Copy number variation of age-related macular degeneration relevant genes in the Korean population.
Studies that analyzed single nucleotide polymorphisms (SNP) in various genes have shown that genetic factors are strongly associated with age-related macular degeneration (AMD) susceptibility. Copy number variation (CNV) may be an additional type of genetic variation that contributes to AMD pathogenesis. This study investigated CNV in 4 AMD-relevant genes in Korean AMD patients and control subjects. Four CNV candidate regions located in AMD-relevant genes (VEGFA, ARMS2/HTRA1, CFH and VLDLR), were selected based on the outcomes of our previous study which elucidated common CNVs in the Asian populations. Real-time PCR based TaqMan Copy Number Assays were performed on CNV candidates in 273 AMD patients and 257 control subjects. The predicted copy number (PCN, 0, 1, 2 or 3+) of each region was called using the CopyCaller program. All candidate genes except ARMS2/HTRA1 showed CNV in at least one individual, in which losses of VEGFA and VLDLR represent novel findings in the Asian population. When the frequencies of PCN were compared, only the gain in VLDLR showed significant differences between AMD patients and control subjects (p = 0.025). Comparisons of the raw copy values (RCV) revealed that 3 of 4 candidate genes showed significant differences (2.03 vs. 1.92 for VEGFA, p<0.01; 2.01 vs. 1.97 for CFH, p<0.01; 1.97 vs. 2.01, p<0.01 for ARMS2/HTRA1). CNVs located in AMD-relevant genes may be associated with AMD susceptibility. Further investigations encompassing larger patient cohorts are needed to elucidate the role of CNV in AMD pathogenesis.


'The perfect is the enemy of the good' - ergonomics research and practice. Institute of Ergonomics and Human Factors Annual Lecture 2010.
The relationship between research and practice in ergonomics and human factors has rarely been addressed in the literature. This presents specific problems for researchers when seeking to relate their work to the research community. Equally, practitioners are often frustrated by the lack of appropriate research to meet their needs. This paper seeks to identify current drivers for ergonomics research along with an analysis of how these are changing. Specifically, the use of bibliometric data to assess research output and its impact on a multi-disciplinary subject such as ergonomics is examined. Areas where action may be required to stimulate better research and improved practice are proposed. These include a greater role for the practitioner in completing the circle of knowledge and improving the evidence base for practice with, in particular, practitioners becoming more active in determining research priorities. It is concluded that combined effort is needed by researcher and practitioner communities to enable and promote a more effective understanding of the true impact of ergonomics across industry and society. STATEMENT OF RELEVANCE: The relationship between ergonomics research and practice is examined. Research 'drivers' are identified, including the influence of bibliometric data. Implications for researchers and practitioners are discussed. The role of practitioners in completing the circle of knowledge and improving the ergonomics evidence base is stressed, as is the need to promote the impact of ergonomics across society.


Identification of a novel antigen from Corynebacterium pseudotuberculosis that protects sheep against caseous lymphadenitis.
A 40-kDa protein antigen from Corynebacterium pseudotuberculosis has been identified by application of a strategy that employs locally derived antibody-secreting cells (ASC). ASC probes generated by culture of ASC obtained from the lymph node draining the site of infection showed a specificity restricted to a 40-kDa antigen. Analysis of immunoblots with sequential serum samples taken from sheep during the course of experimental primary infection with C. pseudotuberculosis also revealed the 40-kDa antigen as an early immunodominant antigen. Sheep vaccinated with two 100-micrograms doses of a 40-kDa antigen preparation in aluminium hydroxide adjuvant were protected against infection with C. pseudotuberculosis, with an 82% reduction in the proportion of infected sheep and a 98% reduction in lung lesions. Sera from vaccinated sheep exhibited a strong response only to the 40-kDa antigen on immunoblots. These results strongly suggest that the 40-kDa antigen plays a major role in immunity to caseous lymphadenitis.


Glacial effects limiting mountain height.
The height of mountain ranges reflects the balance between tectonic rock uplift, crustal strength and surface denudation. Tectonic deformation and surface denudation are interdependent, however, and feedback mechanisms-in particular, the potential link to climate-are subjects of intense debate. Spatial variations in fluvial denudation rate caused by precipitation gradients are known to provide first-order controls on mountain range width, crustal deformation rates and rock uplift. Moreover, limits to crustal strength are thought to constrain the maximum elevation of large continental plateaus, such as those in Tibet and the central Andes. There are indications that the general height of mountain ranges is also directly influenced by the extent of glaciation through an efficient denudation mechanism known as the glacial buzzsaw. Here we use a global analysis of topography and show that variations in maximum mountain height correlate closely with climate-controlled gradients in snowline altitude for many high mountain ranges across orogenic ages and tectonic styles. With the aid of a numerical model, we further demonstrate how a combination of erosional destruction of topography above the snowline by glacier-sliding and commensurate isostatic landscape uplift caused by erosional unloading can explain observations of maximum mountain height by driving elevations towards an altitude window just below the snowline. The model thereby self-consistently produces the hypsometric signature of the glacial buzzsaw, and suggests that differences in the height of mountain ranges mainly reflect variations in local climate rather than tectonic forces.


The Effect of an Exercise Intervention During Early Lactation on Bone Mineral Density During the First Year Postpartum.
During lactation, women may lose up to 10% of bone mineral density (BMD) at trabecular-rich sites. Previous studies show that resistance exercise may slow BMD; however, the long-term effects of exercise on BMD during lactation have not been reported. To evaluate the effect of two 16-week exercise interventions (4- to 20-wk postpartum) in lactating women at 1-year postpartum on lumbar spine, total body, and hip BMD. To increase sample size at 1-year postpartum, two 16-week exercise interventions were combined for analysis. At 4-week postpartum, 55 women were randomized to intervention group (weight bearing aerobic exercise and resistance exercise) or control group (no exercise) for 16-week, with a 1-year postpartum follow-up. BMD was measured by dual-energy X-ray absorptiometry. Repeated-measures analysis of covariance was used to test for time and group differences for BMD controlling for prolactin concentration and dietary calcium at 1-year postpartum. Change in lumbar spine BMD was significantly different over time and between groups from 4-week to 1-year postpartum, when controlling for prolactin concentration and dietary calcium. There were no significant differences between groups in total body and hip BMD. These results suggest that resistance exercise may slow bone loss during lactation, resulting in higher BMD levels at 1-year postpartum.


Solidification/stabilization of landfill leachate concentrate using different aggregate materials.
The application of reverse osmosis for the treatment of landfill leachate is becoming widespread in Turkey as well as in Europe. A major drawback of this process is the production of concentrate, which could be as much as 30% of the feed stream, and high concentrations of salts and contaminants. The reverse osmosis concentrate is disposed of by using several methods including re-infiltration, drying, incineration and solidification/stabilization. In this study, solidification/stabilization (S/S) technology was studied for the treatment of reverse osmosis concentrate produced from landfill leachate. In order to benefit from its capability to absorb heavy metals, ammonia and some other pollutants, zeolite and different aggregate materials were used in solidification experiments. Main pollutants in the leachate concentrate, TOC, DOC, TDS and ammonia were successfully solidified and approximately 1% of TOC, DOC, TDS and ammonia remained in the eluate water. The results indicated that the landfill disposal limits could be attained by solidification/stabilization process.


Mutations in KIF11 cause autosomal-dominant microcephaly variably associated with congenital lymphedema and chorioretinopathy.
We have identified KIF11 mutations in individuals with syndromic autosomal-dominant microcephaly associated with lymphedema and/or chorioretinopathy. Initial whole-exome sequencing revealed heterozygous KIF11 mutations in three individuals with a combination of microcephaly and lymphedema from a microcephaly-lymphedema-chorioretinal-dysplasia cohort. Subsequent Sanger sequencing of KIF11 in a further 15 unrelated microcephalic probands with lymphedema and/or chorioretinopathy identified additional heterozygous mutations in 12 of them. KIF11 encodes EG5, a homotetramer kinesin motor. The variety of mutations we have found (two nonsense, two splice site, four missense, and six indels causing frameshifts) are all predicted to have an impact on protein function. EG5 has previously been shown to play a role in spindle assembly and function, and these findings highlight the critical role of proteins necessary for spindle formation in CNS development. Moreover, identification of KIF11 mutations in patients with chorioretinopathy and lymphedema suggests that EG5 is involved in the development and maintenance of retinal and lymphatic structures.


[Acute pharyngo-tonsillitis. Penicillin, yes or no?].
Acute tonsillitis and acute pharyngitis show a high incidence in the healthy population. Recent microbiological studies have demonstrated changes in the frequency with which different microorganisms promote such infections. This fac, together with the variations in sensibility or resistance of germs to the diverse therapeutic agents, have led to the conclusion that penicillin must not be considered as the solo drug of choice in these infections.


