Utilization of maternal health services is associated with improved maternal and neonatal health outcomes. Considering global and national interests in the Millennium Development Goal and Nigeria's high level of maternal mortality, understanding the factors affecting maternal health use is crucial. Studies on the use of maternal care services have largely overlooked community and other contextual factors. This study examined the determinants of maternal services utilization in Nigeria, with a focus on individual, household, community and state-level factors.Data from the 2005 National HIV/AIDS and Reproductive Health Survey - an interviewer-administered nationally representative survey - were analyzed to identify individual, household and community factors that were significantly associated with utilization of maternal care services among 2148 women who had a baby during the five years preceding the survey. In view of the nested nature of the data, we used multilevel analytic methods and assessed state-level random effects.Approximately three-fifths (60.3%) of the mothers used antenatal services at least once during their most recent pregnancy, while 43.5% had skilled attendants at delivery and 41.2% received postnatal care. There are commonalities and differences in the predictors of the three indicators of maternal health service utilization. Education is the only individual-level variable that is consistently a significant predictor of service utilization, while socio-economic level is a consistent significant predictor at the household level. At the community level, urban residence and community media saturation are consistently strong predictors. In contrast, some factors are significant in predicting one or more of the indicators of use but not for all. These inconsistent predictors include some individual level variables , a community-level variable , and a state-level variable (ratio of PHC to the population).Factors influencing maternal health services utilization operate at various levels - individual, household, community and state. Depending on the indicator of maternal health services, the relevant determinants vary. Effective interventions to promote maternal health service utilization should target the underlying individual, household, community and policy-level factors. The interventions should reflect the relative roles of the various underlying factors. Approximately 536,000 maternal deaths occur annually, of which over 95% occur in sub-Saharan Africa and Asia . Africa Scientific evidence has clearly established the inverse relationship between skilled attendants at birth and the occurrence of maternal deaths. Thus, the considerable variation in the maternal mortality estimates between different locations within the same region can be attributed, to a large degree, to the differences in the availability of and access to modern maternal health services . The useWhile available evidence indicates limited benefit from traditional antenatal care services, focused antenatal care provides opportunity for early detection of diseases and timely treatment. It also provides opportunities for preventive health care services such as immunization against neonatal tetanus, prophylactic treatment of malaria through the use of intermittent presumptive treatment approach, and HIV counseling and testing. Furthermore, antenatal care exposes pregnant women to counseling and education about their own health and the care of their children. Thus, antenatal care may be particularly advantageous in resource-poor developing countries, where health seeking behavior is inadequate, access to health services is otherwise limited, and most mothers are poor, illiterate or rural dwellers. With the strong positive association that has been shown to exist between level of care obtained during pregnancy and the use of safe delivery care, antenatal care also stands to contribute indirectly to maternal mortality reduction . AccordiSeveral studies have assessed the individual and household determinants of utilization of maternal services. These studies have not yielded a consistent pattern of relationships between service utilization and individual and household predictors. In some cases, even when a strong association has been reported, such as in the case of the positive relationship between education and the use of skilled health attendants at birth, the extent and nature of the relationship are not uniform across social settings. For example, whereas studies in Peru  and GuatOne important inference from the review of existing literature is that the role of individual and household factors differs from one geographic and social setting to another. Thus, as several authors have aptly noted, the determinants of maternal health care service utilization vary across and within cultures ,25.It is reasonable to assume that utilization of maternal health services depends on individual and household factors, as well as factors operating at the community or policy levels. The review of extant literature however shows that very few studies have gone beyond individual and household factors to consider factors at the community and higher levels. The implication of this omission is that some determinants are inadvertently missed, leaving a serious research and programmatic lacuna. Secondly, failure to consider the role of factors operating beyond the household level in service utilization may result in serious bias in the estimates. Individuals are nested within families, which are in turn nested within communities. Methodologically, it is important to take this nested structure into account. This demands the use of multilevel modeling, which would calculate the standard errors more accurately and reduce the chance of misestimating the significance of variables, as some of the assumptions inherent in traditional regression methods are not valid for nested data .Very few population-based studies have been carried out in Nigeria regarding determinants of maternal service utilization; most maternal health studies in the country have been institution-based. Most of the population-based studies were small-scale research, focusing on a handful of communities, usually small-sized rural communities -29. TheiThe data that we analyze in this paper derive from the 2005 National HIV/AIDS and Reproductive Health Survey (NARHS), a household survey designed to provide quantitative data for monitoring the impact of reproductive health interventions in Nigeria. The survey covered all the 36 states of Nigeria and participants were selected through a multi-stage probability sampling method. Details about the sampling have been provided elsewhere . The oriIn addition to using data from the 2005 NARHS, we also accessed some state-level data published by National Bureau of Statistics for the year 2005 . SpecifiWe analyze the predictors of three indicators of use of maternal health services: use of antenatal care, delivery assisted by a trained medical personnel (doctor or nurse/nurse-midwife), and use of postnatal care services. We assess the predictors of each of these indicators separately and with reference to the most recent birth.We examined the predictive value of a number of individual and household variables, including rank of the most recent birth, education, ethnicity, age at last birth, attitudes towards family planning, ideal family size and socio-economic status. We examined the role of three community level variables: type of place of residence , media saturation in the local government area (LGA) of residence, and prevalence of the small family norm in the LGA of residence. At the state level, we assessed the role of the ratio of Primary Health Care (PHC) facilities to the population. In addition, we assessed random effects at the state level. We selected these predictors based on information from extant literature and because they were significant predictors in initial bivariate analyses of the data. We describe the various predictors in Table Individuals are nested within households, households are nested within LGAs and LGAs are nested within states. In order to assess the roles of measured individual, household, community and state factors as well as unmeasured factors at the state level, we use multilevel modeling in this paper. The nature of nested data makes the use of traditional regression methods inappropriate: some of the assumptions inherent in traditional regression methods, including the assumption of independence among individuals within the same group and the assumption of equal variance across groups are not valid in the case of nested data .gllamm command in Stata [We estimated a multilevel model that assessed the predictive values of measured individual, household, community and state factors (fixed effects) in addition to state-level random effects using the in Stata . For eacin Stata ,34.About three-fifths (60.3%) of the respondents used antenatal services at least once during their most recent pregnancy. The percentage of last births whose delivery was assisted by qualified medical personnel  was 43.4% while only two fifths 41.2%) received postnatal care  personnel for delivery include education, ethnicity, and family size ideals Table . As we sFurthermore, the odds of reporting this indicator of use increase monotonically with household socio-economic status and are higher for urban residence compared to their rural peers. In addition, both community media saturation and the prevalence of the small family norm in the community present a graduated, dose-response relationship with use of medical personnel for delivery. State-level random effects are also significant and there is evidence of clustering at the state level even after controlling for individual, household and community variables.At the individual level, education, age at the birth of the last child, ethnicity, approval of family planning and family size ideals are the strongest predictors of postnatal care Table . SpecifiAt the household level, socio-economic status is a significant positive predictor. Two community-level variables - urban residence and community media saturation - are significant predictors but the prevalence of the small family norm is not. Unlike what we observed for the two previous indicators of service utilization, the indicator of health services availability in the state does not appear to make a significant difference for use of postnatal care. Nonetheless, the state-level random effects are significant with unmeasured state-level factors accounting for 16% of total variance in the use of postnatal care.This study is based on the NARHS, which involved a nationally representative population sample, and marks a departure from most of the previously reported studies on maternal health services utilization in Nigeria in terms of its national coverage. In addition, unlike most previous studies, we covered the three dimensions of pregnancy-related care - antenatal, delivery and postnatal services.Our results show that the level of utilization of orthodox health care facilities for maternal care among women in Nigeria is low. Indeed utilization of maternal health care services is lower in Nigeria than in many countries in sub-Saharan Africa. For example, whereas we found that 60.3% of Nigerian mothers utilized antenatal care services during their last birth, the comparative figures were 88.0% for Benin (2006 DHS), 72.8% for Burkina Faso (2007 DHS), 83.4% for Cameroon (2004 DHS), and 91.9% for Ghana (2003 DHS) .Similarly, the indicators of skilled assistance during delivery and use of postnatal care are considerably lower in Nigeria than in most African countries. A recent UNICEF report  shows thThe finding that utilization of antenatal services is higher than use of skilled assistance during delivery is consistent with the results of previous studies conducted in Nigeria ,37 and eThe poor staffing of the health facilities, particularly the primary health care facilities, which makes it difficult to guarantee 24-hour availability of services had also been reported as a factor that discourages women in Nigeria, even when they had received antenatal care services, to seek medical services when labor commences . The rolOur finding regarding the significant positive association between education and each of the three indicators of maternal services use agrees with previous reports ,12,45,46The absence of a statistically significant association between the child's rank of birth and maternal services utilization among Nigerian women is surprising. Previous studies have found a strong negative association between parity and maternal services utilization ,46,53,54Hausas of Northern Nigeria, for example, has highlighted the strong influence of cultural beliefs and practices on childbirth and related fertility-related behaviors, and their significant contribution to the maternal morbidity and mortality picture [Kunya, or 'shame' plays an extremely important role in Hausa childbirth, particularly in the first pregnancy. The newly pregnant girl should not draw attention to her gravid state, and all mention of the pregnancy should be avoided in conversation and action. This