also observed. Generally, the frequencies of these three TFBSs are higher in the first introns than in the non-first introns, suggesting the potential for the first introns to bind TFs and participate in gene expression regulation.One additional finding of this study is the differences in sequence features between introns within HK genes and TSP genes. The HK genes have shorter introns than the TSP genes. In addition, the frequencies of CpG islands and GC boxes are higher in the HK genes than those in the TSP genes, whereas the HK genes contain fewer TATA and CAAT boxes than the TSP genes. The results hint that there are the different mechanisms of transcriptional regulation between the HK and TSP genes. For example, one possibility is that there are more CG-rich regulatory elements in the HK genes but more AT-rich elements in the TSP genes since the differences of contents of CpG island and TATA box between introns of HK and TSP genes. Besides, there are also differences among the introns within different kinds of TSP genes, indicating the laws of transcriptional regulation between these groups of TSP genes are not the same. Since the differences between HK genes and TSP genes, our next plan is to detect the transcriptional regulatory elements located in the first introns of HK genes and each group of TSP genes and explore the transcriptional regulation mechanism concerned with introns in these genes.Our results support the hypothesis that the first introns may contain transcriptional regulatory elements and provide intriguing hints into the regulatory potential of the first introns. Therefore, the promoter regions might be extended to at least the first introns while studying the transcriptional regulations of genes.Table S1List of houskeeping and tissue-specific genes. (XLS)(XLS)Click here for additional data file.Figure S1Characteristic lengths of introns in housekeeping and tissue-specific genes. (TIF)(TIF)Click here for additional data file.Figure S2Frequencies of introns overlapped with at least one CpG island in housekeeping and tissue-specific genes. (TIF)(TIF)Click here for additional data file.Figure S3TATA, CAAT and GC boxes frequencies of introns in housekeeping and tissue-specific genes. (A) Frequency of introns with TATA boxes. (B) Frequency of introns with CAAT boxes. (C) Frequency of introns with GC boxes. (TIF)(TIF)Click here for additional data file.


The nature, sources and format of evidence used by managers and clinicians is important in introducing innovations in healthcare. We investigate the organisational decision making process focusing on the adoption of innovative technologies in the context of infection prevention and control (IPC) and the nature of evidence used.Qualitative, multi-level, multiple case study design involving primary & acute care trusts. We conducted 121 semi-structured interviews drawing on a purposive multi-level, multi-stakeholder sample. Data was analysed using an integrated approach.We mapped out 38 organisational technology selection decisions from July 2009 to August 2010. We specifically mapped the organisational adoption decisions to three types of innovation knowledge: 'awareness' (awareness that the innovation exists), 'principles' (its functioning principles) and 'how to' . The leadership role adopted by the Director of IPC and the professional background of key decision makers influenced this asymmetry to different types of knowledge considered.awareness and how to knowledge. In our study we found the converse; overall less attention was given to how to knowledge at the point of innovation adoption decision and more attention was attributed to principles knowledge both by decision makers and change agents. Attending to ‘how to’ knowledge at decision making stage may enhance successful technology adoption and effective use. This has important implications for suppliers, managers and clinicians.In the commercial sector innovation adoption focuses at the individual level and majority of attention by change agencies is around None declared.


Tracheobronchial tree colonization is considered an important risk factor for the development of ventilator-associated pneumonia (VAP). The aim of the present study was to examine microbiologically the respiratory tract flora of mechanically ventilated patients hospitalized in the Coronary Care Unit (CCU) of our institution for the detection of colonization with important bacterial pathogens.Cultures of bronchial excretions were taken the first 24h of intubation and before extubation, in a total of 39 CCU patients . Risk factors for colonization, including APACHE II score, Clinical Pulmonary Infection Score (CPIS), placement of an invasive device as well as the duration of mechanical ventilation (MV), were recorded.Acinetobacter spp, MRSA, MSSA, Escherichia coli, Candida albicans, Enterobacter spp and Serratia marcescens. Patients who were colonized by potential pathogens had higher CPIS compared to those who were not . Colonization with a potential pathogen was associated with placement of a nasogastric catheter  or a central vein catheter , with the duration of MV and placement of an Intra-Aortic Balloon Pump for a prolonged period.46% of the participants with normal flora in the first 24 hours of intubation, were colonized with potential pathogens by the day of extubation. The most frequently isolated colonizers were High rates of bacterial colonization were identified in this cohort of CCU patients. The risk factors identified will assist in the establishment of a better infection control protocol in the future.None declared.


