Activity of CeOx and TiOx nanoparticles grown on Au(111) in the water-gas shift reaction.
The high performance of Au-CeO2 and Au-TiO2 catalysts in the water-gas shift (WGS) reaction (H2O + CO-->H2 + CO2) relies heavily on the direct participation of the oxide in the catalytic process. Although clean Au(111) is not catalytically active for the WGS, gold surfaces that are 20 to 30% covered by ceria or titania nanoparticles have activities comparable to those of good WGS catalysts such as Cu(111) or Cu(100). In TiO(2-x)/Au(111) and CeO(2-x)/Au(111), water dissociates on O vacancies of the oxide nanoparticles, CO adsorbs on Au sites located nearby, and subsequent reaction steps take place at the metal-oxide interface. In these inverse catalysts, the moderate chemical activity of bulk gold is coupled to that of a more reactive oxide.


Web search behavior and information needs of people with multiple sclerosis: focus group study and analysis of online postings.
Multiple sclerosis (MS) patients and their family members increasingly seek health information on the Internet. There has been little exploration of how MS patients integrate health information with their needs, preferences, and values for decision making. The INtegrating and Deriving Evidence, Experiences, and Preferences (IN-DEEP) project is a collaboration between Italian and Australian researchers and MS patients, aimed to make high-quality evidence accessible and meaningful to MS patients and families, developing a Web-based resource of evidence-based information starting from their information needs. The objective of this study was to analyze MS patients and their family members' experience about the Web-based health information, to evaluate how they asses this information, and how they integrate health information with personal values. We organized 6 focus groups, 3 with MS patients and 3 with family members, in the Northern, Central, and Southern parts of Italy (April-June 2011). They included 40 MS patients aged between 18 and 60, diagnosed as having MS at least 3 months earlier, and 20 family members aged 18 and over, being relatives of a person with at least a 3-months MS diagnosis. The focus groups were audio-recorded and transcribed verbatim (Atlas software, V 6.0). Data were analyzed from a conceptual point of view through a coding system. An online forum was hosted by the Italian MS society on its Web platform to widen the collection of information. Nine questions were posted covering searching behavior, use of Web-based information, truthfulness of Web information. At the end, posts were downloaded and transcribed. Information needs covered a comprehensive communication of diagnosis, prognosis, and adverse events of treatments, MS causes or risk factors, new drugs, practical, and lifestyle-related information. The Internet is considered useful by MS patients, however, at the beginning or in a later stage of the disease a refusal to actively search for information could occur. Participants used to search on the Web before or after their neurologist's visit or when a new therapy was proposed. Social networks are widely used to read others' stories and retrieve information about daily management. A critical issue was the difficulty of recognizing reliable information on the Web. Many sources were used but the neurologist was mostly the final source of treatment decisions. MS patients used the Internet as a tool to integrate information about the illness. Information needs covered a wide spectrum, the searched topics changed with progression of the disease. Criteria for evaluating Internet accuracy and credibility of information were often lacking or generic. This may limit the empowerment of patients in health care choices.


Baseline Predictors for Good Versus Poor Visual Outcomes in the Treatment of Neovascular Age-Related Macular Degeneration With Intravitreal Anti-VEGF Therapy.
To examine the baseline factors associated with good (20/60 or better) versus poor (20/200 or worse) visual outcomes in eyes with treatment-naïve neovascular age-related macular degeneration (AMD) receiving intravitreal antivascular endothelial growth factor (VEGF) on a treat-and-extend regimen (TER). An observational, retrospective series of patients managed with a TER, identified as having either good or poor visual outcomes, was examined. A multivariate regression analysis of baseline characteristics identified factors associated with good and poor vision at 2, 3, and 4 years. Neovascular subtypes were identified using fluorescein angiography (FA) alone and the anatomic classification system with FA and optical coherence tomography (OCT). One hundred thirty-eight patients (154 eyes) fit the inclusion criteria at 2 years, 106 patients (113 eyes) at 3 years, and 72 patients (74 eyes) at 4 years. In the multivariate analysis, type 1 lesions, according to anatomic classification, had better vision at 24 months (95% CI: [3.1, 82.7], P = 0.01), 36 months (95% CI: [1.97, 24.17], P = 0.003), and 48 months (95% CI: [2.01, 65.47], P = 0.006). Clopidogrel use was associated with poor vision at 24 months (95% CI: [0.03, 0.68], P = 0.013). Vision at 3 months was the best predictor of vision at year 4 (β = -4.277, P = 0.002). Eyes with neovascular AMD managed with a TER of anti-VEGF therapy having type 1 neovascularization at baseline were more likely to maintain good vision over 4 years, whereas clopidogrel use predicted poor vision at 2 years. Vision at 3 months was the best predictor for favorable long-term vision.


Increased interleukin-6 correlates with myelin oligodendrocyte glycoprotein antibodies in pediatric monophasic demyelinating diseases and multiple sclerosis.
Acquired demyelinating syndromes (ADS) in children evolve either as a monophasic disease diagnosed as acute demyelinating encephalomyelitis (ADEM), transverse myelitis (TM) or optic neuritis (ON), or a multiphasic one with several relapses most often leading to the diagnosis of multiple sclerosis (MS) or neuromyelitis optica (NMO). These neuroinflammatory disorders are increasingly associated with autoantibodies against proteins such as aquaporin-4 in rare instances, and more frequently against myelin oligodendrocyte glycoprotein (MOG). Recently, in adult NMO patients, C5a levels were shown to be elevated in cerebrospinal fluid (CSF) during acute exacerbation. We investigated the CSF levels of anaphylatoxins and pro-inflammatory cytokines, and plasma MOG antibodies in onset samples from children with ADS. Thirty four children presenting with a first episode of ADS, 17 with monophasic ADS (9 with ADEM, 4 with TM and 4 with ON) and 17 with MS, who had paired blood and CSF samples at onset were included and compared to 12 patients with other non-inflammatory neurological disorders (OND). Cytokines and anaphylatoxins in CSF were measured by Cytometric Bead Array immunoassay. MOG antibody titers in plasma were tested by flow cytometry using a stable cell line expressing full-length human MOG. We found a significant increase in C5a levels in the CSF of patients with monophasic ADS (n=17) compared to OND (n=12, p=0.0036) and to MS (n=17, p=0.0371). The C5a levels in MS were higher than in OND without reaching significance (p=0.2). CSF IL-6 levels were significantly increased in monophasic ADS compared to OND (p=0.0027) and to MS (p=0.0046). MOG antibody plasma levels were significantly higher in monophasic ADS (p<0.0001) and, to a lesser extent, in MS compared to OND (p=0.0023). Plasma MOG antibodies and CSF IL-6 levels were significantly correlated (r=0.51, p=0.018). CSF C5a and IL-6 levels are increased in monophasic ADS but not in MS when compared to OND, suggesting that these markers may help to predict monophasic or relapsing fate of ADS at onset. MOG antibody titers, which were higher in monophasic ADS than in MS, correlated with IL-6 levels, but not with C5a, suggesting an association between MOG antibodies and neuroinflammation in pediatric ADS.


Reexploration for hemorrhage following coronary artery bypass grafting: incidence and risk factors. Northern New England Cardiovascular Disease Study Group.
To assess mortality and risk factors associated with reexploration for hemorrhage in patients undergoing coronary artery bypass grafting (CABG). Regional cohort study. Patient characteristics, treatment variables, and outcome measures were collected prospectively. All 5 centers performing cardiac surgery in Maine, New Hampshire, and Vermont. A consecutive cohort of 8586 patients undergoing isolated CABG between 1992 and 1995. Postoperative hemorrhage leading to reexploration, in-hospital mortality, and length of stay. A total of 305 patients (3.6%) underwent reexploration for bleeding. In these patients, in-hospital mortality was nearly 3 times higher (9.5% vs 3.3% for patients not requiring reoperation, P<.001) and average length of stay from surgery to discharge was significantly longer (14.5 days vs 8.6 days, P<.001). High rates of reexploration for hemorrhage were observed in patients with prolonged (> 150 minutes) cardiopulmonary bypass (39 [11.1%] of 351) and in those requiring an intra-aortic balloon pump intraoperatively (12 [8%] of 139). In multivariate analysis, older age, smaller body surface area, prolonged cardiopulmonary bypass, and number of distal anastomoses were associated with increased bleeding risks. The use of thrombolytic therapy within 48 hours of surgery was weakly but not significantly associated with the need for reexploration. Factors not significantly associated with reexploration included patient sex, preoperative ejection fraction, surgical priority, history of liver disease, myocardial infarction, prior CABG, renal failure, and diabetes mellitus. Hemorrhage requiring reexploration after CABG is associated with markedly increased mortality and length of stay. Patients predicted to have increased risks of bleeding may benefit from prophylactic use of aprotinin, aminocaproic acid, or other agents shown to reduce hemorrhage.


Stratifying patients with peripheral neuropathic pain based on sensory profiles: algorithm and sample size recommendations.
In a recent cluster analysis, it has been shown that patients with peripheral neuropathic pain can be grouped into 3 sensory phenotypes based on quantitative sensory testing profiles, which are mainly characterized by either sensory loss, intact sensory function and mild thermal hyperalgesia and/or allodynia, or loss of thermal detection and mild mechanical hyperalgesia and/or allodynia. Here, we present an algorithm for allocation of individual patients to these subgroups. The algorithm is nondeterministic-ie, a patient can be sorted to more than one phenotype-and can separate patients with neuropathic pain from healthy subjects (sensitivity: 78%, specificity: 94%). We evaluated the frequency of each phenotype in a population of patients with painful diabetic polyneuropathy (n = 151), painful peripheral nerve injury (n = 335), and postherpetic neuralgia (n = 97) and propose sample sizes of study populations that need to be screened to reach a subpopulation large enough to conduct a phenotype-stratified study. The most common phenotype in diabetic polyneuropathy was sensory loss (83%), followed by mechanical hyperalgesia (75%) and thermal hyperalgesia (34%, note that percentages are overlapping and not additive). In peripheral nerve injury, frequencies were 37%, 59%, and 50%, and in postherpetic neuralgia, frequencies were 31%, 63%, and 46%. For parallel study design, either the estimated effect size of the treatment needs to be high (>0.7) or only phenotypes that are frequent in the clinical entity under study can realistically be performed. For crossover design, populations under 200 patients screened are sufficient for all phenotypes and clinical entities with a minimum estimated treatment effect size of 0.5.


