Kinematics of the quadrate bone during feeding in mallard ducks.
Avian cranial kinesis, in which mobility of the quadrate, pterygoid and palatine bones contribute to upper bill elevation, is believed to occur in all extant birds. The most widely accepted model for upper bill elevation is that the quadrate rotates rostrally and medially towards the pterygoid, transferring force to the mobile pterygoid-palatine complex, which pushes on the upper bill. Until now, however, it has not been possible to test this hypothesis in vivo because quadrate motions are rapid, three-dimensionally complex and not visible externally. Here we use a new in vivo X-ray motion analysis technique, X-ray reconstruction of moving morphology (XROMM), to create precise (±0.06 mm) 3-D animations of the quadrate, braincase, upper bill and mandible of three mallard ducks, Anas platyrhynchos. We defined a joint coordinate system (JCS) for the quadrato-squamosal joint with the axes aligned to the anatomical planes of the skull. In this coordinate system, the quadrate's 3-D rotations produce an elliptical path of pterygoid process motion, with medial and rostrodorsal then lateral and rostrodorsal motion as the upper bill elevates. As the upper bill depresses, the pterygoid process continues along the ellipsoidal path, with lateral and caudoventral then medial and caudoventral motion. We also found that the mandibular rami bow outwards (streptognathy) during mandibular depression, which may cause the lateral component of quadrate rotation that we observed. Relative to the JCS aligned with the anatomical planes of the skull, a second JCS aligned with quadrato-squamosal joint anatomy did not produce a simpler description of quadrate kinematics.


Strategies for research engagement of clinicians in allied health (STRETCH): a mixed methods research protocol.
Allied health professionals (AHPs) report positive attitudes to using research evidence in clinical practice, yet often lack time, confidence and skills to use, participate in and conduct research. A range of multifaceted strategies including education, mentoring and guidance have been implemented to increase AHPs' use of and participation in research. Emerging evidence suggests that knowledge brokering activities have the potential to support research engagement, but it is not clear which knowledge brokering strategies are most effective and in what contexts they work best to support and maintain clinicians' research engagement. This protocol describes an exploratory concurrent mixed methods study that is designed to understand how allied health research fellows use knowledge brokering strategies within tailored evidence-based interventions, to facilitate research engagement by allied health clinicians. Simultaneously, a realist approach will guide a systematic process evaluation of the research fellows' pattern of use of knowledge brokering strategies within each case study to build a programme theory explaining which knowledge brokering strategies work best, in what contexts and why. Learning and behavioural theories will inform this critical explanation. An explanation of how locally tailored evidence-based interventions improve AHPs use of, participation in and leadership of research projects will be summarised and shared with all participating clinicians and within each case study. It is expected that local recommendations will be developed and shared with medical and nursing professionals in and beyond the health service, to facilitate building research capacity in a systematic and effective way.


Isolation of 35S- and 3H-labelled proteoglycans from cultures of human embryonic skin fibroblasts.
35SO42- - and [3H]-leucine-labelled proteoglycans were isolated from the medium of a fibroblast culture, from an EDTA extract of the monolayer, and from consecutive dithiothreitol and guanidine hydrochloride extracts of the cells. Proteoglycans of different sizes were isolated from the extracts by gel chromatography on Sepharose 4B. In the medium and the EDTA extract the largest proteoglycans contained only 35S-labelled galactosaminoglycan, whereas all other fractions contained in addition heparan [35S-labelled galactosaminoglycan, whereas all other fractions contained in addition heparin [35S]sulphate. The galactosaminoglycan-containing proteoglycans of the various extracts were separated into a larger component, containing chondroitin sulphate-like side chains, and a smaller component, containing dermatan sulphate. The larger proteoglycan of the medium showed reversible association-dissociation behaviour when chromatographed on Sepharose CL2B in phosphate-buffered saline and 4M-guanidine hydrochloride respectively. This property remained after removal of extraneous proteins by CsCl-density-gradient centrifugation in guanidine hydrochloride. The association was markedly increased by the addition of high-molecular-weight hyaluronic acid.


Meteorological factors and non-pharmaceutical interventions explain local differences in the spread of SARS-CoV-2 in Austria.
The drivers behind regional differences of SARS-CoV-2 spread on finer spatio-temporal scales are yet to be fully understood. Here we develop a data-driven modelling approach based on an age-structured compartmental model that compares 116 Austrian regions to a suitably chosen control set of regions to explain variations in local transmission rates through a combination of meteorological factors, non-pharmaceutical interventions and mobility. We find that more than 60% of the observed regional variations can be explained by these factors. Decreasing temperature and humidity, increasing cloudiness, precipitation and the absence of mitigation measures for public events are the strongest drivers for increased virus transmission, leading in combination to a doubling of the transmission rates compared to regions with more favourable weather. We conjecture that regions with little mitigation measures for large events that experience shifts toward unfavourable weather conditions are particularly predisposed as nucleation points for the next seasonal SARS-CoV-2 waves.


Inflammatory airway responses by nasal inoculation of suspended particulate matter in NC/Nga mice.
To evaluate the allergic effect of airborne particulate matter (PM) on the airway, separated soluble supernatant (Sup) and insoluble precipitate (Pre) in suspended PM were inoculated into NC/Nga mice with a high sensitivity for mite allergens. Sup, Pre, or both Sup and Pre with or without pronase treatment were inoculated via the nasal route five times for sensitization and a challenge inoculation on the 11th day in NC/Nga mice. On the 14th day, mice were examined for airway hyperresponsiveness (AHR), bronchoalveolar lavage fluid (BALF) cell count, mRNA expression of Th1 and Th2 cytokines in the lung tissue, and histopathology. Synergistic effects of Sup and Pre were observed as increases in AHR and a histopathological change of Periodic acid-Schiff (PAS) staining. Increases in neutrophils, macrophages, and lymphocytes of BALF cells were dependent on Pre. The expression of IL-4 mRNA was increased by Sup, and those of IL-5 mRNA and Il-13 mRNA was increased by Sup and Pre. Augmented AHR, mRNA expression of IL-4, peribronchial inflammation, and PAS staining by Sup plus Pre were attenuated by treatment of Sup with pronase to digest proteins. These results suggest that some proteins of ambient PM may be important environmental factors for AHR and airway inflammation with the aid of insoluble particulates, although some soluble factors such as endotoxins cannot be ruled out.


Steps through the revision process of reproductive health sections of ICD-11.
In 2007, the WHO initiated an organizational structure for the 11th revision of the International Classification of Diseases (ICD). Effective deployment of ICD-derived tools facilitates the use and collection of health information in a variety of resource settings, promoting quantitatively informed decisions. They also facilitate comparison of disease incidence and outcomes between different countries and different health care systems around the world. The Department of Reproductive Health and Research (RHR) coordinates the revision of chapters 14 (diseases of the genitourinary system), 15 (pregnancy, childbirth, and puerperium), and 16 (conditions originating in the perinatal period). RHR convened a technical advisory group (TAG), the Genito-Urinary Reproductive Medicine (GURM) TAG, for the ICD revision. The TAG's work reflects the collective understanding of sexual and reproductive health and is now available for review within the ICD-11 revision process.


Impaired control of IRES-mediated translation in X-linked dyskeratosis congenita.
The DKC1 gene encodes a pseudouridine synthase that modifies ribosomal RNA (rRNA). DKC1 is mutated in people with X-linked dyskeratosis congenita (X-DC), a disease characterized by bone marrow failure, skin abnormalities, and increased susceptibility to cancer. How alterations in ribosome modification might lead to cancer and other features of the disease remains unknown. Using an unbiased proteomics strategy, we discovered a specific defect in IRES (internal ribosome entry site)-dependent translation in Dkc1(m) mice and in cells from X-DC patients. This defect results in impaired translation of messenger RNAs containing IRES elements, including those encoding the tumor suppressor p27(Kip1) and the antiapoptotic factors Bcl-xL and XIAP (X-linked Inhibitor of Apoptosis Protein). Moreover, Dkc1(m) ribosomes were unable to direct translation from IRES elements present in viral messenger RNAs. These findings reveal a potential mechanism by which defective ribosome activity leads to disease and cancer.


Type I Collagen and Strontium-Containing Mesoporous Glass Particles as Hybrid Material for 3D Printing of Bone-Like Materials.
Bone tissue engineering offers an alternative promising solution to treat a large number of bone injuries with special focus on pathological conditions, such as osteoporosis. In this scenario, the bone tissue regeneration may be promoted using bioactive and biomimetic materials able to direct cell response, while the desired scaffold architecture can be tailored by means of 3D printing technologies. In this context, our study aimed to develop a hybrid bioactive material suitable for 3D printing of scaffolds mimicking the natural composition and structure of healthy bone. Type I collagen and strontium-containing mesoporous bioactive glasses were combined to obtain suspensions able to perform a sol-gel transition under physiological conditions. Field emission scanning electron microscopy (FESEM) analyses confirmed the formation of fibrous nanostructures homogeneously embedding inorganic particles, whereas bioactivity studies demonstrated the large calcium phosphate deposition. The high-water content promoted the strontium ion release from the embedded glass particles, potentially enhancing the osteogenic behaviour of the composite. Furthermore, the suspension printability was assessed by means of rheological studies and preliminary extrusion tests, showing shear thinning and fast material recovery upon deposition. In conclusion, the reported results suggest that promising hybrid systems suitable for 3D printing of bioactive scaffolds for bone tissue engineering have been developed.


Variation in kinematics and dynamics of the landing flights of pigeons on a novel perch
Pigeons made 10 flights to a novel perch. Kinematic measurements of these flights were obtained from video recordings, and the forces exerted on the perch on each landing were measured. There was wide variation (20-fold range) in the kinetic energy of the pigeons just before landing, arising almost entirely from variation in horizontal velocity. The maximum force exerted on the perch varied in magnitude from approximately twice to eight times the pigeons' body weight, and in direction from 40 to 90 below the horizontal. In landings with high final kinetic energy, the maximum force exerted on the perch was larger and was applied at a shallower angle than in those with low final kinetic energy. Landing flights with high final kinetic energy showed straighter trajectories and a larger peak deceleration during the last 300 ms of approach flight than those with low final kinetic energy, which had downward-curving trajectories and a more prolonged and steady pattern of deceleration. Mean final kinetic energy was lower in the first two landings made on the perch than in subsequent landings, indicating that pigeons are more likely to adopt a slow, downward-curving approach to a novel perch and a fast, straight approach to a familiar one.