Flavivirus) which is closely related to Japanese encephalitis virus, West Nile virus and St. Louis encephalitis virus. MVEV is enzootic in northern Australia and Papua New Guinea and epizootic in other parts of Australia. Activity of MVEV in Western Australia (WA) is monitored by detection of seroconversions in flocks of sentinel chickens at selected sample sites throughout WA.Murray Valley encephalitis virus (MVEV) is a mosquito-borne Flavivirus  data represent an attractive alternative to ground measurements. However, a number of competing alternatives are available and careful evaluation is essential to determine the most appropriate product for a given problem.The Tropical Rainfall Measurement Mission (TRMM) Multi-satellite Precipitation Analysis (TMPA) 3B42 product was chosen from a range of RS rainfall products to develop rainfall-based predictor variables and build logistic regression models for the prediction of MVEV activity in the Kimberley and Pilbara regions of WA. Two models employing monthly time-lagged rainfall variables showed the strongest discriminatory ability of 0.74 and 0.80 as measured by the Receiver Operating Characteristics area under the curve (ROC AUC).TMPA data provide a state-of-the-art data source for the development of rainfall-based predictive models for Flavivirus activity in tropical WA. Compared to ground measurements these data have the advantage of being collected spatially regularly, irrespective of remoteness. We found that increases in monthly rainfall and monthly number of days above average rainfall increased the risk of MVEV activity in the Pilbara at a time-lag of two months. Increases in monthly rainfall and monthly number of days above average rainfall increased the risk of MVEV activity in the Kimberley at a lag of three months. Flavivirus) is a mosquito-borne arbovirus endemic to northern Australia and Papua New Guinea. MVEV virus can cause fatal disease in humans. While the fatality rate lies at 25%, 25-50% of people who develop clinical symptoms are permanently affected due to neurological damage [Murray Valley encephalitis virus , West Nile virus (WNV) and St. Louis encephalitis virus (SLEV). or hosts . As withor hosts -7. TheseFlavivirus activity in WA is monitored through the Western Australian Arbovirus Surveillance and Research Program . The proThe data gathered by the program are subject to temporal and particularly spatial limitations, as virus activity is monitored at a limited number of locations. Due to the time and cost intensiveness this method of surveillance is not practicable in remote and inaccessible areas. The work reported here aims to enhance the current arbovirus surveillance system and to overcome limitations. By employing a combination of the ground based serological data and RS derived rainfall data, existing spatio-temporal relationships between arbovirus occurrence and rainfall related environmental conditions can be analysed and used to model MVEV occurrence risks.In this paper, we are dealing exclusively with rainfall since it is one of the principal environmental factors influencing spatio-temporal vector and host dynamics and hence MVEV occurrence ,16,17. ASatellite precipitation data are operationally derived from cloud properties . The quaThe International Precipitation Working Group (IPWG) hosts several projects dealing with the validation and intercomparison of different satellite precipitation and numerical model forecasts for many regions in the world including Australia , Europe From the great variety of satellite-based precipitation data sources, the Tropical Rainfall Measuring Mission (TRMM) 3B42, the Real-Time TRMM 3B42RT  and the The TRMM 3B42 product has been available since 1998. It includes merged high quality passive microwave (PMW) and infrared precipitation estimates and Root Mean Square (RMS) precipitation-error estimates adjusted and combined with rain gauge data at a 0.25° by 0.25° resolution, which approximates to a 25 km by 25 km resolution for Northern Australia. The Real-Time TRMM product 3B42RT is computed in near-real time, and constitutes the most timely source of TMPA estimates. While the processing of the 3B42RT dataset requires several simplifications, the 3B42 algorithm is designed to maximise the quality of the estimates .The CMORPH precipitation product incorporates similar data sources to TRMM 3B42. A detailed description of the algorithm can be found in Joyce et al. . CMORPH In the work presented, we show how data should be chosen carefully from the vast amount of available data to be most beneficial to a study. We also illustrate how RS rainfall data can be applied to develop models for the prediction of MVEV activity in large and remote areas.The sentinel chicken data used in this study was limited to the period of 2000 onwards due to the availability of suitable contemporary remotely sensed environmental data. The sentinel chicken seroconversion data were organised in a relational database and the R statistical programming environment  was used1. no seroconversion was detected in a flock when testing recommenced after a testing-free period; and2. no changes occurred to the flock during the testing-free period.The remaining gaps (i.e. when seroconversions occurred after a testing-free period) could not be filled and the relevant datasets were further processed by excluding those sample sites with gaps of longer than three months. Datasets with gaps of three months or less were adjusted by setting the date of seroconversion to be at the midpoints of the testing free period. After processing, 20 sentinel chicken flocks remained: 9 locations in the Kimberley and 11 locations in the Pilbara covering the time period from 1 March 2000 until 31 December 2007  or false alarm ratio (FAR) were used to assess each algorithm for its rain occurrence detection skills. As detailed in the Results section below, this led to the selection of TRMM 3B42 for further investigation.