Dendritic Cell Protection from Cisplatin Nephrotoxicity Is Independent of Neutrophils.
Cisplatin is a very effective chemotherapeutic agent used against a wide range of solid tumors. A major adverse effect of cisplatin therapy is acute kidney injury (AKI). Neutrophils are reported to infiltrate and exacerbate injury in a wide range of sterile inflammatory models of tissue injury. Here, we studied the kinetics of neutrophil infiltration into kidneys and their role in cisplatin-mediated AKI. Mice treated with cisplatin showed an increase in circulating neutrophils 24 and 48 h after cisplatin administration. Cisplatin treatment caused an increase in kidney leukocytes with neutrophils accounting for the majority of the infiltrating leukocytes. The extent of neutrophil infiltration coincided with the severity of kidney injury and renal dysfunction. To examine the functional relevance of infiltrating neutrophils in cisplatin nephrotoxicity, we depleted neutrophils using a neutrophil-specific antibody (anti-Ly-6G). This antibody resulted in greater than 90% depletion of neutrophils in both the blood and kidney. Of note, depletion of neutrophils had no impact on the extent of cisplatin-induced AKI as compared to non-depleted mice. Earlier, we reported that dendritic cell depletion in CD11c-DTRtg mice causes exacerbation of AKI and a dramatic increase in renal neutrophils. Thus, we also examined the role of neutrophils in dendritic cell-depleted mice treated with cisplatin. Dendritic cell depletion exacerbated AKI in spite of neutrophil depletion. These data demonstrate that cisplatin nephrotoxicity is not mediated by neutrophils and that dendritic cells protect kidneys via neutrophil-independent mechanisms.


Family history of exceptional longevity is associated with lower serum uric acid levels in Ashkenazi Jews.
To test whether lower serum uric acid (UA) levels are associated with longevity independent of renal function. Cross-sectional cohort study. Ashkenazi Jewish individuals with exceptional longevity (Longevity Genes Project at Albert Einstein College of Medicine). Long-lived individuals (LLI) of Ashkenazi Jewish ethnicity (mean age ± standard deviation 97.7 ± 2.9, n = 365), their offspring (mean age ± standard deviation 68.2 ± 8.2, n = 593) and controls (without family history of longevity, mean age ± standard deviation 72.5 ± 9.9, n = 356). Association between UA levels and estimated glomerular filtration rate (eGFR) as well as chronic kidney disease (CKD) stage, and correlation of UA levels of LLI and offspring were determined. Because LLI lack an appropriate control group, UA levels, eGFR, and prevalence of hyperuricemia and CKD stages were compared between offspring and controls. Offspring were less likely to have hyperuricemia and had lower UA levels than controls. Despite negative correlation between UA levels and eGFR and positive correlation between UA levels and CKD stages, eGFR and the prevalence of CKD stage III to V were not found to be different between offspring and controls. Furthermore, significant association between UA levels in LLI and their offspring (β estimate 0.1544, 95% confidence interval = 0.08-0.23, P < .001) has been observed. Offspring had lower UA levels than controls despite similar renal function, suggesting that other factors such as UA metabolism or renal tubular transport determine UA levels. The association between UA levels and longevity is particularly intriguing because UA levels are potentially modifiable with diet and drugs.


Assessing the effects of symmetry on motif discovery and modeling.
Identifying the DNA binding sites for transcription factors is a key task in modeling the gene regulatory network of a cell. Predicting DNA binding sites computationally suffers from high false positives and false negatives due to various contributing factors, including the inaccurate models for transcription factor specificity. One source of inaccuracy in the specificity models is the assumption of asymmetry for symmetric models. Using simulation studies, so that the correct binding site model is known and various parameters of the process can be systematically controlled, we test different motif finding algorithms on both symmetric and asymmetric binding site data. We show that if the true binding site is asymmetric the results are unambiguous and the asymmetric model is clearly superior to the symmetric model. But if the true binding specificity is symmetric commonly used methods can infer, incorrectly, that the motif is asymmetric. The resulting inaccurate motifs lead to lower sensitivity and specificity than would the correct, symmetric models. We also show how the correct model can be obtained by the use of appropriate measures of statistical significance. This study demonstrates that the most commonly used motif-finding approaches usually model symmetric motifs incorrectly, which leads to higher than necessary false prediction errors. It also demonstrates how alternative motif-finding methods can correct the problem, providing more accurate motif models and reducing the errors. Furthermore, it provides criteria for determining whether a symmetric or asymmetric model is the most appropriate for any experimental dataset.


Serum Response Factor Is Essential for Prenatal Gastrointestinal Smooth Muscle Development and Maintenance of Differentiated Phenotype.
Smooth muscle cells (SMCs) characteristically express serum response factor (SRF), which regulates their development. The role of SRF in SMC plasticity in the pathophysiological conditions of gastrointestinal (GI) tract is less characterized. We generated SMC-specific Srf knockout mice and characterized the prenatally lethal phenotype using ultrasound biomicroscopy and histological analysis. We used small bowel partial obstruction surgeries and primary cell culture using cell-specific enhanced green fluorescent protein (EGFP) mouse lines to study phenotypic and molecular changes of SMCs by immunofluorescence, Western blotting, and quantitative polymerase chain reaction. Finally we examined SRF change in human rectal prolapse tissue by immunofluorescence. Congenital SMC-specific Srf knockout mice died before birth and displayed severe GI and cardiac defects. Partial obstruction resulted in an overall increase in SRF protein expression. However, individual SMCs appeared to gradually lose SRF in the hypertrophic muscle. Cells expressing low levels of SRF also expressed low levels of platelet-derived growth factor receptor alpha (PDGFRα(low)) and Ki67. SMCs grown in culture recaptured the phenotypic switch from differentiated SMCs to proliferative PDGFRα(low) cells. The immediate and dramatic reduction of Srf and Myh11 mRNA expression confirmed the phenotypic change. Human rectal prolapse tissue also demonstrated significant loss of SRF expression. SRF expression in SMCs is essential for prenatal development of the GI tract and heart. Following partial obstruction, SMCs down-regulate SRF to transition into proliferative PDGFRα(low) cells that may represent a phenotype responsible for their plasticity. These findings demonstrate that SRF also plays a critical role in the remodeling process following GI injury.


Relationship between structural joint damage and urate deposition in gout: a plain radiography and dual-energy CT study.
The aim of this work was to examine the relationship between joint damage and monosodium urate (MSU) crystal deposition in gout. Plain radiographs and dual-energy CT (DECT) scans of the feet were prospectively obtained from 92 people with tophaceous gout. Subcutaneous tophus count was recorded. The ten metatarsophalangeal joints were scored on plain radiography for Sharp-van der Heijde erosion and joint space narrowing (JSN) scores, and presence of spur, osteophyte, periosteal new bone and sclerosis (920 total joints). DECT scans were analysed for the presence of MSU crystal deposition at the same joints. DECT MSU crystal deposition was more frequently observed in joints with erosion (OR (95% CI) 8.5 (5.5 to 13.1)), JSN (4.2 (2.7 to 6.7%)), spur (7.9 (4.9 to 12.8)), osteophyte (3.9 (2.5 to 6.0)), periosteal new bone (7.0 (4.0 to 12.2)) and sclerosis (6.9 (4.6 to 10.2)), p<0.0001 for all. A strong linear relationship was observed in the frequency of joints affected by MSU crystals with radiographic erosion score (p<0.0001). The number of joints at each site with MSU crystal deposition correlated with all features of radiographic joint damage (r>0.88, p<0.05 for all). In linear regression models, the relationship between MSU crystal deposition and all radiographic changes except JSN and osteophytes persisted after adjusting for subcutaneous tophus count, serum urate concentration and disease duration. MSU crystals are frequently present in joints affected by radiographic damage in gout. These findings support the concept that MSU crystals interact with articular tissues to influence the development of structural joint damage in this disease.


Syncope and Twitching at the Emergency Department.
BACKGROUND Anti-LGI1 encephalitis is a type of autoimmune limbic encephalitis. This case report elucidates features of anti-LGI1 limbic encephalitis, focusing on clinical findings and outcome as well as on rarely reported sinus arrest and its pathophysiology. CASE REPORT A 49-year-old female patient presented at the Emergency Department (ED) because of twitching and an acute confusional state. Initial neurological examination revealed cognitive disturbance with disorientation, inattention, and amnestic deficits. While in the ED, twitching of the right arm was observed and shortly thereafter she experienced a sinus arrest. A temporary cardiac pacemaker was implanted. Laboratory investigations demonstrated mild hyponatremia and positive LGI1-IgG antibodies in serum. An initial head MRI was unremarkable and electroencephalography showed epileptic seizure activity starting focally in the left hemisphere synchronous with the intermittent twitching of the right arm. A seizure-suppressant therapy with levetiracetam, valproate, and gabapentin was initiated, as well as an immunosuppressive pulse therapy with methylprednisolone followed by a tapering oral regimen of prednisolone. Within a few days, the seizures ceased. One month later, neurocognitive test results were back to normal. At 2 years, mild depressive symptoms and anxiety disorder were the main clinical problems, as well as episodic migraine-like headaches. CONCLUSIONS Repetitive focal dystonic seizures, confusion, amnestic deficits, sinus arrest, and mild-to-moderate hyponatremia are pathognomonic features of anti-LGI1 limbic encephalitis. Sinus arrest may occur because of a direct pathophysiological dysfunction of the structures involved in autonomic cardiac rhythm control or as an ictal or postictal phenomenon. Early diagnosis and initiation of immunosuppressive therapy are both of utmost importance for favorable clinical outcome.