Alcohol Use, Alcohol-Related Outcome Expectancies, and Partner Aggression Among Males Court-Mandated to Batterer Intervention Programs: A Brief Report.
Additional work is needed to determine how and/or why the relationship between alcohol use and increased risk of partner aggression (PA) exists. Researchers have begun to examine whether alcohol-related outcome expectancies (i.e., beliefs about the cognitive and behavioral effects of alcohol) are associated with PA irrespective of alcohol use. We examined the relationship between alcohol use, alcohol expectancies, and PA among 360 males arrested for a domestic violence offense and court-mandated to treatment. Results indicate that certain alcohol expectancies do play a role in the relationship between alcohol use and some forms of PA.


Intracellular antibody capture (IAC) methods for single domain antibodies.
Intracellular single domain antibodies are recombinant proteins, comprising one variable region domain fragment, that bind specifically to intracellular molecules and can interfere with their particular functions within various cellular compartments. They are valuable tools in bioscience and potential macrodrugs in biotherapeutics; however, their application is still limited because of the difficulty and inefficiency of acquisition of functional intracellular antibodies. We describe here the new generation protocol for intracellular antibody capture to facilitate selection of functional single domains. This protocol uses a series of optimized single domain libraries, based on designed intracellular variable (VH or VL) region scaffolds, for direct in vivo isolation of single domains that bind to target proteins and interaction and for affinity maturation to develop sub-nM affinity antibody fragments. The method has advantages over other methods in that specific single domains are isolated directly within the reducing cellular environment and can be selected without in vitro antigen protein preparation.In an accompanying methods paper, we describe a simple extension of the methodology to isolate subsets of IAC-captured single domains that interfere with protein-protein interactions.


Empowerment: the emperor's new clothes.
Everyone talks about empowerment, but it's not working. CEOs subtly undermine empowerment. Employees are often unprepared or unwilling to assume the new responsibilities it entails. Even change professionals stifle it. When empowerment is used as the ultimate criteria of success in organizations, it covers up many of the deeper problems that they must overcome. To understand this apparent contradiction, the author explores two kinds of commitment: external and internal. External commitment--or contractual compliance--is what employees display when they have little control over their destinies and are accustomed to working under the command-and-control model. Internal commitment occurs when employees are committed to a particular project, person, or program for their own individual reasons or motivations. Internal commitment is very closely allied with empowerment. The problem with change programs designed to encourage empowerment is that they actually end up creating more external than internal commitment. One reason is that these programs are rife with inner contradictions and send out mixed messages like "do your own thing--the way we tell you." The result is that employees feel little responsibility for the change program, and people throughout the organization feel less empowered. What can be done? Companies would do well to recognize potential inconsistencies in their change programs; to understand that empowerment has its limits; to establish working conditions that encourage employees' internal commitment; and to realize that morale and even empowerment are penultimate criteria in organizations. The ultimate goal is performance.


Vigour-related traits and immunity in hybrids of evolutionary divergent cyprinoid species: advantages of hybrid heterosis?
Hybrid advantage, described as the superiority of hybrids in some traits over their parents and termed the "heterosis effect," is widely documented in the case of reciprocal crosses of parental species (i.e., hybrids representing the F1 generation). In fish, high survival, fast growth and better health status have been widely documented in F1 hybrids. Nonetheless, the effects of interspecific hybridization on vigour, physiology and immunity-related traits in fish are largely unknown, especially concerning native systems of coexisting parental and hybrid genomes in the same habitat. The present study examined the potential physiological and immune aspects of hybrid heterosis by comparing condition status (measured especially by indexes), haematological profile, glucose concentration and selected parameters of non-specific and specific immunity between the evolutionarily divergent non-congeneric cyprinoid species Abramis brama and Rutilus rutilus and their hybrids representing the F1 generation, all of them caught in nature. Clear differences were documented for vigour-related, physiological and immune parameters between the two divergent species. Hybrids generally tended to express intermediate characters of the measured traits, likely generated by the evolutionary divergence of the hybridizing species; nonetheless, for some traits, hybrids exhibited a character that was more similar to one parental species than to the other. This was interpreted as the heterozygote advantage for F1 hybrids. It is suggested that a maternally inherited genetic background may potentially influence the expression of some branches of non-specific immunity or other aspects related to the fish health status.


Cost-effectiveness of integrated pest management compared with insecticidal spraying against the German cockroach in apartment buildings.
This study assessed the cost and effectiveness of an integrated pest management (IPM) program using hydramethylnon gel baits compared with conventional spraying for controlling the German cockroach, Blattella germanica (L.) (Blattodea: Blattellidae), in two residential buildings in Yasuj, Iran. The IPM approach was based on educational programs using pamphlets, posters and lectures, sanitation using vacuuming and application of hydramethylnon gel baits. Conventional approach used cypermethrin (10% EC) on baseboard and cracks-and-crevices. Sticky traps were used as tools for monitoring cockroach population densities. The IPM approach reduced (943%) the rate of insecticide application compared to the conventional spray. Cockroach populations in the IPM treatment were significantly reduced from an average of 12.2 ± 3.01 cockroaches per unit before treatment to zero cockroach per unit by week four and thereafter. Cockroach populations in the conventional spray treatment were reduced from an average of 11.5 ± 4.43 cockroaches per unit before treatment to an average of 3.4 ± 0.99 cockroach per unit after 11 weeks of post treatment. The IPM treatment improved 100% of infested units compared to 78% for spray treatment to obtain a clean level of infestation (< 1cockroach per trap per unit). The results suggest that the intervention by IPM using hydramethylnon gel baits significantly reduced cockroach infestation compared to cypermethrin spray throughout the 11 weeks of post-treatment period. However, within the study period, the IPM system involving gel baits, educational program and sanitation was 363.2% more expensive than the conventional method.


Searching for the source of Ebola: the elusive factors driving its spillover into humans during the West African outbreak of 2013-2016.
The natural ecology of Ebola virus infection remains enigmatic. No clear reservoir species has been confirmed but there is evidence of infection in a wide spectrum of mammals, including humans, non-human primates, domestic and wild ungulates and a variety of bat species, both frugivorous and insectivorous. Humans and most other species examined appear to be spillover hosts and suffer disease. Bats are the exception and are tolerant to infection in some laboratory studies. Some surveys show a low prevalence of antibodies against Zaire Ebola virus (ZEBOV) strains in bats during human outbreaks and inter-epidemic periods, and this order of mammals is considered to be the likely reservoir for the virus. Other putative sources include insects but this hypothesis is unproven in the field or laboratory. Moreover, some potential sources, such as aquatic species, have yet to be investigated. There are a number of environmental, human behavioural and ecological risk factors proposed with respect to spillover and spread. In the West African outbreak, which was unprecedented in scale and geographic spread, the source of the spillover remains unproven, although an association exists between the proposed index case and a colony of insectivorous bats. In all but a few Ebola virus disease events, spillover has only been superficially investigated and this was also the case in the West African epidemic. The authors suggest that, to address risks at the human-animal-environmental interface, using a One Health approach, more effort is needed to investigate spillover factors at the time of a ZEBOV epidemic, in addition to conducting inter-epidemic surveys in peridomestic environments. The true prevalence of ZEBOV infection in any species of bats remains unknown. Large-scale, expensive, non-randomised surveys, with low sampling numbers per species, are unlikely to provide evidence for Ebola virus reservoirs or to improve our epidemiological understanding.


Central nervous system delivery of recombinant ciliary neurotrophic factor by polymer encapsulated differentiated C2C12 myoblasts.
Neurotrophic factors hold promise for the treatment of neurodegenerative diseases. Intrathecal transplantation of polymer encapsulated cell lines genetically engineered to release neurotrophic factors provides a means to deliver them continuously behind the blood-brain barrier. Long-term delivery, however, may benefit from the use of conditionally mitotic cells to avoid the overgrowth observed with continuously dividing cell lines. Myoblast lines have all the advantages of dividing cell lines, i.e., unlimited availability, possibility for in vitro screening for the presence of pathogens, suitability for stable gene transfer and clonal selection. Furthermore they can be differentiated into a nonmitotic stage upon exposure to low-serum-containing medium. In this study, mouse C2C12 myoblasts were transfected with a pNUT expression vector containing the human ciliary neurotrophic factor (CNTF) gene. hCNTF expression and bioactivity were demonstrated by Northern blot, ELISA assay, and measurement of choline acetyltransferase (ChAT) activity in embryonic spinal cord motor neuron cultures. One C2C12 clone was found to secrete 200 ng of CNTF/10(6) cells per day. The rate of secretion of hCNTF was not altered upon differentiation of C2C12 myoblasts. A bromodeoxyuridine (BrdU) proliferation assay indicated that approximately 12% of the myoblasts continue to divide after 4 days in low-serum-containing medium. The presence of the herpes simplex thymidine kinase gene (HSV-tk) in the expression vector, however, provides a way to eliminate these dividing myoblasts upon exposure to ganciclovir, therefore increasing the safety of the encapsulation technology using established cell lines. Encapsulated hCNTF-C2C12 cells can partially rescue motor neurons from axotomy-induced cell death. In adult rats, intrathecal implantation of encapsulated hCNTF-C2C12 cells or control C2C12 confirmed the long-term survival of these cells and their potential use as a source of neurotophic factors for the treatment of neurodegenerative diseases.