Cognitive-behavioral treatment for severe anger in posttraumatic stress disorder.
With a randomized group design, a 12-session anger treatment was evaluated with severely angry Vietnam War veterans suffering combat-related posttraumatic stress disorder (PTSD). Eight participants in anger treatment and 7 in a routine clinical care control condition completed multiple measures of anger control, anger reaction, and anger disposition, as well as measures of anxiety, depression, and PTSD at pre- and posttreatment. Controlling for pretreatment scores, significant effects were found on anger reaction and anger control measures but not on anger disposition or physiological measures. Eighteen-months follow-up (for both completers and dropouts) supported the posttreatment anger control findings. The challenges of treatment research with this refractory population are discussed.


Gentamicin concentration gradients in scala tympani perilymph following systemic applications.
It has been shown in prior studies that round window membrane (RWM) application of gentamicin produced a robust basal-apical concentration gradient in the perilymph of scala tympani (ST) with peak concentrations in the basal turn of ST. These gradients potentially contribute to the clinical efficacy and safety of intratympanic gentamicin applications for the treatment of Ménière's disease. The present study aimed to establish the distribution of gentamicin along ST perilymph after systemic applications. Gentamicin sulfate was applied intravenously in the amounts of 100, 300 and 600 mg/kg body weight (BW) over a period of 3 h or as a 300 mg/kg BW subcutaneous bolus injection. At 3 and 5 h after the start of the application perilymph of ST was aspirated from the cochlea apex of the right and left cochlea, respectively, and 10 sequential 1-µl perilymph samples from the apex of each cochlea were quantitatively analyzed using a fluorescence polarization immunoassay. In contrast to local RWM delivery, systemic application of gentamicin resulted in the highest perilymph levels in the apex of the cochlea with decreasing concentrations towards the basal regions of ST. The absolute gentamicin concentrations increased with the amount of drug applied and time before sampling. While it is likely that the basal-apical gradient measured after local drug applications to the round window niche is the result of the direct uptake of drugs into the perilymph of the ST, distribution by diffusion and a very low perilymph flow towards the cochlear apex, computer simulations suggested that the apical-basal gradient observed with these systemic applications can be explained by higher entry rates of gentamicin in the apex compared to the basal turns of the cochlea. It is also possible that gentamicin enters perilymph indirectly from the blood via the endolymph. In this case the faster kinetics in apical turns could be due to the smaller cross-sectional area of ST relative to endolymph in the apical turns.


Dissociable networks for the expectancy and perception of emotional stimuli in the human brain.
William James posited that comparable brain regions were implicated in the anticipation and perception of a stimulus; however, dissociable networks (at least in part) may also underlie these processes. Recent functional neuroimaging studies have addressed this issue by comparing brain systems associated with the expectancy and perception of visual, tactile, nociceptive, and reward stimuli. In the present fMRI study, we addressed this issue in the domain of pictorial emotional stimuli (IAPS). Our paradigm involved the experimental conditions emotional expectancy, neutral expectancy, emotional picture perception, and neutral picture perception. Specifically, the emotional expectancy cue was uncertain in that it did not provide additional information regarding the positive or negative valence of the subsequent picture. Neutral expectancy and neutral picture perception served as control conditions, allowing the identification of expectancy and perception effects specific for emotion processing. To avoid contamination of the perception conditions by the preceding expectancy periods, 50% of the pictorial stimuli were presented without preceding expectancy cues. We found that the emotional expectancy cue specifically produced activation in the supracallosal anterior cingulate, cingulate motor area, and parieto-occipital sulcus. These regions were not significantly activated by emotional picture perception which recruited a different neuronal network, including the amygdala, insula, medial and lateral prefrontal cortex, cerebellum, and occipitotemporal areas. This dissociation may reflect a distinction between anticipatory and perceptive components of emotional stimulus processing.


Changes in megakaryocytes in cases of thrombocytopenia: bone marrow aspiration and biopsy analysis.
Thrombocytopenia (platelet counts less than 150,000/μl) is commonly encountered in various hematological disorders including myelodysplastic syndromes as well as various non-myelodysplastic hematological conditions. The present study was undertaken to calculate the prevalence of various conditions associated with thrombocytopenia and to record the megakaryocytic alterations in various cases of thrombocytopenia. Apart from this by means of statistical analysis it was tried to analyze whether a significant difference existed in megakaryocytic alteration noted in myelodysplastic versus non- myelodysplastic conditions. A prospective series of 60 bone marrow aspirations along with concomitant bone marrow biopsies was conducted in a tertiary care centre catering to both urban as well as rural population in north India. The distribution of morphological changes in cases of non myelodysplastic conditions and myelodysplastic were compared using Chi-Square test. A p-value less than 0.05 was considered significant. The commonest cause of thrombocytopenia for which bone marrow examination was sought was dimorphic anaemia (18 cases, 30%), followed by myelodysplastic syndrome (06 cases, 10%) which was followed equally by acute lymphocytic leukemia and blast crisis of chronic myeloid leukemia (CML). Of all the non-MDS conditions apart from dimorphic anaemia, idiopathic thrombocytopenic purpura and chronic myeloid leukemia (blast crisis); megakaryocytic dysplastic forms were not noted in any other condition. In cases of myelodysplasia; dysplastic forms, bare megakaryocytic nuclei, hypogranular forms and micromegakaryocytes were seen. Comparison between frequencies of normal, high and low number of nuclear lobes among MDS (n=9) and non MDS (n=68) conditions were found to be statistically significant. Further studies on the evaluation of megakaryocytic alteration and their contribution to thrombocytopenia can provide growing knowledge to the pathogenesis of numerous hematopoietic disorders that may identify broader clinical applications of the newer strategies to regulate platelet count and functioning.


Protective role of resveratrol on testicular germ cells in mice with testicular toxicity.
The aim of the present study was to investigate the possible beneficial effects of resveratrol in mice subjected to vinyl cyclohexene dieposide (VCD) -induced testicular toxicity. A total of thirty- six Swiss albino male mice aged 28-days were used in the present study. The study was composed of two stages where mice which received or did not receive VCD (320 mg/kg/day) were administered resveratrol. The animals were assigned into control and resveratrol-treated groups in the first stage and into groups of VCD- and VCD+resveratrol-treated groups in the second stage. At the end of the experiments, relative testicular weight (TW/BW) and dry/wet weight of testis (TDW/TWW) were calculated. Histological analysis by hematoxylin and eosin (H&E) staining and immunohistochemical staining by BAX and Bcl-2 were performed. Serum testosterone, LH and FSH levels were measured by a commercially available ELISA kit. Resveratrol caused a dose-dependent increase in TW/BW and decrease in TDW/TWW (p<0.05). Resveratrol at a dose of 20 mg/kg resulted in an improvement in testosterone, LH and FSH levels in mice with VCD-induced testicular toxicity (p<0.001). Resveratrol also improved apoptotic index and epithelial cell height of testicular seminipherous tubuli significantly after VCD exposure (p<0.001). Results of the present study suggest that resveratrol can be used as a protective and/or therapeutic agent particularly for cases with male infertility caused by testicular toxicity.


Imaging of small high-density structures in CT A phantom study.
The aim of this work is to study how the limited spatial resolution of a computed tomographic (CT) system affects the imaging of small high-density structures. This knowledge is relevant not only to understand and interpret clinical data, but also to apply and develop quantification methods for calcifications and stented vessels. A dedicated phantom containing small differently sized aluminum cylinders was imaged on a 64-slice multidetector row CT (MDCT) while varying acquisition and reconstruction parameters from a high-resolution protocol. In addition, a bead phantom was imaged to estimate the point spread function (PSF) for the different parameter settings. The accuracy in determining object density and size was established for various imaging protocols and compared with simulations based on the estimated PSF. Attenuation values and size measurements were accurate for objects larger than two times the size of the system PSF at the full-width-at-half-maximum. For smaller objects, attenuation values were increasingly underestimated and size was increasingly overestimated. The convolution kernel had the most influence on object signal and size. Use of edge-enhancing kernels yielded more accurate size measurements and higher signal for small objects. However, their application was constrained by noise amplification and edge-ringing artifacts, which led to lower signal-to-noise ratio, degrading the visualization of low densities and small high-density objects. Results presented in this report provide insight into limitations in the quantification of small high-density structures and their effect on the visualization of surrounding tissues with recently developed MDCT systems.


5-(Hydroxymethyl)uracil and -cytosine as potential epigenetic marks enhancing or inhibiting transcription with bacterial RNA polymerase.
DNA templates containing 5-hydroxymethyluracil or 5-hydroxymethylcytosine were used in an in vitro transcription assay with RNA polymerase from Escherichia coli. A strong enhancement of transcription was observed from DNA containing the Pveg promoter whereas a decrease was observed from DNA containing the rrnB P1 promoter, suggesting that they may act as epigenetic marks.