Pyrochlore Ce2Zr2O7 decorated over rGO: a photocatalyst that proves to be efficient towards the reduction of 4-nitrophenol and degradation of ciprofloxacin under visible light.
In the present study, a series of Ce2Zr2O7@rGO nanocomposites were synthesized using a simple solution combustion method followed by a photoreduction technique. The as-prepared samples were well characterised using various analytical techniques to determine the morphological, optical, structural, electrochemical and compositional properties. The presence of oxygen defects was observed from Raman and photoluminescence spectra. The photoreduction of GO to rGO was determined from Raman and Fourier-transform infrared (FTIR) spectroscopy results. The role of rGO proved to be quite significant for the enhanced photocatalytic activity of the nanocomposites. The synergistic communication between Ce2Zr2O7 and rGO accelerates the photoreduction of 4-nitrophenol along with the degradation of ciprofloxacin under visible light irradiation. Of the rGO nanocomposites, 3 wt% GO loaded Ce2Zr2O7 reduces 99% of 20 ppm of 4-nitrophenol to 4-aminophenol in 120 min and decomposes 10 ppm of ciprofloxacin by up to 89% in 60 min. The significant enhancement in the activity of the Ce2Zr2O7@rGO nanocomposite was ascribed to the effective charge separation of excitons through π-conjugation of graphene at the interface, which is well supported by the impedance, photoluminescence and photocatalytic results.


Enhancing genomic laboratory reports: A qualitative analysis of provider review.
This study reports on the responses of physicians who reviewed provider and patient versions of a genomic laboratory report designed to communicate results of whole genome sequencing. Semi-structured interviews addressed concept communication, elements, and format of example genome reports. Analysis of the coded transcripts resulted in recognition of three constructs around communication of genome sequencing results: (1) Providers agreed that whole genomic sequencing results are complex and they welcomed a report that provided supportive interpretation information to accompany sequencing results; (2) Providers strongly endorsed a report that included active clinical guidance, such as reference to practice guidelines, if available; and (3) Providers valued the genomic report as a resource that would serve as the basis to facilitate communication of genome sequencing results with their patients and families. Providers valued both versions of the report, though they affirmed the need for a provider-oriented report. Critical elements of the report included clear language to explain the result, as well as consolidated yet comprehensive prognostic information with clear guidance over time for the clinical care of the patient. Most importantly, it appears a report with this design has the potential not only to return results but also serves as a communication tool to help providers and patients discuss and coordinate care over time.


Cytisine-like alkaloids from Ormosia hosiei Hemsl. & E.H. Wilson.
Four alkaloids named hosieines A-D were isolated from the root and stem of Ormosia hosiei. Their flat structures were established by mass spectrometry and by a combination of NMR experiments. These molecules probably share a common biosynthetic origin with the lupin alkaloids but they differ in the formation of the last ring, being here part of a rare 2-azabicyclo[3.2.1]octane system. Their absolute configuration was determined by X-ray crystallography using CuKα radiation. As has been described for cytisine, they display a remarkable affinity towards neuronal nicotinic acetylcholine α4β2 receptor.


Limits of 3D dipole localization and orientation estimation for single-molecule imaging: towards Green's tensor engineering.
The 3D orientation and location of individual molecules is an important marker for the local environment and the state of a molecule. Therefore dipole localization and orientation estimation is important for biological sensing and imaging. Precise dipole localization is also critical for superresolution imaging. We propose and analyze wide field microscope configurations to simultaneously measure these parameters for multiple fixed dipole emitters. Examination of the images of radiating dipoles reveals how information transfer and precise detection can be improved. We use an information theoretic analysis to quantify the performance limits of position and orientation estimation through comparison of the Cramer-Rao lower bounds in a photon limited environment. We show that bi-focal and double-helix polarization-sensitive systems are attractive candidates for simultaneously estimating the 3D dipole location and orientation.


Experiences with workflows for automating data-intensive bioinformatics.
High-throughput technologies, such as next-generation sequencing, have turned molecular biology into a data-intensive discipline, requiring bioinformaticians to use high-performance computing resources and carry out data management and analysis tasks on large scale. Workflow systems can be useful to simplify construction of analysis pipelines that automate tasks, support reproducibility and provide measures for fault-tolerance. However, workflow systems can incur significant development and administration overhead so bioinformatics pipelines are often still built without them. We present the experiences with workflows and workflow systems within the bioinformatics community participating in a series of hackathons and workshops of the EU COST action SeqAhead. The organizations are working on similar problems, but we have addressed them with different strategies and solutions. This fragmentation of efforts is inefficient and leads to redundant and incompatible solutions. Based on our experiences we define a set of recommendations for future systems to enable efficient yet simple bioinformatics workflow construction and execution.


Sex-specific differentiation of a male-specific abdominal muscle, the Muscle of Lawrence, is abnormal in hydroxyurea-treated and in fruitless male flies.
A prominent sex-specific abdominal muscle in male Drosophila is the Muscle of Lawrence (MOL), which is induced by male-specific innervation. We have examined MOL development in wild-type males, in males fed hydroxyurea to ablate the muscle precursors and in fruitless mutants, in which the MOL muscle develops aberrantly. One striking feature of MOLs in wild-type males was the presence of additional muscle nuclei compared with neighboring muscles or MOL-homologues in females. We tested whether muscle length and the sex-specific expression of a reporter gene depended critically on the number of nuclei present within a MOL fiber. MOL fibers developing from a reduced myoblast pool in hydroxyurea-affected hemisegments were recognizable by their attachment points and still contained more nuclei than did neighboring medial fibers, suggesting that these MOL fibers were able to actively recruit myoblasts nearly as well as wild-type MOLs. However, many of the hydroxyurea-affected MOL fibers were incapable of the normal male-specific expression of a muscle-specific reporter gene. We suggest that early events in MOL development, such as finding the correct muscle attachment points, are relatively insensitive to the number of MOL nuclei compared with later events, such as the sex-specific expression of a reporter gene. In fruitless mutant males, MOL-position fibers are smaller and had substantially fewer nuclei compared to wild-type MOLs. Since the number and distribution of muscle precursors was the same in fruitless mutant and wild-type animals, we propose that one fru+ function is to direct the male-specific recruitment of myoblasts into MOL-myotubes. However, fruitless+ must have more than one role in MOL fiber development, since simple reduction in the number of muscle nuclei, as demonstrated by the hydroxyurea ablations, is insufficient to account for all of the MOL muscle phenotypes in fruitless mutant males.


Vivianite as the main phosphate mineral in digested sewage sludge and its role for phosphate recovery.
Phosphate recovery from sewage sludge is essential in a circular economy. Currently, the main focus in centralized municipal wastewater treatment plants (MWTPs) lies on struvite recovery routes, land application of sludge or on technologies that rely on sludge incineration. These routes have several disadvantages. Our study shows that the mineral vivianite, Fe2(PO4)3 × 8H2O, is present in digested sludge and can be the major form of phosphate in the sludge. Thus, we suggest vivianite can be the nucleus for alternative phosphate recovery options. Excess and digested sewage sludge was sampled from full-scale MWTPs and analysed using x-ray diffraction (XRD), conventional scanning electron microscopy with energy dispersive X-ray spectroscopy (SEM-EDX), environmental SEM-EDX (eSEM-EDX) and Mössbauer spectroscopy. Vivianite was observed in all plants where iron was used for phosphate removal. In excess sludge before the anaerobic digestion, ferrous iron dominated the iron pool (≥50%) as shown by Mössbauer spectroscopy. XRD and Mössbauer spectroscopy showed no clear correlation between vivianite bound phosphate versus the iron content in excess sludge. In digested sludge, ferrous iron was the dominant iron form (>85%). Phosphate bound in vivianite increased with the iron content of the digested sludge but levelled off at high iron levels. 70-90% of all phosphate was bound in vivianite in the sludge with the highest iron content (molar Fe:P = 2.5). The quantification of vivianite was difficult and bears some uncertainty probably because of the presence of impure vivianite as indicated by SEM-EDX. eSEM-EDX indicates that the vivianite occurs as relatively small (20-100 μm) but free particles. We envisage very efficient phosphate recovery technologies that separate these particles based on their magnetic properties from the complex sludge matrix.


Still Looking for Mechanisms: A Realist Review of Batterer Intervention Programs.
Complex interventions, including batterer intervention or treatment programs (BIPs), require that program strategies interact with contextual factors to trigger often unseen mechanisms in individuals or communities. Although hundreds of evaluations of BIPs have been published, few identify mechanisms or explain for whom, under what conditions, and why programs are effective. The goal of this realist review is to identify evidence of the mechanisms that contribute to successful immediate outcomes in BIPs. In accordance with published realist review standards, we defined the review questions and rational, defined outcomes and formulating initial theories, searched the literature, applied inclusion and exclusion criteria, and analyzed and synthesizing data. An initial search yielded 5,149 citations, and after a systematic process using realist principles, six articles with sufficient information were included. Few evaluations contain the detail necessary to discern clear generative explanations of program processes. Evidence suggested that under some contextual conditions, strategies that trigger a self-reflexive process in participants may lead to changes in attitudes about violence, which may lead to the development of empathy for their partner. Additionally, programs that help participants differentiate between shame and guilt appear to increase both acceptance of responsibility and empathy. This realist synthesis illustrates several gaps in the evaluative literature. Few evaluations captured sufficient detail to examine the influence of contextual factors. Likewise, most evaluations only describe if specific outcomes were achieved, not how, or through what mechanisms, those outcomes were accomplished. Recommendations to strengthen program theory and further examine self-reflection as a mechanism are discussed.


Autonomic dysfunction in the Lambert-Eaton myasthenic syndrome: serologic and clinical correlates.
Autonomic dysfunction is a recognized feature of the Lambert-Eaton myasthenic syndrome (LES). However, the characteristic pattern of dysautonomia has not been clearly documented and its pathophysiologic basis is not known. We therefore abstracted autonomic symptomatology and results of quantitative tests for salivation, and vasomotor, cardiovagal, and sudomotor reflexes from records of 30 LES patients. Dry mouth (77%) and impotence (45% of men) were the most common symptoms. Composite Autonomic Scoring Scale results were abnormal in 93% of patients, and autonomic failure was severe in 20%. The frequency of specific test abnormalities were the following: sudomotor function, 83%; cardiovagal reflexes, 75%; salivation, 44%; and adrenergic function, 37%. Although voltage-gated N-type calcium (Ca2+) channels are implicated in autonomic transmission, the low frequency of serum antibodies to N-type Ca2+ channels found in the patients of this study (31% positive) argues against a pathogenic role in mediating LES-related dysautonomia. In contrast, 93% of the patients were seropositive for P/Q-type Ca2+ channel antibodies. A subset of these antibodies is thought to impair neuromuscular transmission. Autoantibodies of thyrogastric or glutamic acid decarboxylase specificity (markers of predisposition to type 1 diabetes mellitus) were found in 45% of patients, and type 1 antineuronal nuclear antibody (or anti-Hu, a marker of autoimmune neuropathy associated with small-cell lung carcinoma) was found in 3%. No autoantibody correlated with autonomic dysfunction severity. Sensorimotor neuropathy was documented in five patients, and was not significantly associated with autonomic neuropathy. Autonomic failure was most severe in older subjects with cancer (p = 0.02, age by cancer interaction).


