Predictive value of intraoperative neurophysiological monitoring during cervical spine surgery: a prospective analysis of 1055 consecutive patients.
Despite the growing use of multimodal intraoperative monitoring (IOM) in cervical spinal surgery, limited data exist regarding the sensitivity, specificity, and predictive values of such a technique in detecting new neurological deficits in this setting. The authors sought to define the incidence of significant intraoperative electrophysiological changes and new postoperative neurological deficits in a cohort of patients undergoing cervical surgery. The authors conducted a prospective analysis of a consecutive series of patients who had undergone cervical surgery during a 5-year period at a university-based neurosurgical unit, in which multimodal IOM was recorded. Sensitivity, specificity, positive predictive values (PPVs), and negative predictive values (NPVs) were determined using standard Bayesian techniques. The study population included 1055 patients (614 male and 441 female) with a mean age of 55 years. The IOM modalities performed included somatosensory evoked potential (SSEP) recording in 1055 patients, motor evoked potential (MEP) recording in 26, and electromyography (EMG) in 427. Twenty-six patients (2.5%) had significant SSEP changes. Electromyographic activity was transient in 212 patients (49.6%), and 115 patients (26.9%) had sustained burst or train activity. New postoperative neurological deficits occurred in 34 patients (3.2%): 6 had combined sensory and motor deficits, 7 had new sensory deficits, 9 had increased motor weakness, and 12 had new root deficits. Of these 34 patients, 12 had spinal tumors, of which 7 were intramedullary. Overall, of the 34 new postoperative deficits, 21 completely resolved, 9 partially resolved, and 4 had no improvement. The deficits that completely resolved did so on average 3.3 months after surgery. Patients with deficits that did not fully resolve (partial or no improvement) were followed up for an average of 1.8 years after surgery. Somatosensory evoked potentials had a sensitivity of 52%, a specificity of 100%, a PPV of 100%, and an NPV of 97%. Motor evoked potential sensitivity was 100%, specificity 96%, PPV 96%, and NPV 100%. Electromyography had a sensitivity of 46%, specificity of 73%, PPV of 3%, and an NPV of 97%. Combined neurophysiological IOM with EMG and SSEP recording and the selective use of MEPs is helpful for predicting and possibly preventing neurological injury during cervical spine surgery.


Chlamydial pneumonia in children requiring hospitalization: effect of mixed infection on clinical outcome.
The etiology of community-acquired pneumonia (CAP) in a children's hospital was studied among 209 previously healthy children treated from August 1, 2001 to July 31, 2002. A total of 26 children (12.4%) with a diagnosis of chlamydial infection were included in this study. The diagnosis of chlamydial infection was based on either a positive immunofluorescent assay result for chlamydial antigen in sputum, or positive serologic results for immunoglobulin M (IgM), an IgG titer >/=1:640 or a 4-fold rise in IgG titer by microimmunofluorescence test. Fourteen patients (53.8%) were female and 20 (76.9%) were less than 5 years of age. The onset of infection occurred between August and January in 21 cases (80.7%). Twenty one patients (80.8%) had other pathogens identified. Fever and cough were the most common presenting symptoms. The signs and symptoms were similar for the children with and without coinfection except for tachypnea and wheezing sound, which were significantly more common in patients with mixed infection. None of the laboratory parameters seemed to be specific for chlamydial infection; however, serum C-reactive protein level was significantly higher in cases with mixed infection. Among the 26 children, 12 (46.2%) needed respiratory therapy, and most of them (91.7%, 11/12) had coinfection. Two patients (7.7%) with mixed infection were admitted to the pediatric intensive care unit. One had lobar pneumonia with pleural effusion and the other had necrotizing pneumonia requiring surgical intervention. None of the patients died. In conclusion, Chlamydia sp. was identified in 12.4% of children with CAP in this series, and mixed infections were common (80.8%) among these patients. The clinical course of chlamydial pneumonia was not serious in most patients, but alertness is needed to the possibility of developing severe pneumonia in cases with bacterial coinfection.


Effect of microinjections of apamin into the A10 dopamine region of rats: a behavioral and neurochemical analysis.
Hyperpolarization of dopamine neurons by activation of D2 and gamma-aminobutyric acidB receptors involves an increased conductance of K+ ions. Apamin, a blocker of Ca2(+)-activated K+ channels, has been reported to increase activity of dopamine neurons. Increased activity of the mesolimbic dopamine system is associated with increased motor activity. Thus, we investigated the behavioral and neurochemical effects of acute and daily microinjections of apamin into the A10 region of the rat. Apamin increased motor activity in a dose-dependent manner, and this effect was blocked by pretreatment with 0.1 mg/kg haloperidol. In postmortem analysis, 6.0 pmol of apamin significantly increased the levels of dihydroxyphenylacetic acid in the A10 region and of dihydroxyphenylacetic acid and homovanillic acid in the nucleus accumbens, and 2.0 pmol of apamin significantly increased the level of dopamine in the prefrontal cortex. In vivo dialysis in the nucleus accumbens of freely moving rats revealed that apamin elevated extracellular dopamine metabolites. Rats receiving daily microinjections of apamin into the A10 region did not exhibit an augmentation in motor activity, suggesting that rats did not become sensitized to chronic treatment. These data are discussed in terms of the role of apamin-sensitive dopamine mechanisms in motor behavior and sensitization of these motor behaviors.


Utility of 211At-Trastuzumab for the Treatment of Metastatic Gastric Cancer in the Liver: Evaluation of a Preclinical α-Radioimmunotherapy Approach in a Clinically Relevant Mouse Model.
A liver metastasis from a primary gastric cancer (LMGC) is relatively common and results in an extremely poor prognosis due to a lack of effective therapeutics. We here demonstrate in a clinically relevant mouse model that an α-particle radioimmunotherapy approach with 211At-labeled trastuzumab has efficacy against LMGCs that are positive for human epidermal growth factor receptor 2 (HER2). Methods:211At was produced in a cyclotron via a 209Bi (α,2n) 211At reaction. 211At-trastuzumab was subsequently generated using a single-step labeling method. NCI-N87 cells (HER2-positive human gastric cancer cells) carrying a luciferase gene were intrasplenically transplanted into severe combined immunodeficiency mice to generate an HER2-positive LMGC model. A biodistribution study was then conducted through the intravenous injection of 211At-trastuzumab (1 MBq) into these LMGC xenograft mice. In parallel with this experimental therapy, phosphate-buffered saline, intact trastuzumab, or 211At-nonspecific human IgG (1 MBq) was injected into control groups. The therapeutic efficacy was evaluated by monitoring tumor changes by chemiluminescence imaging. Body weights, white blood cell counts, and serum markers of tissue damage were monitored at regular intervals. Microdosimetry using a CR-39 plastic detector was also performed. Results: The biodistribution analysis revealed an increased uptake of 211At-trastuzumab in the metastasized tumors that reached approximately 12% of the injected dose per gram of tissue (%ID/g) at 24 h. In contrast, its uptake to the surrounding liver was about 4 %ID/g. The LMGCs in the mouse model reduced dramatically at 1 wk after the single systemic injection of 211At-trastuzumab. No recurrences were observed in 6 of 8 mice treated with this single injection, and their survival time was significantly prolonged compared with the control groups, including the animals treated with 211At-nonspecific antibodies. No severe toxicities or abnormalities in terms of body weight, white blood cell number, liver function, or kidney parameters were observed in the 211At-trastuzumab group. Microdosimetric studies further revealed that 211At-trastuzumab had been delivered at an 11.5-fold higher dose to the LMGC lesions than to the normal liver. Conclusion: α-radioimmunotherapy with 211At-trastuzumab has considerable potential as an effective and safe therapeutic option for LMGC.


Behavioral and neural indices of affective coloring for neutral social stimuli.
Emotional processing often continues beyond the presentation of emotionally evocative stimuli, which can result in affective biasing or coloring of subsequently encountered events. Here, we describe neural correlates of affective coloring and examine how individual differences in affective style impact the magnitude of affective coloring. We conducted functional magnetic resonance imaging in 117 adults who passively viewed negative, neutral and positive pictures presented 2 s prior to neutral faces. Brain responses to neutral faces were modulated by the valence of preceding pictures, with greater activation for faces following negative (vs positive) pictures in the amygdala, dorsomedial and lateral prefrontal cortex, ventral visual cortices, posterior superior temporal sulcus, and angular gyrus. Three days after the magnetic resonance imaging scan, participants rated their memory and liking of previously encountered neutral faces. Individuals higher in trait positive affect and emotional reappraisal rated faces as more likable when preceded by emotionally arousing (negative or positive) pictures. In addition, greater amygdala responses to neutral faces preceded by positively valenced pictures were associated with greater memory for these faces 3 days later. Collectively, these results reveal individual differences in how emotions spill over onto the processing of unrelated social stimuli, resulting in persistent and affectively biased evaluations of such stimuli.


An instrumented valved holding chamber with facemask to measure application forces and flow in young asthmatic children.
Pressurized metered dose inhalers (pMDIs), combined with a valved holding chamber (VHC) and facemask, are often used for young asthmatic children. When using a VHC with facemask, a tight seal between the facemask and the patient's face is crucial for efficient pulmonary aerosol delivery. Realistic parameters for in vitro bench testing are not well known. A custom instrumented OptiChamber Diamond VHC, known as the Facemask Datalogger, was developed to measure the real-time application of force and the air flow through the VHC and facemask. Thirty asthmatic children aged 1-4 years from the Kinderhaven outpatient clinic, who were prescribed a pMDI/VHC with facemask for regular use, were included in the study. Using the Facemask Datalogger, the parent applied the facemask to the face of the child during normal tidal breathing, and force and flow were recorded. This was repeated three times. A video of the procedure was made and scored on cooperation (scale of 1-5). Mean application force was 4 N (± 1.5) equal to 411 g (± 156) when expressed as a weight equivalent; intrasubject variability in application force was 23% (± 23); intersubject variability in application force was 39%; time needed to empty the VHC was 4.5 sec (± 2.9); breaths needed to empty the VHC were 2.9 (± 1.1); and mean cooperation score was 4.3 (± 0.8). Age was correlated with time (r=-0.49; p=0.006) and breaths needed to empty the VHC (r=-0.75; p<0.001), and observer cooperation score (r=0.65; p<0.001). The Facemask Datalogger is useful for measuring application force and air flow in vivo. Mean application force was lower than assumed in other studies. Older children emptied the VHC faster, with fewer breaths and better cooperation. The data from this study can be used in the future development and testing of new facemasks and VHCs.