Pseudoteredinibacter isoporae gen. nov., sp. nov., a marine bacterium isolated from the reef-building coral Isopora palifera.
A Gram-negative, heterotrophic, marine bacterium, designated strain SW-11(T), was isolated from the reef-building coral Isopora palifera in Kenting, Taiwan. Cells were rods and were motile by a single polar flagellum. The strain grew at 10-45 °C (optimum, 30-35 °C), at pH 7.0-8.0 (optimum, pH 7.5) and with 2.0-4.0 % NaCl (optimum, 2.5-3.0 %). The polar lipids comprised phosphatidylethanolamine, phosphatidylglycerol, phosphatidylserine, diphosphatidylglycerol and four unknown phospholipids. Isoprenoid quinones consisted of ubiquinone 9 (78.8 %) and ubiquinone 8 (21.1 %). Major cellular fatty acids were summed feature 3 (C(16 : 1)ω7c and/or C(16 : 1)ω6c; 22.3 %), C(17 : 1)ω8c (13.4 %), summed feature 8 (C(18 : 1)ω6c and/or C(18 : 1)ω7c; 13.1 %), C(16 : 0) (10.3 %) and anteiso-C(17 : 1)ω9c (10.0 %). The DNA G+C content was 51.6 mol%. 16S rRNA gene sequence analysis indicated that strain SW-11(T) belongs to the class Gammaproteobacteria and is a member of the order Alteromonadales. Strain SW-11(T) shared 93.2 % 16S rRNA gene sequence similarity with Teredinibacter turnerae T7902(T) and 92.1 % with Saccharophagus degradans 2-40(T), and can be further distinguished from these two related strains by distinct patterns of fatty acid content and differences in the polar lipid profile, the ability to utilize different compounds as carbon sources, the ability to degrade various compounds and differences in enzyme activities. The phylogenetic data and those from physiological, morphological and chemotaxonomic characterizations indicate that strain SW-11(T) represents a novel species and genus, for which the name Pseudoteredinibacter isoporae gen. nov., sp. nov. is proposed. The type strain of Pseudoteredinibacter isoporae is SW-11(T) ( = BCRC 17935(T) = LMG 25246(T)).


The electronic states of a double carbon vacancy defect in pyrene: a model study for graphene.
The electronic states occurring in a double vacancy defect for graphene nanoribbons have been calculated in detail based on a pyrene model. Extended ab initio calculations using the MR configuration interaction (MRCI) method have been performed to describe in a balanced way the manifold of electronic states derived from the dangling bonds created by initial removal of two neighboring carbon atoms from the graphene network. In total, this study took into account the characterization of 16 electronic states (eight singlets and eight triplets) considering unrelaxed and relaxed defect structures. The ground state was found to be of (1)Ag character with around 50% closed shell character. The geometry optimization process leads to the formation of two five-membered rings in a pentagon-octagon-pentagon (5-8-5) structure. The closed shell character increases thereby to ∼70%; the analysis of unpaired density shows only small contributions confirming the chemical stability of that entity. For the unrelaxed structure the first five excited states ((3)B3g, (3)B2u, (3)B1u, (3)Au and (1)Au) are separated from the ground state by less than 2.5 eV. For comparison, unrestricted density functional theory (DFT) calculations using several types of functionals have been performed within different symmetry subspaces defined by the open shell orbitals. Comparison with the MRCI results gave good agreement in terms of finding the (1)Ag state as a ground state and in assigning the lowest excited states. Linear interpolation curves between the unrelaxed and relaxed defect structures also showed good agreement between the two classes of methods opening up the possibilities of using extended nanoflakes for multistate investigations at the DFT level.


Cochlear basal and apical differences reflected in the effects of cooling on responses of single auditory nerve fibers.
Responses of single auditory nerve fibers in the Mongolian gerbil were examined before and during rapid, moderate cooling of the cochlea. Reducing cochlear temperature from 35-39 degrees C to 29-32 degrees C led to stable, reversible changes in spontaneous firing rates (SRs), and responses to tonebursts, as characterized by frequency tuning curves and rate-versus-intensity curves. The nature and extent of effects of cooling were strongly linked to characteristic frequency (CF). Rate thresholds at the CF were increased by 0-15 dB for fibers with CFs below 8 kHz, and by 10-30 dB for higher CFs. Although SRs were generally reduced, the percent reduction in SR was striking CF dependent. For fibers with CFs below 4 kHz, the reduction did not exceed 50% of the initial SR. For higher CFs, the reduction was always greater than 50%. The effects of cooling on intensity curve shape differed qualitatively for fibers with CFs below and above 3-4 kHz. The slope of the curve was reduced by an average of 50% for lower CFs, but on average was unchanged for higher CFs. Cooling-related increases in CF threshold probably reflect impairment of active mechanical processes. The CF dependence of these increases suggests either that active mechanical processes are more impaired in the cochlear base relative to the apex, or that they play a more crucial role in determining sensitivity in the base. The CF-dependent changes in SR and in the shape of rate-intensity curves caused by cooling correspond to an enhancement of basal/apical differences seen at normal temperatures. They are best explained by longitudinal gradients in the properties of the inner hair cells and their afferent synapses. Basal and apical differences in the distribution of SRs and in supra-threshold response properties suggest that stimulus coding strategies differ between low and high frequency regions of the cochlea.


A massive update of non-indigenous species records in Mediterranean marinas.
The Mediterranean Sea is home to over 2/3 of the world's charter boat traffic and hosts an estimated 1.5 million recreational boats. Studies elsewhere have demonstrated marinas as important hubs for the stepping-stone transfer of non-indigenous species (NIS), but these unique anthropogenic, and typically artificial habitats have largely gone overlooked in the Mediterranean as sources of NIS hot-spots. From April 2015 to November 2016, 34 marinas were sampled across the following Mediterranean countries: Spain, France, Italy, Malta, Greece, Turkey and Cyprus to investigate the NIS presence and richness in the specialized hard substrate material of these marina habitats. All macroinvertebrate taxa were collected and identified. Additionally, fouling samples were collected from approximately 600 boat-hulls from 25 of these marinas to determine if boats host diverse NIS not present in the marina. Here, we present data revealing that Mediterranean marinas indeed act as major hubs for the transfer of marine NIS, and we also provide evidence that recreational boats act as effective vectors of spread. From this wide-ranging geographical study, we report here numerous new NIS records at the basin, subregional, country and locality level. At the basin level, we report three NIS new to the Mediterranean Sea (Achelia sawayai sensu lato, Aorides longimerus, Cymodoce aff. fuscina), and the re-appearance of two NIS previously known but currently considered extinct in the Mediterranean (Bemlos leptocheirus, Saccostrea glomerata). We also compellingly update the distributions of many NIS in the Mediterranean Sea showing some recent spreading; we provide details for 11 new subregional records for NIS (Watersipora arcuata, Hydroides brachyacantha sensu lato and Saccostrea glomerata now present in the Western Mediterranean; Symplegma brakenhielmi, Stenothoe georgiana, Spirobranchus tertaceros sensu lato, Dendostrea folium sensu lato and Parasmittina egyptiaca now present in the Central Mediterranean, and W. arcuata, Bemlos leptocheirus and Dyspanopeus sayi in the Eastern Mediterranean). We also report 51 new NIS country records from recreational marinas: 12 for Malta, 10 for Cyprus, nine for Greece, six for Spain and France, five for Turkey and three for Italy, representing 32 species. Finally, we report 20 new NIS records (representing 17 species) found on recreational boat-hulls (mobile habitats), not yet found in the same marina, or in most cases, even the country. For each new NIS record, their native origin and global and Mediterranean distributions are provided, along with details of the new record. Additionally, taxonomic characters used for identification and photos of the specimens are also provided. These new NIS records should now be added to the relevant NIS databases compiled by several entities. Records of uncertain identity are also discussed, to assess the probability of valid non-indigenous status.


Marijuana use and treatment outcome among opioid-dependent patients.
Information concerning the association between marijuana use and opioid dependence and its treatment is needed to determine effective clinical guidelines for addressing marijuana use among opioid abusers. Marijuana use was assessed in 107 people enrolled in treatment for opioid dependence. Univariate comparisons of marijuana users and non-users and multivariate regression analyses were performed to examine associations between marijuana use and socio-demographic, psychosocial, medical and substance-use variables. The relationship between marijuana use and treatment outcome was also explored in a subset of this sample who received treatment that included buprenorphine detoxification and behavior therapy (N = 79). Sixty-six per cent of participants were current marijuana users and almost all (94%) continued to use during treatment. Users were less likely to be married than non-users, and more likely to report financial difficulties, be involved in drug dealing and engage in sharing of needles (p < 0.05). A unique effect of marijuana use on drug dealing and sharing needles was retained after statistically controlling for the influence of heroin and alcohol use and other socio-demographic variables. No significant adverse relations were observed between marijuana use and treatment outcome. Pending a more comprehensive understanding of the function and consequences of marijuana use on psychosocial functioning, it appears that progress in treatment for opioid dependence can be made without mandating that patients abstain from marijuana use.