Analogues of erectile dysfunction drugs: an under-recognised threat.
To investigate the problem of drug analogue adulteration in male erectile dysfunction health products. Survey of over-the-counter male erectile dysfunction health products available in convenience stores and pharmacies in Hong Kong. Tertiary referral centre for clinical toxicology analysis in Hong Kong. The pattern and extent of adulteration of male erectile dysfunction health products with sildenafil, tadalafil, and vardenafil as well as their structurally modified analogues. Of 26 products studied, one (4%) was found to contain undeclared sildenafil, while 14 (54%) contained drug analogues of different kinds. The latter included acetildenafil, hydroxyacetildenafil, hydroxyhomosildenafil, and piperidenafil. The first three were analogues of sildenafil and the last was an analogue of vardenafil. One young patient presented with ataxia after taking an acetildenafil-containing product. The positive rate of concealed drug analogues in male erectile dysfunction health products is alarmingly high. Such analogues are difficult to detect by ordinary laboratory methods, and might be used in an attempt to evade regulatory inspection. Without going through the stringent drug testing process, the adverse effects of these chemicals remain largely unknown and unpredictable. Effective surveillance system and control measures are needed urgently. The medical profession and the public should be alerted to this under-recognised threat.


Learning in friendship groups: developing students' conceptual understanding through social interaction.
The role that student friendship groups play in learning was investigated here. Employing a critical realist design, two focus groups on undergraduates were conducted to explore their experience of studying. Data from the "case-by-case" analysis suggested student-to-student friendships produced social contexts which facilitated conceptual understanding through discussion, explanation, and application to "real life" contemporary issues. However, the students did not conceive this as a learning experience or suggest the function of their friendships involved learning. These data therefore challenge the perspective that student groups in higher education are formed and regulated for the primary function of learning. Given these findings, further research is needed to assess the role student friendships play in developing disciplinary conceptual understanding.


Effect of daily cod liver oil and a multivitamin-mineral supplement with selenium on upper respiratory tract pediatric visits by young, inner-city, Latino children: randomized pediatric sites.
We studied the effect of daily supplementation with lemon-flavored cod liver oil and a children's multivitamin-mineral supplement containing selenium on the number of pediatric visits by young, inner-city, Latino children from late autumn of 2002 through early spring of 2003. Two private pediatric offices with similar demographics, located 1.1 miles apart in upper Manhattan, New York City, were randomized to a supplementation site and a medical records control site. Ninety-four children (47 at each site), 6 months to 5 years of age, were enrolled. The mean age of the supplementation group was 2.03 years (SD, +/- 1.04 years); that of the control group was 2.08 years (SD, +/- 1.10 years). Children > or = 1 year of age in the supplementation group received 1 teaspoon of lemon-flavored cod liver oil per day and one half-tablet of a children's multivitamin-mineral; the starting dose was halved for children < 1 year of age. The supplements were given from enrollment through May 1, 2003. The primary outcome measure was the number of upper respiratory tract pediatric visits during the follow-up/supplementation period. The supplementation group had a statistically significant decrease in the mean number of upper respiratory tract visits over time (p = .042; r = 0.893; y = 0.602 - 0.002x); the medical records control group had no change in this parameter (p = .999; r = 0.0006; y = 0.259 + 1.43 x 10(-6)x). The supplements were well tolerated; per parental report, 70% of children completed the 5- to 6-month course of cod liver oil. Use of these nutritional supplements was acceptable to the inner-city Latino families and their young children, and was associated with a decrease in upper respiratory tract pediatric visits over time; this approach therefore deserves further research and attention.


Policing Education: An Empirical Review of the Challenges and Impact of the Work of School Police Officers.
Public concerns regarding school safety and zero-tolerance education policies have contributed to the growth of a workforce of school police, or frontline school safety professionals who are typically placed in schools with the authority to arrest students (Brown, 2006). Thus, school police represent a workforce positioned at the nexus of multiple systems, including education and juvenile justice, and whose work likely brings them into contact with underserved youth and families. Despite national representation of this growing workforce (e.g., National Association of School Resource Officers), little is known about the responsibilities, roles, training, and influence of school police. This manuscript aims to (a) advance understanding of the school police workforce, including in relation to school police training, needs, roles, and influence, through a systematic review of scholarship in the social sciences, with a focus on peer-reviewed research in education, psychology, social work, criminology, and juvenile justice; and (b) generate empirically supported recommendations integrating key conclusions that pertain specifically to targeting the challenges faced by the school police workforce and identifying the best strategies to enhance safety-related goals while mitigating disproportionate legal and educational consequences for underserved youth and families.


Interventions for treating neuropathic pain in people with sickle cell disease.
Pain is the hallmark of sickle cell disease (SCD) and it can be severe, frequent and unpredictable. Although nociceptive pain is more common, at times, people with SCD may have neuropathic pain. The latter can occur due to peripheral or central nerve injury. This review is focused on identifying treatment of only painful sensory neuropathy in people with SCD. To determine the effectiveness and safety of any pharmacological or non-pharmacological therapies for treating neuropathic pain in people with SCD. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched trial registries, the reference lists of relevant articles and reviews and contacted experts in the field.Date of last search: 31 January 2019. Randomised controlled trials (RCTs) (parallel or cross-over in design), quasi-RCTs of pharmacological or non-pharmacological therapies for treating neuropathic pain in people with SCD compared to placebo or another intervention in any category (i.e. pharmacological or non-pharmacological). Two review authors independently assessed all trials identified by the searches and extracted relevant data. Two authors independently assessed the risk of bias in the selected trials using the Cochrane risk of bias tool. Two review authors independently rated the quality of the evidence for each outcome using the GRADE guidelines. One RCT of 22 participants with SCD, conducted in the USA was included in this review. Participants were randomly assigned to either pregabalin (n = 11) or placebo (n = 11). Oral pregabalin was administered at an initial dose of 75 mg twice daily. The drug was titrated at increments of 75 mg to a maximum of 600 mg daily or decreased by 75 mg per day if necessary, based on clinical presentation and pain level. Neuropathic pain was assessed using self-reports on the Leeds Assessment of Neuropathic Symptoms and Signs (S-LANNS) scale and the Neuropathic Pain Symptom Inventory (NPSI), where higher scores were indicative of more pain. Outcomes included self-reported pain, quality of life and withdrawal due to adverse effects measured at baseline and monthly for three months post-intervention. The overall risk of bias was low with a high risk of bias due to attrition.In relation to this reviews primary outcomes, for self-reported neuropathic pain relief, given the paucity of data, we are very uncertain whether there is a difference between the pregabalin and placebo groups at the end of three months as measured by the S-LANSS scale, mean difference (MD) -2.00 (95% confidence interval (CI) -9.18 to 5.18), or the NPSI scale, MD -11.10 (95% CI -33.97 to 11.77) (very low-quality evidence). There was no report of 'Patient Global Impression of Change' in the included trial.Although the mean quality of life scores (Short Form-36) at three months showed small increases in seven of the eight domains post-intervention in the pregabalin group as compared to the placebo group, this was very low-quality evidence and we are very uncertain whether pregabalin increases quality of life. Neither of our pre-defined outcomes of 'time to improvement of symptoms' or 'changes in sleep quality', were measured in the included trial.While treatment-related adverse effects appeared higher in pregabalin group than the placebo group at three months, this was very low-quality evidence and we are very uncertain whether there is a difference, RR 1.33 (95% CI 0.39 to 4.62) (very low-quality evidence). There was one withdrawal for adverse effects in the pregabalin group while three people withdrew or dropped out from the placebo group due to adverse effects and complications and hospitalisation related to SCD. The included trial provided very low-quality evidence. Self-reported pain relief was greater in the pregabalin group compared to the placebo control group but only using the S-LANSS scale and we are very unsure whether there is a difference. While the pregabalin group tended to have improved quality of life over the duration of the trial, this was very low-quality evidence and we are uncertain whether there is a difference. Adverse effects and withdrawals were similar across the treatment and placebo control group in trial. There are both insufficient trials addressing this review question and insufficient outcomes addressed in the single included RCT. Therefore, there is still a significant gap in evidence on interventions for neuropathic pain in people with SCD.


Quantitative relationships of exposure to chrysotile asbestos and mesothelioma mortality.
While asbestos has long been known to cause mesothelioma, quantitative exposure-response data on the relation of mesothelioma risk and exposure to chrysotile asbestos are sparse. Quantitative relationships of mortality from mesothelioma and pleural cancer were investigated in an established cohort of 5397 asbestos textile manufacturing workers in North Carolina, USA. Eligible workers were those employed between 1950 and 1973 with mortality follow-up through 2003. Individual exposure to chrysotile fibres was estimated on the basis of 3420 air samples covering the entire study period linked to work history records. Exposure coefficients adjusted for age, race, and time-related covariates were estimated by Poisson regression. Positive, statistically significant associations were observed between mortality from all pleural cancer (including mesothelioma) and time since first exposure (TSFE) to asbestos (rate ratio [RR], 1.19; 95% confidence interval [CI], 1.06-1.34 per year), duration of exposure, and cumulative asbestos fibre exposure (RR, 1.15; 95% CI, 1.04-1.28 per 100 f-years/mL; 10-year lag). Analyses of the shape of exposure-response functions suggested a linear relationship with TSFE and a less-than-linear relationship with cumulative exposure. Restricting the analysis to years when mesothelioma was coded as a unique cause of death yielded stronger but less precise associations. These observations support with quantitative data the conclusion that chrysotile causes mesothelioma and encourage exposure-response analyses of mesothelioma in other cohorts exposed to chrysotile.


Fractional Quantum Hall States at ν=13/5 and 12/5 and Their Non-Abelian Nature.
Topological quantum states with non-Abelian Fibonacci anyonic excitations are widely sought after for the exotic fundamental physics they would exhibit, and for universal quantum computing applications. The fractional quantum Hall (FQH) state at a filling factor of ν=12/5 is a promising candidate; however, its precise nature is still under debate and no consensus has been achieved so far. Here, we investigate the nature of the FQH ν=13/5 state and its particle-hole conjugate state at 12/5 with the Coulomb interaction, and we address the issue of possible competing states. Based on a large-scale density-matrix renormalization group calculation in spherical geometry, we present evidence that the essential physics of the Coulomb ground state (GS) at ν=13/5 and 12/5 is captured by the k=3 parafermion Read-Rezayi state (RR_{3}), including a robust excitation gap and the topological fingerprint from the entanglement spectrum and topological entanglement entropy. Furthermore, by considering the infinite-cylinder geometry (topologically equivalent to torus geometry), we expose the non-Abelian GS sector corresponding to a Fibonacci anyonic quasiparticle, which serves as a signature of the RR_{3} state at 13/5 and 12/5 filling numbers.