[Psychiatry as a clinical science. From Emil Kraepelin to neo-Kraepelinism].
The fundamentals of Kraepelin's theory have been revisited by researchers known as "neokraepelians", from the stand point of the neurobiology. In the case of the revision of Kraepelin, as it happens with other authors, there are some acritical reductionisms. This article tries to make a contribution to the understanding of Kraepelin's thought as well as the historical context of his work, starting with a revision of the clinical and practical position in the present psychiatry.


Dissecting cellulitis in a white male: a case report and review of the literature.
Dissecting cellulitis is an uncommon, chronic, progressive suppurative disease of unknown etiology. It is characterized by painful papules and nodules, interconnecting sinus tracts, purulent drainage, and scarring alopecia. This disease predominately affects young black men, but is rarely reported in white males. The refractory nature of this process makes treatment difficult. We report a case of dissecting cellulitis in a white male, which responded to oral isotretinoin.


Evolution and Spatiotemporal Dynamics of Enterovirus A71 Subgenogroups in Vietnam.
Enterovirus A71 (EV-A71) is the major cause of severe hand, foot, and mouth disease and viral encephalitis in children across the Asia-Pacific region, including in Vietnam, which has experienced a high burden of disease in recent years. Multiple subgenogroups (C1, C4, C5, and B5) concurrently circulate in the region with a large variation in epidemic severity. The relative differences in their evolution and epidemiology were examined within Vietnam and globally. A total of 752 VP1 gene sequences were analyzed (413 generated in this study combined with 339 obtained from GenBank), collected from patients in 36 provinces in Vietnam during 2003-2013, along with epidemiological metadata. Globally representative VP1 gene datasets of subgenogroups were used to coestimate time-resolved phylogenies and relative genetic diversity to infer virus origins and regional transmission network. Despite frequent virus migration between countries, the highest genetic diversity of individual subgenogroups was maintained independently for several years in specific Asian countries representing genogroup-specific sources of EV-A71 diversity. This study highlights a persistent transmission network of EV-A71, with specific Asian countries seeding other countries in the region and beyond, emphasizing the need for improved EV-A71 surveillance and detailed genetic and antigenic characterization.


An engineered hyaluronan synthase: characterization for recombinant human hyaluronan synthase 2 Escherichia coli.
The Class I hyaluronan synthase (HAS) is a unique glycosyltransferase synthesizing hyaluronan (HA), a polysaccharide composed of GlcUA and GlcNAc, by using one catalytic domain that elongates two different monosaccharides. As for the synthetic mechanism, there are two alternative manners for the sugar elongation process. Some bacterial HASs add new sugars to the non-reducing end of the acceptor to grow polymers. On the other hand, some vertebrate enzymes seem to transfer sugars to the reducing end. Expression of vertebrate HASs as active and soluble proteins will accelerate further precise insight into mechanisms of sugar elongation reactions by natural HASs. Since large scale production of HA polymers and oligomers would become powerful tools both for basic studies and new biotechnology to create functional carbohydrates in medicinal purposes, advent of an efficient method for the expression of HASs in Escherichia coli is strongly expected. Here we communicate the first success of the production of recombinant human HAS2 proteins composed of only the catalytic region in E. coli as the active form. It was demonstrated that an engineered HAS2 expressed in E. coli exhibited significant activity to synthesize a mixture of HAS oligomers from 8-mer (HA8) to 16-mer (HA16). Engineered HAS2 prepared herein elongated sugars from exogenous tetrasaccharide to form polymers with a direction to the non-reducing end. According to the present results, large scale production of engineered recombinant HASs is to be performed using E. coli that will provide practical and economic advantages in manufacturing enzymes for use in the synthesis of various oligomeric HA molecules and their industrial applications.


Prevalence and Influencing Factors of Post-Traumatic Stress Disorder Among Survivors in the Hard-Hit Areas Ten Years After the Wenchuan Earthquake: A Cross-Sectional Study.
Post-traumatic stress disorder (PTSD) is common psychological distress after natural disasters, which is persistent. Chronic PTSD leads to a heavy disease burden. The purpose of this study is to explore the prevalence and influencing factors of chronic PTSD among survivors in the hard-hit areas ten years after the Wenchuan earthquake. A cross-sectional survey was conducted on residents aged 16 or above in hard-hit areas through a multi-stage sampling approach ten years after the Wenchuan earthquake. The items of the questionnaire included demographic characteristics and earthquake exposure factors, and the PTSD Checklist-Civilian Version (PCL-C) was used to evaluate the PTSD of the respondents. A total of 1039 complete questionnaires were obtained. The median age of 1039 respondents was 60 years, 63.2% of whom were female, 70.2% were illiterate or had received primary education, and 58% had an annual household income of less than 20,000 yuan (US$ 2871.3). The rate of PTSD was 9.1% (95/1039). After controlling for confounding factors, it was found that higher income level and education level, and moving to concentrated rural settlement (CRS) after the earthquake might be protective factors for the long-term mental health of survivors in the hard-hit areas, and the loss of immediate families in the earthquake was an important risk factor. Even though ten years have passed since the Wenchuan earthquake, the survivors in the hard-hit areas still have a serious mental disorder. The local government and health-care institutions should take appropriate measures to improve the mental health of residents.


When can Muslims withdraw or withhold life support? A narrative review of Islamic juridical rulings.
When it is ethically justifiable to stop medical treatment? For many Muslim patients, families, and clinicians this ethical question remains a challenging one as Islamic ethico-legal guidance on such matters remains scattered and difficult to interpret. In light of this gap, we conducted a systematic literature review to aggregate rulings from Islamic jurists and juridical councils on whether, and when, it is permitted to withdraw and/or withhold life-sustaining care. A total of 16 fatwās were found, 8 of which were single-author rulings, and 8 represented the collective view of a juridical council. The fatwās are similar in that nearly all judge that Islamic law, provided certain conditions are met, permits abstaining from life-sustaining treatment. Notably, the justifying conditions appear to rely on physician assessment of the clinical prognosis. The fatwās differ when it comes to what conditions justify withdrawing or withholding life- sustaining care. Our analyses suggest that while notions of futility greatly impact the bioethical discourse regarding with holding and/or withdrawal of treatment, the conceptualization of futility lacks nuance. Therefore, clinicians, Islamic jurists, and bioethicists need to come together in order to unify a conception of medical futility and relate it to the ethics of withholding and/or withdrawal of treatment.


Active tuning of nonlinear absorption in a supramolecular zinc diphenylporphyrin-pyridine system.
We report on an active tuning of nonlinear absorption from reverse saturable absorption to saturable absorption in supramolecular zinc diphenylporphyrins by the combination of molecular and supramolecular levels at 532, 542 and 552 nm. Firstly, the modifications of molecular structures with bromination result in a discrete but regular change in magnitude and sign of nonlinear absorption (NLA). Furthermore, a fine tuning of NLA was obtained by the intermolecular weak interaction of pyridine and zinc porphyrins. Using an association model, we theoretically simulate the change of NLA. Compared with modifying molecular structures of conventional organic materials, the weak intermolecular interaction of supramolecular porphyrins has another advantage that it can be realized more easily and flexibly to change NLA.


Brief recommendations for participation in leisure time or competitive sports in athletes-patients with coronary artery disease: Summary of a Position Statement from the Sports Cardiology Section of the European Association of Preventive Cardiology (EAPC).
This paper presents a brief summary of the recommendations from the Sports Cardiology section of the European Association of Preventive Cardiology (EAPC) on sports-participation in patients with coronary artery disease, coronary artery anomalies or spontaneous dissection of the coronary arteries, all entities being associated with myocardial ischaemia.1 Given the wealth of evidence supporting the benefits of exercise for primary and secondary prevention of coronary artery disease, individuals should be restricted from competitive sport only when a substantial risk of adverse event or disease progression is present. These recommendations aim to encourage regular physical activity including participation in sports and, with reasonable precaution, ensure a high level of safety for all individuals with coronary artery disease. The present document is based on available current evidence, but in most instances because of lack of evidence, also on clinical experience and expert opinion.


Dissociable brain mechanisms underlying the conscious and unconscious control of behavior.
Cognitive control allows humans to overrule and inhibit habitual responses to optimize performance in challenging situations. Contradicting traditional views, recent studies suggest that cognitive control processes can be initiated unconsciously. To further capture the relation between consciousness and cognitive control, we studied the dynamics of inhibitory control processes when triggered consciously versus unconsciously in a modified version of the stop task. Attempts to inhibit an imminent response were often successful after unmasked (visible) stop signals. Masked (invisible) stop signals rarely succeeded in instigating overt inhibition but did trigger slowing down of response times. Masked stop signals elicited a sequence of distinct ERP components that were also observed on unmasked stop signals. The N2 component correlated with the efficiency of inhibitory control when elicited by unmasked stop signals and with the magnitude of slowdown when elicited by masked stop signals. Thus, the N2 likely reflects the initiation of inhibitory control, irrespective of conscious awareness. The P3 component was much reduced in amplitude and duration on masked versus unmasked stop trials. These patterns of differences and similarities between conscious and unconscious cognitive control processes are discussed in a framework that differentiates between feedforward and feedback connections in yielding conscious experience.


The deduced evolution history of Omsk hemorrhagic fever virus.
Omsk hemorrhagic fever (OHF) is a severe disease that emerged in the 1940s in Siberia, Russia. It is caused by the OHF virus (OHFV), belonging to the Flavivirus genus. In wildlife, the principal vector of OHFV is the Dermacentor reticulatus tick. However, humans are mainly infected after contact with an infected muskrat Ondatra zibethicus. The evolutionary history of OHFV is not yet clarified. In an attempt to reconstruct the temporal and spatial phylodynamics of OHFV, a collection of 25 OHFV strains was studied. Maximum likelihood analysis, the Bayesian MCMC approach, and procedures based on continuous-time Markov Chain process, were used for the investigation of OHFV E gene nucleotide sequences. Six statistically supported clusters of OHFV were identified; five of them joined in a main clade A. The first revealed evolutionary event, when OHFV clade A and clade B divided, dated to about 700 years ago. Clusters C, D, and E, within clade A, separated 230 years ago and further evolved during last century. The phylogeographic analysis showed that clade A originated in the Omsk Province, whereas clusters B, C, and E appeared to originate in Kurgan, Novosibirsk, and Omsk Provinces, respectively. In conclusion, OHFV, as a member of the mammalian tick-borne group of flaviviruses, evolved in Western Siberia during the last millennium. When a highly susceptible species, O.zibethicus, was introduced into the region, in the 1930s, OHFV used this species as an amplifying host that lead to numerous fatal epizootics in muskrats and to human OHF outbreaks.