Dexamethasone treatment of infants at risk for chronic lung disease: surfactant components and inflammatory parameters in airway specimens.
The mechanisms explaining the beneficial effects of glucocorticoid in ventilator-dependent preterm infants are not known. In the present randomized trial, we evaluated the hypothesis that dexamethasone (DEX) treatment of small, preterm infants at risk for chronic lung disease favorably affects the surfactant system. Twenty-three ventilator-dependent infants, with a mean +/- SD gestational age of 26 +/- 2 wk and a mean birth weight of 836 +/- 173 g, received 1 wk of treatment with either DEX (dose 0.5 mg/kg/d) or placebo beginning at 2 wk of age. The airway specimens were analyzed for surfactant components, surface activity, surfactant inhibitors, and inflammatory mediators. The concentrations of these parameters in epithelial lining fluid were calculated using the urea method. DEX treatment decreased the concentration of nonsedimentable protein in epithelial lining fluid within 3 d (p < 0.05). The nonsedimentable fraction of airway specimens decreased the surface activity of surfactant as a function of protein concentration. At a constant protein concentration, the protein from placebo-treated infants inhibited the surface activity of human surfactant in vitro more than protein from DEX-treated infants (p < 0.05). DEX transiently increased the concentration of surfactant protein-A in epithelial lining fluid but had no effect on surface activity of the sedimentable surfactant complex or on concentrations of phosphatidylcholine, IL-1 beta, lactoferrin, or myeloperoxidase. We conclude that the acute beneficial effect of DEX treatment in preterm ventilator-dependent infants may in part be mediated through a decrease in the concentration of non-sedimentable protein and a decrease in the capacity of this protein to inhibit surface activity.


Three-dimensional microscale hanging drop arrays with geometric control for drug screening and live tissue imaging.
Existing three-dimensional (3D) culture techniques are limited by trade-offs between throughput, capacity for high-resolution imaging in living state, and geometric control. Here, we introduce a modular microscale hanging drop culture where simple design elements allow high replicates for drug screening, direct on-chip real-time or high-resolution confocal microscopy, and geometric control in 3D. Thousands of spheroids can be formed on our microchip in a single step and without any selective pressure from specific matrices. Microchip cultures from human LN229 glioblastoma and patient-derived mouse xenograft cells retained genomic alterations of originating tumors based on mate pair sequencing. We measured response to drugs over time with real-time microscopy on-chip. Last, by engineering droplets to form predetermined geometric shapes, we were able to manipulate the geometry of cultured cell masses. These outcomes can enable broad applications in advancing personalized medicine for cancer and drug discovery, tissue engineering, and stem cell research.


Characterization and preliminary in vivo evaluation of a novel modified hydroxyapatite produced by extrusion and spheronization techniques.
A glass-reinforced hydroxyapatite (HA) composite, recently registered as Bonelike®, was developed for bone grafting. This biomaterial is composed of a modified HA matrix with α- and β-tricalcium phosphate secondary phases and ionic species that mimic the chemical composition of human bone. Several in vitro and in vivo studies have confirmed the benefits of these properties. However, these studies were all executed with Bonelike® polygonal granules obtained by crushing. In this study, Bonelike® pellets were produced through a patented process, which required the use of techniques such as extrusion and spheronization. The final product presented a homogeneous size, a 55.1% global porosity and a spherical shape. This spherical shape permitted a better adaptation to the implantation site and improved injectability. Additionally, it also may contribute to formation of macropores as pellets packaging leaves open spaces. After implantation of Bonelike® polygonal granules and Bonelike® pellets in monocortical defects in sheep for 8 and 12 weeks, light microscopy and scanning electron microscopy showed extensive osteointegration simultaneously with bone regeneration for both presentations. Histomorphometric analysis did not reveal statistically significant differences between defects treated with Bonelike® polygonal granules and Bonelike® pellets, which suggests similar in vivo performances.


Fibroepithelial polyps of the vagina: are they old granulation tissue polyps?
To study the nature of fibroepithelial polyps of the vagina. Sixty five fibroepithelial polyps of the vagina and 64 granulation tissue polyps diagnosed over 15 years were reviewed histologically. Cytologically benign multinucleated stromal cells were present in large numbers in 19 of the fibroepithelial polyps of the vagina (FEPV). Only one polyp contained atypical stromal cells, a high mitotic count, and abnormal mitoses and was indistinguishable from a malignant tumour. Immunostaining showed the presence of vimentin and desmin positive mono- and multinucleated stromal cells in FEPV and occasional oestrogen receptor positive nuclei. Desmin positive cells could not be shown in granulation tissue polyps. FEPV are common lesions with benign mono- and multinucleated fibroblastic stromal cells in which myoid differentiation is often present. FEPV may develop as a result of a granulation tissue reaction after some local injury of the vaginal mucosa. Hormonal factors may modulate the growth of FEPVs. Delayed differentiation of myofibroblastic cells may explain why granulation tissue sometimes does not contract properly but turns into polyps.


Milk intolerance in children with persistent sleeplessness: a prospective double-blind crossover evaluation.
From July 1986 to July 1988, 146 children less than 5 years of age were referred by their physicians to our university sleep clinic for continual waking and crying during sleep hours. For 85 children (58.2%), the sleeplessness was attributed to inappropriate sleep habits. For 17 children (11.6%), no explanation was found for the sleep difficulties in spite of an extensive workup. Their median age at referral was 13.5 months (range 2.5 to 29 months). Their persistent sleeplessness was tentatively attributed to an undiagnosed intolerance to cow's milk. Cow's milk was excluded from their diet. In 15 children sleep normalized after 5 weeks (range 4 to 6 weeks). As seen from the parents' logs, the median time needed by the children to fall asleep decreased from 15 minutes (range 15 to 60 minutes) to 10 minutes (range 10 to 15 minutes, P = .001). The number of complete arousals decreased from 5 (range 1 to 12) to less than 1 per night (range 0 to 2) (P = .001). Total sleep time per 24 hours increased from 5.5 hours (range 3 to 8.5 hours) to 13.0 hours (range 10 to 14.5 hours, P = .001). Sleep normalized in one child who continued to receive no cow's milk only after the hydrolyzed hypoallergenic diet was discontinued. In every child, a double-blind crossover challenge was conducted involving a control diet containing no cow's milk and a diet containing cow's milk. The challenge induced the reappearance of insomnia and agitated behavior in all except one child. The child's initial sleep difficulties were retrospectively attributed to inappropriate sleep habits.(ABSTRACT TRUNCATED AT 250 WORDS)


Optimum green energy solution to address the remote islands' water-energy nexus: the case study of Nisyros island.
A great number of islands are dispersed across the Aegean Archipelagos, most of which have restricted water resources, affecting in this way the economic growth of local societies. To confront this issue, the solution addressed by the relevant stakeholders is the particularly costly and of questionable quality process of potable water transportation from the mainland using tanker ships. An alternative strategy consists of the deployment of seawater desalination configurations, leading however to a quite notable increase in the pertinent load demand. Nisyros island is a remote volcanic island, located in the center of the Greek island complex of Dodecanese, in the southeast (SE) Aegean Archipelagos, which is an area characterized by plentiful Renewable Energy Sources (RES). In the present work, a systematic effort to evaluate the per economic sector energy needs of the island and its current water resources status and infrastructure has been conducted. Moreover, the solar energy potential prevalent in the island has been identified. To this end, a PV-based power configuration has been introduced, under the prism of covering in a sustainable way the island's desalination units' energy needs and decrease the environmental burden. The inherent first installation cost estimation reveals the economic benefits that can be attained in such a case. The feasibility of the proposed green energy solution unveils the prospects of comparable applications in relevant remote insular locations.


Quantitative risk assessment of FMD virus transmission via water.
Foot-and-mouth disease (FMD) is a viral disease of domesticated and wild cloven-hoofed animals. FMD virus is known to spread by direct contact between infected and susceptible animals, by animal products such as meat and milk, by the airborne route, and mechanical transfer on people, wild animals, birds, and by vehicles. During the outbreak of 2001 in the Netherlands, milk from dairy cattle was illegally discharged into the sewerage as a consequence of transport prohibition. This may lead to contaminated discharges of biologically treated and raw sewage in surface water that is given to cattle to drink. The objective of the present study was to assess the probability of infecting dairy cows that were drinking FMD virus contaminated surface water due to illegal discharges of contaminated milk. So, the following data were collected from literature: FMD virus inactivation in aqueous environments, FMD virus concentrations in milk, dilution in sewage water, virus removal by sewage treatment, dilution in surface water, water consumption of cows, size of a herd in a meadow, and dose-response data for ingested FMD virus by cattle. In the case of 1.6 x 10(2) FMD virus per milliliter in milk and discharge of treated sewage in surface water, the probability of infecting a herd of cows was estimated to be 3.3 x 10(-7) to 8.5 x 10(-5), dependent on dilution in the receiving surface water. In the case of discharge of raw sewage, all probabilities of infection were 100 times higher. In the case of little dilution in small rivers, the high level of 8.5 x 10(-3) is reached. For 10(4) times higher FMD virus concentrations in milk, the probabilities of infecting a herd of cows are high in the case of discharge of treated sewage (3.3 x 10(-3) to 5.7 x 10(-1)) and very high in the case of discharge of raw sewage (0.28-1.0). It can be concluded that illegal and uncontrolled discharges of contaminated milk into the sewerage system may lead to high risks to other cattle farms at 6-50 km distance of the location of discharge within one day. This clearly underlines current measures that prohibit such discharges, and also asks for strict control. This risk assessment clearly demonstrated the potential significance of FMD virus transmission via water, and the results will be useful on an international scale, and could also serve as a basis for other FMD risk-assessment models.