Consistent condom use among men with non-marital partners in four sub-Saharan African countries.
Data from the Demographic and Health Surveys for Namibia, Swaziland, and Zambia and the AIDS Indicator Survey from Tanzania were used to examine the influence of marital status and number of partners on consistent condom use among men with casual sexual partnerships in four generalized HIV epidemic settings. We restrict the sample to the 26% (Zambia), 29% (Tanzania), 35% (Swaziland), and 42% (Namibia) of men, who, in the last 12 months before the survey, had any non-marital/non-cohabiting (i.e., casual) sexual partners. We use "condom always used with any partner in the last 12 months" as a dichotomous-dependent measure of consistent condom use. Analyses were stratified by country. Of men with casual partners, 41% (Zambia) to 70% (Namibia) used a condom every time with at least one partner. The majority of men were unmarried/non-cohabiting with one casual partner in the last year. In Swaziland and Zambia, multivariate results suggest that unmarried/non-cohabiting men with one casual partner had significantly lower odds than married/cohabiting men with casual partners to use condoms consistently (odds ratio [OR]=0.56, p=0.01 and OR=0.41, p<0.001, respectively.). In Namibia, unmarried/non-cohabiting men with two or more casual partners had significantly greater odds than married/cohabiting men with casual partners to use condoms consistently (OR=2.80, p<0.01). With some exceptions by country, higher education, religious group, wealth, having no children, knowing HIV results, having an STI, having one lifetime partner, and positive condom knowledge and beliefs also were significantly associated with using a condom every time with any partner. We conclude that consistent condom use remains an elusive goal even among men with casual sexual relationships. Condom use messages should be refined and targeted to men based on their number and types of relationships and combined with other messages to decrease concurrent relationships.


Application of monoliths as supports for affinity chromatography and fast enzymatic conversion.
Monoliths are useful chromatographic supports, as their structure allows improved mass transport. This results in fast separation. Once the ligand of interest has been immobilized, chromatographic separation can also be accomplished in affinity mode. Ligands with low molecular mass have been shown to be the easiest to immobilize. Nowadays, ligands with low molecular mass are often designed by combinatorial chemical techniques. In addition, many applications have been described where ligands with high molecular mass, such as Proteins A and G, antibodies, lectins and receptors are used. The immobilization of an enzyme on the monolithic support creates a flow-through reactor. Small proteins, such as carbonic anhydrase, can be directly immobilized on the support. However, in the case of large molecules, the active center of the enzyme is no longer accessible at all or only to a limited degree. An improvement can be achieved by introducing a spacer, which allows maximum enzymatic conversion. Fast conversion of substrates with high molecular mass has been investigated with immobilized trypsin. It was shown that in case of high-molecular-mass substrates, the conversion rate depends very much on the flow-rate. Most applications described have been performed on an analytical or semi-preparative scale. However, the technical problems of up-scaling are close to being definitely solved, enabling enzymatic conversion on a preparative scale in the future.


Inactivation of the protein phosphatase 2A regulatory subunit A results in morphological and transcriptional defects in Saccharomyces cerevisiae.
We have determined that TPD3, a gene previously identified in a screen for mutants defective in tRNA biosynthesis, most likely encodes the A regulatory subunit of the major protein phosphatase 2A species in the yeast Saccharomyces cerevisiae. The predicted amino acid sequence of the product of TPD3 is highly homologous to the sequence of the mammalian A subunit of protein phosphatase 2A. In addition, antibodies raised against Tpd3p specifically precipitate a significant fraction of the protein phosphatase 2A activity in the cell, and extracts of tpd3 strains yield a different chromatographic profile of protein phosphatase 2A than do extracts of isogenic TPD3 strains. tpd3 deletion strains generally grow poorly and have at least two distinct phenotypes. At reduced temperatures, tpd3 strains appear to be defective in cytokinesis, since most cells become multibudded and multinucleate following a shift to 13 degrees C. This is similar to the phenotype obtained by overexpression of the protein phosphatase 2A catalytic subunit or by loss of CDC55, a gene that encodes a protein with homology to a second regulatory subunit of protein phosphatase 2A. At elevated temperatures, tpd3 strains are defective in transcription by RNA polymerase III. Consistent with this in vivo phenotype, extracts of tpd3 strains fail to support in vitro transcription of tRNA genes, a defect that can be reversed by addition of either purified RNA polymerase III or TFIIIB. These results reinforce the notion that protein phosphatase 2A affects a variety of biological processes in the cell and provide an initial identification of critical substrates for this phosphatase.


The rubber tree genome shows expansion of gene family associated with rubber biosynthesis.
Hevea brasiliensis Muell. Arg, a member of the family Euphorbiaceae, is the sole natural resource exploited for commercial production of high-quality natural rubber. The properties of natural rubber latex are almost irreplaceable by synthetic counterparts for many industrial applications. A paucity of knowledge on the molecular mechanisms of rubber biosynthesis in high yield traits still persists. Here we report the comprehensive genome-wide analysis of the widely planted H. brasiliensis clone, RRIM 600. The genome was assembled based on ~155-fold combined coverage with Illumina and PacBio sequence data and has a total length of 1.55 Gb with 72.5% comprising repetitive DNA sequences. A total of 84,440 high-confidence protein-coding genes were predicted. Comparative genomic analysis revealed strong synteny between H. brasiliensis and other Euphorbiaceae genomes. Our data suggest that H. brasiliensis's capacity to produce high levels of latex can be attributed to the expansion of rubber biosynthesis-related genes in its genome and the high expression of these genes in latex. Using cap analysis gene expression data, we illustrate the tissue-specific transcription profiles of rubber biosynthesis-related genes, revealing alternative means of transcriptional regulation. Our study adds to the understanding of H. brasiliensis biology and provides valuable genomic resources for future agronomic-related improvement of the rubber tree.


General practice training and virtual communities of practice - a review of the literature.
Good General Practice is essential for an effective health system. Good General Practice training is essential to sustain the workforce, however training for General Practice can be hampered by a number of pressures, including professional, structural and social isolation. General Practice trainees may be under more pressure than fully registered General Practitioners, and yet isolation can lead doctors to reduce hours and move away from rural practice. Virtual communities of practice (VCoPs) in business have been shown to be effective in improving knowledge sharing, thus reducing professional and structural isolation. This literature review will critically examine the current evidence relevant to virtual communities of practice in General Practice training, identify evidence-based principles that might guide their construction and suggest further avenues for research. Major online databases Scopus, Psychlit and Pubmed were searched for the terms "Community of Practice" (CoP) AND (Online OR Virtual OR Electronic) AND (health OR healthcare OR medicine OR "Allied Health"). Only peer-reviewed journal articles in English were selected. A total of 76 articles were identified, with 23 meeting the inclusion criteria. There were no studies on CoP or VCoP in General Practice training. The review was structured using a framework of six themes for establishing communities of practice, derived from a key study from the business literature. This framework has been used to analyse the literature to determine whether similar themes are present in the health literature and to identify evidence in support of virtual communities of practice for General Practice training. The framework developed by Probst is mirrored in the health literature, albeit with some variations. In particular the roles of facilitator or moderator and leader whilst overlapping, are different. VCoPs are usually collaborations between stakeholders rather than single company VCoPs. Specific goals are important, but in specialised health fields sometimes less important than in business. Boundary spanning can involve the interactions of different professional groups, as well as using external experts seen in business VCoPs. There was less use of measurement in health VCoPs. Environments must be supportive as well as risk free. Additional findings were that ease of use of technology is paramount and it is desirable for VCoPs to blend online and face-to-face involvement. The business themes of leadership, sponsorship, objectives and goals, boundary spanning, risk-free environment and measurements become, in the health literature, facilitation, champion and support, objectives and goals, a broad church, supportive environment, measurement benchmarking and feedback, and technology and community.General Practice training is under pressure from isolation and virtual communities of practice may be a way of overcoming isolation. The health literature supports, with some variation, the business CoP framework developed by Probst. Further research is needed to clarify whether this framework is an effective method of health VCoP development and if these VCoPs overcome isolation and thus improve rural retention of General Practice registrars.


Identification of Cyst Nematodes of Agronomic and Regulatory Concern with PCR-RFLP of ITS1.
The first internally transcribed spacer region (ITS1) from cyst nematode species (Heteroderidae) was compared by nucleotide sequencing and PCR-RFLP. European, Asian, and North American isolates of five heterodefid species were examined to assess intraspecific variation. PCR-RFLP patterns of amplified ITS1 DNA from pea cyst nematode, Heterodera goettingiana, from Northern Ireland were identical with patterns from Washington State. Sequencing demonstrated that ITS1 heterogeneity existed within individuals and between isolates, but did not result in different restriction patterns. Three Indian and two U.S. isolates of the corn cyst nematode, Heterodera zeae, were compared. Sequencing detected variation among ITS1 clones from the same individual, between individuals, and between isolates. PCR-RFLP detected several restriction site differences between Indian and U.S. isolates. The basis for the restriction site differences between isolates from India and the U.S. appeared to be the result of additional, variant ITS1 regions amplified from the U.S. isolates, which were not found in the three India isolates. PCR-RFLP from individuals of the U.S. isolates created a composite pattern derived from several ITS1 types. A second primer set was specifically designed to permit discrimination between soybean (H. glycines) and sugar beet (H. schachtii) cyst nematodes. Fok I digestion of amplified product from soybean cyst nematode isolates displayed a uniform pattern, readily discernible from the pattern of sugar beet and clover cyst nematode (H. trifolii).