Biochemical and cytogenetic biomarkers of pollutant exposure in marine fish (Aldrichetta forsteri Valenciennes and Sillago schomburgkii Peters) near industrial and metropolitan centres in South Australia.
This project aimed to measure biochemical and cytogenetic biomarkers in marine fish (Aldrichetta forsteri and Sillago schomburgkii) associated with industrial and urban centres in South Australia. These sites were Port Pirie (affected by metal-contaminated outflows), Barker Inlet (adjacent to Metropolitan Adelaide), and Wills Creek (reference site). The biochemical biomarkers included sorbitol dehydrogenase (SDH) and alanine aminotransferase (ALAT) in serum, adenylate levels (ATP, ADP and AMP) and adenylate energy charge (AEC) in gill and liver, and sodium/potassium ATPase (Na(+), K(+)-ATPase) in gill. Erythrocyte micronucleus frequency was a marker of cytogenetic effect. Serum enzyme levels were generally higher in fish from Port Pirie and Barker Inlet than in those from Wills Creek, with SDH demonstrating the clearest site-associated differences. Tissue adenylates were consistently lower at Port Pirie than elsewhere, suggesting a greater metabolic strain in fish at this site. AEC in gill and liver were consistently lower at Port Pirie than at Wills Creek, with Barker Inlet generally between these two. The reversed rank order was observed with erythrocyte micronucleus frequencies. Seasonal variations in the biomarkers may be attributed either to seasonal physiological changes in fish or changes in pollutant input levels or compositions. Na(+), K(+)-ATPase did not differ between sites nor seasons in this study. This work shows that biochemical and cytogenetic differences occur in marine fish at specific locations in South Australia. It also shows that of these tests, serum SDH and erythrocyte micronuclei are potentially the most sensitive and reliable biomarkers of pollutants effects on marine fish. The results also suggest that these data may be used as a baseline against which future changes in marine water quality, and their consequent biological effects, can be compared.


A new Vibrio fischeri lux gene precedes a bidirectional termination site for the lux operon.
The DNA downstream of the lux structural genes in the Vibrio fischeri lux operon has been sequenced and a new lux gene (luxG) has been identified. A hairpin loop that begins with a poly(A) region and ends with a poly(T) region and thus can function as a bidirectional termination site for luxG and a convergent gene is located immediately downstream of luxG. 3' S1 nuclease mapping has demonstrated that the luxG mRNA was induced in a cell-density-dependent fashion consistent with it being part of the lux system and that the lux mRNA terminated immediately after the hairpin loop. The mRNA coded by an open reading frame convergent to luxG on the complementary strand was also shown by S1 nuclease mapping to overlap the lux mRNA for at least 20 nucleotides before termination. Expression of DNA containing the hairpin loop, placed between a strong promoter and a reporter gene and transferred by conjugation into luminescent bacteria, demonstrated the very high efficiency of termination by this hairpin loop oriented in either direction. These results also demonstrate that the organization of the genes at the 3' ends of the lux operons of V. fischeri and V. harveyi has clearly diverged.


Severe Phenotype of Keratitis-Ichthyosis-Deafness Syndrome With Presumed Ocular Surface Squamous Neoplasia.
The aim of this study was to describe a case of severe keratitis-ichthyosis-deafness (KID) syndrome with ocular surface squamous neoplasia. The affected patient underwent complete ocular and systemic examinations. The molecular studies included polymerase chain reaction amplification and automated DNA sequencing of the complete gap junction beta-2 (GJB2) gene coding sequence. A 30-year-old man presented with generalized erythro-hyperkeratosis and deafness and complaints of decreased visual acuity, tearing, and photophobia. Ophthalmic examination showed corneal erosion, vascularization, and a gray gelatinous lesion partially covering the right cornea, suggestive of squamous neoplasia. The clinical features were characteristic of KID syndrome. This diagnosis was confirmed with a DNA analysis showing the pathogenic variant p.D50N in the GJB2 gene. Presumed squamous neoplasia was treated with topical interferon α2b. KID syndrome is a very rare disease that has been reported with an incremental incidence of squamous cell carcinoma of the mucous membranes and skin (12%-15%). Here, we presented a case of severe systemic KID syndrome with ocular surface squamous neoplasia.


Consultation-Liaison outcome evaluation system. I. Consultant-consultee interaction.
The Consultation-Liaison Outcome Evaluation System characterizes the effectiveness of consultative activities. The initial phase of the system identifies consultees' responses to psychiatric consultants' recommendations and diagnoses and the variables critical to concordance with the use of quantitative measures. The observed incidence and concordance rates of the consultant-consultee interaction were integrated (1) to establish a concordance hierarchy clarifying consultees' priorities in seeking psychiatric consultation, (2) to provide reference points to guide psychiatric consultants' clinical actions, (3) to establish tentative standards with which to evaluate the effectiveness of psychiatric consultation, and (4) to signal the need for further outcome studies and the development of data-based consultation practices.


[The assistance of the Portuguese Colony of Brazil, 1918-1973].
This article seeks to redeem the historical memory of a health institution in Portugal which reconfigured itself and adapted to the social and medical needs and concerns during the twentieth century. The trajectory of this institution contributes to the history of Portuguese medicine and to the history of the philanthropy of the Portuguese colony resident in Brazil and the so called "Brazilians" that returned to Portugal, whose remittances provided the means to set up a benchmark health institution in the twenty-first century. The methodology was based on archival research in Portugal (Coimbra, Bissaya Barreto Foundation) and in Brazil (Rio de Janeiro, Real Gabinete Português de Leitura) and the cross-checking of these primary sources with due historical and social contextualization.


General practitioners' continuing education: a review of policies, strategies and effectiveness, and their implications for the future.
The accreditation and provision of continuing education for general practitioners (GPs) is set to change with new proposals from the General Medical Council, the Government, and the Chief Medical Officer. To review the theories, policies, strategies, and effectiveness in GP continuing education in the past 10 years. A systematic review of the literature by computerized and manual searches of relevant journals and books. Educational theory suggests that continuing education (CE) should be work-based and use the learner's experiences. Audit can play an important role in determining performance and needs assessment, but at present is largely a separate activity. Educational and professional support, such as through mentors or co-tutors, has been successfully piloted but awaits larger scale evaluation. Most accredited educational events are still the postgraduate centre lecture, and GP Tutors have a variable role in CE management and provision. Controlled trials of CE strategies suggest effectiveness is enhanced by personal feedback and work prompts. Qualitative studies have demonstrated that education plays only a small part in influencing doctors' behavior. Maintaining good clinical practice is on many stakeholders' agendas. A variety of methods may be effective in CE, and larger scale trials or evaluations are needed.


Identification of two FoxP3 genes in rainbow trout (Oncorhynchus mykiss) with differential induction patterns.
FoxP3 is a master transcription factor for the development and function of regulatory T cells in mammals, but little is known about this molecule in fish. Two paralogues of mammalian FoxP3 that share 83.9% identity at the amino acid level have been identified in rainbow trout (Oncorhynchus mykiss). The C-terminal region containing a Zn_C2H2 domain, a leucine zipper-like domain and a forkhead (FH) domain important for dimerization, nuclear translocation, and DNA binding, is well conserved between fish and other vertebrate FoxP3. However, the N-terminal of FoxP3 that is required for FoxP3-mediated repression of transcription is greatly diverged between fish, amphibians and monotreme mammals compared to eutherian mammals, suggesting that FoxP3 in fish, frog and platypus may have a different role to the human and mouse counterpart that defines the Treg cellular lineage and mediates the immune regulatory function. The expression of both trout (t) FoxP3a and tFoxP3b are detectable in all the 14 tissues examined without any significant difference except in muscle in which the expression of tFoxP3a was higher. Both tFoxP3a and tFoxP3b are highly expressed in thymus and in immune related organs including the spleen, kidney, gills and intestine, and are up-regulated by phytohaemagglutinin (PHA) in splenocytes and thymocytes. Whilst the up-regulated tFoxP3b expression induced by PHA was dose-dependent it required a higher PHA concentration to achieve maximal expression relative to tFoxP3a where the highest expression level was seen using 1 μg/ml PHA with higher concentrations having no further effects. In addition, the tFoxP3b expression increased during development from eyed eggs to fry, when it reached a comparable level to that of tFoxP3a. In contrast, tFoxP3a expression was at a high and almost constant level over all of the developmental stages examined. The high level of tFoxP3a expression in early development may be related to the relatively high constitutive level of tFoxP3a expression seen in muscle, perhaps suggesting novel roles of tFoxP3 in fish muscle. The structural and expression analysis suggests that the tFoxP3a and tFoxP3b are subject to differential modulation of expression and may have evolved novel functions. The identification of the two trout FoxP3 paralogues will help to clarify the existence of Treg cells and to dissect the T cell differentiation pathways in fish.


Naphthalenebisimides as photofunctional surfactants for SWCNTs - towards water-soluble electron donor-acceptor hybrids.
A water soluble naphthalenebisimide derivative (NBI) was synthesized and probed to individualize, suspend, and stabilize single wall carbon nanotubes (SWCNTs). Besides a comprehensive photophysical and electrochemical characterization of NBI, stable suspensions of SWCNTs were realized in buffered D2O. Overall, the dispersion efficiency of the NBI surfactant was determined by comparison with naphthalene based references. Successful individualization of SWCNTs was corroborated in several microscopic assays. In addition, emission spectroscopy points to the strong quenching of SWCNT centered band gap emission, when NBIs are immobilized onto SWCNTs. The origin of the quenching was found to be strong electronic communication, which leads to charge separation between NBIs and photoexcited SWCNTs, and, which yields reduced NBIs as well oxidized SWCNTs. Notably, electrochemical considerations revealed that the energy content of these charge separated states is one of the highest reported for SWCNT based electron donor-acceptor hybrids so far.