Ketogenic diets and Ketone suplementation: A strategy for therapeutic intervention.
Ketogenic diets and orally administered exogenous ketone supplements are strategies to increase serum ketone bodies serving as an alternative energy fuel for high energy demanding tissues, such as the brain, muscles, and the heart. The ketogenic diet is a low-carbohydrate and fat-rich diet, whereas ketone supplements are usually supplied as esters or salts. Nutritional ketosis, defined as serum ketone concentrations of ≥ 0.5 mmol/L, has a fasting-like effect and results in all sorts of metabolic shifts and thereby enhancing the health status. In this review, we thus discuss the different interventions to reach nutritional ketosis, and summarize the effects on heart diseases, epilepsy, mitochondrial diseases, and neurodegenerative disorders. Interest in the proposed therapeutic benefits of nutritional ketosis has been growing the past recent years. The implication of this nutritional intervention is becoming more evident and has shown interesting potential. Mechanistic insights explaining the overall health effects of the ketogenic state, will lead to precision nutrition for the latter diseases.


Effect of water of hydration on the measurement of the protein efficiency ratio of casein and soybean protein with rats.
The hydration of soybean protein or casein prior to mixing of the diet improves the apparent protein efficiency ratio (PER). The PER of soybean protein was improved more than that of casein, so that an increase in adjusted PER of soybean protein was observed also. The improvement did not appear to be associated with digestibility. It is theorized that some diets with dry protein isolates may be less acceptable to the rat due to the dusty nature of the isolate. Consequently, diets with such isolates may have a lower PER. The effect can be overcome by hydrating the protein isolates prior to mixing the diet.


Cyclophilin A levels dictate infection efficiency of human immunodeficiency virus type 1 capsid escape mutants A92E and G94D.
Cyclophilin A (CypA) is an important human immunodeficiency virus type 1 (HIV-1) cofactor in human cells. HIV-1 A92E and G94D capsid escape mutants arise during CypA inhibition and in certain cell lines are dependent on CypA inhibition. Here we show that dependence on CypA inhibition is due to high CypA levels. Restricted HIV-1 is stable, and remarkably, restriction is augmented by arresting cell division. Nuclear entry is not inhibited. We propose that high CypA levels and capsid mutations combine to disturb uncoating, leading to poor infectivity, particularly in arrested cells. Our data suggest a role for CypA in uncoating the core of HIV-1 to facilitate integration.


Defibrotide for prophylaxis of hepatic veno-occlusive disease in paediatric haemopoietic stem-cell transplantation: an open-label, phase 3, randomised controlled trial.
Hepatic veno-occlusive disease is a leading cause of morbidity and mortality after haemopoietic stem-cell transplantation (HSCT). We aimed to assess whether defibrotide can reduce the incidence of veno-occlusive disease in this setting. In our phase 3 open-label, randomised controlled trial, we enrolled patients at 28 European university hospitals or academic medical centres. Eligible patients were younger than 18 years, had undergone myeloablative conditioning before allogeneic or autologous HSCT, and had one or more risk factor for veno-occlusive disease based on modified Seattle criteria. We centrally assigned eligible participants on the basis of a computer-generated randomisation sequence (1:1), stratified by centre and presence of osteopetrosis, to receive intravenous defibrotide prophylaxis (treatment group) or not (control group). The primary endpoint was incidence of veno-occlusive disease by 30 days after HSCT, adjudicated by a masked, independent review committee, in eligible patients who consented to randomisation (intention-to-treat population), and was assessed with a competing risk approach. Patients in either group who developed veno-occlusive disease received defibrotide for treatment. We assessed adverse events to 180 days after HSCT in all patients who received allocated prophylaxis. This trial is registered with ClinicalTrials.gov, number NCT00272948. Between Jan 25, 2006, and Jan 29, 2009, we enrolled 356 eligible patients to the intention-to-treat population. 22 (12%) of 180 patients randomly allocated to the defibrotide group had veno-occlusive disease by 30 days after HSCT compared with 35 (20%) of 176 controls (risk difference -7·7%, 95% CI -15·3 to -0·1; Z test for competing risk analysis p=0·0488; log-rank test p=0·0507). 154 (87%) of 177 patients in the defibrotide group had adverse events by day 180 compared with 155 (88%) of 176 controls. Defibrotide prophylaxis seems to reduce incidence of veno-occlusive disease and is well tolerated. Thus, such prophylaxis could present a useful clinical option for this serious complication of HSCT. Gentium SpA, European Group for Blood and Marrow Transplantation.


What's the physiological role of domain II-less Aux/IAA proteins?
Arabidopsis has Aux/IAA proteins that lack domain II which is a binding site for the TIR1 auxin receptor. These proteins have been shown to be more stable than the canonical Aux/IAA proteins. We investigated the phenotypes of overexpression lines of domain II-less Aux/IAA proteins, IAA20 and IAA30, by the use of 35S promoter. The transgenic lines showed many aberrant phenotypes in auxin physiology. The most conspicuous phenotype was collapse of the root apical meristem as occurred in plt1 plt2 double mutants. Because IAA20 and IAA30 were early auxin-inducible and were expressed in the root apical meristem, they may have a physiological role in maintaining the stem cell niche of root, by keeping the activity of MP/ARF5 and NPH4/ARF7 at an acceptable level. On the other hand, domain-II less Aux/IAA proteins are not present in balck cottonwood tree or grapevine, suggesting wide diversification of Aux/IAA proteins in higher plants.


Adverse Effects of Common Sports and Recreational Activities on Male Reproduction.
Male factor infertility plays a significant role in infertility. Many factors have been associated with male infertility; however, the link between many sports and recreational factors and male reproduction remains poorly characterized. To evaluate the current literature regarding the impact of many common sports and recreational factors on male reproduction. A comprehensive PubMed and Embase search for relevant articles published between 1970 and 2017 was performed by combining the following search terms: male, sports (including individual sports), traumatic brain injury, sauna, hot tub, fertility, erectile dysfunction, varicocele, environment, cell phone, and laptop computer. Hypogonadism and erectile dysfunction can be associated with sports with high rates of head injuries, such as American football. Although early reports linked other sports, such as bicycling, to erectile dysfunction, subsequent studies isolated these associations to sports cycling rather than recreational cycling. Certain sports (football, basketball, handball, and volleyball) were linked to increasing prevalence and severity of varicocele, offering a potential link to male infertility. In addition, recreational activities such as sauna, hot tubs, Jacuzzis, heated car seats, and laptop use were associated with high testicular temperature, which can impair spermatogenesis. Radio frequency electromagnetic waves from cell phones and laptops have also been shown to have deleterious effects on sperm viability and motility. Many common sports and daily activities represent potential sources of male infertility. Clinicians should be aware of these associations in explaining idiopathic infertility in males. Male infertility is an often overlooked component of a couple's inability to conceive. We outline many common and often overlooked sports and recreational exposures that have been associated with male infertility.


Real-time imaging of the axonal transport of granules containing a tissue plasminogen activator/green fluorescent protein hybrid.
A hybrid protein, tPA/GFP, consisting of rat tissue plasminogen activator (tPA) and green fluorescent protein (GFP) was expressed in PC12 cells and used to study the distribution, secretory behavior, and dynamics of secretory granules containing tPA in living cells with a neuronal phenotype. High-resolution images demonstrate that tPA/GFP has a growth cone-biased distribution in differentiated cells and that tPA/GFP is transported in granules of the regulated secretory pathway that colocalize with granules containing secretogranin II. Time-lapse images of secretion reveal that secretagogues induce substantial loss of cellular tPA/GFP fluorescence, most importantly from growth cones. Time-lapse images of the axonal transport of granules containing tPA/GFP reveal a surprising complexity to granule dynamics. Some granules undergo canonical fast axonal transport; others move somewhat more slowly, especially in highly fluorescent neurites. Most strikingly, granules traffic bidirectionally along neurites to an extent that depends on granule accumulation, and individual granules can reverse their direction of motion. The retrograde component of this bidirectional transport may help to maintain cellular homeostasis by transporting excess tPA/GFP back toward the cell body. The results presented here provide a novel view of the axonal transport of secretory granules. In addition, the results suggest that tPA is targeted for regulated secretion from growth cones of differentiated cells, strategically positioning tPA to degrade extracellular barriers or to activate other barrier-degrading proteases during axonal elongation.