social pressure to remain 'modest' may well prevent her from asking questions about childbirth, and creates a major barrier to her seeking skilled assistance for delivering in hospital. As Wall further note, the pregnant girl's "mother, other relatives, and a local midwife usually stay with her during labor, but her kunya and her fear may be so great that she does not say anything until labor is well advanced." (p. 353). If there is nobody immediately available, it is unlikely that the girl in labor will send for someone, as "kunya" will prevent her from saying anything. Moreover in the cultural context of the Hausas, delivering her first child alone - unattended to by anyone - is viewed with pride.Our finding with regards to the association between ethnicity and service utilization is an interesting one. Whereas ethnicity seems to make no significant difference for use of antenatal care, it does for use of skilled assistance and postnatal care. For these two indicators of use, the Fulanis, and the Kanuris (in the north) are not statistically different from the Hausas (in the north). In contrast, the level of service utilization was significantly higher among the Igbos (in the south) and the "minority" tribes compared to the Hausas. The pattern is consistent with the general picture of wide regional disparity in health status in Nigeria's diverse and multi-ethnic setting as has been reflected, for example, in the NDHS . Perhaps picture . In addi picture  noted, "Whereas some previous Nigerian studies had reported a significant relationship between age and maternal services utilization ,57, otheExpectedly, fertility-related attitudes, which are reflected in our study by attitudes towards family planning and notion about the ideal family size, have significant relationship with maternal health services utilization. Favorable attitudes towards family planning and a clear notion about what constitutes an ideal smaller family size reflect less conservative behavior and more openness to modern health-related concepts and services.At the household level, we found socio-economic status to be a significant predictor: for each of the three indicators, use of maternal services increases steadily with socio-economic status. Studies elsewhere have also documented positive relationship between economic status and early antenatal care use ,58,59, dA major focus of this study is to go beyond individual and household factors and investigate the effects of community and state level factors on maternal care services utilization. At the community level, urban residence was consistently associated with increased odds of service utilization. This finding is in consonance with previous studies which have reported a significantly higher use of services in urban compared to rural areas in Nigeria ,22,43,62At the state level, we found that the ratio of PHC to the population was a significant predictor for use of antenatal care and skilled attendance at delivery, but not for postnatal care. The relationships are such that the larger the number of residents to a PHC the less the odds of using the services. This negative relationship is understandable since the more people a PHC serves, the more likely it is that access to the services would be difficult and the quality of services received poor.Finally, we found that the random effects of the state of residence on each of the three indicators of maternal care service utilization are significant. Substantively, this finding shows that unmeasured factors operating at the state of residence level play a significant role in determining utilization of maternal health services beyond the influence of individual, household and community factors.The findings from this study have implications for evidence-based programming. Collectively, the findings highlight the need for programs to adopt a multi-level approach and address the factors affecting maternal health services utilization at various levels - individual, household and community. More specifically, programs need to explore effective ways of increasing service utilization among lowly educated and poor women who are the least likely to use maternal health services. Evidence from elsewhere have shown that access to services and cost are serious barriers to service utilization among the poor ,66. As FThe strong role of community-level normative factors point to the need for interventions that target social norms. For example, using the media to disseminate consistent messages promoting the use of maternal health services could help to increase discussion of these issues within the community, a relevant step towards changing prevailing negative norms. Also relevant are efforts that involve community leaders and other key persons as agents of change. The findings that the prevalence of the small family norm in the community and personal fertility-related attitudes are associated with differences in service utilization suggest that promoting the use of family planning may ultimately help to foster the utilization of other maternal health services. In other words, programs that seek to promote the small family norm and change attitudes that are unfavorable towards family planning are relevant.The significant state-level random effects that our study found demonstrate the need to contextualize efforts aimed at promoting maternal service utilization. There are obviously some unmeasured factors at the state level that predict service utilization. An effective strategy should be state-specific and seek to identify and address state-level factors that affect service utilization.This study has some limitations that should be noted. First, the NARHS, the source of data for our study, was based on the self-report of respondents, and provided no validation of obtained information with any objective source such as health facility cards. The validity of self-reported behavior constitutes a concern in the literature, but it is logical to assume that biases are less likely in pregnancy-related events as compared to sensitive issues such as sexual behavior and drug abuse. Social desirability bias may also be an issue in cases that women feel they need to respond in a way expected of them. The comparability of our results with that of NDHS with regards to antenatal care use, for example, suggests that such bias is not likely to have affected our findings in any significant way.Second, some known predictors of service utilization are obviously missing from our analyses. For example, availability of maternal health services within the immediate locality of respondents and the distance of respondents to such health services could have contributed to the picture of utilization pattern. Unfortunately these variables were not available in the NARHS. Although we included the state-level measure of PHC density (the number of residents to a PHC) in our analyses, the extent to which this variable is a good proxy for individual-level variable is uncertain.Third, the study relied on cross-sectional data with the attendant potential selectivity and endogeneity bias. There is a possibility that the relationships that we found in our study are due to the influence of unmeasured individual and community-level variables that are associated with both the dependent and independent variables in our estimated models. It is also possible that the observed relationships reflect reverse causation or are due to measurement error. There are analytic methods to adjust for endogeneity bias in cross-sectional data  . NonetheFactors influencing maternal health services utilization operate at various levels - individual, household, community and state. While education, socio-economic level, and urban residence are consistently strong predictors of all the maternal health services considered in this study, other determinants of service utilization generally vary in magnitude and level of significance by the type of maternal service - ante-natal care, skilled attendant at birth, and postnatal care. To be optimally effective, interventions to promote maternal health service utilization need to take these findings into consideration: they should target the underlying individual, household, community and state-level factors that are relevant to each type of maternal health service. It is particularly important for interventions to explore effective ways of increasing service utilization among lowly educated and poor women in rural areas who are the least likely to use maternal health services.The authors declare that they have no competing interests.SB and AF were equally responsible for designing the study and drafting the manuscript. SB performed the statistical analyses while AF contributed the literature review.The pre-publication history for this paper can be accessed here:


Penile neoplasms are rare and can be primary or represent metastasis or local recurrence. The most common primary cancer of the penis is squamous cell carcinoma, accounting for 95% of all cancers. In spite of the rich vascularity of the organ, penile metastases are uncommon. Cutaneous metastasis of urothelial carcinoma (UC) is extremely rare and generally accepted as the late manifestation of a systemic spread. By 1998, approximately 500 cases of penile metastasis had been reported worldwide. However, only few case reports and series of fine-needle aspiration cytology (FNAC) of penile tumors have been documented. We report a case of penile metastasis from UC diagnosed by FNAC and describe the cytomorphological findings with an emphasis on cercariform cells. Although not commonly used, FNA of penile nodules can be effective in diagnosing recurrence or metastasis and avoiding surgical procedures, thus being an excellent initial procedure in the diagnostic approach. A 71-year-old patient presented with a palpable nodule on the penis shaft noted 2 weeks previously and gradually increasing in size. On clinical examination, a nonpainful, firm, nontender nodule measuring 1.0 cm, without ulceration of the overlying skin was identified. He had undergone radical cystectomy 4 months before for urothelial cell carcinoma of the bladder and was referred to the fine-needle aspiration (FNA) clinic for the aspiration of the nodule.An FNA was performed by a cytopathologist with a 25-gauge needle according to the technique described by Zajicek. The procThe slides showed a highly cellular aspirate consisting of loosely cohesive groups of tumor cells with cuboidal, round, or columnar shape with a dense, basophilic, tapered cytoplasm and large hyperchromatic nuclei . There wAlthough penile metastases are rare, the most common site of origin is the genitourinary system, and within this category, the urinary bladder.3 CutaneoRecurrence of penile cancer after primary surgery and penile metastasis often present as a nonulcerative nodule. Other manifestations of penile metastasis include priapism, urinary symptoms , pain, and retention.It has been argued that the merit of core-needle biopsy lies in its more reliable assessment of the presence of malignant cell infiltration, as well as its histologic extent. However,Assessment of specific differentiation in a metastatic lesion and a probable site of origin are frequently requested in order to develop effective chemotherapy protocols for treatment and possible surgical resection of the primary tumor. Although the material obtained by FNA exhibited cytomorphologic features characteristic of the primary, already known neoplastic site, the presence of CCs was useful to confirm the urothelial origin. This appearance has been described as a distinct cytomorphologic clue that helps in the diagnosis of metastatic transitional cell neoplasms. The charAncillary techniques such as immunocytochemistry can be performed on cytological smears not only to characterize the histological type of the neoplasm, but also to discriminate the primary site of origin.In summary, although not commonly used, FNA of penile nodules can be effective, safe, and highly accurate in diagnosing recurrence or metastasis, especially in nonulcerated lesions. It can minimize patient discomfort, and avoids surgical procedures, thus being an initial choice for diagnostic approach. For the diagnosis of cutaneous metastatic UC, usually a manifestation of systemic spread, the presence of CCs in fine-needle aspirates is a useful morphologic clue.No competing interest to declare by any of the authors.Each author has participated sufficiently in the work and take public responsibility for appropriate portions of the content of this article.GCS conceived the study, performed the FNAC, participated in its design and coordination, helped in drafting, and scrutinized the manuscript.MLA participated in the diagnostic workup, performed literature search, and drafted the manuscript.MKM and VB collected all data and performed the literature search.MFF participated in the surgical pathology diagnostic workup and scrutinized the manuscript.This study was conducted with approval from the UNIFESP Ethics Committee. Authors take responsibility to maintain relevant documentation in this respect.Each author acknowledges that the final version was read and approved.