Prevalence of chronic cerebrospinal venous insufficiency in multiple sclerosis: a blinded sonographic evaluation.
To verify the prevalence of chronic cerebrospinal venous insufficiency in patients affected by different clinical forms of multiple sclerosis and in healthy subjects using the Zamboni ultrasound protocol combined with M-mode ultrasound examination. We enrolled 112 patients with multiple sclerosis and 67 healthy subjects from 20 to 67 years of age. All the patients underwent Duplex and color-Doppler sonography of the neck vessels, transcranial colour duplex sonography, M-mode study of the valve system and of venous abnormalities. Subjects were positive for chronic cerebrospinal venous insufficiency when at least two of five hemodynamic criteria of the Zamboni protocol were fulfilled. Chronic cerebrospinal venous insufficiency condition was further analyzed by a multivariate analysis including age, sex, disease duration, subtypes of multiple sclerosis and expanded disability status scale score as independent variables. No healthy subjects was positive for chronic cerebrospinal venous insufficiency, while in the sample of patients affected by multiple sclerosis the diagnosis was made in 59.8% of cases (p < 0.0001). The first criterion was the most frequent in patients affected by multiple sclerosis and chronic cerebrospinal venous insufficiency (respectively 54.4% and 76.1%, p < 0.001). The second, third and fourth criteria were never present in healthy subjects but were detected in patients with multiple sclerosis. The positivity of the second criterion was associated with diagnosis of chronic cerebrospinal venous insufficiency in 100% of cases. The third criterion had a prevalence of 52.2% in the subgroup of chronic cerebrospinal venous insufficiency patients. It was positive in 36 multiple sclerosis patients and was associated with chronic cerebrospinal venous insufficiency diagnosis in all cases except one. The multivariate analysis showed that age, disease duration, sex, subtypes of multiple sclerosis and expanded disability status scale score were not considered predictors of this haemodynamic condition. Chronic cerebrospinal venous insufficiency is a haemodynamic condition strongly associated with multiple sclerosis and is not found in normal controls. The addition of M-mode ultrasound to the diagnostic protocol allows improved observation of venous valve abnormalities.


Prospective evaluation of the association of adherent perinephric fat with perioperative outcomes of robotic-assisted partial nephrectomy.
To prospectively analyze the association of adherent perinephric fat (APF) with perioperative outcomes of robotic-assisted partial nephrectomy (RAPN). We analyzed 100 consecutive RAPNs performed by a single experienced surgeon and defined APF as the necessity of subcapsular renal dissection to mobilize the kidney and isolate the renal tumor for RAPN. Our primary analysis focused on comparing perioperative outcomes, including operative time, warm ischemia time, estimated blood loss, postoperative complications, length of stay, and margins, ischemia, and complications score between patients with and without APF. To control the probability of obtaining a false-positive finding at 5% after the numerous statistical comparisons that were performed, we used a Bonferroni correction for multiple comparisons, after which P values of ≤.0042 were considered to be statistically significant. Thirty patients (30%) had APF. Presence of APF was not significantly associated with blood loss, warm ischemia time, hospital stay, postoperative complications, or margins, ischemia, and complications score. We noted some evidence of longer operative times in patients with APF compared with those without APF (median, 223 vs199 minutes; P = .026); however, this was not significant after adjustment for multiple comparisons. In multivariate analysis, we noted stronger evidence of associations with increased operative time for RENAL score (P <.001) and body mass index (P = .020) than for the presence of APF (P = .32). APF may be associated with slightly longer operative times but does not appear to affect perioperative complications or outcomes.


KLF4 and PBX1 directly regulate NANOG expression in human embryonic stem cells.
Insight into the regulation of core transcription factors is important for a better understanding of the molecular mechanisms that control self-renewal and pluripotency of human ESCs (hESCs). However, the transcriptional regulation of NANOG itself in hESCs has largely been elusive. We established a NANOG promoter luciferase reporter assay as a fast read-out for indicating the pluripotent status of hESCs. From the functional cDNA screens and NANOG promoter characterization, we successfully identified a zinc finger transcription factor KLF4 and a homeodomain transcription factor PBX1 as two novel transcriptional regulators that maintain the pluripotent and undifferentiated state of hESCs. We showed that both KLF4 and PBX1 mRNA and protein expression were downregulated during hESC differentiation. In addition, overexpression of KLF4 and PBX1 upregulated NANOG promoter activity and also the endogenous NANOG protein expression in hESCs. Direct binding of KLF4 on NANOG proximal promoter and PBX1 on a new upstream enhancer and proximal promoter were confirmed by chromatin immunoprecipitation and electrophoretic mobility shift assay. Knockdown of KLF4/PBX1 or mutation of KLF4/PBX1 binding motifs significantly downregulated NANOG promoter activity. We also showed that specific members of the SP/KLF and PBX family are functionally redundant at the NANOG promoter and that KLF4 and PBX1 cooperated with OCT4 and SOX2, and transactivated synergistically the NANOG promoter activity. Our results show two novel upstream transcription activators of NANOG that are functionally important for the self-renewal of hESC and provide new insights into the expanded regulatory circuitry that maintains hESC pluripotency.


Computational phlebology: reviewing computer models of the venous system.
Relatively little attention has been paid to the venous system and valves from a cardiovascular engineering perspective up to now. Given the involvement of venous valve haemodynamics in the development of deep vein thrombosis this is an area that needs more detailed investigation and close collaboration between clinicians and cardiovascular engineers. The purpose of this review article is to provide an indication of the physiological conditions that need to be included in any computational model of the venous system, based on recommendations from clinicians, and to summarize published computational models of the venous system by trying to explore their limitations and application range. A MEDLINE search was carried out on the relevant literature from 1940 until today. Several models have been developed with a specific purpose in mind to coincide with the aim of each individual study. The model complexity and laws used in each model vary significantly. There are more simplistic computational models based on electric circuit analogies, termed as lumped parameter models, which can be used to provide boundary conditions to one-dimensional (1D) and three-dimensional (3D) domain models, followed by 1D continuous models based on analytical equations, which allow the description of pressure wave and can be non-linear in nature. Finally, there are the more advanced 3D models, which are based on the principles of haemodynamics, and consider the compliance of the venous system and the effect that venous valves have on the cardiovascular system. In conclusion, it appears that computer modelling of the venous system can contribute greatly to our understanding of venous physiology and allow us to evaluate the haemodynamic interactions that occur in the venous system under different physiological conditions.


Almost all antipsychotics result in weight gain: a meta-analysis.
Antipsychotics (AP) induce weight gain. However, reviews and meta-analyses generally are restricted to second generation antipsychotics (SGA) and do not stratify for duration of AP use. It is hypothesised that patients gain more weight if duration of AP use is longer. A meta-analysis was conducted of clinical trials of AP that reported weight change. Outcome measures were body weight change, change in BMI and clinically relevant weight change (7% weight gain or loss). Duration of AP-use was stratified as follows: ≤6 weeks, 6-16 weeks, 16-38 weeks and >38 weeks. Forest plots stratified by AP as well as by duration of use were generated and results were summarised in figures. 307 articles met inclusion criteria. The majority were AP switch studies. Almost all AP showed a degree of weight gain after prolonged use, except for amisulpride, aripiprazole and ziprasidone, for which prolonged exposure resulted in negligible weight change. The level of weight gain per AP varied from discrete to severe. Contrary to expectations, switch of AP did not result in weight loss for amisulpride, aripiprazole or ziprasidone. In AP-naive patients, weight gain was much more pronounced for all AP. Given prolonged exposure, virtually all AP are associated with weight gain. The rational of switching AP to achieve weight reduction may be overrated. In AP-naive patients, weight gain is more pronounced.


Generation and characterisation of recombinant FMDV antibodies: Applications for advancing diagnostic and laboratory assays.
Foot-and-mouth disease (FMD) affects economically important livestock and is one of the most contagious viral diseases. The most commonly used FMD diagnostic assay is a sandwich ELISA. However, the main disadvantage of this ELISA is that it requires anti-FMD virus (FMDV) serotype-specific antibodies raised in small animals. This problem can be, in part, overcome by using anti-FMDV monoclonal antibodies (MAbs) as detecting reagents. However, the long-term use of MAbs may be problematic and they may need to be replaced. Here we have constructed chimeric antibodies (mouse/rabbit D9) and Fabs (fragment antigen-binding) (mouse/cattle D9) using the Fv (fragment variable) regions of a mouse MAb, D9 (MAb D9), which recognises type O FMDV. The mouse/rabbit D9 chimeric antibody retained the FMDV serotype-specificity of MAb D9 and performed well in a FMDV detection ELISA as well as in routine laboratory assays. Cryo-electron microscopy analysis confirmed engagement with antigenic site 1 and peptide competition studies identified the aspartic acid at residue VP1 147 as a novel component of the D9 epitope. This chimeric expression approach is a simple but effective way to preserve valuable FMDV antibodies, and has the potential for unlimited generation of antibodies and antibody fragments in recombinant systems with the concomitant positive impacts on the 3Rs (Replacement, Reduction and Refinement) principles.


Bioaccumulation and toxic effects of nanoparticulate and ionic silver in Saccostrea glomerata (rock oyster).
The increasing production of Ag nanoparticle (AgNP) containing products has inevitably led to a growing concern about their release into the aquatic environment, along with their potential behaviour, toxicity, and bioaccumulation in marine organisms exposed to NPs released from these products. Hence, this study is focused on the effects of AgNPs in Saccostrea glomerata (rock oyster) in artificial seawater (ASW); evaluating the NP's stability, dissolution, and bioaccumulation rate. AgNPs NM300K (20 ± 5 nm) in concentrations of 12.5 μgL-1 and 125 μgL-1 were used to conduct the experiments, and were compared to a blank and a positive control of 12.5 μgL-1 AgNO3. Dissolution in ASW was measured by ICP-OES and stability was assessed by TEM after 1 h and 3, 5, and 7 days of exposure. Bioaccumulation in gills and digestive glands was measured after 7 days of exposure. The higher concentration of AgNPs induced more aggregation, underwent less dissolution, and showed less bioaccumulation, while the lower concentration showed less aggregation, more dissolution and higher bioaccumulation. Five biomarkers (EROD: ethoxyresorufin-o-deethylase, DNA strand breaks, LPO: lipid peroxidation, GST: glutathione S-transferase and GR: glutathione reductase) were analysed at 0, 3, 5 and 7 days. Significant differences compared to the initial day of exposure (day 0) were reported in DNA strand breaks after 5 and 7 days of exposure, GST, from the third day of exposure, in all the Ag samples, and in some samples for LPO and GR biomarkers, while no significant induction of EROD was observed. A combined effect for each type of treatment and time of exposure was also reported for DNA strand breaks and GST biomarkers measured at the digestive glands. In general, the significant inductions measured showed the following trend: 125 μgL-1 AgNPs >12.5 μgL-1 AgNPs ∼12.5 μgL-1 AgNO3 even though bioaccumulation followed the opposite trend.