Duration of action of a broad range of selective κ-opioid receptor antagonists is positively correlated with c-Jun N-terminal kinase-1 activation.
The κ-opioid receptor is a widely expressed G-protein-coupled receptor that has been implicated in biological responses to pain, stress, anxiety, and depression, and its potential as a therapeutic target in these syndromes is becoming increasingly apparent. However, the prototypical selective κ-opioid antagonists have very long durations of action that have been attributed to c-Jun N-terminal kinase (JNK) 1 activation in vivo. To test generality of this proposed noncompetitive mechanism, we used C57BL/6 wild type mice to determine the durations of antagonist action of novel κ-opioid receptor ligands and examined their efficacies for JNK1 activation compared with conventional competitive antagonists. Of the 12 compounds tested, 5 had long durations of action that positively correlated with JNK activation: RTI-5989-97 [(3S)-7-hydroxy-N-[(1S)-1-[(3R,4R)-4-(3-hydroxyphenyl)-3,4-dimethyl-1-piperidinyl]methyl}-(2-methylpropyl]-2-methyl-1,2,3,4-tetrahydro-3-isoquinolinecarboxamide], RTI-5989-194 [(3R)-7-hydroxy-N-[(1S)-1-[(3R,4R)-4-(3-hydroxyphenyl)-3,4-dimethyl-1-piperidinyl]methyl}-(2-methylbutyl]-1,2,3,4-tetrahydro-3-isoquinolinecarboxamide], RTI-5989-241 [(3R)-7-hydroxy-N-[(1S)-1-{[(3R,4R)-4-(3-methoxyphenyl)-3,4-dimethyl-1-piperidinyl]methyl}-2-methylpropyl]-1,2,3,4-tetrahydroisoquinoline-3-carboxamide)], nor-binaltorphimine (nor-BNI); and (3R)-7-hydroxy-N-((1S)-1-{[(3R,4R)-4-(3-hydroxyphenyl)-3,4-dimethyl-1-piperidinyl]methyl}-2-methylpropyl)-1,2,3,4-tetrahydro-3-isoquinolinecarboxamide (JDTic). Seven had short durations of action and did not increase phospho-JNK-ir: RTI-5989-212[(3R)-N-[(1S)-1-[(3R,4R)-4-(3-hydroxyphenyl)-3,4-dimethyl-1-piperidinyl]methyl}-(2-methylpropyl]-7-methoxy-1,2,3,4-tetrahydroisoquinoline-3-carboxamide], RTI-5989-240 [(3R)-7-hydroxy-N-[(1S)-1-[(3R,4R)-4-(3-hydroxyphenyl)-3,4-dimethylpiperidin-1-yl]methyl}-(2-methylpropyl]-3-methyl-1,2,3,4-tetrahydroisoquinoline-3-carboxamide], JSPA0658 [(S)-3-fluoro-4-(4-((2-(3,5-dimethylphenyl)pyrrolidin-1-yl)methyl)phenoxy)benzamide], JSPA071B [(S)-3-fluoro-4-(4-((2-(3,5-bis(trifluoromethyl)phenyl)pyrrolidin-1-yl)methyl)phenoxy)benzamide]. PF-4455242 [2-methyl-N-((2'-(pyrrolidin-1-ylsulfonyl)biphenyl-4-yl)methyl)propan-1-amine], PF-4455242 [2-methyl-N-((2'-(pyrrolidin-1-ylsulfonyl)biphenyl-4-yl)methyl)propan-1-amine], FP3FBZ [(S)-3-fluoro-4-(4-((2-(3-fluorophenyl)pyrrolidin-1-yl)methyl)phenoxy)benzamide], and naloxone. After long-acting antagonist treatment, pJNK-ir did not increase in mice lacking the κ-opioid receptor; increased pJNK-ir returned to baseline by 48 h after treatment; and a second challenge with nor-BNI 72 h after the first did not increase pJNK-ir. Long-lasting antagonism and increased phospho-JNK-ir were not seen in animals lacking the JNK1 isoform. These results support the hypothesis that the duration of action of small molecule κ-opioid receptor antagonists in vivo is determined by their efficacy in activating JNK1 and that persistent inactivation of the κ-receptor does not require sustained JNK activation.


Mean circulatory filling pressure: its meaning and measurement.
The volume-pressure relationship of the vasculature of the body as a whole, its vascular capacitance, requires a measurement of the mean circulatory filling pressure (Pmcf). A change in vascular capacitance induced by reflexes, hormones, or drugs has physiological consequences similar to a rapid change in blood volume and thus strongly influences cardiac output. The Pmcf is defined as the mean vascular pressure that exists after a stop in cardiac output and redistribution of blood, so that all pressures are the same throughout the system. The Pmcf is thus related to the fullness of the circulatory system. A change in Pmcf provides a uniquely useful index of a change in overall venous smooth muscle tone if the blood volume is not concomitantly changed. The Pmcf also provides an estimate of the distending pressure in the small veins and venules, which contain most of the blood in the body and comprise most of the vascular compliance. Thus the Pmcf, which is normally independent of the magnitude of the cardiac output, provides an estimate of the upstream pressure that determines the rate of flow returning to the heart.


Intestinal pseudo-obstruction in myotonic dystrophy.
We describe four myotonic dystrophy (DM) patients who developed recurrent intestinal pseudo-obstruction. Some episodes were associated with gastroenteritis, while abdominal crowding may have occurred in one case during the third trimester of pregnancy. In most instances, however, no apparent cause could be identified. Intestinal pseudo-obstruction may occur at any stage of DM. In one of our cases intestinal pseudo-obstruction preceded significant muscle weakness by 15 years. Intestinal pseudo-obstruction is usually treated effectively with conservative measures. These include restriction of oral intake, intravenous fluids, and multiple enemas or colonoscopy. Improved intestinal function was noted in one case treated with the prokinetic agent cisapride. A partial sigmoid resection was performed in three cases with dolichomegacolon. No abnormalities were reported on histological examination. Since intestinal pseudo-obstruction is a rare complication of DM, it is of interest that two of our cases are sibs. Review of published reports showed several reports of familial occurrence of specific complications. These include cardiac conduction disturbances, focal myocarditis, mitral valve prolapse, pilomatrixomas, polyneuropathy, normal pressure hydrocephalus, and dilatation of the urinary tract. Myotonic dystrophy may show a tendency to familial clustering of organ specific involvement.


Helicobacter pylori induced interleukin-8 expression in gastric epithelial cells is associated with CagA positive phenotype.
To use a range of natural phenotypically variant strains of Helicobacter pylori with disparate CagA and VacA (vacuolating cytotoxin) expression to determine which bacterial factors are more closely associated with epithelial interleukin-8 (IL-8) induction. Gastric epithelial cells (AGS and KATO-3) were co-cultured with five H pylori strains which were variously shown to express the cagA gene/CagA protein, VacA and/or to exhibit biological cytotoxicity. Secreted IL-8 was assayed by enzyme leaked immunosorbent assay (ELISA) and IL-8 messenger RNA (mRNA) was assayed using a reverse transcription polymerase chain reaction based technique (RT-PCR). Strains expressing CagA, including a variant strain (D931) which is non-cytotoxic and does not express the VacA protein, were found to upregulate epithelial IL-8 secretion and gene expression. In contrast, strains with no CagA expression, even in the presence of VacA and/or biological cytotoxicity, (G104, BA142), failed to induce IL-8 protein or mRNA above control values. These results strongly support a role for H pylori CagA or coexpressed factors other than the cytotoxin in upregulation of gastric epithelial IL-8. Increased epithelial IL-8 secretion and concomitant neutrophil chemotaxis and activation in addition to direct cytotoxicity may be an important factor in tissue damage and ulceration.


Reduction of atherosclerosis in cholesterol-fed rabbits and decrease of expressions of intracellular adhesion molecule-1 and vascular endothelial growth factor in foam cells by a water-soluble fraction of Polygonum multiflorum.
Polygonum multiflorum stilbeneglycoside (PMS) is a water-soluble fraction of Polygonum multiflorum Thunb., one of the most famous tonic traditional Chinese medicines, that has protective effects on the cardiovascular system. The purpose of the present study is to elucidate the effects of PMS on macrophage-derived foam cell functions and the reduction of severity of atherosclerosis in hypercholesterolemic New Zealand White (NZW) rabbits. NZW rabbits were fed for 12 weeks with a normal diet, a high cholesterol diet, or a high cholesterol diet associated with irrigation with different doses of PMS (25, 50, or 100 mg/kg). Treatment of NZW rabbits fed with high cholesterol diet with 100 mg/kg PMS attenuated the increase in plasma cholesterol, low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol, and plasma triglyceride. Treatment with 50 and 100 mg/kg PMS caused 43% and 60% decrease in atherosclerotic lesioned area ratio to total surface area, respectively. In U937 foam cells, PMS could decrease the high expression of intercellular adhesion molecule (ICAM)-1 protein and the vascular endothelial growth factor (VEGF) protein levels in the medium induced by oxidized lipoprotein when analyzed by flow cytometry. The results proved that PMS is a powerful agent against atherosclerosis and that PMS action could possibly be through the inhibition of the expression of ICAM-1 and VEGF in foam cells.


A single phosphatase can convert a robust step response into a graded, tunable or adaptive response.
Many biological signalling pathways have evolved to produce responses to environmental signals that are robust to fluctuations in protein copy number and noise. Whilst beneficial for biology, this robustness can be problematic for synthetic biologists wishing to re-engineer and subsequently tune the response of a given system. Here we show that the well-characterized EnvZ/OmpR two-component signalling system from Escherichia coli possesses one such robust step response. However, the synthetic addition of just a single component into the system, an extra independently controllable phosphatase, can change this behaviour to become graded and tunable, and even show adaptation. Our approach introduces a new design principle which can be implemented simply in engineering and redesigning fast signal transduction pathways for synthetic biology.