For treatment of malignancies, physical and metabolic differences between tumour cells and host cellshave guided the development of new approaches. In this review, two new approaches to be used in thetreatment of liver malignancies are outlined: ischaemic therapy and interferences with the glucosemetabolism. Ischaemic therapy of liver malignancies has been used in different forms during the last 20years: from ligation of the hepatic artery, embolization of the arterial tree, transient occlusion of thehepatic artery to the present day use of temporary, intermittent, transient hepatic arterial occlusion. Thebeneficial effect of ischaemic therapy on malignancies is supposed to depend on oxygen and nutritionaldeficiency, formation of oxygen-derived free radicals and loss of function in cellular enzymes. The tumourcells seem thereby to be more sensitive than the host cells. Also, ischaemia might potentiate the effect ofcytotoxic drugs. Intereferencies with glucose metabolism might be directed either towards theexaggerated tumour glycolysis, for example by glucose analogues like 2-deoxy-glucose, or towards theexaggerated host gluconeogenesis, for example by hydrazine sulphate. These treatments result inreduction of the glucose availability in the intracellular glucose metabolism in the tumour cells and haveexperimentally been demonstrated to be correlated to reduced tumour growth. It is concluded that boththese approaches, ischaemic therapy and manipulations with the glucose metabolism, seem promising forthe future. What is needed now is research to clarify the mechanims behind the effects, to establish theirfull consequences, and to identify the clinical use of these treatments and their possible combinations.


Inflammation is a response of the immune system to foreign insult or physical damage. Variouscellular and humoral components of the immune system are recruited from the vascularsystem and are translocated through endothelium, and into extracellular matrix (ECM) compartmentsof inflamed tissues. This translocation is orchestrated by various types of accessorysignals, in the form of soluble or complexed molecules, which evoke remarkable transitionsin leukocyte activities. Recruited inflammatory cells give rise to mechanisms of migration,including the secretion of enzymes and other pro-inflammatory mediators and the alterationof their adhesive contacts with the ECM. Hence, migrating cells secrete enzymes, chemokines,and cytokines which interact with the ECM, and thereby, provide the cells with intrinsicsignals for coordinating their responses. Resultant products of enzymatic modifications to theECM microenvironment, such as cytokine- and ECM-derived molecules, may be also part ofa cell-signaling mechanism that provides leukocytes with information about the nature oftheir inflammatory activity; such a mechanism may give the immune system data that can becognitively interpreted for consequential activities. This article reviews the findings that supportthis notion and describe the dynamic interactions between participants of the inflammatoryprocesses.


Explosions and bombings are the most common deliberate cause of disasters with large numbers of casualties. Despite this fact, disaster medical response training has traditionally focused on the management of injuries following natural disasters and terrorist attacks with biological, chemical, and nuclear agents. The following article is a clinical primer for physicians regarding traumatic brain injury (TBI) caused by explosions and bombings. The history, physics, and treatment of TBI are outlined. Disaster medical response training has traditionally focused on the management of injuries following natural disasters and terrorist attacks involving biological, chemical, and nuclear agents. However, explosions and bombings remain the most common deliberate cause of disasters involving a large number of casualties, leading some experts to consider blasts or explosions as the ‘fourth weapon of mass destruction.’ Despite There are an average of five criminal bombing incidents per day in the United States. Major domestic terrorist bombings include events at the World Trade Center (New York City) in 1993, the Frank L. Murrah Federal Building (Oklahoma City) in 1995, and the Olympic Park bombing (Atlanta) in 1996. Yet, mosSevere head trauma has been identified as a common cause of death in terrorist bombings and has been found to be a major cause of critical injury in a number of these events.5 During Blast-associated traumatic brain injury (TBI) is a condition that requires rapid recognition and therapy. The time-critical nature of this condition requires that acute care providers become familiar with the pathophysiology, diagnosis, and treatment considerations for blast-associated TBI in advance of an explosive event. It is also important for acute care providers to recognize and understand the long-term sequelae of blast-associated TBI to insure appropriate referral and follow-up.Potential central nervous system sequelae of bomb blast injury include concussion, post-concussion syndrome (PCS), mild traumatic brain injury (MTBI), post-traumatic stress disorder (PTSD), and acute stress disorder (ASD). Definitions of these terms vary and the sign–symptom complexes overlap, adding to the confusion and uncertainty regarding the nature of brain injuries following exposure to blast effects. Hence, it is important to address the definitions and relationships among these entities .The Defense and Veterans’ Brain Injury Center (DVBIC) Working Group on the Acute Management of MTBI in Military Operational Settings defines MTBI as an injury to the brain resulting from an external force and/or acceleration/deceleration mechanism from an event such as a blast, fall, direct impact, or motor vehicle accident, which causes an alteration in mental status that typically results in the temporally related onset of symptoms such as headache, nausea, vomiting, dizziness/balance problems, fatigue, insomnia/sleep disturbances, drowsiness, sensitivity to light/noise, blurred vision, difficulty remembering, and/or difficulty concentrating.As defined by the American Academy of Neurology (AAN), concussion is a trauma-induced alteration in mental status that may or may not involve loss of consciousness. Mild forPCS refers to the cluster of symptoms that frequently occur in the days or weeks following an MTBI and include headache, dizziness, irritability, difficulty concentrating, memory problems, fatigue, visual disturbances, sensitivity to noise, judgment problems, depression, and anxiety. Although PCS often resolves within a month, it is not uncommon for individuals to experience a persistent PCS, with symptoms lasting months to years after an MTBI.Diagnostic and Statistical Manual of Mental Disorders (DSM-III) in 1980. Since then, PTSD has been used in both the civilian and military populations to describe a symptom complex that occurs after exposure to a psychologically traumatizing event and lasts for longer than 1 month. Symptoms include mood lability, agitation, anxiety, depression, fatigue, and nightmares., etc.) create high-energy supersonic blast waves upon detonation. In general, shear waves predominate in higher-order explosive events and stress waves predominate in lower-energy events.[Blast physics also depend upon whether low-order or high-order explosives are involved. Propellants  are low-order explosives designed to release energy relatively slowly by a burning process called ‘deflagration.’ The blasy events. High-ordy events.37The severity of blast injuries may be augmented by the addition of certain materials to the bomb. Incendiary agents  increase the adherence of flammable products and prolong burning time, resulting in greater burn injuries. Bombs can be designed to release noxious chemical, radiological, and biological agents upon detonation. Metallic objects  can be added to IEDs to increase the number of penetrating injuries, includinPrimary blast injuries are those caused by barotrauma from the overpressurization blast wave. Generally, the parts of the body most susceptible to primary blast injury are air-filled organs and body areas with air–fluid interfaces. Ruptured tympanic membrane and blast lung injury are examples of primary blast injuries. Secondary blast injuries result from penetrating or blunt trauma by projectiles hurled as a consequence of blast waves or blast wind. Tertiary blast injuries result from forceful displacement of the body by the blast wind and any resulting impact against obstacles. Quaternary injuries are those injuries related to explosions, but not caused by either primary, secondary, or tertiary mechanisms. Examples include burns, toxic inhalations, radiation injury, chemical exposures, as well as exacerbations or complications of preexisting conditions .[Quinary effects have also been postulated. In the quinary mechanism of blast injury, a hyperinflammatory, hyperpyrexic body reaction is induced by the toxicity of some unconventional explosive materials utilized in the bomb, .[Blast injuries are categorized by primary, secondary, tertiary, and quaternary effects. arction). Injuriesarction). Quinaryilizers).The presence of bony protuberances on the inferior cranial vault, as well as the delicate composition of the cerebral cortex, brainstem, and axonal fibers, render the brain especially vulnerable to injury. The mostWhile secondary and tertiary blast mechanisms result in blunt or penetrating trauma similar to head injury from causes other than explosions, a discussion of primary blast injury to the brain is more complicated and controversial. One mechanism of primary blast injury is arterial air embolism to the central nervous system as a consequence of alveolar damage in blast lung injury. These air emboli are life threatening and can cause temporary unconsciousness or focal neurological complaints similar to that seen in a stroke. An extre34Researchers do not agree whether primary blast effects cause nonfatal brain injuries. While some say the homogeneous nature of the brain makes this unlikely, others sThe clinical presentation of survivors with TBI from explosion is similar to those with open or closed brain injuries due to other mechanisms, and the approach to diagnosis remains the same. The diagnosis of penetrating head wounds is generally as straightforward as the presentation is dramatic. Diagnosis of open and closed skull fractures, concussions, contusions, and subarachnoid, subdural, and epidural hematomas presents the same challenges in survivors of bombings as in those injured by other mechanisms.vs closed space, proximity of victim to bomb, etc.) can alert the acute care clinician to the possibility of primary blast injury.In the diagnosis of TBI resulting from explosion, the first step is a clinical assessment that includes a history of the mechanism of injury, context of the event, and presence or absence of periods of loss of consciousness and posttraumatic amnesia (PTA). In the unconscious or uncommunicative patient, a history should be obtained from bystanders or prehospital personnel, if possible. The environment of the bombing  can be a useful tool in