Correlation between antioxidant activity and phenolic acids profile and content of Algerian propolis: Influence of solvent.
We aimed in the reported study to investigate the impact of using various solvents in the extraction of potentially active compounds from Algerian propolis. Phenolic and flavonoids contents in association with antioxidant activity of the tested extracts were evaluated. Moreover phenolic composition was determined using UFLC-MS/MS. The tested parameters varied according to the used solvent. Total phenolic and flavononid contents ranged from 0.81±0.16 to 8.97±0.25 EGA mg/g and from 0.57±0.01 to 3.53±0.84 EQ mg/g respectively. All the investigated extracts demonstrated notable antiradical and reducing activities. Ethyl acetate and n-butanol were found to contain the highest amounts of phenolic and flavonoid compounds and the strongest antioxidant properties. The antioxidant activity of propolis extracts appears to be largely influenced by total phenolic and flavonoid contents. Rutin, chlorogenic, ferulic, caffeic and gallic acids were found to be the main phenolic compounds in Algerian propolis. Our results suggest that Algerian propolis may be a poplar-type propolis.


Mortality of Swedish horses with complete life insurance between 1997 and 2000: variations with sex, age, breed and diagnosis.
The aim of this study was to evaluate the potential usefulness of the database maintained by the Swedish insurance company Agria for providing mortality statistics on Swedish horses. Mortality statistics (incidence rates and survival) were calculated, both crudely and stratified by sex, age, breed, breed group and diagnosis, for the horses with complete life insurance, which covers most health problems. The total mortality was 415 (95 per cent confidence interval [CI] 399 to 432) deaths per 10,000 horse-years at risk, and the diagnostic mortality, including only deaths with an assigned diagnosis, was 370 (95 per cent CI 355 to 386) deaths per 10,000 horse-years at risk. The diagnostic mortality of geldings was 459 (95 per cent CI 431 to 487), of mares 345 (95 per cent CI 322 to 365) and of stallions 214 (95 per cent CI 182 to 247) deaths per 10,000 horse-years at risk. The mortality rates increased with age and differed widely between breeds. Survival analysis showed that the median age at death of the horses enrolled before they were one year of age was 18.8 years. The most common cause of death or euthanasia was joint problems, which were responsible for 140 (95 per cent CI 130 to 149) deaths per 10,000 horse-years at risk. The results of multivariable models developed by using Poisson regression generally agreed well with the crude results.


Zika virus alters osteogenic lineage progression of human mesenchymal stromal cells.
Arboviruses target bone forming osteoblasts and perturb bone remodeling via paracrine factors. We previously reported that Zika virus (ZIKV) infection of early-stage human mesenchymal stromal cells (MSCs) inhibited the osteogenic lineage commitment of MSCs. To understand the physiological interplay between bone development and ZIKV pathogenesis, we employed a primary in vitro model to examine the biological responses of MSCs to ZIKV infection at different stages of osteogenesis. Precommitted MSCs were infected at the late stage of osteogenic stimulation (Day 7) with ZIKV (multiplicity of infection of 5). We observe that MSCs infected at the late stage of differentiation are highly susceptible to ZIKV infection similar to previous observations with early stage infected MSCs (Day 0). However, in contrast to ZIKV infection at the early stage of differentiation, infection at a later stage significantly elevates the key osteogenic markers and calcium content. Comparative RNA sequencing (RNA-seq) of early and late stage infected MSCs reveals that ZIKV infection alters the mRNA transcriptome during osteogenic induction of MSCs (1251 genes). ZIKV infection provokes a robust antiviral response at both stages of osteogenic differentiation as reflected by the upregulation of interferon responsive genes (n > 140). ZIKV infection enhances the expression of immune-related genes in early stage MSCs while increasing cell cycle genes in late stage MSCs. Remarkably, ZIKA infection in early stage MSCs also activates lipid metabolism-related pathways. In conclusion, ZIKV infection has differentiation stage-dependent effects on MSCs and this mechanistic understanding may permit the development of new therapeutic or preventative measures for bone-related effects of ZIKV infection.


[ROX index to predict failure with low flow devices in COVID-19].
The ROX index (iROX) obtained from pulse oximetry saturation/inspired fraction of oxygen and respiratory rate, predicts success with high-flow nasal cannula (HFNC), however its performance for low-flow oxygenation devices (DOBF) is unknown. To determine suitability of iROX at 12 hours as a predictor of mechanical ventilation (VMI) in hospitalized patients with severe COVID-19 and DOBF. An historical cohort was performed. Adults with COVID-19, hospitalized, with supplemental oxygen supply are included, excluding patients with pathologies in chronic stages that could alter the results, calculating the iROX at 12 hours, obtaining the cut-off point using a ROC curve and Youden index, the risk of VMI is prolonged using relative risk (RR), with 95% confidence intervals (95%CI). Confounding variables were evaluated to determine the performance of the iROX. The dependent variable mechanical ventilation recorded as reported in the file and the independent iROX obtained in the same way as the previous one. 63 patients with a median age of 62 years were included. The best iROX cut-off point at 12 hours was 5.35. With this cut-off point, VMI was associated with a RR of 8.75 (95% CI 2.36-32.35). In the multivariate model with an OR of 9.26; (95% CI, 2.39 - 35.78), after initiation of DOBF was consistently associated with an increased risk of intubation. In hospitalized patients with severe COVID-19, an iROX < 5.35 at 12 hours appears to be a predictor for the onset of VMI.


Structural and morphological transitions in extension-induced crystallization of poly(1-butene) melt.
Structural and morphological transitions of flow-induced crystallization (FIC) in poly(1-butene) (PB-1) melt have been studied by combining extensional rheology and in situ synchrotron radiation ultrafast wide- and small-angle X-ray scattering (WAXD/SAXS) measurements. Unexpectedly, metastable Form III is crystallized directly from the PB-1 melt by high-speed extension, which has a short lifetime of several tens of milliseconds and manifests the thermodynamic and kinetic competition among Form III, Form II and melt under flow. Relative crystallinity evolution of Form II after extension reveals a crystal melting dominated process within the observation time of 120 s even under high supercooling. This is opposite to the common case of FIC but supports the idea that flow alters the obtained crystal size and its thermodynamic stability. Additionally, a morphological transition from a flow-induced network to shish is observed by SAXS with increasing extension temperature from below to above the melting point of Form II. With above observations, we construct nonequilibrium structural and morphological diagrams of FIC in strain rate-temperature space, which may guide the industrial processing of the PB-1 material.


[Shigella flexneri mutation giving rise to the appearance of fosfomycin-resistant avirulent forms with disordered carbohydrate utilization].
The present work analyzes pt44 mutation in Sh. flexneri resulting in the appearance of the following phenotypical properties: resistance to phosphomycin, avirulence, pleiotropic disturbances in carbohydrate utilization. The data provided by the biochemical and genetic analysis have indicated that pts44 mutation occupies the region between purC and ptsI loci on the chromosome of Sh. flexneri. Merodiploids containing the mutant allele pts44 and the plasmid including purC-ptsI-ptsH genes from E. coli K12 acquired the capacity for fermenting carbohydrates, but at the same time retained resistance to phosphomycin and avirulent properties. The presence of phosphoenol pyruvate-dependent carbohydrate phosphotransferase system in Sh. flexneri has been proved.


The Ghana essential health interventions program: a plausibility trial of the impact of health systems strengthening on maternal & child survival.
During the 1990s, researchers at the Navrongo Health Research Centre in northern Ghana developed a highly successful community health program. The keystone of the Navrongo approach was the deployment of nurses termed community health officers to village locations. A trial showed that, compared to areas relying on existing services alone, the approach reduced child mortality by half, maternal mortality by 40%, and fertility by nearly a birth - from a total fertility rate of 5.5 in only five years. In 2000, the government of Ghana launched a national program called Community-based Health Planning and Services (CHPS) to scale up the Navrongo model. However, CHPS scale-up has been slow in districts located outside of the Upper East Region, where the "Navrongo Experiment" was first carried out. This paper describes the Ghana Essential Health Intervention Project (GEHIP), a plausibility trial of strategies for strengthening CHPS, especially in the areas of maternal and newborn health, and generating the political will to scale up the program with strategies that are faithful to the original design. GEHIP improves the CHPS model by 1) extending the range and quality of services for newborns; 2) training community volunteers to conduct the World Health Organization service regimen known as integrated management of childhood illness (IMCI); 3) simplifying the collection of health management information and ensuring its use for decision making; 4) enabling community health nurses to manage emergencies, particularly obstetric complications and refer cases without delay; 5) adding $0.85 per capita annually to district budgets and marshalling grassroots political commitment to financing CHPS implementation; and 6) strengthening CHPS leadership at all levels of the system. GEHIP impact is assessed by conducting baseline and endline survey research and computing the Heckman "difference in difference" test for under-5 mortality in three intervention districts relative to four comparison districts for core indicators of health status and survival rates. To elucidate results, hierarchical child survival hazard models will be estimated that incorporate measures of health system strength as survival determinants, adjusting for the potentially confounding effects of parental and household characteristics. Qualitative systems appraisal procedures will be used to monitor and explain GEHIP implementation innovations, constraints, and progress. By demonstrating practical means of strengthening a real-world health system while monitoring costs and assessing maternal and child survival impact, GEHIP is expected to contribute to national health policy, planning, and resource allocation that will be needed to accelerate progress with the Millennium Development Goals.