Intraruminal administration of Megasphaera elsdenii modulated rumen fermentation profile in mid-lactation dairy cows.
This study evaluated the effects of intraruminal administration of Megasphaera elsdenii on ruminal fermentation patterns, the profile of plasma metabolites, and milk yield and composition of mid-lactation dairy cows. Eight primiparous, ruminally cannulated Holstein cows were arranged in a paired 2×2 crossover design. Cows were randomly assigned to one of two treatments: 1) intraruminal inoculation of 35 ml suspension per day of M. elsdenii ATCC 25940 (MEGA), containing 108 cfu/ml of bacteria, dissolved in 35 ml of saline (0·15 m), or 2) carrier alone (35 ml saline; CTR). Both postprandial and preprandial rumen volatile fatty acids (VFA) and plasma metabolite measurements were analysed. Postprandial VFA patterns were affected the most, with butyrate (P<0·01) and valerate (P<0·01) proportions increasing, and acetate (P<0·01), isobutyrate (P=0·05) and isovalerate (P<0·01) decreasing in MEGA cows. Preprandial data measured at various days showed that MEGA dosage tended to increase the molar proportion of propionate (P=0·09) and lower the acetate to propionate ratio (P=0·07) in the rumen fluid. There was no effect of treatment on rumen pH and on the concentration of lactate in the rumen as well as on selected preprandial plasma metabolites. Postprandial plasma concentrations of cholesterol tended to increase (P=0·07) in MEGA cows compared with CTR. Concentrations of non-esterified fatty acids (NEFA) in the plasma were lower in MEGA cows after the morning feeding (P<0·01). Sampling hour also affected plasma NEFA in this study. Plasma β-hydroxybutyrate (BHBA) were not affected by the treatment (P>0·05); however, after the morning feeding BHBA concentration was increased in both groups of cows. Dry matter intake and milk yield and composition were not affected by treatment. In conclusion, results indicate that M. elsdenii has the potential to modulate the rumen fermentation profile in mid-lactation Holstein cows, but these effects were only slightly reflected in changes in plasma metabolites and milk composition.


Antistaphylococcal immunoglobulins to prevent staphylococcal infection in very low birth weight infants.
Nosocomial infection is a major problem affecting the immediate health and long-term outcome of preterm and very low birth weight neonates. More than half of these infections are caused by staphylococci. Various type specific antibodies targeted at different antigenic markers of Staphylococcus have been developed and have shown promise in animal studies. To evaluate the efficacy and safety of antistaphylococcal immunoglobulins in the prevention of Staphylococcal infection in very low birth weight infants. Medline, Embase, CINAHL, Cochrane Central Register of Controlled Trials (The Cochrane Library) were searched from their inception until February 2009. In addition, abstracts of major pediatric meetings of last seven years were searched. Randomized and quasi-randomized studies of antistaphylococcal immunoglobulins for the prevention of staphylococcal infections in preterm or very low birth weight neonates were reviewed by both authors for their eligibility for inclusion. Studies of any dose and/or route were included. Quality of studies was evaluated using criteria of masking of randomization, masking of intervention, completeness of follow-up and masking of outcome assessment by both review authors. Data from the primary author were obtained where published data provided inadequate information for the review or where relevant data could not be abstracted. Data were abstracted independently by both review authors. Statistical methods included calculation of relative risk (RR), risk difference (RD), number needed to treat (NNT) and weighted mean difference (WMD) when appropriate. Ninety five percent confidence intervals (CI) was used for these estimates of treatment effects. A fixed effect model was used for meta-analyses. Three eligible studies were included (two studies of INH A-21 and one study of Altastaph involving a total of 2,701 neonates). Three reports of Pagibaximab were published as abstracts and will be considered for inclusion when further information is obtained. There were no significant differences noted in the risk of Staphylococcal infection between INH A-21 vs. placebo (typical RR 1.07, 95% CI 0.94, 1.22) or Altastaph vs. placebo (RR 0.86, 95% CI 0.32, 2.28); the risk of other bacterial infection between INH A-21 vs. placebo (typical RR 0.87, 95% CI 0.72, 1.06) or Altastaph vs. placebo (RR 0.93, 95% CI 0.53, 1.64); or the risk of any infection between INH A-21 vs. placebo (RR 1.00, 95% CI 0.91, 1.09) or Altastaph vs. placebo (RR 0.93, 95% CI 0.54, 1.62). There was no significant difference in the incidence of relevant secondary outcomes (chronic lung disease at 28 days, patent ductus arteriosus, necrotizing enterocolitis, intraventricular hemorrhage, retinopathy of prematurity or duration of antibiotic and vancomycin use). Antistaphylococcal immunoglobulins (INH A-21 and Altastaph) are not recommended for prevention of staphylococcal infections in preterm or VLBW neonates. Further research to investigate the efficacy of other products such as Pagibaximab is needed.


Invisible women in reproductive technologies: Critical reflections.
The recent spectacular progress in assisted reproductive technologies (ARTs) has resulted in new ethical dilemmas. Though women occupy a central role in the reproductive process, within the ART paradigm, the importance accorded to the embryo commonly surpasses that given to the mother. This commentary questions the increasing tendency to position the embryonic subject in an antagonistic relation with the mother. I examine how the mother's reproductive autonomy is compromised in relation to that of her embryo and argue in favour of doing away with the subject-object dyad between them, particularly in the contexts of surrogacy and abortion. I also engage with the Surrogacy (Regulation) Bill, 2016. A critical discussion of the privacy judgment passed by the Supreme Court of India helps examine how personal autonomy of the body and mind extends to include the reproductive autonomy of women as well.


Contraceptive method choice among women in slum and non-slum communities in Nairobi, Kenya.
Understanding women's contraceptive method choices is key to enhancing family planning services provision and programming. Currently however, very little research has addressed inter and intra-regional disparities in women's contraceptive method choice. Using data from slum and non-slum contexts in Nairobi, Kenya, the current study investigates the prevalence of and factors associated with contraceptive method choice among women. Data were from a cross-sectional quantitative study conducted among a random sample of 1,873 women (aged 15-49 years) in two non-slum and two slum settlement areas in Nairobi, Kenya. The study locations were purposively sampled by virtue of being part of the Nairobi Urban Health and Demographic Surveillance System. Bivariate and multivariate logistic regression were used to explore the association between the outcome variable, contraceptive method choice, and explanatory variables. The prevalence of contraceptive method choice was relatively similar across slum and non-slum settlements. 34.3 % of women in slum communities and 28.1 % of women in non-slum communities reported using short-term methods. Slightly more women living in the non-slum settlements reported use of long-term methods, 9.2 %, compared to 3.6 % in slum communities. Older women were less likely to use short-term methods than their younger counterparts but more likely to use long-term methods. Currently married women were more likely than never married women to use short-term and long-term methods. Compared to those with no children, women with three or more children were more likely to report using long term methods. Women working outside the home or those in formal employment also used modern methods of contraception more than those in self-employment or unemployed. Use of short-term and long-term methods is generally low among women living in slum and non-slum contexts in Nairobi. Investments in increasing women's access to various contraceptive options are urgently needed to help increase contraceptive prevalence rate. Thus, interventions that focus on more disadvantaged segments of the population will accelerate contraceptive uptake and improve maternal and child health in Kenya.


An anti-ACVR1 antibody exacerbates heterotopic ossification by fibro-adipogenic progenitors in fibrodysplasia ossificans progressiva mice.
Fibrodysplasia ossificans progressiva (FOP) is a rare genetic disease characterized by progressive and catastrophic heterotopic ossification (HO) of skeletal muscle and associated soft tissues. FOP is caused by dominantly acting mutations in the gene encoding the bone morphogenetic protein (BMP) type I receptor, ACVR1 (ALK2), the most prevalent of which results in an arginine to histidine substitution at position 206 (ACVR1[R206H]). The fundamental pathological consequence of FOP-causing ACVR1 receptor mutations is to enable activin A to initiate canonical BMP signaling in fibro-adipogenic progenitors (FAPs), which drives HO. We developed a monoclonal blocking antibody (JAB0505) against the extracellular domain of ACVR1 and tested its effect on HO in 2 independent FOP mouse models. Although JAB0505 inhibited BMP-dependent gene expression in wild-type and ACVR1(R206H)-overexpressing cell lines, JAB0505 treatment profoundly exacerbated injury-induced HO. JAB0505-treated mice exhibited multiple, distinct foci of heterotopic lesions, suggesting an atypically broad anatomical domain of FAP recruitment to endochondral ossification. This was accompanied by dysregulated FAP population growth and an abnormally sustained immunological reaction following muscle injury. JAB0505 drove injury-induced HO in the absence of activin A, indicating that JAB0505 has receptor agonist activity. These data raise serious safety and efficacy concerns for the use of bivalent anti-ACVR1 antibodies to treat patients with FOP.