evaluating central nervous system (CNS) function. Serial sThe clinical approach to the diagnosis of MTBI requires a high index of suspicion and should ideally incorporate the use of neurocognitive screening tools. Examples of such tools are the Military Acute Concussion Evaluation (MACE) developed by the DVBIC, and the Standardized Assessment of Concussion (SAC) developed by the 2004 Prague International Conference on Concussion in Sport. In generThe 2002 American College of Emergency Physicians (ACEP) evidence-based clinical policy addressing neuroimaging and decision making in adult MTBI in the acute setting discourages the use of skull radiographs in the evaluation of MTBI because of lack of sensitivity. An updatThis same 2008 ACEP evidence-based policy document indicated that the scientific literature is not adequate to make any recommendation regarding the role for head MRI in the ED evaluation of a patient with acute MTBI, even though MRI potentially increases the sensitivity for detection of acute traumatic intracranial injury by up to 30% in patients with MTBI. There isThere is no readily available biochemical marker currently recommended for clinical use in evaluation for MTBI; however, the cellular mechanisms of injury in the cascade of neurochemical changes that accompany physical injury to the brain, including lipid peroxidation, mitochondrial damage, and apoptosis, lend themselves to definite possibilities for the development of biochemical markers. Potential markers studied thus far include glucose, norepinephrine, epinephrine, and dopamine; the neuronal proteins neuron-specific enolase and tau; and the astrocyte proteins S-100B, creatine kinase BB isoenzyme, and glial fibrillary acidic protein. Though the Food and Drug Administration (FDA) has not yet approved S-100B for clinical use in the United States, ACEP has included a level C recommendation regarding its possible use as an aid to neuroimaging decision making based on European research. The recommendation applies only to MTBI patients without significant extracranial injuries seen within 4 h of injury. In this well-defined group, a serum S-100B level less than 0.1 µg/l may permit the clinician to consider not performing a head CT in the ED.Survivors who have been in proximity to explosions may also have signs and symptoms of ASD immediately following the event. Symptoms include recurrent images in dreams or flashbacks, extreme anxiety, or a numb or detached affect. When symptoms persist for more than a month, patients may have PTSD. Symptoms can also include hypervigilence, insomnia, and an exaggerated startle response. An important caveat for the clinician is that a diagnosis of ASD or PTSD does not exclude the possibility of an underlying MTBI. Treatment options and outcome depend upon appropriate diagnosis or combination of diagnoses.Lack of consensus in definitions and overlapping of the signs and symptoms complicates the diagnosis of concussion, PCS, MTBI, ASD, and PTSD, each of which may occur following blast exposure. An important caveat for the clinician is that a diagnosis of ASD, PCS, or PTSD does not exclude the possibility of an underlying MTBI. For the busy emergency physician providing medical treatment to multiple victims of an explosion, sufficient time to administer one of the neurocognitive screening tools for MTBI may not be available. Although these diagnoses may not be initially made by the emergency physician, admitting physicians as well as patients and family should be made aware of possible MTBI signs and symptoms that could later lead to diagnosis of MTBI. The emergency physician should be prepared to make the diagnosis of post-blast concussion and consider the diagnosis of MTBI in patients with a GCS of 13-15, moderate TBI in patients with GCS 9-12, and severe TBI in patients with GCS 3-8.[One clinical entity unique to the blast-injured patient is arterial air embolism (AAE) secondary to pulmonary parenchymal disruption in blast lung injury. An altered mental status or focal neurological deficit in a patient with blast lung injury, especially following positive-pressure ventilation, should arouse suspicion of AAE.The treatment of open and closed skull fractures, penetrating brain injuries, and subarachnoid, subdural, and epidural hematomas resulting from an explosion is similar to treatment of these conditions resulting from other trauma. Initial treatment should follow established clinical protocols. In the more severely injured patient, exacerbation of brain injuries or development of secondary brain injuries may be related to hypotension and hypoxemia. Aggressive prehospital and ED airway control, ventilation, oxygenation, and fluid therapy as indicated may be required to preserve optimal neurologic status. Routine hyper ventilation of the brain-injured patient is no longer advocated.One important clinical treatment caveat in the setting of TBI from explosions is in the diagnosis and treatment of AAE that results from blast lung injury. The symptoms of AAE may not begin until the onset of positive-pressure ventilation, so an awareness of this possibility is important for differential diagnosis and treatment of altered mental status in the bomb blast victim. Fowler positioning for shock may increase the likelihood of cerebral AAE. To prevent air embolism, the patient should instead be positioned in such a way that the coronary artery ostia lies in their lowest positions. The prone or semi-left lateral  positioning is recommended. The treatment of choice for AAE is hyperbaric oxygen therapy.Some authors suggest that physical activity following the event may also increase the likelihood of AAE and other adverse sequelae of blast injury. Physical activity of victims exposed to blast waves should therefore be limited in the field. Bomb blaTreatment of concussion injuries includes providing the patient and family with educational materials and observation guidelines to determine any deterioration of function after discharge. Two randomized clinical trials have shown the importance of patient education and follow-up in reducing the number and severity of post-concussive symptoms.55 EducatA period of relative rest for the first 2-5 days following concussion is generally recommended, with a stepwise increase in physical activity. Acetaminophen is generally recommended for headaches in these individuals. In additThe potential for major terrorist bombing attacks in the United States is a reality for which acute care clinicians must prepare. Terrorist bombing is a more likely scenario than an attack with chemical or biological weapons. TBI is an important cause of morbidity and mortality following a high-order explosive event. The severity and nature of brain injuries that occur depend partly upon the nature and quantity of the explosive used. Severity of injury is markedly increased for victims within an enclosed space, and severity is inversely proportional to the cube of the distance between the victim and the epicenter of the event.Both open and closed brain injuries can occur as a result of a blast, and include penetrating brain injury, skull fracture, diffuse axonal injury, cerebral contusion, and epidural and subdural hemorrhage. AAE of the brain can also occur as a consequence of blast lung injury, and can be precipitated by positive-pressure ventilation. Concussion, PCS, MTBI, ASD, and PTSD can also occur as a result of exposure to blast events.Diagnosis and treatment for TBIs that occur as a result of explosion is similar to that for brain injury that occurs as a result of other traumas. Emergency physicians should always maintain an awareness that concussion and MTBI can occur in blast victims. These conditions could go undiagnosed in the ED due to time and resource constraints imposed by multicasualty bombing events. Patients admitted to the hospital for other injuries should be screened for these conditions before discharge. Patients should be provided appropriate educational materials and referral upon discharge in the event that new signs and symptoms emerge, or if existing symptoms worsen or fail to resolve.Improvement in treatment and outcome for patients with MTBI resulting from a blast event can only occur if this entity is recognized. Enhanced recognition can be achieved through greater awareness and pre-event education. Further clarifications and consensus among experts on definitions and diagnostic criteria will increase the likelihood of accurate diagnoses of concussion, PCS, MTBI, ASD, and PTSD. Further research and development in the fields of neuroimaging and biochemical markers should improve the ability to diagnose TBI secondary to blast events. Well-designed studies of current and future treatment modalities are essential for evidence-based care recommendations following TBI resulting from a blast event.


Determination of the electrophoretic mobility of test cells has been widely used in an attempt to detect so-called lymphokines in a laboratory test for cancer, but operational difficulties are inherent in conventional cytopherometers. This study therefore investigates the technical and operational aspects of cell electrophoresis, using the Zeiss cytopherometer; e.g. influence of electro-osmosis, focus uncertainty, movement due to convection and other sources of error. Implications and possible improvements in the test are discussed.


Microarrays have become an important technology for the global analysis of gene expression in humans, animals, plants, and microbes. Implemented in the contextof a well-designed experiment, cDNA and oligonucleotide arrays can provide highthroughput,simultaneous analysis of transcript abundance for hundreds, if notthousands, of genes. However, despite widespread acceptance, the use of microarraysas a tool to better understand processes of interest to the plant physiologist is stillbeing explored. To help illustrate current uses of microarrays in the plant sciences,several case studies that we believe demonstrate the emerging application of geneexpression arrays in plant physiology were selected from among the many postersand presentations at the 2003 Plant and Animal Genome XI Conference. Basedon this survey, microarrays are being used to assess gene expression in plantsexposed to the experimental manipulation of air temperature, soil water content andaluminium concentration in the root zone. Analysis often includes characterizingtranscript profiles for multiple post-treatment sampling periods and categorizinggenes with common patterns of response using hierarchical clustering techniques.In addition, microarrays are also providing insights into developmental changesin gene expression associated with fibre and root elongation in cotton and maize,respectively. Technical and analytical limitations of microarrays are discussed andprojects attempting to advance areas of microarray design and data analysis arehighlighted. Finally, although much work remains, we conclude that microarraysare a valuable tool for the plant physiologist interested in the characterization andidentification of individual genes and gene families with potential application in thefields of agriculture, horticulture and forestry.