Isolated hypoxic hepatic perfusion with tumor necrosis factor-alpha, melphalan, and mitomycin C using balloon catheter techniques: a pharmacokinetic study in pigs.
To validate the methodology of isolated hypoxic hepatic perfusion (IHHP) using balloon catheter techniques and to gain insight into the distribution of tumor necrosis factor-alpha (TNF), melphalan, and mitomycin C (MMC) through the regional and systemic blood compartments when applying these techniques. There is no standard treatment for unresectable liver tumors. Clinical results of isolated limb perfusion with high-dose TNF and melphalan for the treatment of melanoma and sarcoma have been promising, and attempts have been made to extrapolate this success to the isolated liver perfusion setting. The magnitude and toxicity of the surgical procedure, however, have limited clinical applicability. Pigs underwent IHHP with TNF, melphalan, and MMC using balloon catheters or served as controls, receiving equivalent dosages of these agents intravenously. After a 20-minute perfusion, a washout procedure was performed for 10 minutes, after which isolation was terminated. Throughout the procedure and afterward, blood samples were obtained from the hepatic and systemic blood compartments and concentrations of perfused agents were determined. During perfusion, locoregional plasma drug concentrations were 20- to 40-fold higher than systemic concentrations. Compared with systemic concentrations after intravenous administration, regional concentrations during IHHP were up to 10-fold higher. Regional MMC and melphalan levels steadily declined during perfusion, indicating rapid uptake by the liver tissue; minimal systemic concentrations indicated virtually no leakage to the systemic blood compartment. During isolation, concentrations of TNF in the perfusate declined only slightly, indicating limited uptake by the liver tissue; no leakage of TNF to the systemic circulation was observed. After termination of isolation, systemic TNF levels showed only a minor transient elevation, indicating that the washout procedure at the end of the perfusions was fully effective. Complete isolation of the hepatic vascular bed can be accomplished when performing IHHP using this balloon catheter technique. Thus, as in extremities, an ideal leakage-free perfusion of the liver can now be performed, and repeated, without major surgery. The effective washout allows the addition of TNF in this setting.


Moment-to-moment fluctuations in fMRI amplitude and interregion coupling are predictive of inhibitory performance.
We investigated how moment-to-moment fluctuations in fMRI amplitude and interregional coupling are linked to behavioral performance during a stop signal task. To quantify the relationship between single-trial amplitude and behavior on a trial-by-trial basis, we modeled the probability of successful inhibition as a function of response amplitude via logistic regression analysis. At the group level, significant logistic slopes were observed in, among other regions, the inferior frontal gyrus (IFG), caudate, and putamen, all bilaterally. Furthermore, we investigated how trial-by-trial fluctuations in responses in attentional regions covaried with fluctuations in inhibition-related regions. The coupling between several frontoparietal attentional regions and the right IFG increased during successful versus unsuccessful performance, suggesting that efficacious network interactions are important in determining behavioral outcome during the stop signal task. In particular, the link between responses in the right IFG and behavior were moderated by moment-to-moment fluctuations in evoked responses in the left intraparietal sulcus. A supplemental figure for this article may be downloaded from http://cabn.psychonomic-journals.org/content/supplemental.


Gene expression and feeding ecology: evolution of piscivory in the venomous gastropod genus Conus.
Differential expression of gene-family members is typically associated with the specific development of certain tissues and organs, but its importance in the ecological adaptation of organisms has rarely been investigated. Several specialized feeding modes have evolved within the predatory marine gastropod genus Conus, including molluscivory and piscivory. Based on phylogenetic investigations of Conus species, it has been concluded that piscivory arose at least twice in this genus. Moreover, molecular analyses of conotoxin mRNA transcripts reveal that piscivores from independent evolutionary lineages express the same subset of four-loop conotoxins, contrary to phylogenetic expectations. These results demonstrate that differential expression of gene-family members can play a key role in adaptive evolution, particularly during shifts to new ecological niches.


Morphometric study of the small intestinal mucosa in young, adult, and old rats submitted to protein deficiency and rehabilitation.
Linear and stereological morphometric methods were applied to the jejunal and ileal mucosa of young, adult, and old male Wistar rats submitted to protein deficiency and rehabilitation. The animals were fed ad libitum a 2% casein diet during 42 days and then received a 20% casein diet for 30 days. Food intake, body weights, and plasma protein concentrations were recorded. In the young protein deficient rats values of mucosal height, surface area, and volume of the lamina propria were significantly lower than those of their age controls in both jejunum and ileum. In adults the differences were less marked and in the old rats all parameters were found to be unaltered by the protein deficient diet. The surface-to-volume ratio showed no significant differences between control and protein deficient in all three age groups, meaning that villus pattern did not change with protein deficiency. On rehabilitation, a striking difference between jejunum and ileum was observed in the young rats; all parameters returned to control levels in the jejunum, while they remained lower than those of their controls in the ileum.


[Organization of clinical care of North Fleet hospitals in XVIII century].
Clinical care of national navy hospitals was normed from reception of patients till hospital discharge. After admission to the hospital, patient got competent medical care and corresponding attendance. But the situation changed in XVIII century, period of wars. In conditions of war time hospitals were overcrowded with patients and wounded. The number of patients went beyond the bedspace. Deficit of vacant beds was supplied with the help of additional beds; deficit of medical staff was supplied with the help of participation of another medial staff. Huge number of patients with different diseases, including contagious diseases, conduced communication of contagious diseases inside the hospital. Diagnostics and methods of treatment of these diseases were not enough researched. Taking into account results of statistical analysis of data about the number of fatality cases (peace time--4-10%, war time--20%), we can make a conclusion that clinical care of national navy hospitals was satisfying.


Self-sorting in supramolecular assemblies.
Supramolecular self-assembly enables living organisms to form highly functional hierarchical structures with individual components self-organized across multiple length scales. This has inspired work on multicomponent supramolecular materials to understand factors behind co-assembly versus self-sorting of molecules. We report here on a supramolecular system comprised of negatively charged peptide amphiphile (PA) molecules, in which only a tiny fraction of the molecules (0.7 mol%) were covalently conjugated to one of two different fluorophores, half to fluorescein isothiocyanate (FTIC) and the other half to tetramethylrhodamine (TAMRA). Confocal microscopy of the system revealed self-sorting of the two different fluorescent PA molecules, where TAMRA PA is concentrated in micron-scale domains while FITC PA remains dispersed throughout the sample. From Förster resonance energy transfer and fluorescence recovery experiments, we conclude that conjugation of the negatively charged FITC to PA significantly disrupts its co-assembly with the 99.3 mol% of unlabeled molecules, which are responsible for formation of micron-scale domains. Conversely, conjugation of the zwitterionic TAMRA causes no such disruption. Interestingly, this dissimilar behavior between FITC and TAMRA PA causes them to self-sort at large length scales in the supramolecular system, mediated not by specific interactions among the individual fluorophores but instead by their different propensities to co-assemble with the majority component. We also found that greater ionic strength in the aqueous environment of the system promotes mixing by lowering the electrostatic barriers involved in self-sorting. Our results demonstrate great thermodynamic subtlety in the driving forces that mediate self-sorting versus co-assembly in supramolecular peptide assemblies.


Structural and kinetic investigations on the 15-21 and 42-45 loops of muscle acylphosphatase: evidence for their involvement in enzyme catalysis and conformational stabilization.
The structural and catalytic importance of the 15-21 and 42-45 loop residues of the acylphosphatase muscular isoenzyme has been investigated by oligonucleotide-directed mutagenesis. Seven mutants involving conserved residues of the two loops have been prepared and characterized for structural, kinetic, and stability features by using different spectroscopic techniques and compared to the wild-type enzyme. The results are discussed in light of the crystal structure of the highly homologous common type acylphosphatase [Thunnissen et al. (1997) Structure 5, 69-79]. A differential role of the two loops has emerged: the 15-21 and the 42-45 loops appear mainly involved in active site formation and enzyme structural stabilization, respectively. These conclusions are supported by a strong impairment of the catalytic efficiency, in terms of enzymatic activity and substrate binding capability, for most of the 15-21 loop mutants. In particular, the Gly15Ala mutant is completely inactive and displays a native-like overall fold, indicating that the correct geometry of the 15-21 loop is an essential requisite for optimal enzymatic catalysis. Instead, the Gly45Ala mutant, though revealing unchanged catalytic properties, shows a considerably reduced conformational stability, as judged by circular dichroism and 1H NMR spectroscopy. This finding confirms previous results relative to Thr42 and Thr46 residues [Taddei et al. (1996) Biochemistry 35, 7077-7083] underlining the structural importance of the 42-45 loop as a linker for the two beta alpha beta units constituting the overall enzyme structure.


Comparison of CT scanning and radionuclide imaging in liver disease.
Early experience with body CT suggested its usefulness in many diagnostic problems; jaundice, renal and pancreatic masses, and in the evaluation of relatively inaccessible parts of the body, such as the retroperitineum, mediastinum, and pelvis. Investigation of hepatic disease by CT was not unexpectedly compared to radionuclide liver scanning, the major preexisting modality for imaging the liver. In the evaluation of the jaundiced patient, CT rapidly assumed a major role, providing more specific information about the liver than the RN liver scan, as well as demonstrating adjacent organs. CT differentiate obstructive from non-obstructive jaundice, and frequently the cause of the obstructive jaundice. With respect to mass lesions of the liver, the RN liver scan is more sensitive than CT but less specific. The abnormalities on an isotope image of the liver consist of normal variants in configuration, extrinsic compression by adjacent structures, cysts, hemangiomata, abscesses, and neoplasms. These suspected lesions may then be better delineated by the CT image, and a more precise diagnosis made. The physiologic information provided by the RN liver scan is an added facet which is helpful in the patient with diffuse hepatic disease. The CT image will be normal in many of these patients, however, hemochromatosis and fatty infiltration lend themselves especially to density evaluation by CT. The evaluation of lymphoma is more thorough with CT. Structures other than the liver, such as lymph nodes, are visualized. Gallium, however, provides additional isotopic information in patients with lymphoma, and in addition, is known to be useful in the investigation of a febrile patient with an abscess. Newer isotopic agents expand hepatic imaging in other directions, visualizing the biliary tree and evaluating the jaundiced patient.