The determinants of the quality of clinical management among diabetic and hypertensive patients in a context of fragility: A cross-sectional survey from Lebanon.
The management of NCDs is a growing challenge in low- and middle-income settings with the increasing prevalence and the associated demands that such conditions make on health systems. Fragile settings both exacerbate the risk of NCDs and undermine systems capacity. Lebanon is a setting where strategies to address rising NCDs burden have faced particularly acute contextual challenges. We conducted a cross-sectional survey with patients accessing non-communicable disease across 11 primary care centers within the Greater Beirut and Beqaa areas. Response were received from 1,700 patients. We generated a Clinical Management Index Score as a measure of quality of care, and scores related to a range of socio-demographic characteristics and other context specific variables. Significantly higher clinical management index scores (better quality of care) were associated with patients living in the semi-urban/rural context of Beqaa (compared to Greater Beirut), having health insurance coverage, aged above 60, having high levels of educational attainment, and making partial or full payment for their treatment. Relatively lower index scores (poorer quality of care) were associated with Syrian nationality (compared to Lebanese) and with patients suffering from diabetes or hypertension (compared to comorbid patients). The study identified a wide margin for improving quality of NCDs care in fragile contexts with particular gaps identified in referral to ophthalmology, accessing all prescribed medication and receiving counseling for smoking cessation. Additionally, findings indicate a number of predictors of comparatively poor quality of care that warrant attention, notably with regard to Syrian nationality/legal status, lack of health coverage, seeking free health provision and lower educational attachment. Although these are all relevant risk factors, the findings call on donor agencies, NGOs and provider institutions to design targeted programs and activities that especially ensure equitable delivery of services to diabetic and hypertensive patients with compounded vulnerability as a result of a number of these factors.


Prospective trial for the treatment of malignant peritoneal mesothelioma.
Malignant peritoneal mesothelioma (MPM) is a rare and often rapidly fatal disease with median survival of 5 to 12 months for untreated cases and 16 months reported after multimodality treatment. We report a prospective clinical treatment study using cytoreductive surgery combined with intraoperative intraperitoneal heated chemotherapy (IPHC) perfusion using mitomycin C for MPM. Twelve patients (11 male with a mean age 51 years) were treated. Seven patients presented with bulky disease and seven with ascites. All underwent exploratory laparotomy with histologically confirmed diagnosis of MPM. Surgical debulking as feasible was performed. Complete gross tumor removal was possible in only one patient. Cytoreduction was followed by a 2-hour closed low-volume IPHC using mitomycin C. One patient died 50 days postoperatively from complications relating to small bowel perforation. Hematologic toxicity of the procedure was minimal. Ascites was controlled in all patients and permanently in 86 per cent of patients presenting with ascites. To date median survival is 34.2 months with median follow-up of 45.2 months. One patient was re-explored for ventral hernia 2 years post-IPHC, had negative peritoneal biopsies, and remains disease-free at 5 years. Given the dismal prognosis associated with MPM the results of treatment with cytoreductive surgery combined with IPHC perfusion are encouraging. The rarity of MPM makes appropriately powered prospective randomized trials unlikely. Therefore, we now offer this approach off protocol; however, further study of this combined modality therapy is warranted.


Intravenous immunoglobulin for the prevention of infection in chronic lymphocytic leukemia. A randomized, controlled clinical trial.
In a double-blind study, we randomly assigned 84 patients with chronic lymphocytic leukemia who were judged to be at increased risk of bacterial infection to receive intravenous immunoglobulin G (400 mg per kilogram of body weight) or a placebo every three weeks for one year. Eligible patients had hypogammaglobulinemia, a history of infection, or both. The patients receiving immunoglobulin had significantly fewer bacterial infections during the study period than those receiving placebo (23 vs. 42; P = 0.01). This reduction was most striking in the patients who completed a full year of treatment (14 vs. 36; P = 0.001). The period from study entry to the first serious bacterial infection was significantly longer in the patients receiving immunoglobulin (P = 0.026). There was no significant difference between the two groups in the incidence of nonbacterial infection. Immunoglobulin therapy was tolerated well; there were no serious adverse reactions, and the incidence of minor reactions was low. We conclude that selected patients with chronic lymphocytic leukemia who are at risk of bacterial infection can be substantially protected from this complication by the regular intravenous administration of immunoglobulin.


Waldenström macroglobulinemia.
Waldenström macroglobulinemia (WM) is a low-grade lymphoproliferative disorder characterized by the presence of an immunoglobulin M monoclonal protein in the blood and monoclonal small lymphocytes and lymphoplasmacytoid cells in the marrow. The disease is uncommon and there is a lack of clear diagnostic criteria. WM is treatable but not curable and long-term survival is possible. Therefore, the treating physician needs to carefully balance the risks and benefits of treatment. Treatments are aimed at relieving symptoms resulting from marrow infiltration and the hyperviscosity syndrome. Therapies available for initiation of treatment include alkylating agents, purine nucleoside analogs, and rituximab. Chlorambucil has been the mainstay of treatment for many years and remains useful, especially in older patients. Rituximab has become an important new therapy for this disease because of its positive treatment responses, acceptable toxicity, and lack of therapy-associated myelosuppression and myelodysplasia. Currently, rituximab is being combined with chemotherapy. Other options of treatment include interferon and corticosteroids. Emerging therapies include stem cell transplantation (autologous and allogeneic) for younger patients. Currently, there are few comparative data on which to state an absolute opinion concerning the best available treatment for patients with WM.


Depletion of macrophages in mice results in higher dengue virus titers and highlights the role of macrophages for virus control.
Monocytes and macrophages are target cells for dengue infection. Besides their potential role for virus replication, activated monocytes/macrophages produce cytokines that may be critical for dengue pathology. To study the in vivo role of monocytes and macrophages for virus replication, we depleted monocytes and macrophages in IFN-alphabetagammaR knockout mice with clodronate liposomes before dengue infection. Although less virus was first recovered in the draining LN in the absence of macrophages, monocyte/macrophage depletion eventually resulted in a ten-fold higher systemic viral titer. A massive infiltration of CD11b(+)CD11c(low)Ly6C(low) monocytes into infected organs was observed in parallel with increasing virus titers before viremia was controlled. Depletion of monocytes in the blood before or after local infection had no impact on virus titers, suggesting that monocytes are not required as "virus-shuttles". Our data provide evidence that systemic viremia is established independently of tissue macrophages present at the site of infection and blood monocytes. Instead, we demonstrate the importance of monocytes/macrophages for the control of dengue virus.


Anti-HIV-1 activity in vitro of ceftazidime degradation products.
Cephalosporins in aqueous solutions generate degradation products that inhibit in vitro HIV-1 replication in cell lines, as well as in primary cells (lymphocytes and macrophages). This effect is observed at concentrations that do not interfere with the normal functions of these cells. Upon chromatographic fractionation of an aqueous solution of hydrolysed ceftazidime, a high molecular weight fraction (MW 8000) with antiviral activity was isolated. The exact chemical nature of the active component responsible for the anti-HIV activity in vitro appears to be complex and is currently unknown. Inhibition of HIV-1 reverse transcriptase and RNase H activity was observed, however, higher concentrations than those needed to inhibit HIV replication were required. The inhibitory action of the hydrolysed ceftazidime was manifested during the early phase of the HIV-1 life-cycle. Despite a lack of a direct effect of the CD4/gp120 interaction, HIV-1 mediated cell fusion was inhibited by the hydrolysed ceftazidime, suggesting that the active principle acts in a very early stage of the viral life-cycle.


Corticotropin-releasing factor-1 receptor involvement in behavioral neuroadaptation to ethanol: a urocortin1-independent mechanism.
A common expression of neuroadaptations induced by repeated exposure to addictive drugs is a persistent sensitized behavioral response to their stimulant properties. Neuroplasticity underlying drug-induced sensitization has been proposed to explain compulsive drug pursuit and consumption characteristic of addiction. The hypothalamic-pituitary-adrenal (HPA) axis-activating neuropeptide, corticotropin-releasing factor (CRF), may be the keystone in drug-induced neuroadaptation. Corticosterone-activated glucocorticoid receptors (GRs) mediate the development of sensitization to ethanol (EtOH), implicating the HPA axis in this process. EtOH-induced increases in corticosterone require CRF activation of CRF1 receptors. We posited that CRF1 signaling pathways are crucial for EtOH-induced sensitization. We demonstrate that mice lacking CRF1 receptors do not show psychomotor sensitization to EtOH, a phenomenon that was also absent in CRF1 + 2 receptor double-knockout mice. Deletion of CRF2 receptors alone did not prevent sensitization. A blunted endocrine response to EtOH was found only in the genotypes showing no sensitization. The CRF1 receptor antagonist CP-154,526 attenuated the acquisition and prevented the expression of EtOH-induced psychomotor sensitization. Because CRF1 receptors are also activated by urocortin-1 (Ucn1), we tested Ucn1 knockout mice for EtOH sensitization and found normal sensitization in this genotype. Finally, we show that the GR antagonist mifepristone does not block the expression of EtOH sensitization. CRF and CRF1 receptors, therefore, are involved in the neurobiological adaptations that underlie the development and expression of psychomotor sensitization to EtOH. A CRF/CRF1-mediated mechanism involving the HPA axis is proposed for acquisition, whereas an extrahypothalamic CRF/CRF1 participation is suggested for expression of sensitization to EtOH.


Utilization of Magnetic Resonance Imaging in Research Involving Animal Models of Fetal Alcohol Spectrum Disorders.
It is well recognized that fetal alcohol exposure can profoundly damage the developing brain. The term fetal alcohol spectrum disorder (FASD) describes the range of deficits that result from prenatal alcohol exposure. Over the past two decades, researchers have used magnetic resonance imaging (MRI) as a noninvasive technique to characterize anatomical, physiological, and metabolic changes in the human brain that are part of FASD. As using animal models can circumvent many of the complications inherent to human studies, researchers have established and explored a number of models involving a range of species. Using MRI-based modalities, the FASD animal models have demonstrated decreased brain volume and abnormal brain shape, disrupted cellular morphology differentiation, altered neurochemistry, and blood perfusion. These animal studies have facilitated characterization of the direct effects of ethanol; in many cases identifying specific sequelae related to the timing and dose of exposure. Further, as a result of the ability to perform traditional (such as histological) analyses on animal brains following neuroimaging experiments, this work leads to improvements in the accuracy of our interpretations of neuroimaging findings in human studies.