Prognostic validation and clinical implications of the EANO ESMO classification of leptomeningeal metastasis from solid tumors.
The EANO ESMO guidelines have proposed a classification of leptomeningeal metastases (LM) from solid cancers based on clinical, magnetic resonance imaging (MRI), and cerebrospinal fluid (CSF) cytology presentation. MRI patterns are classified as linear, nodular, both, or neither. Type I LM is defined by positive CSF cytology (confirmed LM) whereas type II LM is defined by typical clinical and MRI signs (probable or possible LM). Here we explored the clinical utility of these LM subtypes. We retrospectively assembled data from 254 patients with newly diagnosed LM from solid tumors. Survival curves were derived using the Kaplan-Meier method and compared by Log-rank test. Median age at LM diagnosis was 56 years. Typical clinical LM features were noted in 225 patients (89%); 13 patients (5%) were clinically asymptomatic. Tumor cells in the CSF were observed in 186 patients (73%) whereas the CSF was equivocal in 24 patients (9.5%) and negative in 44 patients (17.5%). Patients with confirmed LM had inferior outcome compared with patients with probable or possible LM (P = 0.006). Type I patients had inferior outcome than type II patients (P = 0.002). Nodular disease on MRI was a negative prognostic factor in type II LM (P = 0.014), but not in type I LM. Administration of either intrathecal pharmacotherapy (P = 0.020) or systemic pharmacotherapy (P = 0.0004) was associated with improved outcome in type I LM, but not in type II LM. The EANO ESMO LM subtypes are highly prognostic and should be considered for stratification and overall design of clinical trials.


Risk factors for positive resection margins of breast cancer tumorectomy specimen following breast-conserving surgery.
Background The aim of the study was to identify risk factors for positive surgical margins in breast-conserving surgery for breast cancer and to evaluate the influence of surgical experience in obtaining complete resection. Methods All lumpectomies for invasive breast carcinoma and ductal carcinoma in situ (DCIS) between April 2008 and March 2010 were selected from the database of a single institution. Re-excision rates for positive margins as well as patient and histopathologic tumor characteristics were analyzed. Surgical experience was staged by pairs made of Resident plus Specialist or Consultant. Two periods were defined. During period A, the majority of operations were performed by Residents under supervision of Specialist or Consultant. During period B, only palpable tumors were operated by Residents. Results The global re-excision rate was 27% (50 of 183 patients). The presence of DCIS increased the risk for positive margins: 60% (nine of 15 patients) in the case of sole DCIS compared to 26% (41 of 160 patients) for invasive cancer (p = 0.005) and 35% (42 of 120 patients) in the case of peritumoral DCIS compared to 11% (seven of 62 patients) in the case of sole invasive cancer (p = 0.001). Re-excision rate decreased from 36% (23 of 64 patients) during period A to 23% (27 of 119 patients) during period B (p = 0.055). There was no significant difference between the surgical pairs. Conclusion In our study, DCIS was the only risk factor for positive surgical margins. Breast-conserving surgery for non-palpable tumors should be performed by Specialists, however, palpable tumors can be safely operated by Residents under supervision.


Nutritional composition of commonly consumed composite dishes in Trinidad.
To calculate the nutritional composition of commonly consumed composite dishes in Trinidad in order to analyze dietary intakes obtained using a quantitative food frequency questionnaire developed specifically for the Trinidadian population. Multiple weighed versions of each dish were collected from 53 participants throughout Trinidad. Nutritional composition was calculated using NutriBase Clinical Nutrition Manager. A total of 359 recipes were collected for 89 composite dishes: 19 vegetable, 15 starches, 21 meat/meat alternatives, eight seafood, 10 sweets, five beverages, 11 snacks/miscellaneous items. For each dish, the average nutritional composition (energy and 32 macronutrients/micronutrients) was calculated per 100 g. The calculated nutritional composition data of 89 commonly consumed dishes in Trinidad can now be used to assess dietary intakes and determine dietary risk factors for chronic disease.


Supermassive Black Holes, Ultralight Dark Matter, and Gravitational Waves from a First Order Phase Transition.
The formation of ultrarare supermassive black holes (SMBHs), with masses of O(10^{9} M_{⊙}), in the first billion years of the Universe remains an open question in astrophysics. At the same time, ultralight dark matter (DM) with mass in the vicinity of O(10^{-20} eV) has been motivated by small scale DM distributions. Though this type of DM is constrained by various astrophysical considerations, certain observations could be pointing to modest evidence for it. We present a model with a confining first order phase transition at ∼10 keV temperatures, facilitating production of O(10^{9} M_{⊙}) primordial SMBHs. Such a phase transition can also naturally lead to the implied mass for a motivated ultralight axion DM candidate, suggesting that SMBHs and ultralight DM may be two sides of the same cosmic coin. We consider constraints and avenues to discovery from superradiance and a modification to N_{eff}. On general grounds, we also expect primordial gravitational waves-from the assumed first order phase transition-characterized by frequencies of O(10^{-12}-10^{-9} Hz). This frequency regime is largely uncharted, but could be accessible to pulsar timing arrays if the primordial gravitational waves are at the higher end of this frequency range, as could be the case in our assumed confining phase transition.


Robot-assisted pyeloplasty: outcomes for primary and secondary repairs, a single institution experience.
Robotic Pyeloplasty (RAP) is a technique for management of ureteropelvic junction obstruction (UPJO). To report outcomes of RAP for primary and secondary (after failed primary treatment) UPJO. Single institution data of adult RAP performed from 2007 to 2009 was collected retrospectively following approval by our IRB. Database analysis included patient age, race, pre and post-operative imaging studies and perioperative variables including operative time, blood loss, pain and complications. Fifty-five adult patients underwent RAP (26 left/29 right) for UPJO including 9 secondary procedures from 2007 to 2009. Average follow-up was 16 months (1-36). Mean age was 41 years (18-71) with an average BMI of 27 (17-42); 32 were female. Most patients were diagnosed with preoperative diuretic renal scintigraphy and the obstructed side demonstrated mean function of 41% and t1/2 of 70 minutes. Mean operative time was 194 minutes with average blood loss less than 100 mL. Mean hospital stay was 1.7 days with an average narcotic equivalent dose of 15 mg. RAP for secondary UPJO took longer with more blood loss and had a lower success rate. Failure was defined as the need of another procedure due to persistent pain and/or obstruction after diuretic renal imaging. One patient (2%) with primary UPJO failed and 2 patients (22%) with secondary UPJO failed. One major complication occurred. RAP is a good option for the treatment of patients with UPJO. Reported series have established that endopyelotomy has inferior success rate for the treatment of primary UPJO which compromises the success of subsequent treatment as demonstrated in our higher failure rate with secondary UPJO repair.


Case series of 406 vernal keratoconjunctivitis patients: a demographic and epidemiological study.
To evaluate the specific allergic sensitization and epidemiological characteristics of vernal keratoconjunctivitis (VKC). This retrospective non-comparative case series included 406 VKC patients. Data included patient and family histories, and results of allergic tests. Annual incidence and prevalence rates were calculated for a cohort of 128 VKC patients from the greater Padua area. The great majority of VKC patients were male (76%), with a male : female ratio of 3.3 : 1. A skin prick test, specific serum IgE or conjunctival challenge was positive in 43%, 56% and 58% of patients, respectively. In the cohort of patients from the Padua area, the prevalence of the disease was 7.8/100,000, with a higher rate in young males (57/100,000) compared with young females (22/100,000), and lower rates in people over 16 years of age (3.8/100,000 in males, 1/100,000 in females). The incidence of VKC was 1/100,000, with a higher rate in males under 16 years of age (10/100,000) compared with females (4.2/100,000). In people over 16 years of age, the incidence of the disease was 0.06/100,000, with no difference between males and females. An IgE-mediated sensitization was found in only half of the VKC patients. Vernal keratoconjunctivitis is not a rare event in the paediatric population but is an extremely rare new disease in adults.