Preoperative visualization of neurovascular anatomy in trigeminal neuralgia.
The authors report on a novel technique to identify neurovascular compression in trigeminal neuralgia (TN). Using 3D reconstructed high-resolution balanced fast-field echo (BFFE) images fused with 3D time-of-flight (TOF) magnetic resonance (MR) angiography and Gd-enhanced 3D spoiled gradient recalled sequence, it is possible to objectively visualize the trigeminal nerve and nearby arteries and veins. Magnetic resonance imaging was performed in 18 patients with unilateral TN using 3 sequences: BFFE, 3D TOF angiography, and 3D Gd-enhanced imaging. The images were imported into OsiriX imaging software; after their fusion, a 3D false-color reconstruction was produced using surface rendering. The reconstructed images objectively differentiate nerves and vessels and can be viewed from any angle, including the anticipated surgical approach. Fifteen patients were predicted to have neurovascular compression on the symptomatic side (9 arterial and 6 venous compressions). All patients had a vascular structure that was identical in location and configuration to that predicted on preoperative analysis. The 3 patients without predicted compression underwent surgical exploration because they manifested the classic symptoms. As expected, exploration in 2 of these patients revealed no offending vessel. The third patient had a small vein embedded in the trigeminal nerve that was beyond the resolution of the 3D Gd-enhanced study. Combining BFFE with MR angiography and Gd-enhanced MR images capitalizes on the advantages of both techniques, enabling MR angiography and contrast-enhanced MR imaging discrimination of vascular structures at BFFE resolution. This results in an unambiguous 3D image that can be used to identify the neurovascular compression and plan the surgical approach.


Effects of in vitro treatment with 4-hydroperoxycyclophosphamide and hyperthermia on leukemic progenitor cells.
A key point of autologous bone marrow transplantation for leukemic patients is how to remove leukemic cells from their own bone marrow grafts. In this study a leukemic progenitor cell assay was used to evaluate the antileukemic efficacy of marrow-purging protocols that employed hyperthermia or 4-hydroperoxycyclophosphamide (4HC) against leukemic blasts obtained from patients. After the treatment of 2 x 10(7) nucleated bone marrow cells/ml with 100 micrograms/ml of 4HC in the presence of 7% suspension of packed autologous erythrocytes, leukemic colonies were eradicated in 10 of 13 cases and reduced to less than 0.3% as compared with the colony count in untreated cultures in two cases. More than 10% of leukemic progenitor cells survived after hyperthermia treatment (42 degrees C 60 min) in 7 of 9 cases. It is suggested that treatment of leukemic cells and 7% autologous erythrocytes with 100 micrograms/ml of 4HC is effective to eliminate leukemic progenitor cells. Treatment with hyperthermia may not be effective enough to eliminate leukemic progenitor cells from autologous bone marrow.


[Macrolides in the treatment of children with Mediterranean spotted fever].
Till now there is not a gold standard therapy for Mediterranean spotted fever (MSF) in children. Standard treatment for MSF is the administration of tetracycline or chloramphenicol, however both these drugs can cause significant adverse effects in children (tetracyclines can cause staining of teeth, chloramphenicol severe hematological adverse events such as aplastic anemia, gray baby syndrome and hemolytic anemia in patients with the Mediterranean form of G6PD deficiency). We conducted two randomized clinical trials; the first compared clarithromycin versus chloramphenicol: mean time to defervescence was 36.7 +/- 18.1 h in the clarithromycin group and 47.1+/- 21.9 h in the chloramphenicol group (P= 0.047). The second trial compared clarithromycin versus azithromycin and did not show any statistically significant difference: mean time to defervescence was 46.2 +/- 36.4 h in the clarithromycin group and 39.3 +/- 31.3 h in the azithromycin group (P= 0.34). On the basis of these studies we think that clarithromycin and azithromycin could constitute an acceptable alternative to chloramphenicol and to tetracyclines for the treatment of MSF in children


A Young Iranian Woman with Pure Primary Ovarian Neuroendocrine Tumor: A Case Report.
Pure ovarian neuroendocrine tumors are very rare. Herein, we present a young Iranian woman with a pure primary ovarian neuroendocrine tumor. A 26-year-old female presented with chronic abdominal pain and progressive constipation and was referred to the emergency room. Imaging findings confirmed a mass in the right adnexa. Following the resectional surgery of the ovarian mass, histopathological and immunohistochemistry results disclosed a mixed type of primary ovarian neuroendocrine tumor. The patient did not experience tumor recurrence afterward. Due to the rarity and low prevalence of primary pure ovarian neuroendocrine tumors, the histopathologic diagnosis should be confirmed by an immunohistochemistry study.


Rates of ketone-body formation in the perfused rat liver.
1. The rates of formation of acetoacetate and beta-hydroxybutyrate by the isolated perfused rat liver were measured under various conditions. 2. The rates found after addition of butyrate, octanoate, oleate and linoleate were about 100mumoles/hr./g. wet wt. in the liver of starved rats. These rates are much higher than those found with rat liver slices. 3. The differences between the rates given by slices and by the perfused organ were much higher with the long-chain than with short-chain fatty acids. The increments caused by oleate and linoleate were 12 and 16 times as large in the perfused organ as in the slices, whereas the increments caused by butyrate and octanoate were about four times as large. 4. The rates of ketogenesis in the unsupplemented perfused liver of well-fed rats, and the increments caused by the addition of fatty acids, were about half of those in the liver from starved rats. 5. The value of the [beta-hydroxybutyrate]/[acetoacetate] ratio of the medium was raised by octanoate, oleate and linoleate. 6. Carnitine did not significantly accelerate ketogenesis from fatty acids. 7. Oleate formed up to 82% of the expected yield of ketone bodies. 8. In the liver of alloxan-diabetic rats the endogenous rates of ketogenesis were raised, in some cases as high as in the liver from starved rats, after addition of oleate. 9. On addition of either beta-hydroxybutyrate or acetoacetate to the perfusion medium the liver gradually adjusted the [beta-hydroxybutyrate]/[acetoacetate] ratio towards the normal range. 10. The [beta-hydroxybutyrate]/[acetoacetate] ratio of the medium was about 0.4 when slices were incubated, but near the physiological value of 2 when the liver was perfused. 11. The experiments demonstrate that for the study of ketogenesis slices are in many ways grossly inferior to the perfused liver.


FLASH correlation: a new method for 3-D ultrasound tissue motion tracking and blood velocity estimation.
We report a new method for tracking tissue motion and blood flow in three dimensions (3-D) using successive volumetric ultrasound scans. The method is based on combining the concepts of feature tracking and 3-D correlation search to achieve a compromise between accuracy and computational efficiency. This paper introduces the new method and the experimental setup used for its evaluation in a tissue-mimicking material. Results are presented demonstrating that the new method has both satisfactory tracking performance and the potential for practical real-time implementation.


Childhood abuse is related to working memory impairment for positive emotion in female university students.
Childhood abuse is an important risk factor for depression, anxiety disorders, and substance use later in life. One possible mechanism underlying this association could be deficits in cognitive processing of emotional information. This study tested the impact of distracting emotional information on working memory performance in 21 young women with a history of sexual and physical abuse during childhood/adolescence (mean age = 20.0), and compared their performance to 17 individuals reporting nonabuse-related childhood stress (mean age = 19.6) and a control group of 17 women without a history of childhood stress (mean age = 20.0). During the most difficult distractor condition, working memory accuracy for positive versus neutral incidental emotional stimuli was reduced in women reporting a history of abuse relative to both control groups (with and without nonabuse-related childhood stress). The current results reveal aberrant responses to positive stimuli and are consistent with the notion of persistent influence of childhood abuse on processes critical for emotional well-being and emotion control.


Denosumab-mediated increase in hand bone mineral density associated with decreased progression of bone erosion in rheumatoid arthritis patients.
Periarticular osteoporosis is one of the earliest radiographic signs of bone damage in rheumatoid arthritis (RA). Denosumab, an investigational fully human monoclonal antibody that binds to RANKL, inhibits bone erosion and systemic bone loss in clinical studies of patients with RA. In this hand bone mineral density (BMD) substudy, we investigated the effects of denosumab on hand BMD and its correlation with hand erosion scores. Patients receiving methotrexate for erosive RA were randomized in a 1:1:1 ratio to receive subcutaneous placebo, denosumab 60 mg, or denosumab 180 mg at 0 and 6 months. Measurements included BMD (by dual x-ray absorptiometry [DXA]) of both hands (0, 1, 6, and 12 months), magnetic resonance images of the hands/wrists (0 and 6 months), and radiographs of the hands/wrists and feet (0, 6, and 12 months). There were 56 patients (13 placebo, 21 denosumab 60 mg, and 22 denosumab 180 mg). Mean changes in hand BMD at 6 and 12 months were: +0.8% and +1.0%, respectively, for denosumab 60 mg; +2.0% and +2.5%, respectively, for denosumab 180 mg; and -1.2% and -2.0%, respectively, for placebo. Erosion scores remained near baseline in the denosumab groups and increased from baseline in the placebo group. A negative correlation was observed between hand BMD and erosion scores. In patients with RA, denosumab provided protection against erosion, and not only prevented bone loss but increased hand BMD as measured by DXA.


Defining motility in the Staphylococci.
The ability of bacteria to move is critical for their survival in diverse environments and multiple ways have evolved to achieve this. Two forms of motility have recently been described for Staphylococcus aureus, an organism previously considered to be non-motile. One form is called spreading, which is a type of sliding motility and the second form involves comet formation, which has many observable characteristics associated with gliding motility. Darting motility has also been observed in Staphylococcus epidermidis. This review describes how motility is defined and how we distinguish between passive and active motility. We discuss the characteristics of the various forms of Staphylococci motility, the molecular mechanisms involved and the potential future research directions.


Prolactin profile in a cohort of Chinese systemic lupus erythematosus patients.
Prolactin (PRL) is an important immunoregulatory hormone secreted by the anterior pituitary gland. Hyperprolactinaemia has been implicated in the pathogenesis of systemic lupus erythematosus (SLE). However, clinical studies regarding the PRL level and lupus disease activity have yielded contradictory results. The aim of our present study was, therefore, to re-evaluate the association of PRL level and disease activity in SLE by analysing a larger patient cohort and following them up serially. Seventy-two consecutive SLE patients were recruited and the serum PRL level was measured at each visit. Our results showed that hyperprolactinaemia (> 500 mIU/l) occurred in 35% (25/72) of the patients. A total of 72% (18/25) of the hyperprolactinaemic patients had mild elevation (arbitrarily defined as 500-800 mIU/l) of the level only. No correlation could be found between the PRL level and various clinical and serological parameters of lupus disease activity. On serial follow-up of 44 patients, again no correlation between PRL and disease activity could be demonstrated. We conclude that hyperprolactinaemia occurs in some patients with SLE, but the serum level of PRL does not correlate with clinical or serological disease activity and is not a reliable marker for disease monitoring. The mechanism and pathoaetiological and clinical significance of hyperprolactinaemia in a small subset of SLE patients remain unclear and a longer follow-up is necessary.