White matter hyperintensities are related to pain intensity in an outpatient memory clinic population: preliminary findings.
Background: The association between pain and dementia is complicated and may depend on underlying brain pathology. It was hypothesized that both medial temporal atrophy (MTA) and global cortical atrophy (GCA) predicted no/mild pain, while white matter hyperintensities (WMH) predicted moderate/severe pain. Objectives: To study the association between pain intensity and measures of brain pathology, more specifically MTA, GCA, and WMH. Methods: In total, 115 consecutive patients visiting an outpatient memory clinic were included. In total, diagnoses included dementia (N=70), mild cognitive impairment (N=30), and subjective cognitive impairment (N=15). Without administering stimuli, pain intensity was assessed with the Brief Pain Inventory. MTA, GCA, and WMH were measured with a MRI visual rating scale. Logistic regression analyses to examine the relationship between WMH, MTA, GCA, and self-reported pain intensity (no/mild pain versus moderate/severe pain) were adjusted for confounders. Results: Mean age of the patients was 81 years (IQR: 78-85, 53% female). Moderate/severe pain was reported by 23.5% and associated with greater WMH (OR =3.34, 95% CI =1.01-10.97, p=0.047), but not MTA or GCA. Conclusions: In contrast to the present results, earlier studies have reported either a positive or negative relationship between pain and brain volume. It is suggested that the presence of dementia may explain the absence of a relationship between pain and brain volume. WMH is positively related with pain in an older memory outpatient population. Considering the small sample size, our findings should be interpreted with caution. Hence, our conclusions are preliminary findings, warranting future replication.


Adaptive Evolution of Escherichia coli to Ciprofloxacin in Controlled Stress Environments: Contrasting Patterns of Resistance in Spatially Varying versus Uniformly Mixed Concentration Conditions.
A microfluidic gradient chamber (MGC) and a homogeneous batch culturing system were used to evaluate whether spatial concentration gradients of the antibiotic ciprofloxacin allow development of greater antibiotic resistance in Escherichia coli strain 307 (E. coli 307) compared to exclusively temporal concentration gradients, as indicated in an earlier study. A linear spatial gradient of ciprofloxacin and Luria-Bertani broth (LB) medium was established and maintained by diffusion over 5 days across a well array in the MGC, with relative concentrations along the gradient of 1.7-7.7× the original minimum inhibitory concentration (MICoriginal). The E. coli biomass increased in wells with lower ciprofloxacin concentrations, and only a low level of resistance to ciprofloxacin was detected in the recovered cells (∼2× MICoriginal). Homogeneous batch culture experiments were performed with the same temporal exposure history to ciprofloxacin concentration, the same and higher initial cell densities, and the same and higher nutrient (i.e., LB) concentrations as in the MGC. In all batch experiments, E. coli 307 developed higher ciprofloxacin resistance after exposure, ranging from 4 to 24× MICoriginal in all replicates. Hence, these results suggest that the presence of spatial gradients appears to reduce the driving force for E. coli 307 adaptation to ciprofloxacin, which suggests that results from batch experiments may over predict the development of antibiotic resistance in natural environments.


Use of prescription pain medications among medical cannabis patients: comparisons of pain levels, functioning, and patterns of alcohol and other drug use.
Management of chronic pain is one of the most common reasons given by individuals seeking medical cannabis. However, very little information exists about the concurrent use of cannabis and prescription pain medication (PPM). This study fills this gap in knowledge by systematically comparing medical cannabis users who use or do not use PPM, with an emphasis on understanding whether concurrent use of cannabis and PPM is associated with more serious forms of alcohol and other drug involvement. Data from this study were collected from a medical cannabis clinic in southwestern Michigan (N = 273). Systematic comparisons were made on measures of sociodemographics, reasons for substance use, pain, functioning, and perceptions of PPM and medical cannabis efficacy. PPM users tended to be older and reported higher levels of pain and lower levels of functioning. The overall sample exhibited higher lifetime and past-3-month rates of alcohol and other noncannabis drug use than did the general population. Approximately 40% of subjects reported combining cannabis with alcohol, but no significant difference was observed between PPM users and nonusers. PPM users and nonusers did not exhibit any difference in either lifetime or past-3-month use of other drugs, including cocaine, sedatives, street opioids, and amphetamines. PPM users rated the efficacy of cannabis higher than PPM for pain management and indicated a strong desire to reduce PPM usage. Use of PPM among medical cannabis users was not identified as a correlate for more serious forms of alcohol and other drug involvement. However, longitudinal study designs are needed to better understand the trajectories of alcohol and other drug involvement over time among medical cannabis users.


A rare cause of bacteremia in a pediatric patient with Down syndrome: Sphingomonas paucimobilis.
Sphingomonas paucimobilis, is a yellow-pigmented, aerobic, non fermentative, gram negative motile bacillus. S. paucimobilis which is widely found in nature and hospital environments rarely cause serious or life threatening infections. In this report, a case of hospital acquired bloodstream infection due to S. paucimobilis in a patient with Down syndrome who was on treatment for presumed pneumonia is presented. A one year-old child patient who was a known case of Down syndrome and had previously experienced cardiac surgery was hospitalized and treated for pneumonia. On the 12th day of hospitalization, blood cultures were taken because of a high body temperature. One of the blood cultures was positive for gram-negative rods. After 48 hour of incubation, the sub-cultures on blood agar medium yielded pure growth of a yellow, non-fermentative, gram-negative, rod-shaped bacterium. The microorganism was positive for oxidase, and esculin hydrolysis, while negative for urea and nitrate reduction, citrate utilisation and motility. The isolate had been identified as S. paucimobilis by using Vitek 2 system. The antibiotic susceptibility test was also performed with the same system and the strain was found to be susceptible to piperacillin-tazobactam and other antibiotics. Treatment with intravenous piperacilin-tazobactam (150 mg/kg/day) was initiated. He responded well to the treatment and was discharged after 10 days. This case is reported to emphasize that S. paucimobilis should be kept in mind as a nosocomial infectious agent in patients with Down syndrome and immunosuppressive patients and the infections should be treated according to the sensitivity test results.


Dbp7p, a putative ATP-dependent RNA helicase from Saccharomyces cerevisiae, is required for 60S ribosomal subunit assembly.
Putative ATP-dependent RNA helicases are ubiquitous, highly conserved proteins that are found in most organisms and they are implicated in all aspects of cellular RNA metabolism. Here we present the functional characterization of the Dbp7 protein, a putative ATP-dependent RNA helicase of the DEAD-box protein family from Saccharomyces cerevisiae. The complete deletion of the DBP7 ORF causes a severe slow-growth phenotype. In addition, the absence of Dbp7p results in a reduced amount of 60S ribosomal subunits and an accumulation of halfmer polysomes. Subsequent analysis of pre-rRNA processing indicates that this 60S ribosomal subunit deficit is due to a strong decrease in the production of 27S and 7S precursor rRNAs, which leads to reduced levels of the mature 25S and 5.8S rRNAs. Noticeably, the overall decrease of the 27S pre-rRNA species is neither associated with the accumulation of preceding precursors nor with the emergence of abnormal processing intermediates, suggesting that these 27S pre-rRNA species are degraded rapidly in the absence of Dbp7p. Finally, an HA epitope-tagged Dbp7 protein is localized in the nucleolus. We propose that Dbp7p is involved in the assembly of the pre-ribosomal particle during the biogenesis of the 60S ribosomal subunit.


Resonance-enhanced x-rays in thin films: a structure probe for membranes and surface layers.
An x-ray resonance effect in an organic thin film on an x-ray reflecting mirror is reported. The resonance effect is the result of interference between reflected and refracted x-rays at the air-organic thin film interface and occurs at incident angles slightly above the critical angle of the film. In excellent agreement with theory, the primary resonant x-ray electric field that is confined in the organic thin film is approximately 20 times as intense as the electric field of the incident beam when measured at a position close to the center of the film. Resonance-enhanced x-rays can be used to characterize the internal structure of Langmuir-Blodgett thin film membranes. This effect may also find use in x-ray-based thin film devices and in the structural analysis of adlayers and surfaces that have thus far proved difficult, if not impossible, to study because of sensitivity limitations.


Quantitative trait loci for thermal time to flowering and photoperiod responsiveness discovered in summer annual-type Brassica napus L.
Time of flowering is a key adaptive trait in plants and is conditioned by the interaction of genes and environmental cues including length of photoperiod, ambient temperature and vernalisation. Here we investigated the photoperiod responsiveness of summer annual-types of Brassica napus (rapeseed, canola). A population of 131 doubled haploid lines derived from a cross between European and Australian parents was evaluated for days to flowering, thermal time to flowering (measured in degree-days) and the number of leaf nodes at flowering in a compact and efficient glasshouse-based experiment with replicated short and long day treatments. All three traits were under strong genetic control with heritability estimates ranging from 0.85-0.93. There was a very strong photoperiod effect with flowering in the population accelerated by 765 degree-days in the long day versus short day treatments. However, there was a strong genetic correlation of line effects (0.91) between the long and short day treatments and relatively low genotype x treatment interaction indicating that photoperiod had a similar effect across the population. Bivariate analysis of thermal time to flowering in short and long days revealed three main effect quantitative trait loci (QTLs) that accounted for 57.7% of the variation in the population and no significant interaction QTLs. These results provided insight into the contrasting adaptations of Australian and European varieties. Both parents responded to photoperiod and their alleles shifted the population to earlier flowering under long days. In addition, segregation of QTLs in the population caused wide transgressive segregation in thermal time to flowering. Potential candidate flowering time homologues located near QTLs were identified with the aid of the Brassica rapa reference genome sequence. We discuss how these results will help to guide the breeding of summer annual types of B. napus adapted to new and changing environments.