Let's get back to work: survival analysis on the return-to-work after depression.
Absence from work due to mental disorders is substantial. Additionally, long-term absence from work is associated with a reduced probability of return-to-work (RTW). Major depressive disorder (MDD) is a prevalent condition in Dutch occupational health care settings. An early estimate of the prognosis regarding RTW in patients with MDD could serve both as a point of departure for the identification of high-risk cases and as an instrument to monitor the course of the disorder and of RTW. In the current study, we aimed to assess the added value of health-related quality of life (HRQoL) and severity of depression to predict the time to RTW. Data were derived from a prospective longitudinal study aimed to evaluate the cost effectiveness of a collaborative care treatment in sick-listed workers with MDD. We included demographic, job-related, and health-related variables. Severity of depression was measured using the Patient Health Questionnaire Depression Scale-9 (PHQ-9). HRQoL was measured using two generic preference-based instruments, the EuroQol 5-Dimension (EQ-5D™) and the Medical Outcomes Study Short Form Health Survey (SF-36). A survival model was constructed by applying different survival functions to assess the best fit for the data. Additionally, survival analyses were performed to assess the added value of the two HRQoL measures and depression severity for predicting RTW. Females and older patients had a longer time to RTW. The same was true for patients with a full-time job and patients with more decision latitude. Patients in a management position and patients with more social support had a shorter time to RTW. Severity of depression was not predictive for the time to RTW. HRQoL measured by the SF-36 was a significant predictor for the time to RTW. HRQoL emerged as a significant predictor for the time to RTW. However, severity of depression was not predictive for the time to RTW. These results suggest the importance of assessing HRQoL in addition to severity of disease to assess functionality.


TNF-alpha promotes lymphangiogenesis and lymphatic metastasis of gallbladder cancer through the ERK1/2/AP-1/VEGF-D pathway.
Tumor necrosis factor-alpha (TNF-α), a key player in cancer-related inflammation, was recently demonstrated to be involved in the lymphatic metastasis of gallbladder cancer (GBC). Vascular endothelial growth factor D (VEGF-D) is a key lymphangiogenic factor that is associated with lymphangiogenesis and lymph node metastasis in GBC. However, whether VEGF-D is involved in TNF-α-induced lymphatic metastasis of GBC remains undetermined. The expression of VEGF-D in patient specimens was detected by immunohistochemistry and the relationship between VEGF-D in the tissue and TNF-α in the bile of the matching patients was analyzed. The VEGF-D mRNA and protein levels after treatment with exogenous TNF-α in NOZ, GBC-SD and SGC-996 cell lines were measured by real-time PCR and ELISA. The promoter activity and transcriptional regulation of VEGF-D were analyzed with the relative luciferase reporter assay, mutant constructs, electrophoretic mobility shift assay (EMSA), chromatin immunoprecipitation (ChIP) assay, RNA interference and Western blotting. Inhibitors of JNK, p38 MAPK and ERK1/2 were used to explore the upstream signaling effector of AP-1. We used lentiviral vector expressing a VEGF-D shRNA construct to knockdown VEGF-D gene in NOZ and GBC-SD cells. The role of the TNF-α-VEGF-D axis in the tube formation of human dermal lymphatic endothelial cells (HDLECs) was determined using a three-dimensional coculture system. The role of the TNF-α - VEGF-D axis in lymphangiogenesis and lymph node metastasis was studied via animal experiment. TNF-α levels in the bile of GBC patients were positively correlated with VEGF-D expression in the clinical specimens. TNF-α can upregulate the protein expression and promoter activity of VEGF-D through the ERK1/2 - AP-1 pathway. Moreover, TNF-α can promote tube formation of HDLECs, lymphangiogenesis and lymph node metastasis of GBC by upregulation of VEGF-D in vitro and in vivo. Taken together, our data suggest that TNF-α can promote lymphangiogenesis and lymphatic metastasis of GBC through the ERK1/2/AP-1/VEGF-D pathway.


Maternal DRD2, SLC6A3, and OXTR genotypes as potential moderators of the relation between maternal history of care and maternal cortisol secretion in the context of mother-infant separation.
A mother's cortisol secretion is importantly associated with her own mental health and her infant's cortisol secretion. This study investigated the influences of maternal history of care and maternal DRD2, SLC6A3, and OXTR genotypes on maternal cortisol in the context of infant stress. A community sample of 296 mother-infant dyads completed a maternal separation at infant age 17 months. Maternal salivary cortisol, buccal cells, and self-reported history of care were collected. Multilevel models revealed that history of care had a greater influence on maternal baseline cortisol (but not cortisol trajectory) for mothers with more plasticity alleles of SLC6A3 (10R) and OXTR (G), relative to mothers with fewer or no plasticity alleles. Findings indicate that a mother's history of care is related to her cortisol secretion in anticipation of infant stress, but that this relation depends on her genetic characteristics. Findings are discussed in relation to the maternal protective system and anticipatory cortisol secretion.


Transtympanic pilocarpine in tinnitus.
In 48 patients who had neurosensory hypoacusia and whose main complaint was tinnitus, a 1% pilocarpine solution or a 2% carbachol Isopto solution was placed in the tympanic cavity by means of a No. 26 pencil-tipped lumbar puncture needle through the front quadrant of the eardrum. Patients were chosen without regard for age, gender, or topographical damage of the acoustic pathway. Evaluation of the drug's effect was performed audiometrically by masking with the minimum intensity of the pure sound or narrow band that most closely resembled the patients' own noises. The results of this medical therapy were positive and ranged from complete annulment to attenuation of the tinnitus, which was confirmed by audiometric masking 30 minutes after the intratympanic injection. These positive results reached 50% and would have been higher if the several cases submitted by accident insurance companies and cases of presbyacusia were discarded. The unsatisfactory element of the study was the short-term effect of the therapy, which usually lasted no more than 12-72 hours. Tinnitus reappeared in all patients at its original intensity. The best results involved the use of carbachol as compared with pilocarpine. The decision to replace pilocarpine with carbachol was based on the idea that the inhibitory cholinergic efferent pathways are damaged before the afferent pathways. The use of pilocarpine depends on efficient cholinergic functioning, as its activity is as an indirect agonist (i.e., to annul the cholinesterase enzyme).


Intimate partner violence before and during the COVID-19 lockdown: findings from a cross-sectional study in Singapore.
The coronavirus diseases 2019 (COVID-19) pandemic resulted in lockdowns worldwide, with reports suggesting a concomitant increase in the incidence of intimate partner violence (IPV). This study was part of the International Sexual and Reproductive Health (I-SHARE) Consortium, examining IPV and its correlates before and during lockdown in April 2020. This cross-sectional observational study, conducted online during August-September 2020, recruited 259 participants from Singapore who reported having a steady partner. Alongside socio-demographic data before and during COVID-19 lockdown, the respondents self-reported their encounters with partner violence. Partner violence was measured using an adapted six-item version of the WHO IPV scale. Data revealed an incidence of 17.2%, 25.0%, 16.7%, 17.6%, 17.5% and 18.5% of restriction of contact with others, verbal abuse, restriction of access to finances, physical violence, pressured sex and forced sex, respectively, before COVID-19 lockdown. During lockdown, incidences of these forms of violence were 17.4%, 19.8%, 14.7%, 13.5%, 14.7% and 15.2%, respectively. Multivariable analyses showed that being younger, being non-heterosexual, and having more children and adolescents at home were significantly associated with partner violence both before and during lockdown. Analyses also revealed that being of Chinese ethnicity and having a monthly income above SGD3000 were not significantly correlated to partner violence before lockdown but emerged as significant during lockdown. Some sociodemographic factors were associated with violence regardless of lockdown, while other factors were exacerbated by lockdown. Interventions should consider these key correlates of partner-based violence, ensuring adequate and appropriate support for vulnerable populations both within and outside of lockdown contexts.


IL-32 is expressed by human primary keratinocytes and modulates keratinocyte apoptosis in atopic dermatitis.
Keratinocyte (KC) apoptosis is an important mechanism of eczema and spongiosis in patients with atopic dermatitis (AD) and is mediated by IFN-gamma, which is secreted by T(H)1 cells. IL-32 is a proinflammatory cytokine that is involved in the inflammatory processes of rheumatoid arthritis, chronic obstructive pulmonary disease, and Crohn disease. Recently, it was shown that upregulation of IL-32 induces apoptosis. The aim of the study was to investigate the expression and function of IL-32 in patients with AD. The expression of IL-32 in KCs was analyzed by means of RT-PCR, ELISA, and flow cytometry. Transfections of small interfering RNA were performed in primary KCs, and apoptosis was analyzed by means of terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling, annexin-V, and 7-amino actinomycin D stainings. Immunofluorescence stainings were used to detect IL-32 in skin biopsy specimens, and serum levels of IL-32 were analyzed by means of ELISA. We report that IL-32 is expressed in human primary KCs on stimulation with IFN-gamma, TNF-alpha, and T(H)1 cells in contrast to T(H)2, regulatory T (Treg), or T(H)17 cells, which showed no effect. Transfection of primary KCs and artificial skin equivalents with small interfering RNA to IL-32, which resulted in a clear decrease in IL-32 expression, significantly reduced KC apoptosis. Immunofluorescence staining demonstrated that IL-32 was expressed in AD lesional skin, whereas it was present in neither skin biopsy specimens from healthy donors nor in lesional skin from patients with psoriasis. Serum levels of IL-32 from patients with AD correlated with disease severity, but increased serum levels of IL-32 were also detected in asthmatic patients. The present study demonstrates KCs as a source of IL-32, which modulates KC apoptosis and contributes to the pathophysiology of AD.