Tick-borne encephalitis (TBE) virus can cause severe symptoms in humans. The incidence of this vector-borne pathogen in humans is characterised by spatial and temporal heterogeneity. To explain the variation in reported human TBE cases per county in southern Germany, we designed a time-lagged, spatially-explicit model that incorporates ecological, environmental, and climatic factors.Capreolus capreolus) in the previous year was positively correlated with human TBE incidence, and hunting bag density of red fox (Vulpes vulpes) and red deer (Cervus elaphus) in the previous year were negatively correlated with human TBE incidence.We fitted a logistic regression model to the annual counts of reported human TBE cases in each of 140 counties over an eight year period. The model controlled for spatial autocorrelation and unexplained temporal variation. The occurrence of human TBE was found to be positively correlated with the proportions of broad-leafed, mixed and coniferous forest cover. An index of forest fragmentation was negatively correlated with TBE incidence, suggesting that infection risk is higher in fragmented landscapes. The results contradict previous evidence regarding the relevance of a specific spring-time temperature regime for TBE epidemiology. Hunting bag data of roe deer (Our approach suggests that a combination of landscape and climatic variables as well as host-species dynamics influence TBE infection risk in humans. The model was unable to explain some of the temporal variation, specifically the high counts in 2005 and 2006. Factors such as the exposure of humans to infected ticks and forest rodent population dynamics, for which we have no data, are likely to be explanatory factors. Such information is required to identify the determinants of TBE more reliably. Having records of TBE infection sites at a finer scale would also be necessary. Tick-borne encephalitis (TBE) is the most important flavivirus infection of the central nervous system in Europe and Russia. The annual number of cases is estimated to be as high as 10,000 in Russia and about 3,000 in European countries . Severe Ixodes ricinus, the main vector of TBE virus (TBEV), has three distinct stages, larval, nymphal and adult ticks  according to forest type, but generally broad-leafed forest is considered as a suitable habitat for ticks. In North American forests, black-legged ticks  and/or influenced by hunting effort (red fox), these observations should be regarded cautiously . Yet, "iThe negative relationship found in this study between red fox hunting bags and human TBE cases in the succeeding year is in contrast to a study in TBE endemic areas in Sweden, where this relationship was found to be positive . These cApodemus flavicollis) densities translate into high nymphal densities in the following year [Unfortunately, reliable data on forest rodent dynamics are not available at the appropriate temporal and spatial scale, and could thus not enter our model. Further attempts should be made to test the hypothesis that high rodent . Although the model provides a reasonable fit, some potentially important factors were not investigated due to lack of data. Included here are differing virulence of TBE, variable exposure of humans to ticks, differing immune responses, demography and TBE immunisation coverage. E.g. Kimmig et al.  found diOur modelling approach focussed on ten biotic and abiotic factors possibly influencing the epidemiological risk of TBE. Except for the influence of spring warming, the results are in line with previously published findings. The presented approach might therefore be useful for predicting at least the potential direction, and approximate magnitude of TBE risk, as a function of ecological change . To make further progress, a higher spatial resolution is needed in order to make more reliable interferences about the relationships between eco-environmental factors and TBE incidence. Moreover, neither this analysis nor the in-depth analyses of yearly temperature variability ,34,48 coThe authors declare that they have no competing interests.CK designed the experiment, acquired the data, performed the statistical analysis, interpreted the results and wrote the manuscript. WZ designed the experiment, performed the statistical analysis, contributed to the interpretation of the results and the writing of the MS. PS performed the GIS analyses. FR acquired the data, contributed to the interpretation of the results and the writing of the MS. TV, PH and MN contributed to the interpretation of the results and the writing of the MS. All authors read and approved the final manuscript.


Sympatric corvid species have evolved differences in nesting, habitat choice, diet and foraging. Differences in the frequency with which corvid species use their repertoire of feeding techniques is expected to covary with bill-shape and with the frontal binocular field. Species that frequently probe are expected to have a relatively longer bill and more sidewise oriented orbits in contrast to species that frequently peck. We tested this prediction by analyzing computed tomography scans of skulls of six corvid species by means of three-dimensional geometric morphometrics. We (1) explored patterns of major variation using principal component analysis, (2) compared within and between species relationships of size and shape and (3) quantitatively compared patterns of morphological integration between bill and cranium by means of partial least squares (singular warp) analysis.Major shape variation occurs at the bill, in the orientation of orbits, in the position of the foramen magnum and in the angle between bill and cranium. The first principal component correlated positively with centroid-size, but within-species allometric relationships differed markedly. Major covariation between the bill and cranium lies in the difference in orbit orientation relative to bill-length and in the angle between bill and cranium.Corvid species show pronounced differences in skull shape, which covary with foraging mode. Increasing bill-length, bill-curvature and sidewise orientation of the eyes is associated with an increase in the observed frequency in probing (vice versa in pecking). Hence, the frequency of probing, bill-length, bill-curvature and sidewise orientation of the eyes is progressively increased from jackdaw, to Eurasian jay, to black-billed magpie, to hooded crow, to rook and to common raven (when feeding on carcasses is considered as probing). Our results on the morphological integration suggest that most of the covariation between bill and cranium is due to differences in the topography of the binocular fields and the projection of the bill-tip therein, indicating the importance of visual fields to the foraging ecology of corvids. Sympatric corvids in Central Europe have evolved differences in nesting -3, habitWhile bill morphology has been studied intensively, its covariation with other components of the avian skull has hardly been considered and never been quantified e.g. ,19-21). -21. 19-2In this paper, we analyzed computed tomography (CT) scans of skulls of six corvid species by means of three-dimensional geometric morphometrics to (1) explore patterns of major variation using principal component analysis, (2) compare within and between species relationships of size and shape and (3) quantitatively compare patterns of morphological integration between bill and cranium. We expect corvid species that frequently probe to have a longer and more curved bill and more sidewise oriented orbits, when compared with corvids, which frequently peck and turn objects.Corvus corax), hooded crow (Corvus corone cornix), rook (Corvus frugilegus), jackdaw (Corvus monedula), black-billed magpie (Pica pica) and Eurasian jay (Garrulus glandarius). The specimens are almost equally distributed across species and came from Museum für Naturkunde Berlin, Staatliches Museum für Naturkunde Görlitz and Staatssammlung für Anthropologie und Paläoanatomie München, which are all located in Germany. All corvid skulls were scanned by computed tomography at Charite-Universitätsmedizin Berlin.Our sample consists of 115 adult skulls of six corvid species: common raven , in whiIn birds, especially in those with long bills, landmarks and semilandmarks that are placed closely to the bill-tip will have a great influence on centroid size, because they change the position of the centroid and thus change the distance of the whole landmark set to its centroid. Bills are known to vary greatly according to foraging mode. Hence, centroid sizes calculated from the whole landmark set, i.e. including the bill, will not be a good predictor of overall body-size if bill-length in the studied species is highly variable. Therefore, we adjusted GPA by using centroid size calculated only from landmarks and semilandmarks placed on the cranium and the antorbital fenestra: landmarks 6 – 18 and associated semilandmarks  to explore patterns of major variation across the entire skull. To test the influence of size on shape, a multivariate linear regression of the Procrustes shape coordinates on log centroid size was performed.Partial least squares analysis (PLS) is often referred to as singular warp analysis when applied to Procrustes shape coordinates -33. PLS whole fit" dataset. In addition, landmark coordinates of these functional units were scaled and superimposed separately, which we refer to as the "separate fit" dataset. In the whole fit dataset, the functional units retain their relative position and their size proportions to each other, whereas this geometric information is lost in the separate fit dataset. Hence, the analysis of the separate fit dataset concentrates purely on differences in shape.To study the morphological integration between bill and cranium, the Procrustes shape coordinates were partitioned prior to the PLS into these functional units Fig. , which wwhole fit and the separate fit dataset by subtracting the species mean from the shape coordinates of the corresponding specimens. These Procrustes residuals were subjected to two PLS, one on the residual shape coordinates of the whole fit (PLSwhole) and one on the residual shape coordinates of the separate fit dataset (PLSsep). We used the algorithm introduced by Mitteroecker and Bookstein )Because the shape of the bill, particularly its length, is highly variable ,37, landIn this study we adjusted GPA by using centroid size calculated only from landmarks and semilandmarks placed on the cranium and the antorbital fenestra (see Methods). For similar reasons van der Meij  did not Major shape variation occurs at the bill (PC1), in the position of the orbits and foramen magnum (PC1 and PC2) and in the angle between bill and cranium (PC2). These results are consistent with quantitative studies on avian skull morphology, which also report of major variation at the bill, in the position of the foramen magnum and in the angle between bill and cranium ,37.According to scores in PC 1, the common raven has the longest, widest, most curved bill; the longest, widest and most flattened cranium; the most upward positioned foramen magnum; and the most sidewise oriented orbits, followed by the rook, hooded crow, black-billed magpie and Eurasian jay Fig. , Fig. 3aPC 2 separates the small corvid species . ,43. 