Characterization of wet and dry deposition in the downwind of industrial sources in a dry tropical area.
An atmospheric deposition study was conducted in the downwind of Shaktinagar Thermal Power Plant (STPP), Renusagar Thermal Power Plant (RTPP), and Anpara Thermal Power Plant (ATPP), at Singrauli region, Uttar Pradesh (UP), India to characterize dry and wet deposition in relation to different pollution loading. During the study period, dry and wet depositions and levels of gaseous pollutants (SO2 and NO2) were estimated across the sites. Dry deposition was collected on a monthly basis and wet deposition on an event basis. Depositions were analyzed for pH, nitrate (NO3-), ammonium (NH4+), and sulphate (SO4(2-)) contents. Dry deposition rate both collected as clearfall and throughfall varied between 0.15 to 2.28 and 0.33 to 3.48 g m(-2) day(-1), respectively, at control and maximally polluted sites. The pH of dry deposition varied from 5.81 to 6.89 during winter and 6.09 to 7.02 during summer across the sites. During the rainy season, the mean pH of clear wet deposition varied from 6.56 to 7.04 and throughfall varied from 6.81 to 7.22. The concentrations of NO2 and SO2 pollutants were highest during the winter season. Mean SO2 concentrations varied from 18 to 75 g m(-3) at control and differently polluted sites during the winter season. The variation in NO2 concentrations did not show a pattern similar to that of SO2. The highest NO2 concentration during the winter season was 50 g m(-3), observed near RTPP. NO2 concentration did not show much variation among different sites, suggesting that the sources of NO2 emission are evenly distributed along the sites. The concentrations of NH4+, NO3-, and SO4(2-) ions in dry deposition were found to be higher in summer as compared to the winter season. In dry deposition (clearfall) the concentrations of NH4+, NO3-, and SO4(2-) varied from 0.13 to 1.0, 0.81 to 1.95, and 0.82 to 3.27 mg l(-1), respectively, during winter. In wet deposition (clearfall), the above varied from 0.14 to 0.74, 0.81 to 1.82, and 0.67 to 2.70 mg l(-1), respectively. The study clearly showed that both dry and wet depositions varied between the sites and season, suggesting significant impact of industrial activities in modifying the atmospheric input. The nonacidic deposition suggests that there is no threat of acidification of the receiving ecosystem at present.


Understanding doping strategies in the design of organic electrode materials for Li and Na ion batteries: an electronic structure perspective.
In this paper, we present a systematic study of the effects of p- and n-doping in small molecules on the voltage and capacity of organic electrode materials for electrochemical batteries. In particular, coronene, phenalene derivatives as well as disodium terephthalate and related fused ring derivatives, representing often used building blocks in organic electrode materials, are chosen as model systems. We show that p-doping can drastically increase the binding strength to Li or Na and is therefore an effective strategy to design organic electrode materials for both lithium and sodium ion batteries. It could also be used to increase the theoretical capacity. On the other hand, n-doping generally has a much smaller effect on the voltage. The effects of n- and p-doping are rationalized based on the analysis of changes they induce in the band structure as well as in the molecular structure.


Diffusion tensor imaging of patients with proteolipid protein 1 gene mutations.
Pelizaeus-Merzbacher disease (PMD) is an X-linked disorder of the central nervous system (CNS) caused by a wide variety of mutations affecting proteolipid protein 1 (PLP1). We assessed the effects of PLP1 mutations on water diffusion in CNS white matter by using diffusion tensor imaging. Twelve patients with different PLP1 point mutations encompassing a range of clinical phenotypes were analyzed, and the results were compared with a group of 12 age-matched controls. The parallel (λ// ), perpendicular (λ⊥ ), and apparent diffusion coefficients (ADC) and fractional anisotropy were measured in both limbs of the internal capsule, the genu and splenium of corpus callosum, the base of the pons, and the cerebral peduncles. The mean ADC and λ⊥ in the PMD patient group were both significantly increased in all selected structures, except for the base of the pons, compared with controls. PMD patients with the most severe disease, however, had a significant increase of both λ// and λ⊥ . In contrast, more mildly affected patients had much smaller changes in λ// and λ⊥ . These data suggest that myelin, the structure responsible in part for the λ⊥ barrier, is the major site of disease pathogenesis in this heterogeneous group of patients. Axons, in contrast, the structures mainly responsible for λ// , are much less affected, except within the subgroup of patients with the most severe disease. Clinical disability in patients with PLP1 point mutation is thus likely determined by the extent of pathological involvement of both myelin and axons, with alterations of both structures causing the most severe disease. © 2014 Wiley Periodicals, Inc.


Investigation on reversed domain structures in lithium niobate crystals patterned by interference lithography.
We demonstrate fabrication of periodically poled lithium niobate samples by electric field poling, after patterning by interference lithography. Furthermore we investigate the poling process at an overpoling regime which caused the appearance of submicron dot domains very similar to those induced by backswitch but different in nature. We show the possibility for realizing submicron-scaled threedimensional domain patterns that could be applied to the construction of photonic crystals and in nonlinear optics. We show that high etch-rate applied to such structures allows to obtain pyramidal-like submicron relief structures which in principle could find application for waveguide construction in photonic bandgap devices.


Recent endemic coronavirus infection is associated with less-severe COVID-19.
Four different endemic coronaviruses (eCoVs) are etiologic agents for the seasonal common cold, and these eCoVs share extensive sequence homology with human SARS coronavirus 2 (SARS-CoV-2). Here, we show that individuals with, as compared with those without, a recent documented infection with eCoV were tested at greater frequency for respiratory infections but had a similar rate of SARS-CoV-2 acquisition. Importantly, the patients with a previously detected eCoV had less-severe coronavirus disease 2019 (COVID-19) illness. Our observations suggest that preexisting immune responses against endemic human coronaviruses can mitigate disease manifestations from SARS-CoV-2 infection.


Absorption spectroscopy of gold nanoisland films: optical and structural characterization.
Nanoisland films prepared by annealing thin gold films at high temperatures were imaged using scanning electron microscopy (SEM) and atomic force microscopy, and optically characterized through absorption spectroscopy. Thin gold films of effective thicknesses 2, 5 and 7 nm annealed at 500, 700 and 900 degrees C were fabricated and studied experimentally. The measured absorption characteristics in support of theoretical calculations showed that the shapes of gold islands were partial spheres. The position of the peak absorption wavelength measured with s-polarized light or at normal incidence confirmed that the island shape grew from a near-hemisphere towards a sphere with increasing annealing temperature. The SEM images confirmed that the size of islands increased from 15 nm in diameter to 40 nm in diameter as film thickness increased from 2 to 5 nm. The affect of the index of the substrate material on absorption characteristics were also studied by comparing the absorption spectra of gold island films on quartz and LaSF15 glass substrates. The use of gold nanoisland films for preparing localized surface plasmon resonance substrates was suggested as they held advantages over the gold colloid films.


Acute myeloblastic leukemia in paroxysmal nocturnal hemoglobinuria. Evidence of evolution from the abnormal paroxysmal nocturnal hemoglobinuria clone.
Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired hematopoietic stem cell disorder in which the blood cells demonstrate aberrant interactions with serum complement. In part, this is due to the absence of the complement regulatory protein, decay accelerating factor (DAF). A small number of patients with PNH have gone on to develop acute nonlymphocytic leukemia, which is thought to arise from the injured marrow as a second hematopoietic disorder. We have studied a patient with PNH who developed acute myeloblastic leukemia (AML); the blasts from this patient were found to lack DAF as measured by polyclonal antibody binding and fluorescence flow cytometry as well as by immunoblotting. The blasts from 11 other patients with AML bound anti-DAF antibody in amounts similar to normal mononuclear cells from healthy donors. Cells of the human leukemia cell lines HL-60, K562, U937, and HEL also bound anti-DAF antibody. In addition to DAF deficiency, blasts from the PNH patient had undetectable alkaline phosphatase activity, in contrast to human leukemia cell lines. These data suggest that the leukemic cells of the PNH patient arose out of the PNH clone and that AML in the setting of PNH is not a separate disorder.


Transcriptome Analysis Reveals Novel Genes Associated with Cartilage Degeneration in Posttraumatic Osteoarthritis Progression.
The current therapeutic strategy for posttraumatic osteoarthritis (PTOA) focuses on early intervention to attenuate disease progression, preserve joint function, and defer joint replacement timing. Sequential transcriptomic changes of articular cartilage in a rat model were investigated to explore the molecular mechanism in early PTOA progression. Anterior cruciate ligament transection and medial meniscectomy (ACLT + MMx)-induced PTOA model was applied on male Wistar rats. Articular cartilages were harvested at time 0 (naïve), 2 week, and 4 weeks after surgery. Affymetrix Rat genome 230 2.0 array was utilized to analyze the gene expression changes of articular cartilages. We identified 849 differentially expressed genes (DEGs) at 2 weeks and 223 DEGs at 4 weeks post-ACLT + MMx surgery compared with time 0 (naïve group). Gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed to gain further insights from these DEGs. 22 novel genes and 1 novel KEGG pathway (axon guidance) in cartilage degeneration of osteoarthritis were identified. Axon guidance molecules-Gnai1, Sema4d, Plxnb1, and Srgap2 commonly dysregulated in PTOA progression. Gnai1 gene showed a concordant change in protein expression by immunohistochemistry staining. Our study identified 22 novel dysregulated genes and axon guidance pathway associated with articular cartilage degeneration in PTOA progression. These findings provide the potential candidates of biomarkers and therapeutic targets for further investigation.


Acute withdrawal, protracted abstinence and negative affect in alcoholism: are they linked?
The role of withdrawal-related phenomena in the development and maintenance of alcohol addiction remains under debate. A 'self-medication' framework postulates that emotional changes are induced by a history of alcohol use, persist into abstinence, and are a major factor in maintaining alcoholism. This view initially focused on negative emotional states during early withdrawal: these are pronounced, occur in the vast majority of alcohol-dependent patients, and are characterized by depressed mood and elevated anxiety. This concept lost popularity with the realization that in most patients, these symptoms abate over 3-6 weeks of abstinence, while relapse risk persists long beyond this period. More recently, animal data have established that a prolonged history of alcohol dependence induces more subtle neuroadaptations. These confer altered emotional processing that persists long into protracted abstinence. The resulting behavioral phenotype is characterized by excessive voluntary alcohol intake and increased behavioral sensitivity to stress. Emerging human data support the clinical relevance of negative emotionality for protracted abstinence and relapse. These developments prompt a series of research questions: (1) are processes observed during acute withdrawal, while transient in nature, mechanistically related to those that remain during protracted abstinence?; (2) is susceptibility to negative emotionality in acute withdrawal in part due to heritable factors, similar to what animal models have indicated for susceptibility to physical aspects of withdrawal?; and (3) to what extent is susceptibility to negative affect that persists into protracted abstinence heritable?