®and the R statistical programming environment [® focal statistics operations were employed to aggregate the data spatially [Nine years (3288 files) of daily compilations of TRMM 3B42 3-hourly rain estimates for Australia processed within an intercomparison study , were prironment . Geograppatially . RainfalBased on the knowledge of the ecology of the virus, the principle vector and the principle host, a set of rainfall variables was created and evaluated. These variables represent the rainfall related environmental conditions which influence the dynamics of vector and host populations.ew), December to March (early plus high wet season: ehw), December to May (complete wet season: cw), January to March (high wet season: hw), and March to May (late wet season: lw)  Table . Taking A spatial component was incorporated into the seasonal rainfall variables by using focal mean raster statistics  within amr) were compiled from the TRMM data.When employing seasonal rainfall variables, modeling was restricted to annual MVEV activity. To enable modeling of virus presence probabilities on a monthly basis, monthly serological data were used together with monthly accumulated rainfall. To account for the temporally lagged nature of processes influencing virus transmission and amplification, e.g. establishment of large vector populations after rainfall events, time-series of monthly accumulated rainfall ((md). To take into account anomalies of short- and long-term duration, we used the accumulated number of days below (dba)or above (daa) the mean daily rainfall associated with each month and the consecutive number of months of positive or negative deviation from the average monthly accumulated rainfall associated with each month and each test site (mda).We developed variables based on rainfall anomalies to quantify the magnitude of deviation of the monthly accumulated rainfall from the average monthly accumulated rainfall associated with each month (January till December) at each serological sample site over the study period The rainfall variables described above were extracted from the satellite data at the serological sample sites covering the period from 1 March 2000 until 31 December 2007 for bivariate variable screening. A two-tailed Spearman correlation analysis and the Kruskall-Wallis test were used to assess the strength of association between the proposed seasonal/monthly satellite derived rainfall variables and the annual/monthly test site status (positive or negative to MVEV)  for MVEV sample site status were calculated. Receiver operating characteristics (ROC) curves  were conmrand daa based on the rainfall data of the two years which were not included in the model building process.The logistic regression models developed for the Kimberley and the Pilbara were used to predict MVEV occurrence risk at the sentinel chicken test sites for 2008 and 2009 employing Figure The scores were calculated for the whole of Australia and therefore do not consider regional variations. However, information on the performance of the data in different regions, in the form of difference maps displaying deviations of observed rainfall and satellite estimates, can be found on the CAWCR web site .The Frequency Bias or Bias Score (BIAS) Figure  describeThe POD Figure  measuresThe FAR quantifies the fraction of cases of rainfall estimates in which the event did not occur. Higher FARs seem to be associated with lighter rainfall as illustrated in Figure The correlation coefficients of the observed data and the satellite precipitation data were similar for the 3B42 and the CMORPH products. Higher correlations were displayed for heavier rainfall Figure . Both thIn comparison to the 3B42 and the CMORPH precipitation products, the TMPA real-time data generally showed lower biases, POD scores, and lower correlation coefficients. The FAR score and also the RMS tended to be higher. In summary, the TMPA real-time data did not perform as well as the other data products, which is consistent with the accuracy expectations attributed to these datasets . Based omr  and the influence of the duration of rainfall amounts exceeding the average (daa)  Tables  and 11.Figures TRMM 3B42 data provide us with the most accurate and spatially regular available information for the entire study area. The verification results, particularly the difference maps , showed Logistic regression models employing rainfall based predictor variables had a greater discriminatory ability to predict MVEV activity in the Pilbara (ROC AUC: 0.72 - 0.83) Tables  and 11 thw and the ehw for the Kimberley and ew for the Pilbara were found to be more important overall than the other seasonal variables  were utilised to consider larger areas around the serological sample sites. This was done to account for often widespread rainfall in the study area, potentially leading to the creation of widely dispersed or extensive wetlands, as well as for the ability of flood waters to move over hundreds of kilometres into large drainage basins . SpatialCx. annulirostris two to three weeks after heavy rainfall and widespread flooding in the Northern Territory. Cx. annulirostris requires certain environmental conditions for breeding, such as shallow water with emerging vegetation [Cx. annulirostris mosquitoes exploited shallow water pools with emerging vegetation within hours of their formation. Larvae have been found within two to three days [Cx. annulirostris ranged from four to twelve days. However these times can only be used as an approximate guide and are expected to be different depending on time and location. Furthermore, the time required for development of large vector populations depends on whether and how many vectors are permanently present during the dry season, either in permanent smaller local water bodies  or as long-lived adult mosquitoes, or whether the vector needs to be re-introduced into an area. Furthermore, vector survival, and perhaps virus survival, is possible in the form of desiccation resistant eggs of other species such as Aedes normanensis [The lack of association between monthly MVEV activity and monthly rainfall variables Figure  is explagetation  which ingetation . Vector getation , carriedree days . The devree days . Russellree days  showed tmanensis .The two and three-months time lags suggest that more than one cycle of amplification, as illustrated by Konno  for JapaVirus amplification is influenced by a number of factors such as whether or not the virus is already present in an area, the abundance and population structures of competent vectors and susceptible hosts as well as the development of viraemia in the host, depending on the host species and age . The preThe predictions performed for 1 January 2008 until 31 December 2009 Figures  and 6 shThe model results imply that due to the environmental conditions at a specific location and time, the risk of virus activity may be increased. Other non-rainfall environmental conditions were not considered in this study, but are known to influence MVEV activity. Incorporation of these factors might increase model accuracy.Satellite based precipitation data represent a useful data source for the analysis of spatio-temporal rainfall patterns associated with arbovirus activity, especially for larger  areas. Unlike point measurements, or spatially interpolated surfaces based thereon, which are expected to be inaccurate in areas where ground measurements are sparse, satellite based precipitation estimates are spatially regular and cover remote and difficult to access areas.The data are not only capable of spatially coherent mapping of MVEV risk, but also enable the development of spatio-temporal rainfall variables accounting for the surrounding environment of a location of interest as well as for the temporally lagged nature of ecological processes responding to changing environmental conditions. This is important, since the virus, mosquito vectors and animal hosts are influenced by environmental factors, which are often extremely spatially and temporally variable. Furthermore, the utilisation of the satellite precipitation data enables the consideration of regional and super-regional scale processes such as the assembly of water birds, which are known to move across large areas depending on habitat availability, and also of the influence of rainfall in larger catchment areas.TRMM 3B42 data are currently available one month delayed, which given the significance of the 3-monthly lagged rainfall variables, still enables on-time risk mapping and is therefore capable of providing early warning.The analysis and modelling of MVEV dynamics in response to environmental variability are limited by the scarcity of ground truth information on mosquito vector and host abundance required for verification of the identified relationships. The likely involvement of other mosquito vector and host species ,44 with Nevertheless, based on the knowledge of the ecology of the principle vector and hosts, it was possible to develop key rainfall variables and to employ these in the prediction of the risk of MVEV activity at the serological sample sites. The results shown here are consistent with a range of studies ,47,48, iIn the future the prediction models presented in this paper should be further validated by employing spatially denser ground truth information on virus activity collected in selected sample areas which are easier to access. This would then allow RS rainfall data to be routinely used as a tool to predict the spatial distribution MVEV activity which, in turn, should provide the general public with important information about disease transmission risk. However the acquisition of ground truth data on virus presence/absence in an area is expensive and might therefore be restricted.The frame work of data and methods described in this paper may be valuable for similar applications for other medically important arboviruses with complex ecologies such as WNV and SLEV.The authors declare that they have no competing interests.GS designed the study and acquired the RS data. She processed the RS and sentinel chicken data, derived the environmental variables, carried out the statistical analysis and drafted the manuscript. EEE evaluated and validated the satellite precipitation data on which this research is based and participated in drafting the manuscript. MAS assisted in the construction of the statistical analysis framework as well as in drafting the manuscript. RJC significantly contributed to design the study and to the preparation the manuscript. CAJ participated in conceptualisation of the study design, the interpretation of the analyses and the preparation of the manuscript. The sentinel chicken data were acquired by the Western Australian Arbovirus Surveillance and Research Program lead by CAJ. All authors read and approved the final manuscript.