34,4whole describes differences in bill- and cranium-length and in the orientation of the orbits  it is due to a local effect, i.e. to a change in the position of the cranio-facial hinge  and in the relative position (PLSwhole 2) of the palatinum are likely to influence the properties of the rhynchokinetics .Both, the cranio-facial hinge and the palatinum are part of the mechanism that enables corvids to move the upper bill . HenPrevious studies on the foraging behavior of corvids suggest that the studied species vary in the frequency with which they use their repertoire of foraging techniques -8. RooksThese differences become even more apparent, when feeding on carcasses is considered as probing as well. The common raven, which has the longest and most curved bill of the studied corvid species, feed primarily on carcasses, which are, when unopened, accessed through orifices. Thus, a long bill might be beneficial to intrude deeply into the orifices and in addition a heavily curved bill enhances the ability to rip meet apart ,9,10. AlThe frequency with which corvid species turn objects is not as clear as for probing and pecking -7. All sBirds that frequently probe are also assumed to require a smaller binocular field as opposed to birds that frequently peck and turn objects, because the frontal binocular field is thought to guide the bill towards food objects ,23. It iwhole vectors, which also indicate major covariation between bill-length and orbit orientation, might be considered as an adjustment of the frontal binocular field relative to the bill-tip, so that the horizontal projection of the bill-tip within the binocular field does not change between individuals with different bill-length.Another important aspect of the frontal binocular field in birds is the horizontal projection of the bill-tip. Species that handle food objects between their mandibles have been reported to be able to observe their own bill-tip -51. It hAnother likely explanation for the increased angle between bill and cranium and upward positioned eyes found in Eurasian Jays, when compared with the other corvid-species, might be a more downward projection of the bill-tip within the binocular field and an increased vertical extent of the binocular field. These features might be beneficial when gleaning for caterpillar larvae at the lower surface of leaves as reported in Owen , becausewhole and first PLSsep vectors indicate major covariation between blocks in the angle between bill and cranium, so that differences in the angulation might result in differences in the vertical projection of the bill-tip within the binocular field.On the other hand, the decreased angle between bill and cranium and downward positioned eyes found in jackdaws would result in a more upward projection of the bill-tip within the binocular field and might allow jackdaws to gather visual information below the head when the head is held horizontal. This ability might be beneficial when turning objects and searching for food under surface litter, which is a frequent foraging strategy of jackdaws ,6. AccorCorvus-species are characterized by pointed wingtips and possibly by a horizontal head posture and hence, might show an increased flight ability, compared to Eurasian jay and black-billed magpie [Species with high scores on PC 1 (e.g. common raven) and low scores on PC 2 (e.g. jackdaw) are characterized by an upward positioned foramen magnum, compared to Eurasian jay and black-billed magpie. The within-species multivariate regression of size on shape showed a strong relationship of size on the position of the foramen magnum in hooded crow, black-billed magpie and jackdaw, but either no or a weak relationship in common raven, Eurasian jay and rook . Hence, the frequency of probing, bill-length, bill-curvature and sidewise orientation of the eyes is progressively increased from jackdaw, to Eurasian jay, to black-billed magpie, to hooded crow, to rook and to common raven (when feeding on carcasses is considered as probing). With regards to morphological integration, our results suggest that most of the covariation between bill and cranium is due to differences in the topography of the binocular fields and the projection of the bill-tip therein, indicating the importance of visual fields in the foraging ecology of corvids. Further research, especially the morphological integration between bill, cranium and components that are involved in the rhynchokinetics of birds, is of great interest to study functional and species wide trends.The authors declare that they have no competing interests.CK designed the study, analyzed the data and drafted the manuscript. KA placed landmarks and semilandmarks. PG participated and supervised the data analysis. SF and FB supervised the study and were also involved in drafting the manuscript. All authors read and approved the final manuscript.


Tothis aim, we consider residues that are well-conserved in the structure, even if theirconservation cannot easily be recognized in the sequence alignment of the proteinsholding the function. We also analyse protein surface regions and, through theannotation of the solvent-exposed residues, we annotate protein surface patches via astructural comparison performed with stringent parameters and independently of theresidue order in the sequence. Local surface comparison may also help in identifyingnew sequence patterns, which could not be highlighted with other sequence-basedmethods.Relatively few protein structures are known, compared to the enormous amount of sequence data produced in the sequencing of different genomes, and relatively fewprotein complexes are deposited in the PDB with respect to the great amount ofinteraction data coming from high-throughput experiments (two-hybrid or affinitypurification of protein complexes and mass spectrometry). Nevertheless, we can relyon computational techniques for the extraction of high-quality and information-richdata from the known structures and for their spreading in the protein sequence space.We describe here the ongoing research projects in our group: we analyse the proteincomplexes stored in the PDB and, for each complex involving one domain belongingto a family of interaction domains for which some interaction data are available, wecan calculate its probability of interaction with any protein sequence. We analyse thestructures of proteins encoding a function specified in a PROSITE pattern, whichexhibits relatively low selectivity and specificity, and build


Ultrasound is the preferred imaging modality in diagnosis of vascular complications following cardiac catheterization and intervention. In some cases, however, bleeding surrounding the femoral vessels, may severely distort the color Doppler images, making detection of venous complications especially difficult. This report refers to such a case where post-catheterization haematoma was suspected to cause an obstruction of the femoral vein. Spectral Doppler recordings of blood flow in the common femoral vein, up-stream, distal to the hemorrhagic area, confirmed the diagnosis of obstruction by demonstrating changes in the venous flow pattern in the common femoral vein, consistent with venous hypertension. Due to the poor quality of the ultrasound images, the exact cause of the obstruction had to be established by another imaging modality, not affected by haemorrhages. CT showed that the common femoral vein was compressed at the puncture site by surrounding haemorrhages. Thus, when bleeding due to cardiac catheterization is associated with possible venous obstruction and findings by color Doppler are equivocal due to degradation of the color-Doppler image, detection of venous hypertension by spectral Doppler, performed distal to the bleeding area, strongly supports the presence of venous obstruction where the exact cause may be established by CT. Cardiac catheterization, using the femoral approach, is not infrequently associated with local vascular complications occurring in 1.5–9.0% of cases ,3.Color Doppler is the preferred imaging modality in detection and follow-up of venous obstruction. On plain ultrasound (US) images, major veins appear as oval, echo-free structures surrounded by echogenic subcutaneous tissue. Unobstructed veins are completely compressed when moderate pressure is applied to the skin above by the transducer. Unobstructed venous flow, detected by spectral Doppler, is characterized by velocity variations that are synchronous with respiration. When a vein becomes obstructed by a thrombus it becomes incompressible. Simultaneously there is a rise in the vein pressure distal to the obstruction. When the pressure exceeds the peak pressure level in the abdominal veins the characteristic phasic variations in venous flow velocity disappear -6.Post-interventional bleeding into the tissues surrounding the femoral vessels may cause increased scattering of the US echoes leading to distortion of the US images. In addition the bleeding tends to reduce echoes coming from the vein walls, causing the vein echo to blend in with surrounding hypoechogenic haemorrhages and thus no longer be recognized as a separate entity. In these cases, therefore, color Doppler imaging alone may not be fully adequate in the assessment of a possible venous obstruction.A 54-years-old man was admitted with a non-ST-elevation myocardial infarction. He was treated with standard combined antiplatelet therapy (aspirin and clopidogrel) and low-molecular weight heparin. Using a right femoral approach, he underwent percutaneous coronary intervention with stent implantation in a stenotic right coronary artery. During the first hours after the procedure, despite an apparent successful closure of the hole in the arterial wall by a collagen plug device  and standard compression according to department procedures, he developed pain in the right groin followed by a small haematoma and slight swelling of the right leg.US examination of the proximal right CFV, the following day, showed signs of bleeding at the arterial puncture site, which caused considerable degradation of the color-Doppler image due to scattering of the ultrasound. Despite these problems color Doppler demonstrated a 5 cm long cylindric hypo-echogenic structure with a centrally located channel of venous blood flow medial to the CFV Fig. . A possiLocal vascular complications following cardiac catheterizations are not uncommon, the incidence of which are dependent on procedural and patients characteristics  and may This case report demonstrates that, although color Doppler imaging is the preferred modality in diagnosing venous obstruction following cardiac catheterization, bleeding into the surrounding tissues may in some cases cause severe degradation of the color Doppler images and thus may preclude adequate visualization of the CFV. Due to lack of distinct vein wall echoes, the CFV blends in with the surrounding hypoechogenic, thrombus-like haemorrhages, making differentiation between an intravenous thrombus and a perivascular haematoma compressing the vein from the outside virtually impossible ,7-9.Our findings show that in these cases spectral-Doppler recordings, performed away from the bleeding area, at the distal end of the CFV, was able to demonstrate venous flow disturbances consistent with venous hypertension supporting the clinical suspicion of venous obstruction down-stream, at the groin.The problem of inadequate US visualization of the CFV in connection with cardiac catheterizations has been discussed in a recent publication where it was warned against overlooking short partial obstructions of the CFV . In anotTherefore, in cases where the femoral vessels are insufficiently visualized by color-Doppler due to bleeding at the puncture site, the US operator should use spectral-Doppler recordings to assess venous flow up-stream, at the level of the distal CFV or the proximal part of the superficial femoral vein, looking for signs of venous hypertension secondary to venous obstruction at the groin. Due to inferior quality of color-Doppler images in these cases, CT, which is largely unaffected by bleeding, may be of considerable help in establishing an exact cause of the venous obstruction.Written informed consent was obtained from the patient for publication of this case report and accompanying images.The authors declare that they have no competing interests.MTL carried out the US examination and drafted the manuscript. EG revised the manuscript. JW carried out the interpretation of the CT examination and revised the manuscript. OMP helped in the evaluation of the US examination and drafting of the manuscript.