Simultaneous use of solution, solid-state NMR and X-ray crystallography to study the conformational landscape of the Crh protein during oligomerization and crystallization.
We explore, using the Crh protein dimer as a model, how information from solution NMR, solid-state NMR and X-ray crystallography can be combined using structural bioinformatics methods, in order to get insights into the transition from solution to crystal. Using solid-state NMR chemical shifts, we filtered intra-monomer NMR distance restraints in order to keep only the restraints valid in the solid state. These filtered restraints were added to solid-state NMR restraints recorded on the dimer state to sample the conformational landscape explored during the oligomerization process. The use of non-crystallographic symmetries then permitted the extraction of converged conformers subsets. Ensembles of NMR and crystallographic conformers calculated independently display similar variability in monomer orientation, which supports a funnel shape for the conformational space explored during the solution-crystal transition. Insights into alternative conformations possibly sampled during oligomerization were obtained by analyzing the relative orientation of the two monomers, according to the restraint precision. Molecular dynamics simulations of Crh confirmed the tendencies observed in NMR conformers, as a paradoxical increase of the distance between the two β1a strands, when the structure gets closer to the crystallographic structure, and the role of water bridges in this context.


Artificial light and nocturnal activity in gammarids.
Artificial light is gaining attention as a potential stressor to aquatic ecosystems. Artificial lights located near streams increase light levels experienced by stream invertebrates and we hypothesized light would depress night drift rates. We also hypothesized that the effect of light on drift rates would decrease over time as the invertebrates acclimated to the new light level over the course of one month's exposure. These hypotheses were tested by placing Gammarus spp. in eight, 75 m × 1 m artificial flumes. One flume was exposed to strong (416 lx) artificial light at night. This strong light created a gradient between 4.19 and 0.04 lx over the neighboring six artificial flumes, while a control flume was completely covered with black plastic at night. Night-time light measurements taken in the Berlin area confirm that half the flumes were at light levels experienced by urban aquatic invertebrates. Surprisingly, no light treatment affected gammarid drift rates. In contrast, physical activity measurements of in situ individually caged G. roeseli showed they increased short-term activity levels in nights of complete darkness and decreased activity levels in brightly lit flumes. Both nocturnal and diurnal drift increased, and day drift rates were unexpectadly higher than nocturnal drift.


Pancreas-specific Cre driver lines and considerations for their prudent use.
Cre/LoxP has broad utility for studying the function, development, and oncogenic transformation of pancreatic cells in mice. Here we provide an overview of the Cre driver lines that are available for such studies. We discuss how variegated expression, transgene silencing, and recombination in undesired cell types have conspired to limit the performance of these lines, sometimes leading to serious experimental concerns. We also discuss preferred strategies for achieving high-fidelity driver lines and remind investigators of the continuing need for caution when interpreting results obtained from any Cre/LoxP-based experiment performed in mice.


Interactions between target location and reward size modulate the rate of microsaccades in monkeys.
We have studied how rewards modulate the occurrence of microsaccades by manipulating the size of an expected reward and the location of the cue that sets the expectations for future reward. We found an interaction between the size of the reward and the location of the cue. When monkeys fixated on a cue that signaled the size of future reward, the frequency of microsaccades was higher if the monkey expected a large vs. a small reward. When the cue was presented at a site in the visual field that was remote from the position of fixation, reward size had the opposite effect: the frequency of microsaccades was lower when the monkey was expecting a large reward. The strength of pursuit initiation also was affected by reward size and by the presence of microsaccades just before the onset of target motion. The gain of pursuit initiation increased with reward size and decreased when microsaccades occurred just before or after the onset of target motion. The effect of the reward size on pursuit initiation was much larger than any indirect effects reward might cause through modulation of the rate of microsaccades. We found only a weak relationship between microsaccade direction and the location of the exogenous cue relative to fixation position, even in experiments where the location of the cue indicated the direction of target motion. Our results indicate that the expectation of reward is a powerful modulator of the occurrence of microsaccades, perhaps through attentional mechanisms.


Impact of gastrostomy tube feeding on the quality of life of carers of children with cerebral palsy.
The aim of this prospective cohort study was to evaluate the impact of gastrostomy tube feeding on the quality of life of carers of children with cerebral palsy (CP). Short-Form 36 version II was used to measure quality of life in carers of 57 Caucasian children with CP (28 females, 29 males; median age 4y 4mo, range 5mo to 17y 3mo) six and 12 months after insertion of a gastrostomy tube. Responses were calibrated against a normative dataset (Oxford Healthy Life Survey III). Six months after gastrostomy feeding was started, a substantial rise in mean domain scores for mental health, role limitations due to emotional problems, physical functioning, social functioning, and energy/vitality were observed. At 12 months after gastrostomy placement, carers reported significant improvements in social functioning, mental health, energy/vitality (mean increase >9.8 points;p<0.03), and in general health perception (mean increase 6.35 points;p=0.045) compared with results at baseline. Moreover, the values obtained for these domains at 12 months were not significantly different from the normal reference standard. Carers reported a significant reduction in feeding times, increased ease of drug administration, and reduced concern about their child's nutritional status. This study has demonstrated a significant, measurable improvement in the quality of life of carers after insertion of a gastrostomy feeding tube.


"Ghosts in the Nursery:" Infant sleep and sleep-related cognitions of parents raised under communal sleeping arrangements.
In an experiment of nature, a normal cohort of parents who were raised under communal sleeping arrangements (CSA) in Israeli kibbutzim are raising their infants at home under home-based family sleeping arrangements. The present study focused on exploring the links between the early sleep experiences of CSA parents and their present sleep-related beliefs and behaviors. In particular, the study assessed whether the cognitions of CSA parents regarding infant sleep differ from cognitions of parents who were raised under home-based family sleeping arrangements. Furthermore, parental soothing methods and infant sleep patterns were compared. One hundred forty-one families participated in this study. The children's ages ranged between 4.5 to 30 months. Parental cognitions were evaluated by two questionnaires. Infant sleep was assessed by a questionnaire and by daily parental reports. As expected, CSA parents were more likely than were control parents to: (a) interpret infant night wakings as a sign of distress and (b) actively soothe their infants at bedtime, co-sleep with them, and report more night wakings of their infants. These findings support the hypothesis that early childhood sleep-related experiences of parents ("Ghosts in the Nursery") influence their parental sleep-related cognitions that in turn affect infant sleep patterns.


Characterization of the cytotoxic activities of novel analogues of the antitumor agent, lavendamycin.
Lavendamycin is a bacterially derived quinolinedione that displays significant antimicrobial and antitumor activities. However, preclinical development of lavendamycin as an anticancer agent was halted due to the poor aqueous solubility and relatively nonspecific cytotoxic activity of this compound. In this report, we have examined the cytotoxic activities of a series of novel lavendamycin analogues. The cytotoxic activities of these compounds were evaluated in clonogenic survival assays with A549 lung carcinoma cells. Compounds bearing an amide or amine substituent at the R(3) position were the most potent inhibitors of colony formation. MB-97, the most active member of this subgroup, decreased clonogenic outgrowth by 70% at a concentration of 10 n. Treatment of A549 cells with MB-97 led to an increase in p53 protein expression and phosphorylation and a concomitant increase in the expression of the p53 target gene, p21. Exposure of p53-positive cells to MB-97 triggered cell cycle arrest in G(1) and G(2) phases but induced a selective G(2)-phase arrest in p53-negative cells. MB-97 treatment also induced a higher level of apoptosis in p53-null cells relative to their p53-positive counterparts. Finally, MB-97 showed significant cytotoxic activity in the National Cancer Institute's panel of 60 cancer cell lines and antitumor activity in vivo in hollow fiber tumorigenesis assays.


Evaluation of skin permeation of β-blockers for topical drug delivery.
β-Blockers have recently become the main form of treatment of infantile hemangiomas. Due to the potential systemic adverse effects of β-blockers, topical skin treatment of the drugs is preferred. However, the effect and mechanism of dosage form pH upon skin permeation of these weak bases is not well understood. To develop an effective topical skin delivery system for the β-blockers, the present study evaluated skin permeation of β-blockers propranolol, betaxolol, timolol, and atenolol. Experiments were performed in side-by-side diffusion cells with human epidermal membrane (HEM) in vitro to determine the effect of donor solution pH upon the permeation of the β-blockers across HEM. The apparent permeability coefficients of HEM for the β-blockers increased with their lipophilicity, suggesting the HEM lipoidal pathway as the main permeation mechanism of the β-blockers. The pH in the donor solution was a major factor influencing HEM permeation for the β-blockers with a 2- to 4-fold increase in the permeability coefficient per pH unit increase. This permeability versus pH relationship was found to deviate from theoretical predictions, possibly due to the effective stratum corneum pH being different from the pH in the donor solution. The present results suggest the possibility of topical treatment of hemangioma using β-blockers.


Understanding the psychology of mobile gambling: A behavioural synthesis.
This manuscript reviews the extant literature on key issues related to mobile gambling and considers whether the potential risks of harm emerging from this platform are driven by pre-existing comorbidities or by psychological processes unique to mobile gambling. We propose an account based on associative learning that suggests this form of gambling is likely to show distinctive features compared with other gambling technologies. Smartphones are a rapidly growing platform on which individuals can gamble using specifically designed applications, adapted websites or text messaging. This review considers how mobile phone use interacts with psychological processes relevant to gambling, the games users are likely to play on smartphones, and the interactions afforded by smartphones. Our interpretation of the evidence is that the schedules of reinforcement found in gambling interact with the ways in which people tend to use smartphones that may expedite the acquisition of maladaptive learned behaviours such as problem gambling. This account is consistent with existing theories and frameworks of problem gambling and has relevance to other forms of mobile phone use.


Design and implementation of an online course on research methods in palliative care: lessons learned.
Research capacity in palliative and end-of-life care is less than some other fields of medicine where there is a longer track record of biomedical research. Palliative medicine clinicians often receive little or no formal research training during their postgraduate education; hence, education efforts may prove pivotal to increasing palliative care research capacity. To that end, our group established a national online training program on palliative care research methodologies, called Foundations of Palliative Care Research. This report describes the development and implementation of the course, and its evaluation. To inform decisions on the overall course objectives, length, design, and implementation, formal needs assessments were conducted through surveys of Canadian palliative medicine residency program directors and of Canadian palliative medicine residents. A 12-week, online, module-based course was designed. The first iteration of the course was offered to English-speaking palliative medicine residents from across Canada between October 2008 and March 2009. The course utilized Web-based communication methods, and was delivered using a combination of asynchronous and synchronous learning strategies and activities. Ten palliative care residents from different parts of the country registered and all completed the course with passing marks. Participants evaluated the course through a post course survey. The formal evaluation of the course, along with successes, challenges, and lessons applicable to future ventures, are discussed.