Dynamic regulation of genome-wide pre-mRNA splicing and stress tolerance by the Sm-like protein LSm5 in Arabidopsis.
Sm-like proteins are highly conserved proteins that form the core of the U6 ribonucleoprotein and function in several mRNA metabolism processes, including pre-mRNA splicing. Despite their wide occurrence in all eukaryotes, little is known about the roles of Sm-like proteins in the regulation of splicing. Here, through comprehensive transcriptome analyses, we demonstrate that depletion of the Arabidopsis supersensitive to abscisic acid and drought 1 gene (SAD1), which encodes Sm-like protein 5 (LSm5), promotes an inaccurate selection of splice sites that leads to a genome-wide increase in alternative splicing. In contrast, overexpression of SAD1 strengthens the precision of splice-site recognition and globally inhibits alternative splicing. Further, SAD1 modulates the splicing of stress-responsive genes, particularly under salt-stress conditions. Finally, we find that overexpression of SAD1 in Arabidopsis improves salt tolerance in transgenic plants, which correlates with an increase in splicing accuracy and efficiency for stress-responsive genes. We conclude that SAD1 dynamically controls splicing efficiency and splice-site recognition in Arabidopsis, and propose that this may contribute to SAD1-mediated stress tolerance through the metabolism of transcripts expressed from stress-responsive genes. Our study not only provides novel insights into the function of Sm-like proteins in splicing, but also uncovers new means to improve splicing efficiency and to enhance stress tolerance in a higher eukaryote.


Human and E.coli excinucleases are affected differently by the sequence context of acetylaminofluorene-guanine adduct.
Synthetic DNA substrates containing an acetylaminofluorene (AAF) adduct at each of the three guanine in the G1G2CG3CC sequence were constructed and tested as substrates for reconstituted E.coli (A)BC excinuclease and human excinuclease in HeLa cell-free extract (CFE). The (A)BC excinulcease repaired the three substrates with relative efficiencies of G1:G2:G3 of 100:18:66 in agreement with an earlier report [Seeberg, E., and Fuchs, R.P.P. (1990) Proc. Natl Acad. Sci. USA 87, 191-194]. The same lesions were repaired by the human excinuclease with the strikingly different efficiencies of G1:G2:G3 as 38:100:68. These results reveal that the human excinuclease is affected by the sequence context of the lesion in a different manner than its prokaryotic counterpart.


Recall of intestinal helminthiasis by HIV-infected South Africans and avoidance of possible misinterpretation of egg excretion in worm/HIV co-infection analyses.
Ascariasis and HIV/AIDS are often co-endemic under conditions of poverty in South Africa; and discordant immune responses to the respective infections could theoretically be affecting the epidemic of HIV/AIDS in various ways. It is well-known that sensitisation to helminthic antigens can aggravate or ameliorate several non-helminthic diseases and impair immunisation against cholera, tetanus and tuberculosis. The human genotype can influence immune responses to Ascaris strongly. With these factors in mind, we have started to document the extent of long-term exposure to Ascaris and other helminths in a community where HIV/AIDS is highly prevalent. In more advanced studies, objectives are to analyse relevant immunological variables (e.g. cytokine activity and immunoglobulin levels). We postulate that when Ascaris is hyperendemic, analysis of possible consequences of co-infection by HIV cannot be based primarily on excretion vs non-excretion of eggs. Recall of worms seen in faeces was documented in relation to the age of adult volunteers who were either seropositive (n = 170) or seronegative (n = 65) for HIV. Reasons for HIV testing, deworming treatments used or not used, date and place of birth, and duration of residence in Cape Town, were recorded. Confidence intervals were calculated both for group percentages and the inter-group differences, and were used to make statistical comparisons. In both groups, more than 70% of participants were aware of having passed worms, often both when a child and as an adult. Most of the descriptions fitted Ascaris. Evidence for significantly prolonged exposure to helminthic infection in HIV-positives was supported by more recall of deworming treatment in this group (p < 0.05). Over 90% of the participants had moved to the city from rural areas. There was a long-term history of ascariasis (and probably other helminthic infections) in both of the groups that were studied. In women in the same community, and in children living where housing and sanitation are better, Ascaris sero-prevalence exceeded egg-prevalence by two- and three-fold, respectively. For ongoing and future analyses of possible consequences of co-infection by Ascaris (and/or other helminths) and HIV/AIDS (and/or other bystander conditions), comparisons must be based mainly on disease-related immunological variables. Especially in adults, comparisons cannot be based only on the presence or absence of eggs in excreta.


Biodegradable honeycomb-patterned film composed of poly(lactic acid) and dioleoylphosphatidylethanolamine.
Honeycomb-patterned films have been reported to be useful for scaffolds of cell culture in tissue engineering. In the present study, we investigated a new compound, dioleoylphosphatidylethanolamine (DOPE), a naturally derived phospholipid having unsaturated fatty acid moieties, as a surfactant for fabricating honeycomb-patterned poly(d,l-lactide) (PLA) film. Only DOPE among commercially available phospholipids was useful as a surfactant, and it showed good solubility in PLA/chloroform solution and an excellent property for fabricating honeycomb-patterned film (the concentration of DOPE was from 0.2% to 20% by weight based on the weight of PLA). The pore size of the honeycomb was uniform, and all pores were interconnected with each other. The contact angle of water on the honeycomb-patterned film was affected by the amount of DOPE. Time-of-flight secondary ion mass spectrometer (TOF-SIMS) data suggested that DOPE was concentrated on the surface of the honeycomb-patterned film. To investigate cell proliferation and adhesion on the honeycomb-patterned film, NIH3T3 fibroblast cells were cultured on the film. The NIH3T3 cells adhered well on the honeycomb-patterned PLA film with DOPE (PLA-DOPE) and showed good cell proliferation compared to that on honeycomb-patterned PLA film fabricated with a copolymer (CAP) of dodecylacrylamide and omega-carboxyhexylacrylamide (PLA-CAP). These results suggest that the honeycomb-patterned PLA-DOPE can be applicable as a scaffold for cells with better profiles in comparison with PLA-CAP.


A geographic analysis of motor vehicle collisions with child pedestrians in Long Beach, California: comparing intersection and midblock incident locations.
The purpose of this study was to use geographic information system (GIS) software to locate areas of high risk for child pedestrian-motor vehicle collisions in the city of Long Beach and to compare risk factors between midblock and intersection collisions. Children 0-14 years of age involved in a motor vehicle versus pedestrian collision that occurred on public roadways in Long Beach, CA, between 1 January 1992 and 30 June 1995, were identified retrospectively from police reports. The GIS software program, ArcView, was used for spatial analysis and distance calculations. chi2 Tests were used to compare the distribution of the characteristics between intersection and midblock collisions. The average annual incident and fatality rate was 183.3/100,000 children/ year and 2.4/100,000 children/year, respectively. Children less than 5 years of age were significantly more likely to be hit at a midblock location while those aged 5-9 and 10-14 were more often hit at an intersection. Intersection collisions were more likely to occur on major arterials and local streets, and the driver to be the primary party at fault (p<0.001). While intersection incidents tended to occur further from the child's home (64.4%) the majority of midblock incidents (61.5%) occurred within 0.1 miles of the child's residence. For both midblock and intersection locations, pedestrian collisions tended to occur more frequently in those census tracts with a larger number of families per census tract-a measure of household crowding and density. Future studies taking into consideration traffic volume and vehicle speed would be useful to focus prevention efforts such as environmental modifications, improving police enforcement, and educational efforts targeted at parents of younger children. As GIS illustrative spatial relationships continue to improve, relationships between pedestrian collision sites and other city landmarks can advance the study of pedestrian incidents.


Marital status predicts change in distress and well-being in women newly diagnosed with breast cancer and their peer counselors.
We conducted a nonrandomized study matching 42 women newly diagnosed with breast cancer (sojourners) with 39 trained breast cancer survivors (navigators) who provided one-on-one peer counseling for 3-6 months. Because little is known about how marital status might impact participants in such an intervention, we tested whether being married/partnered buffered navigators and sojourners from distress at baseline and over time. We examined baseline and slopes over time for change in depression and trauma symptoms, and emotional well-being. We were particularly concerned that being matched with a newly diagnosed breast cancer patient might trigger a re-experiencing of trauma symptoms for the navigator, so we examined a re-experiencing subscale. All participants completed baseline, 3-, 6-, and 12-month assessments. Our hypotheses were tested in separate Analyses of Variance (married versus not) for the 39 sojourners and 34 navigators who provided baseline assessments, and the 29 sojourners and 24 navigators who were matched and provided at least one follow-up. We found no significant baseline associations for navigators or sojourners. Being single/not married was associated with increasing depression symptoms over time in both navigators and sojourners compared with being married/partnered. By 12 months, these increases crossed above the clinical cut-off for significant depression symptoms. Single status did not predict increasing trauma symptoms over time. However, being single/not married predicted a significant increase in navigators' re-experiencing of trauma symptoms. Over time, married sojourners increased significantly in emotional well-being, whereas single/not married navigators did not differ from married navigators. In addition to providing ongoing training and emotional support to navigators, our findings indicate the importance of providing additional support for women who are not married or partnered.


Microplates: a new tool for manipulation and mechanical perturbation of individual cells.
We present a new type of microinstrument allowing manipulation and mechanical perturbation of individual cells under an optical microscope. These instruments, which we call microplates, are pulled from rectangular glass bars. They have flat tips, typically 2 microm thick x 20 microm wide, whose specific shape and stiffness can be adjusted through the pulling protocol. After appropriate chemical treatment, microplates can support cell adhesion and/or spreading. Rigid microplates are used to hold cells, whereas more flexible ones serve as stress sensors, i.e. their deflexion is used to probe forces in the range of 1-1000 nN. The main advantages of microplates are their simple geometry and surface properties, and their ability to provide mechanical measurements. In this methodological paper, we give details about microplate preparation and adhesiveness, manipulation set-up, force calibration, and image analysis. Several manipulations have already been carried out on fibroblasts, including uniaxial deformation, micropipet aspiration of adherent cells, and cell-substrate separation. Our results to date provide new insights into the morphology, mechanical properties, and adhesive resistance of cells. Many future applications can be envisaged.


Rheumatoid arthritis antirheumatic drug trials. I. Effects of standardization procedures on observer dependent outcome measures.
A study was designed to assess the effects of standardization procedures on reducing interobserver variability for outcome measures given in the current Food and Drug Administration and European League Against Rheumatism guidelines and others selected from the rheumatology literature. Over 2 days, 6 rheumatologists independently examined 6 patients with rheumatoid arthritis (RA) in predetermined order before and after standardizing their examination techniques. An important and beneficial effect of the standardization procedure was observed on the majority of outcome variables. Such reductions in observer variability have the potential to diminish sample size requirements for antirheumatic drug studies.