Earlier studies indicate that midwife-led birth settings are associated with modest benefits, including reduced medical interventions and increased maternal satisfaction. The generalizability of these studies to birth settings with low intervention rates, like those generally found in Norway, is not obvious. The aim of the present study was to compare intervention rates associated with labour in low-risk women who begin their labour in a midwife-led unit and a conventional care unit.Eligible participants were low-risk primiparas who met the criteria for delivery in the midwife-led ward regardless of which cohort they were allocated to. The two wards are localised at the same floor. Women in both cohorts received the same standardized public antenatal care by general medical practitioners and midwifes who were not involved in the delivery. After admission of a woman to the midwife-led ward, the next woman who met the inclusion criteria, but preferred delivery at the conventional delivery ward, was allocated to the conventional delivery ward cohort. Among the 252 women in the midwife-led ward cohort, 74 (29%) women were transferred to the conventional delivery ward during labour.Emergency caesarean and instrumental delivery rates in women who were admitted to the midwife-led and conventional birth wards were statistically non-different, but more women admitted to the conventional birth ward had episiotomy. More women in the conventional delivery ward received epidural analgesia, pudental nerve block and nitrous oxide, while more women in the midwife-led ward received opiates and non-pharmacological pain relief.We did not find evidence that starting delivery in the midwife-led setting offers the advantage of lower operative delivery rates. However, epidural analgesia, pudental nerve block and episiotomies were less often while non-pharmacological pain relief was often used in the midwife-led ward. In many places world-wide all births are concentrated to larger maternity clinics, regardless of whether the woman is seen as a healthy, low-risk woman, or whether there are underlying illness or other risk factors existent. During recent decades, particularly in parts of the world with thriving private practice, obstetricians have increasingly taken over responsibility for normal birth ,2. ConcoA Cochrane review of all six randomized or quasi-randomized controlled trials compared intervention rates in conventional institutional birth settings and low risk midwife-led units . MidwifeThe aim of the present study was to compare intervention rates associated with labour in low-risk women who begin their labour in a midwife-led unit and a conventional care unit.This was a prospective, non-randomized observational study approved by the regional ethical committee and the Norwegian Data Inspectorate.In the Department of Obstetrics and Gynaecology, Haukeland University Hospital, a total of about 5000 women are giving birth annually. In 1995 the maternity section was reorganised through the establishment of a midwife-led ward (MLW) for women with low risk for complications with the capacity of 1500 deliveries per year. Thus, 3500 deliveries take place in the conventional delivery ward (CDW) per year. Main characteristics of the two wards are presented in Table Pregnant women are selected for delivery at the MLW at different times during pregnancy, mostly according to their own preference if they meet the conditions for admittance to the ward. However, the final selection occurs at admittance for labour at the reception ward by a midwife. If the woman requests or needs epidural analgesia at arrival to the reception ward, she is admitted to the CDW.In the second stage of labour, women were not transferred from the MLW to the CDW unless there was need of emergency caesarean section. The tertiary care CDW with about 3500 labours per year is equipped and staffed for dealing with severe medical situations during labour. Also in the CDW midwifes attend low risk births and obstetricians are usually not present, but are called in case of complications. As in the MLW, pain relief like movement, massage, shower, bathtube, acupuncture, pudental nerve block and opiates were available as were nitrous oxide, epidural analgesia Table , but becWomen in both cohorts received the same standardized public antenatal care by general medical practitioners and midwifes who were not involved in the delivery.To ensure comparability the study was limited to primiparous women. Eligible participants were low-risk primiparous women who met the criteria for delivery in the MLW regardless of whether they were allocated to the MLW- or CDW cohort, and were admitted to labour between 36 and 42 weeks of gestation.Expressed desire of epidural analgesia at admission to the hospital before admission to the labour ward.Allocating the participants, we used as strict as possible alternation between the cohorts. After admission of a woman to the MLW, the next woman who met the inclusion criteria, but preferred delivery at the CDW, was allocated to the CDW cohort. During the study, there were no changes in the inclusion criteria. This observational study did not affect the choice of place of birth. 252 and 201 women were included in the MLW and CDW cohorts, respectively . Differences between birth invention rates and outcomes in the cohorts were assessed by Chi square or Fisher's exact test where appropriate and logistic regression. Unadjusted and adjusted odds ratios (ORs) for maternal age, smoking habits, educational level and marital status with 95% confidence intervals (CI) were calculated. Time from regular contractions to delivery and duration of the second stage of birth in the cohorts were compared after ln-transformation to normality.Pre-study assessment of sample size, given an event rate of 10% in the CDW cohort, indicated a study size of 200 subjects in each cohort.Maternal characteristics in both cohorts are shown in Table n = 103; 51%) and belief that the ward was safer for mother and infant . Among reasons for the choice of the MLW were facilities like bathroom near the delivery room and a generally positive impression of the ward after having been shown around the ward or it had been recommended by women with experience from the wards . Other emphasised the possibility of 'natural' birth  and that they preferred pain relief without analgesia .Place of birth was planned before admittance in 162 (81%) and 203 (81%) women in the CDW and MLW cohorts, respectively (data not presented). Among reasons for the choice of giving birth at the CDW were availability of pain relief other than in the MLW (n = 74) the use of operative delivery was generally higher , forceps  or vacuum ) (Data not presented). There were three main reasons for transfer to the CDW during labour: Need of epidural analgesia according to the woman's preference or on medical indication , need of cardiotocography  and protracted labour . After adjustment, the difference between the cohorts in the proportions of women who had an episiotomy was marginally significant, 36% in the CDW and 29% in the MLW cohort.The rates of operative delivery in the cohorts were statistically equal Table ; the caen = 141, 70%) and side position . In the MLW cohort positions were more various and the most used were kneeling position , birthing stool , half sitting , side position  and use of 'sacco-sack'  (data not presented).In the CDW cohort the most used birth position was half sitting  and intact perineum (without tears grade I-IV and episiotomy) were also statistically non-different (data not presented).In the two cohorts, time from regular contractions to delivery and duration of the second stage of labour, rates of excessive post-partum bleeding (=1000 ml), Apgar scores <7 5 minutes postpartum and transfer to the neonatal intensive care unit were statistically non-different. After adjustment, the rates of perineal tears grades III-IV in the two cohorts  has also been found in other studies . The genWe did not find evidence that starting delivery in the midwife-led setting offers the advantage of lower operative delivery rates. However, epidural analgesia, pudental nerve block and episiotomies were less often and non-pharmacological pain relief more used in the MLW cohort.CDW: conventional delivery ward; MLW: midwife-led ward; OR: odds ratio; WHO: World Health Organization.The authors declare that they have no competing interests.BIE and ABVN discussed study design, supervised the collection of data and wrote the report. SR conducted the analyses and edited the report. All authors are guarantors of the paper.The pre-publication history for this paper can be accessed here:


Telomeres, guanine-rich tandem DNA repeats of the chromosomal end, provide chromosomal stability, and cellular replication causes their loss. In somatic cells, the activity of telomerase, a reverse transcriptase that can elongate telomeric repeats, is usually diminished after birth so that the telomere length is gradually shortened with cell divisions, and triggers cellular senescence. In embryonic stem cells, telomerase is activated and maintains telomere length and cellular immortality; however, the level of telomerase activity is low or absent in the majority of stem cells regardless of their proliferative capacity. Thus, even in stem cells, except for embryonal stem cells and cancer stem cells, telomere shortening occurs during replicative ageing, possibly at a slower rate than that in normal somatic cells. Recently, the importance of telomere maintenance in human stem cells has been highlighted by studies on dyskeratosis congenital, which is a genetic disorder in the human telomerase component. The regulation of telomere length and telomerase activity is a complex and dynamic process that is tightly linked to cell cycle regulation in human stem cells. Here we review the role of telomeres and telomerase in the function and capacity of the human stem cells. Telomere, a complex of guanine-rich repeat sequences and associated proteins, caps and protects every eukaryotic chromosome end against chromosomal fusion, recombination, and terminal DNA degradation . TelomerTERT (telomerase reverse transcriptase) gene and a template RNA TERC (telomerase RNA component). Telomerase can add telomeric repeats onto the chromosome ends, and prevents the replication-dependent loss of telomere and cellular senescence in highly proliferative cells of the germline and in the majority of cancers  . BasicalMutations in telomerase core components, TERT and TERC, have been found in patients suffering from aplastic anaemia and dyskeratosis congenital (DKC), as described later. Both diseases are characterised by bone marrow failure and/or skin abnormalities, resulting from defects in maintaining the haematopoietic stem cell compartment. Moreover, cancer and ageing, two biological processes in which the role of telomerase has been implicated, are increasingly recognised as stem cell diseases. For example, some cancers may originate from the transformants of normal stem cells or progenitor cells, so-called cancer stem cells (CSCs), whereas ageing is induced through a progressive functional decline in certain stem cells . The difference of the levels of telomerase activity in NHSC components of various organs is likely derived from the difference of their cellular turnover among organs. In this review, as representative NHSCs, we focused on MSCs.−1) and telomerase activity was undetectable  in response to shortened telomeres impairs repopulation capacity of stem cells in age-related diseases and senescence  cells display high levels of telomerase activity and hTERT expression, both of which are rapidly downregulated during differentiation . The dowIn cloned animals originating from adult nuclei with shortened telomeres, telomere length in somatic cells has been found to be comparable with that in age-matched normal animals originating from a fertilised egg with long telomeres. This finding indicates that the enucleated oocyte has the ability to reset the telomere length of the nucleus derived from a donor adult somatic cell by the elongation of telomeres (The first evidence that a rare population of stem cells maintain the human cancer came from a study on haematopoietic malignancies , are conTo maintain their characteristic replicative ability, CSCs should have telomere-lengthening mechanisms; however, since the identification and purification of CSCs are difficult in most solid tumors, the telomere and telomerase dynamics in CSCs remain unclear. Regardless of the derivation of CSCs, normal stem cells, committed progenitor cells, or differentiated cells , CSCs miRecent research has focused on telomeres and their role in cell cycle regulation, cellular senescence, and genetic instability; however, much remains to be learned, and what is clear is the complexity of telomere and telomerase interactions in cell cycle progression and cell signaling in both normal somatic cells and malignant cells. Both elements have a key role in determining proliferative capacity in all human cells. Telomere shortening occurs in most human somatic cells and triggers DNA damage responses that mediate cell cycle arrest or apoptosis, while HSCs can escape this trigger by employing a telomerase-dependent telomere lengthening mechanism in replication. This process in normal HSCs, however, appears to have only limited potential in extending the replicative capacity, because the telomere shortening occurs slowly but steadily in blood cells with ageing. In contrast, CSCs should have complete telomere-lengthening mechanisms that provide indefinite proliferation capacity. Research on telomere-telomerase dynamics in stem cells could lead to the development of novel aetiology-based radical therapies in ageing-related diseases and cancers.