Epidermal growth factor receptor inhibition slows progression of diabetic nephropathy in association with a decrease in endoplasmic reticulum stress and an increase in autophagy.
Previous studies by us and others have reported renal epidermal growth factor receptors (EGFRs) are activated in models of diabetic nephropathy. In the present study, we examined the effect of treatment with erlotinib, an inhibitor of EGFR tyrosine kinase activity, on the progression of diabetic nephropathy in a type 1 diabetic mouse model. Inhibition of renal EGFR activation by erlotinib was confirmed by decreased phosphorylation of EGFR and extracellular signal-related kinase 1/2. Increased albumin/creatinine ratio in diabetic mice was markedly attenuated by erlotinib treatment. Erlotinib-treated animals had less histological glomerular injury as well as decreased renal expression of connective tissue growth factor and collagens I and IV. Autophagy plays an important role in the pathophysiology of diabetes mellitus, and impaired autophagy may lead to increased endoplasmic reticulum (ER) stress and subsequent tissue injury. In diabetic mice, erlotinib-treated mice had evidence of increased renal autophagy, as indicated by altered expression and activity of ATG12, beclin, p62, and LC3A II, hallmarks of autophagy, and had decreased ER stress, as indicated by decreased expression of C/EBP homologous protein, binding immunoglobulin protein, and protein kinase RNA-like ER kinase. The mammalian target of rapamycin (mTOR) pathway, a key factor in the development of diabetic nephropathy and an inhibitor of autophagy, is inhibited by AMP-activated protein kinase (AMPK) activation. Erlotinib-treated mice had activated AMPK and inhibition of the mTOR pathway, as evidenced by decreased phosphorylation of raptor and mTOR and the downstream targets S6 kinase and eukaryotic initiation factor 4B. Erlotinib also led to AMPK-dependent phosphorylation of Ulk1, an initiator of mammalian autophagy. These studies demonstrate that inhibition of EGFR with erlotinib attenuates the development of diabetic nephropathy in type 1 diabetes, which is mediated at least in part by inhibition of mTOR and activation of AMPK, with increased autophagy and inhibition of ER stress.


Stapling or suturing for anastomoses of the left side of the large intestine.
Two hundred and fifty patients undergoing elective surgical treatment involving anastomoses of the left side of the colon or colon and rectum have been studied in a randomized trial in which the EEA (U. S. Surgical Corp.) circular stapler has been compared with single layer sutured anastomoses. Only patients in whom either technique was feasible were included in the analysis. The operative techniques were largely standardized. Patients were studied by means of a limited barium enema on the ninth or tenth postoperative day. The data have been analyzed for leakage rate (clinical and roentgenologic), other complications and degree of experience of the surgeon. Eleven patients were excluded from the analysis because the selected technique could not be carried out; of these, eight were in the stapled group in which it was possible to perform a sutured anastomosis. There were no instances in which it was possible to staple but not possible to suture. The remaining three exclusions were patients in whom either a coloanal anastomosis or a Hartmann procedure was performed. There was no over-all difference in the leakage rate--roentgenologic, clinical or total--between the two groups. However, when analyzed by the surgeon, the clinical leakage rate for surgeons in training was greater for sutured anastomoses than for stapled anastomoses (p = 0.053). Thus, it appears that the benefits of experience are more pronounced for sutured anastomoses but that, in experienced hands, neither technique is superior.


Mitochondrial metabolic failure in telomere attrition-provoked aging of bone marrow mesenchymal stem cells.
The proliferation and differentiation potential of bone marrow mesenchymal stem cells (BMMSCs) declines with age and with in vitro passages. However, the underlying mechanisms and putative approaches to maintain their function are not fully understood. Recent studies have revealed telomere attrition as the core initiator determining functional decline in aging of BMMSCs. Telomere attrition activates downstream p53 signaling and compromises mitochondrial metabolism via the peroxisome proliferator-activated receptor gamma co-activator 1α/β (PGC-1α/β), a key process possesses peculiarities in BMMSCs distinct from other stem cells and their mature derivatives. Despite of the shortened telomere, the mitochondrial failure could be overcome through metabolic regulation by caloric restriction (CR) and its mediator Sirtuin 1 (SIRT1). Researches have shown that mitochondrial metabolic reprogramming by CR and SIRT1 alleviates functional decline of BMMSCs in aging. In this review, we intend to summarize our understanding about how telomere attrition initiates and induces mitochondrial compromise in functional decline of BMMSCs in aging, and the potential therapeutic strategies based on metabolic reprogramming.


An open trial of plant-source derived phosphatydilserine for treatment of age-related cognitive decline.
We assessed whether the efficacy of plant-source derived phosphatydilserine (one of the phospholipids which play an important functional role in membrane-related processes in the brain) for treatment of age related cognitive decline is consistent with previous (placebo controlled) positive findings with bovine derivative of PS (BC-PS). Eighteen healthy elderly volunteers meeting Age Associated Memory Impairment inclusion and exclusion criteria were treated for 12 weeks with plant-source derived phosphatydilserine (PS) (100 mg x 3/day p.o.) and evaluated at base line, after 6 weeks of treatment and at the end of the trial. Fifteen concluded the study. All but two outcome measures elicited a significant drug over time effect. Post-hoc paired t-tests showed that the significant effect was attributable to an improvement from base line to week 6 and that effect was maintained at week 12. These results are encouraging. However, they await double-blind controlled verification in a large sample before suggesting that this may be a viable approach to the treatment of age-related cognitive decline, without exposing the patients to possible hazards involved in the treatment with bovine derivative of PS (BC-PS).


Anthropogenic nitrogen deposition enhances carbon sequestration in boreal soils.
It is proposed that carbon (C) sequestration in response to reactive nitrogen (Nr ) deposition in boreal forests accounts for a large portion of the terrestrial sink for anthropogenic CO2 emissions. While studies have helped clarify the magnitude by which Nr deposition enhances C sequestration by forest vegetation, there remains a paucity of long-term experimental studies evaluating how soil C pools respond. We conducted a long-term experiment, maintained since 1996, consisting of three N addition levels (0, 12.5, and 50 kg N ha(-1) yr(-1) ) in the boreal zone of northern Sweden to understand how atmospheric Nr deposition affects soil C accumulation, soil microbial communities, and soil respiration. We hypothesized that soil C sequestration will increase, and soil microbial biomass and soil respiration will decrease, with disproportionately large changes expected compared to low levels of N addition. Our data showed that the low N addition treatment caused a non-significant increase in the organic horizon C pool of ~15% and a significant increase of ~30% in response to the high N treatment relative to the control. The relationship between C sequestration and N addition in the organic horizon was linear, with a slope of 10 kg C kg(-1) N. We also found a concomitant decrease in total microbial and fungal biomasses and a ~11% reduction in soil respiration in response to the high N treatment. Our data complement previous data from the same study system describing aboveground C sequestration, indicating a total ecosystem sequestration rate of 26 kg C kg(-1) N. These estimates are far lower than suggested by some previous modeling studies, and thus will help improve and validate current modeling efforts aimed at separating the effect of multiple global change factors on the C balance of the boreal region.


What Really Matters to You? A Study of Public Perspectives on General Practice in Ireland
Aims In recent years it has been recognised that person-centred care can lead to better outcomes for patients and a reduced burden on healthcare systems. The aim of this study was to explore what really matters to members of the public when they visit a GP in Ireland. Methods This qualitative study used a structured interview methodology with one question; "What really matters to you when you go to see a GP?" Results were analysed using an integrated approach, involving both inductive and deductive methods. Results Responses from the 10 study participants were subdivided into two overarching themes: the General Practitioner as a person and the General Practice as a service. Personality (open, approachable, personable, trusted, interested) and service (time, cost, convenience, personal relationship) traits matter to patients. Conclusion Patients must be facilitated and encouraged to voice what really matters to them in order to inform truly person-centred healthcare improvement.


A survey to identify the clinical coding and classification systems currently in use across Europe.
This is a survey to identify what clinical coding systems are currently in use across the European Union, and the states seeking membership to it. We sought to identify what systems are currently used and to what extent they were subject to local adaptation. Clinical coding should facilitate identifying key medical events in a computerised medical record, and aggregating information across groups of records. The emerging new driver is as the enabler of the life-long computerised medical record. A prerequisite for this level of functionality is the transfer of information between different computer systems. This transfer can be facilitated either by working on the interoperability problems between disparate systems or by harmonising the underlying data. This paper examines the extent to which the latter has occurred across Europe. Literature and Internet search. Requests for information via electronic mail to pan-European mailing lists of health informatics professionals. Coding systems are now a de facto part of health information systems across Europe. There are relatively few coding systems in existence across Europe. ICD9 and ICD 10, ICPC and Read were the most established. However the local adaptation of these classification systems either on a by country or by computer software manufacturer basis; significantly reduces the ability for the meaning coded with patients computer records to be easily transferred from one medical record system to another. There is no longer any debate as to whether a coding or classification system should be used. Convergence of different classifications systems should be encouraged. Countries and computer manufacturers within the EU should be encouraged to stop making local modifications to coding and classification systems, as this practice risks significantly slowing progress towards easy transfer of records between computer systems.