Differential effects of granulocyte-macrophage colony-stimulating factor and granulocyte colony-stimulating factor in children with severe congenital neutropenia.
Severe congenital neutropenia (SCN) is a disorder of myelopoiesis characterized by severe neutropenia secondary to a maturational arrest at the level of promyelocytes. We treated five patients with SCN with recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) for 42 days and subsequently, between 1 and 3 months later, with rhG-CSF for 142 days. The objective was to evaluate the safety and ability of these factors to elicit a neutrophil response. rhGM-CSF was administered at a dose of 3 to 30 micrograms/kg/d (30 to 60 minutes, intravenously). In all patients, a specific, dose-dependent increase in the absolute granulocyte counts was observed. However, in four patients this increase was due to an increase in eosinophils, and in only one patient it was due to an increase in the absolute neutrophil counts (ANC). Subsequently, all patients received rhG-CSF at a dose of 3 to 15 micrograms/kg/d subcutaneously. In contrast to rhGM-CSF treatment, all five patients responded to rhG-CSF during the first 6 weeks of treatment with an increase in the ANC to above 1,000/microL. The level of ANC could be maintained during maintenance treatment. In one patient, the increase in ANC was associated with an improvement of a severe pneumonitis caused by Peptostreptococcus and resistant to antibiotic treatment. No severe bacterial infections occurred in any of the patients during CSF treatment. All patients tolerated rhGM-CSF and rhG-CSF treatment without severe side effects. These results demonstrate the beneficial effect of rhG-CSF in SCN patients.


HDAC inhibitor M344 suppresses MCF-7 breast cancer cell proliferation.
Histone deacetylase (HDAC) inhibitors represent a novel class of drugs that selectively induce cell cycle arrest and apoptosis in transformed cells. This study examined, for the first time, the effects of the relatively new HDAC inhibitor, M344 [4-dimethylamino-N-(6-hydroxycarbamoylhexyl)-benzamide], on the proliferation of MCF-7 breast cancer cells. MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assays revealed significant concentration- and time-dependent decreases in MCF-7 cell proliferation following treatment with M344 (1-100μM). In contrast to the significant induction of p21(waf1/cip1) mRNA expression following treatment with M344 (10μM) for 1 or 3 days, there was a significant decrease in p53 mRNA expression, although p53 protein levels were unchanged. Similar treatment with M344 also induced expression of the pro-apoptotic genes, Puma and Bax, together with the morphological features of apoptosis, in MCF-7 cells. The results of this study reinforce previous findings indicating that HDAC inhibitors are an important group of oncostatic drugs, and show that M344 is a potent suppressor of breast cancer cell proliferation.


Perceptual straightening of natural videos.
Many behaviors rely on predictions derived from recent visual input, but the temporal evolution of those inputs is generally complex and difficult to extrapolate. We propose that the visual system transforms these inputs to follow straighter temporal trajectories. To test this 'temporal straightening' hypothesis, we develop a methodology for estimating the curvature of an internal trajectory from human perceptual judgments. We use this to test three distinct predictions: natural sequences that are highly curved in the space of pixel intensities should be substantially straighter perceptually; in contrast, artificial sequences that are straight in the intensity domain should be more curved perceptually; finally, naturalistic sequences that are straight in the intensity domain should be relatively less curved. Perceptual data validate all three predictions, as do population models of the early visual system, providing evidence that the visual system specifically straightens natural videos, offering a solution for tasks that rely on prediction.


Submarine landslides: processes, triggers and hazard prediction.
Huge landslides, mobilizing hundreds to thousands of km(3) of sediment and rock are ubiquitous in submarine settings ranging from the steepest volcanic island slopes to the gentlest muddy slopes of submarine deltas. Here, we summarize current knowledge of such landslides and the problems of assessing their hazard potential. The major hazards related to submarine landslides include destruction of seabed infrastructure, collapse of coastal areas into the sea and landslide-generated tsunamis. Most submarine slopes are inherently stable. Elevated pore pressures (leading to decreased frictional resistance to sliding) and specific weak layers within stratified sequences appear to be the key factors influencing landslide occurrence. Elevated pore pressures can result from normal depositional processes or from transient processes such as earthquake shaking; historical evidence suggests that the majority of large submarine landslides are triggered by earthquakes. Because of their tsunamigenic potential, ocean-island flank collapses and rockslides in fjords have been identified as the most dangerous of all landslide related hazards. Published models of ocean-island landslides mainly examine 'worst-case scenarios' that have a low probability of occurrence. Areas prone to submarine landsliding are relatively easy to identify, but we are still some way from being able to forecast individual events with precision. Monitoring of critical areas where landslides might be imminent and modelling landslide consequences so that appropriate mitigation strategies can be developed would appear to be areas where advances on current practice are possible.


Molecular biology of pancreatic cancer: how useful is it in clinical practice?
During the recent two decades dramatic advances of molecular biology allowed an in-depth understanding of pancreatic carcinogenesis. It is currently accepted that pancreatic cancer has a genetic component. The real challenge is now how these impressive advances could be used in clinical practice. To critically present currently available data regarding clinical application of molecular biology in pancreatic cancer. Reports about clinical implications of molecular biology in patients with pancreatic cancer were retrieved from PubMed. These reports were selected on the basis of their clinical relevance, and the data of their publication (preferentially within the last 5 years). Emphasis was placed on reports investigating diagnostic, prognostic, and therapeutic implications. Molecular biology can be used to identify individuals at high-risk for pancreatic cancer development. Intensive surveillance is indicated in these patients to detect pancreatic neoplasia ideally at a preinvasive stage, when curative resection is still possible. Molecular biology can also be used in the diagnosis of pancreatic cancer, with molecular analysis on samples of biologic material, such as serum or plasma, duodenal fluid or preferentially pure pancreatic juice, pancreatic cells or tissue, and stools. Molecular indices have also prognostic significance. Finally, molecular biology may have therapeutic implications by using various therapeutic approaches, such as antiangiogenic factors, purine synthesis inhibitors, matrix metalloproteinase inhibitors, factors modulating tumor-stroma interaction, inactivation of the hedgehog pathway, gene therapy, oncolytic viral therapy, immunotherapy (both passive as well as active) etc. Molecular biology may have important clinical implications in patients with pancreatic cancer and represents one of the most active areas on cancer research. Hopefully clinical applications of molecular biology in pancreatic cancer will expand in the future, improving the effectiveness of treatment and prognosis of patients with pancreatic cancer.


Effective Control of Non-Native American Mink by Strategic Trapping in a River Catchment in Mainland Britain.
The introduction of American mink (Neovison vison; hereafter mink) into Europe has had severe impacts on many native wildlife species, including the water vole (Arvicola amphibius) in mainland Britain. Although trapping has been widely used to attempt to control mink, managers have little direct evidence of its effect on mink density or distribution, particularly where immigration of mink from nearby areas is inevitable. Such evidence is needed to justify the use of lethal methods in conservation policy. During 2006-2010 we removed mink from the River Monnow Catchment in western Britain, using track-recording rafts to monitor continuously for mink presence, guiding a strategic trapping effort. The area monitored and trapped was increased in stages, from a core sub-catchment with 109 km of water-course in 2006, to a 421-km2 catchment with 203 km of water-course in 2009. In each successive sub-catchment, mink detection and capture rates declined rapidly to near-zero levels after trapping began. Detections and captures showed seasonal peaks in every year corresponding to known dispersal periods, but also declined steadily from year to year, with increasing periods in which we did not detect mink. These results suggested that each sub-catchment was cleared of mink within a few months, with subsequent captures attributable to immigration. On average, we detected each mink 5.1 times before capture (daily probability of detection = 0.059 per mink and raft), and trapped them 3.4 days after deploying traps in response. On average, mink entering the area were likely to have been present for less than 13 days before capture. Water voles had been extinct in the Monnow Catchment since the 1980s. During 2006-2008 (starting 6 months after mink trapping commenced), we released 700 captive-bred water voles into the treatment area to re-establish a wild population. Persistence of this population through the 4 years of the project was considered indicative of effective mink control. This study demonstrates that, even in a mainland context, a systematic trapping strategy can have a substantial impact on the density and distribution of a damaging species, in this case allowing the restoration of a native prey species. © 2013 The Wildlife Society.


Expression of oxidative stress and antioxidant defense genes in the kidney of inbred mice after intestinal ischemia and reperfusion.
To determine the gene expressions profile related to the oxidative stress and the antioxidant response in the kidneys of mice subjected to intestinal ischemia and reperfusion. Twelve inbred mice (C57BL/6) were randomly assigned to one of two groups: the control group (CG) underwent anesthesia and was observed for 120 min and the ischemia/reperfusion group (IRG), animals were anesthetized and subjected to laparotomy and ischemia for 60 minutes followed by 60 minutes of reperfusion. The expressions of 84 genes from the kidney were determined by the Reverse Transcription qualitative Polymerase Chain Reaction (RT-qPCR). All genes that were up regulated by more than threefold using the algorithm [2(ΔΔCt)] were considered statically significant (p<0.05). In the IRG group 29 (34.52%) of 84 genes, were up regulated by more than threefold. The genes that were differentially up regulated in the glutathione peroxidase cluster (10 genes): were Gpx2 and Gpx7. The genes that were up regulated in the peroxidase cluster (16 genes) were following: Duox1, Epx, Lpo, Mpo, Ptgs2, Rag2, Serpinb1b, Tmod1 and Tpo. The genes that up regulated in the reactive oxygen species cluster (16 genes): Il19, Il22, Nos2, Nox1, Noxa1, Noxo1, Recql4 and Sod2. The genes that were up regulated in the oxidative stress cluster (22 genes) were: Mpp4, Nudt15, Upc3 and Xpa. The genes that were up regulated in the oxygen carriers cluster (12 genes) were: Hbq1, Mb, Ngb, Slc38a1 and Xirp1. The peroxiredoxins genes (10) showed no consistent differential regulation. The genes related to oxidative stress and antioxidant defense showed increased expression in renal tissue trigged intestinal ischemia and reperfusion.