Bile duct injury is a severe and potentially life-threatening complication of laparoscopic cholecystectomy. Several series have described a 0.5% to 0.6% incidence of bile duct injury during laparoscopic cholecystectomy. The aim of this study was to analyze the presentation, characteristics, related investigation, and treatment results of major bile duct injuries after laparoscopic cholecystectomy.A rare case of a 48-year-old Greek woman with a triple bile duct injury (right and left hepatic duct ligation and common bile duct cross-section) is presented. A Roux en Y hepaticojejunostomy was performed after repeated endoscopic retrograde cholangiopancreatographies, percutaneous transhepatic catheterization of the ducts and magnetic resonance cholangiographies to delineate the biliary anatomy and assess the level of injury.Early recognition and an adequate multidisciplinary approach are the cornerstones for the optimal final outcome. Suboptimal management of injuries often leads to more extensive damage to the biliary tree and its vasculature. Early referral to a tertiary care center with experienced hepatobiliary surgeons and skilled interventional radiologists would appear to be necessary to assure optimal results. Gallstone disease is one of the most common digestive health problems . LaparosThe management of patients following major bile duct injury is a surgical challenge often requiring the skills of experienced hepatobiliary surgeons at tertiary referral centers . CollaboThe aim of this study was to analyze the presentation, characteristics, related investigation, and treatment results of a case with major complex bile duct injury after LC.A 48-year-old Greek female patient was referred to our institution for the management of biliary trauma after laparoscopic cholecystectomy. In her medical history, she had had two laparotomies: an ileoanal anastomosis with j pouch for ulcerative colitis 15 years ago, while 5 years ago she was driven to the operating room after a colonoscopy for peritonitis. Due to non-specific upper gastrointestinal symptoms she had had an upper abdominal ultrasound (US) that revealed cholelithiasis  2 months before surgery and elective laparoscopic cholecystectomy was performed 18 months before her referral to us.The duration of laparoscopic cholecystectomy was 150 minutes while the procedure was completed laparoscopically and there is no record of intraoperatively identified biliary injury. From the 2nd postoperative day and up to her referral to our institution, recurrent episodes of cholangitis with severe pain, fever with chills and jaundice began. Magnetic resonance cholangiography (MRC) was performed in order to delineate the biliary anatomy and assess the level of injury. A triple bile duct injury, with right and left hepatic duct ligation and common bile duct cross-section, was revealed  after LC is a difficult problem and depends on the time of diagnosis after the initial injury and the type, extent and level of the injury. The aim of the treatment is immediate management of the associated sepsis, fistula, and obstruction of the biliary system. Identification and categorization of the type of MBDI are the next steps. Once this is done, definitive repair of the injury should be performed. Postoperative follow-up and guidance, are vital parts of this prolonged treatment protocol. The reported incidence of MBDI after laparoscopic cholecystectomy has been shown to be higher than that after open cholecystectomy . SeveralDuring cholecystectomy, much emphasis is given to complete exposure of the operating area. During the exposure of peritoneal attachments in Calot's triangle, anatomical variations should be clearly identified, and the cystic duct should not be separated until the junction of the common hepatic and cystic ducts is positively identified. There is no confluence of any other abnormal ducts into the cystic duct.Sometimes the anatomical structure of Calot's triangle is not very clear because of congestion, edema and fragility of the tissues around the cystic duct in acute suppurative or gangrenous cholecystitis. Fibrous tissue scars are often formed in Calot's triangle in atrophic cholecystitis. It is more difficult to avoid intraoperative bile duct injuries (IBDI) in such conditions, when correct identification of Calot's triangle is less likely.Injuries to the bile duct system during laparoscopic cholecystectomy are an unaltered cause for concern not necessarily related to the "learning curve" of the operating surgeon as suggested in the past . In receProper diagnosis and appropriate treatment of MBDI, are paramount in preventing life-threatening complications of cholangitis, biliary cirrhosis, portal hypertension, end-stage liver disease, and death. At the time of referral, all patients with suspected bile duct injury should undergo US and computed tomography (CT) so that any dilatation or fluid collection can be found. Those techniques must be combined with magnetic resonance cholangiopancreatographies (MRCP), ERCP or percutaneous transhepatic catheterization (PTC) in order to delineate the biliary anatomy . All patPre-operative imaging studies such as magnetic resonance cholangiographies (MRC), ERCP, and PTC correctly delineate the location and nature of MBDI ,14. SurgOnce the sepsis and leaks have been controlled and the MBDI is classified, a hepaticojejunostomy should be constructed to a Roux-en-Y jejunal limb, or less commonly an end to side Roux-en-Y choledochojejunostomy. Satisfactory results have been reported by many authors using the Roux-en-Y hepaticojejunostomy. For strictures involving the bifurcation of left or right hepatic ducts, bilateral hepaticojejunostomies may be necessary. Level of injury is an important factor; the greater the level of the injury, the poorer the outcome after the procedure. Other factors include the timing of the repair, the performance of pre-operative cholangiography, the choice of surgical procedure, the expertise of the surgeon performing the repair, and the presence of concomitant vascular injury . There aIn summary, MBDI after LC is a major problem that requires a multidisciplinary approach at a tertiary level center. Sepsis, biliary leaks, and collections should be managed appropriately, and proper classification of the MBDI via imaging needs to be done before the surgical repair. Roux-en-Y hepaticojejunostomy yields excellent results in these cases. Life-threatening complications can occur as a result of delayed referral or, rarely, after surgical repair. Although overall complications are frequent, almost all can be managed non-operatively. These data support the concept of early referral to a tertiary care center with experienced hepatobiliary surgeons and skilled interventional radiologists to assure optimal short-term and long-term outcomes.CT: computed tomography; ERCP: endoscopic retrograde cholangiopancreatography; LC: laparoscopic cholecystectomy; PTC: percutaneous transhepatic cholangiography; US: ultrasound; IBDI: intraoperative bile duct injuries; MRC: magnetic resonance cholangiography; MBDI: major bile duct injuriesThe authors declare that they have no competing interests.<Author: From the BioMed guidelines, authors IGD, MMK and VK don't seem to qualify as authors. An "author" is generally considered to be someone who has made substantive intellectual contributions to a published study. To qualify as an author one should 1) have made substantial contributions to conception and design, or acquisition of data, or analysis and interpretation of data; 2) have been involved in drafting the manuscript or revising it critically for important intellectual content; and 3) have given final approval of the version to be published. Each author should have participated sufficiently in the work to take public responsibility for appropriate portions of the content. Acquisition of funding, collection of data, or general supervision of the research group, alone, does not justify authorship. All contributors who do not meet the criteria for authorship should be listed in an acknowledgments section. Examples of those who might be acknowledged include a person who provided purely technical help, writing assistance, or a department chair who provided only general support. After all authors meeting they have decided that IGD and MMK should be included to the authors as they have played an importaned role to the manuscript conception and they agree that VK should be listed in the acknowledgement section>AM carried out the operation and contributed to acquisition of consent and critical review of the manuscript. NP, PA, EEL and GP all contributed to manuscript conception, research, acquisition of data, drafting and writing of the manuscript. IGD contributed to research, organizing, drafting, and writing of the manuscript. MMK contributed to writing of the manuscript. All authors read and approved the final manuscript.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.