Evaluating the Toxicity Reduction With Computed Tomographic Ventilation Functional Avoidance Radiation Therapy.
Computed tomographic (CT) ventilation imaging is a new modality that uses 4-dimensional (4D) CT information to calculate lung ventilation. Although retrospective studies have reported on the reduction in dose to functional lung, no work to our knowledge has been published in which the dosimetric improvements have been translated to a reduction in the probability of pulmonary toxicity. Our work estimates the reduction in toxicity for CT ventilation-based functional avoidance planning. Seventy previously treated lung cancer patients who underwent 4DCT imaging were used for the study. CT ventilation maps were calculated with 4DCT deformable image registration and a density change-based algorithm. Pneumonitis was graded on the basis of imaging and clinical presentation. Maximum likelihood methods were used to generate normal tissue complication probability (NTCP) models predicting grade 2 or higher (2+) and grade 3+ pneumonitis as a function of dose (V5 Gy, V10 Gy, V20 Gy, V30 Gy, and mean dose) to functional lung. For 30 patients a functional plan was generated with the goal of reducing dose to the functional lung while meeting Radiation Therapy Oncology Group 0617 constraints. The NTCP models were applied to the functional plans and the clinically used plans to calculate toxicity reduction. By the use of functional avoidance planning, absolute reductions in grade 2+ NTCP of 6.3%, 7.8%, and 4.8% were achieved based on the mean fV20 Gy, fV30 Gy, and mean dose to functional lung metrics, respectively. Absolute grade 3+ NTCP reductions of 3.6%, 4.8%, and 2.4% were achieved with fV20 Gy, fV30 Gy, and mean dose to functional lung. Maximum absolute reductions of 52.3% and 16.4% were seen for grade 2+ and grade 3+ pneumonitis for individual patients. Our study quantifies the possible toxicity reduction from CT ventilation-based functional avoidance planning. Reductions in grades 2+ and 3+ pneumonitis were 7.1% and 4.7% based on mean dose-function metrics, with reductions as high as 52.3% for individual patients. Our work provides seminal data for determining the potential toxicity benefit from incorporating CT ventilation into thoracic treatment planning.


Doxorubicin vs. ladirubicin: methods for improving osteosarcoma treatment.
Osteosarcoma is the most common primary bone tumor in children and adolescents, with a 5-year disease free survival rate of 70%. Current chemotherapy regimens comprise a group of chemotherapeutic agents in which doxorubicin is included. However, tumor resistance to anthracyclines and cardiotoxicity are limiting factors for its usage. Liposomal formulations of doxorubicin improve its anti-cancer effects but are still insufficient. The research in this area has lead to the production of anthracyclines analogues, such as ladirubicin, the leading compound of alkylcyclines. This new anticancer agent has shown promising results in vivo and in vitro, being effective against osteosarcoma cell lines, including those with a multidrug resistant phenotype. In phase I clinical trials, this molecule caused mild side effects and did not induce significant cardiotoxicity at doses ranging from 1 to 16 mg/m(2), resulting in a peak plasma concentration (C(max)) ranging from 0.5 to 1.5 μM. The recommended doses for phase II studies were 12 and 14 mg/m(2) in heavily and minimally pretreated/non-pretreated patients, respectively. Phase II clinical trials in ovary, breast, colorectal cancer, NSCLC and malignant melanoma are underway. Given the improved molecular targeting efficacy of these new compounds, ongoing approaches have sought to improve drug delivery systems, to improve treatment efficacy while reducing systemic toxicity. The combination of these two approaches may be a good start for the discovery of new treatment for osteosarcoma.


The poliovirus 135S particle is infectious.
The molecular mechanism of cell entry by unenveloped viruses is poorly understood. The picornaviruses poliovirus, human rhinovirus, and coxsackievirus convert to an altered form (the 135S or A particle) upon interaction with receptors on susceptible cells at 37 degrees C. The 135S particle is thought to be a necessary intermediate because it accumulates inside susceptible cells soon after infection and drugs which inhibit conversion of the virus to this form also prevent infection. However, since a variable fraction of the altered 135S particles is reported to elute unproductively from the surface of susceptible cells, their precise role remains unclear. We have found that poliovirus 135S particles can infect Chinese hamster ovary (CHO) and murine L cells, neither of which are susceptible to infection by native poliovirus. The infectivity of the particles in tissue culture appears to be between 10(3) to 10(5) times less than that of poliovirus on HeLa cells. The 135S particle infectivity was not sensitive to RNase but was greatly reduced by proteolytic treatment. Proteolysis specifically removed the newly exposed N terminus of VP1, a feature which has previously been shown to mediate interactions of the particle with lipid membranes. These results demonstrate that although the infectivity of the 135S particle appears to be receptor independent, it nonetheless requires some property associated with the protein coat. In particular, the N terminus of VP1 plays an important role in the infection process. Our findings are consistent with the hypothesis that the 135S particle is an intermediate in the normal cell entry pathway of poliovirus infection.


Microplastics in mussels along the coastal waters of China.
Microplastic has been confirmed as an emerging pollutant in marine environments. One of the primary environmental risks of microplastics is their bioavailability for aquatic organisms. Bivalves are of particular interest because their extensive filter-feeding activity exposes them directly to microplastics present in the water column. In the present study, we investigated microplastic pollution in mussels (Mytilus edulis) from 22 sites along 12,400 mile coastlines of China in 2015. The number of total microplastics varied from 0.9 to 4.6 items/g and from 1.5 to 7.6 items/individual. M. edulis contained more microplastics (2.7 items/g) in wild groups than that (1.6 items/g) in farmed groups. The abundance of microplastics was 3.3 items/g in mussels from the areas with intensive human activities and significantly higher than that (1.6 items/g) with less human activities. The most common microplastics were fibers, followed by fragments. The proportion of microplastics less than 250 μm in size arranged from 17% to 79% of the total microplastics. Diatom was distinguished from microplastics in mussels for the first time using Scanning Electron Microscope. Our results suggested that the numbers of microplastic kept within a relatively narrow range in mussels and were closely related to the contamination of the environments. We proposed that mussels could be used as a potential bioindicator of microplastic pollution of the coastal environment.


Primary Giant Splenic Echinococcal Cyst Treated by Laparoscopy.
Cystic echinococcosis (CE) is a zoonosis caused by the larval stage of the dog tapeworm Echinococcus granulosus. Liver and lungs are the most commonly affected organs whereas splenic infection is rarer and its primary involvement occurs in less than 2% of abdominal CE. We report a case of primary giant splenic hydatid cyst in a 75-year-old Peruvian woman that was laparoscopically removed without any complications, perioperative prophylactic chemotherapy with albendazole 400 mg twice a day 5 days before, and 7 days after the surgical procedure was administered, postoperative recovery was uneventful, and; at her 3-month follow-up the patient remains asymptomatic and an abdominal computed tomography scan demonstrated a cystic cavity of 15 cm diameter with no daughter vesicles, neither other abdominal organ involvement. This case is in line with the existing literature on laparoscopical treatment of splenic cystic hydatid disease, suggesting that laparoscopical treatment is a safe and effective approach for large splenic hydatid cysts to be preferred to open surgical techniques.


The uses of poxviruses as vectors.
Poxviruses have played an amazing role in the development of virology, immunology and vaccinology. In 1796, deliberate inoculation of cowpox virus to humans was proved by Dr. Edward Jenner to protect against the antigenically related smallpox virus (variola). This discovery founded the science of immunology and eventually led to smallpox eradication from the earth in 1980 after a world wide vaccination campaign with vaccinia virus (another poxvirus). Paradoxically, despite the eradication of smallpox, there has been an explosion of interest in vaccinia virus in the eighties. This interest has stemmed in part from the application of molecular genetics to clone and express foreign genes from recombinant vaccinia virus. The use of these recombinant vaccinia viruses as efficacious in vitro expression system and live vaccine has raised concerns about their safety. The work of the scientific community of the last 20 years has contributed to improve drastically the safety of poxvirus derived vectors. Firstly, the safety of vaccinia virus has been enhanced by production of genetically attenuated strains. Secondly, alternative poxvirus vectors, such as avipoxviruses, were proved to be extremely safe and efficacious non-replicating vectors when used in non avian species. In the present chapter, the basic concepts of poxvirus biology required to assess the safety of a poxvirus derived vector are provided. The principal poxvirus vectors available to date are described in regards to their biosafety.


Programme theory and linked intervention strategy for large-scale change to improve hospital care in a low and middle-income country - A Study Pre-Protocol.
In low and middle-income countries (LMIC) general hospitals are important for delivering some key acute care services. Neonatal care is emblematic of these acute services as averting deaths requires skilled care over many days from multiple professionals with at least basic equipment. However, hospital care is often of poor quality and large-scale change is needed to improve outcomes. However, achieving large scale change in health systems remains challenging. To set the scene we first characterise the problems of hospital newborn units (NBU) in Kenya. We then combine our understanding of theory and context with reflection on our own position as an embedded research group with no formal authority to help us propose a feasible intervention strategy linked to in initial programme theory. We explain this programme theory and suggest how within a multi-level clinical professional network leaders at the ward or mid-level of hospital hierarchies are key potential change agents. In support of our programme theory we briefly outline and seek to integrate key ideas drawn from a wider set of theories. We propose how an intervention might be developed and employed in a phased approach to create the ownership, relationships and momentum that will be needed to achieve change at scale. Finally, we discuss the implications of such a strategy for our research design that is based on a prospective, in-depth case study that includes quantitative and qualitative data collection linked to specific sub-studies. We suggest using Realistic Evaluation to integrate our findings and develop an updated programme theory that should inform future large-scale change efforts before briefly discussing some of the challenges of evaluating a network as an intervention.


Partnership, sex, and marginalization: Moving the Global Fund sexual orientation and gender identities agenda.
After almost three decades of work to address HIV and AIDS, resources are still failing to adequately address the needs of the most affected and marginalized groups in many societies. In recognition of this ongoing failure, the Global Fund to Fight AIDS, Tuberculosis and Malaria (the Global Fund) has approved a sexual orientation and gender identities (SOGI) Strategy. The Strategy is designed to help its investments more effectively reach men who have sex with men; transgender populations; male, female, and transgender sex workers; and women who have sex with women. The Global Fund financing model is unique and based on ideas of broad partnership. It emphasizes the importance of country-ownership while ensuring that work is appropriately targeted, evidence-based, and rooted in principles of human rights. The classic international development tension of pursuing a rights-based agenda, while also supporting strong country ownership, has moved the Global Fund into a more substantive technical, advocacy, and policy arena, resulting in the creation of the SOGI Strategy, which emphasizes the needs of marginalized groups. A strong commitment to participation and consultation was crucial during the development stages of the Strategy. Now, as the Strategy goes live, it is clear that progress will only be achieved through continued and strengthened partnership. The diverse partners - in particular the governments and other stakeholders in recipient countries that helped develop the Strategy - must now commit to stronger collaboration on this agenda and must demonstrate bold leadership in overcoming the considerable technical and political challenges of implementation that lie ahead.