Involvement of RSK1 activation in malformin-enhanced cellular fibrinolytic activity.
Pharmacological interventions to enhance fibrinolysis are effective for treating thrombotic disorders. Utilizing the in vitro U937 cell line-based fibrin degradation assay, we had previously found a cyclic pentapeptide malformin A1 (MA1) as a novel activating compound for cellular fibrinolytic activity. The mechanism by which MA1 enhances cellular fibrinolytic activity remains unknown. In the present study, we show that RSK1 is a crucial mediator of MA1-induced cellular fibrinolysis. Treatment with rhodamine-conjugated MA1 showed that MA1 localizes mainly in the cytoplasm of U937 cells. Screening with an antibody macroarray revealed that MA1 induces the phosphorylation of RSK1 at Ser380 in U937 cells. SL0101, an inhibitor of RSK, inhibited MA1-induced fibrinolytic activity, and CRISPR/Cas9-mediated knockout of RSK1 but not RSK2 suppressed MA1-enhanced fibrinolysis in U937 cells. Synthetic active MA1 derivatives also induced the phosphorylation of RSK1. Furthermore, MA1 treatment stimulated phosphorylation of ERK1/2 and MEK1/2. PD98059, an inhibitor of MEK1/2, inhibited MA1-induced phosphorylation of RSK1 and ERK1/2, indicating that MA1 induces the activation of the MEK-ERK-RSK pathway. Moreover, MA1 upregulated the expression of urokinase-type plasminogen activator (uPA) and increased uPA secretion. These inductions were abrogated in RSK1 knockout cells. These results indicate that RSK1 is a key regulator of MA1-induced extracellular fibrinolytic activity.


Association of nutrition knowledge, practice, supplement use, and nutrient intake with strength performance among Taekwondo players in Nepal.
Optimum dietary intake and adequate nutritional knowledge have been recognized as the key factors that play a critical role in improving the athlete's health and nutrition status. This study aimed to measure the association of nutritional knowledge, practice, supplement use, and nutrient intake with strength performance among Nepalese Taekwondo players. Between August 2019 and January 2020, a cross-sectional study was conducted among 293 Taekwondo players in Kathmandu Metropolitan City (mean age, 18 years; 63.1% male, 36.9% female). Face-to-face interviews were conducted using semi-structured questionnaires. Anthropometric measures, nutritional intake, nutrition knowledge, and practice were all recorded. The handgrip strength was measured using a handgrip dynamometer as a proxy for strength performance. Univariate and bivariate analyses were used to find out the association between predictor and outcome variables. More than half of the participants had poor nutrition knowledge [54.3% (159/293)], and poor nutrition practice [55.3% (162/293)] scores. Daily mean energy, carbohydrate, protein and fat intake were 48.0 kcal.kg-1.d-1, 8.6, 1.6, and 1.5 g.kg-1.d-1, respectively among Taekwondo players. Daily total energy and carbohydrate intake were 48.2 kcal.kg-1.d-1 and 8.7 g.kg-1.d-1, respectively among male players which is higher than female players. However, daily protein and fat intake were higher in female players (1.7 and 1.6 g.kg-1.d-1, respectively). Both calcium (375.3 mg) and iron (9 mg) intake among Taekwondo players were significantly lower than current sports nutrition guidelines. Nutritional knowledge score (r = 0.117), height (r = 0.538), weight (r = 0.651), body mass index (r = 0.347), fat (r = 0.075), and energy (r = 0.127) intake showed significant positive correlation with strength performance of athletes. The strength performance was positively associated with training hours per day (β = 0.41, 95% CI: 0.09-0.91), body mass index (β = 0.35, 95% CI: 0.09-0.61), nutrition knowledge score (β = 0.13, 95% CI: 0.01-0.25), and energy intake (β = 0.13, 95% CI: 0.12-0.14). The nutritional knowledge and practice both were suboptimal among Taekwondo athletes. Height, weight, body mass index, nutritional knowledge, energy, and fat intake showed a positive correlation with strength performance. Future studies can build on the premise of this study to identify the robust relationship between nutritional knowledge, practice, different supplement use, and nutrient intake among other athletes too.


Intraocular Gnathostoma spinigerum. Clinicopathologic study of two cases with review of literature.
Live intraocular nematode is a rare occurrence that is mostly reported in Southeast Asian countries. Common nematodes that are seen live in the eye are microfilaria, Gnathostoma, and Angiostrongylus. Approximately 12 cases of intraocular gnathostomiasis have been reported in the literature. Two cases of intraocular gnathostoma, removed by vitrectomy in the first case and by paracentesis in the second case, are reported. Morphologic study of the parasites in wet preparation was performed under dissecting microscope and fixed in Karnovosky's fixative. Light microscopic and scanning electron microscopic studies were also performed. The first patient had anterior uveitis, multiple iris holes, and dense vitreous haze with fibrous proliferation over the optic disc. On resolution of the vitreous haze, a live worm was seen in the vitreous cavity. The second patient had anterior uveitis with secondary glaucoma, multiple iris holes, mild vitritis, and focal subretinal haemorrhage with subretinal tracts. Four days later a live worm was seen in the anterior chamber and removed. Microscopic study of the parasites from both patients revealed typical head bulb with four circumferential rows of hooklets, and fine cuticular spines were seen on the surface of the body. Iris holes, uveitis, and subretinal haemorrhage with subretinal tract can be characteristic features of intraocular gnathostomiasis. Identification of this parasite can be made by typical features, which can be identified on light and scanning electron microscopic study.


Treatment of advanced stages of Philadelphia chromosome-positive chronic myelogenous leukemia with interferon-alpha and low-dose cytarabine.
To evaluate the efficacy of interferon-alpha (IFN-A) and low-dose cytarabine (ara-C) combination chemotherapy in patients with chronic myelogenous leukemia (CML). Sixty patients with advanced phases of Philadelphia chromosome (Ph)-positive CML received combination therapy with IFN-A 5 x 10(6) U/m2 daily, and low-dose ara-C 15 mg/m2 daily for 2 weeks every 4 weeks until remission, then for 1 week every month as maintenance. Forty patients were in late chronic-phase CML, and 20 were in accelerated-phase CML (16 with clonal evolution only, four with other criteria). Their outcome was compared with 58 patients (39 late chronic-phase CML and 19 accelerated-phase CML) who had been previously treated with IFN-A alone in the same dose schedule. In late chronic-phase CML, patients receiving IFN-A plus ara-C had a better complete hematologic response (CHR) rate compared with those treated with IFN-A alone (55% v 28%; P = .02), a trend for better Ph suppression (15% v 5%; P = .13), and a longer survival (3-year survival rate 75% v 48%; P less than .01). These differences do not seem to be caused by imbalances in prognostic factors between the two treatment groups. In accelerated-phase CML, the addition of ara-C to IFN-A did not improve the response rate of treated patients, and the difference in survival was accounted for by different patient characteristics. Suppression of clonal evolution was observed in five patients (25%). Patients with clonal evolution as the only criterion for disease acceleration had a longer survival than those with other or additional accelerated-phase criteria (3-year survival rate 67% v 22%; P less than .01). The results with the combination of IFN-A plus ara-C in late chronic-phase CML are encouraging, and suggest the need for its evaluation in early chronic-phase CML.


PROJECT STAR (Midwestern Prevention Project): Overview.
The program designed to prevent substance use should be planned in multiple dimensions. One of these programs is Project Star. This study aims to evaluate the studies on the Project Star and identify the strengths and weaknesses of the program. For this purpose, the keywords "Project Star" and "Midwestern Prevention Project" were scanned from databases. The results of these studies were evaluated by giving a summary of the studies included in the study. As a result, the strengths of Project Star are that it is multidimensional, focuses on early development periods, includes the individual's ecological environment, and reduces substance use in later development periods, and not having an internet-based version. This situation has been identified as its weaknesses since its situation in other societies is unknown due to its cost and limited international applications.


Tissue-Specific Transcriptome for Poeciliopsis prolifica Reveals Evidence for Genetic Adaptation Related to the Evolution of a Placental Fish.
The evolution of the placenta is an excellent model to examine the evolutionary processes underlying adaptive complexity due to the recent, independent derivation of placentation in divergent animal lineages. In fishes, the family Poeciliidae offers the opportunity to study placental evolution with respect to variation in degree of post-fertilization maternal provisioning among closely related sister species. In this study, we present a detailed examination of a new reference transcriptome sequence for the live-bearing, matrotrophic fish, Poeciliopsis prolifica, from multiple-tissue RNA-seq data. We describe the genetic components active in liver, brain, late-stage embryo, and the maternal placental/ovarian complex, as well as associated patterns of positive selection in a suite of orthologous genes found in fishes. Results indicate the expression of many signaling transcripts, "non-coding" sequences and repetitive elements in the maternal placental/ovarian complex. Moreover, patterns of positive selection in protein sequence evolution were found associated with live-bearing fishes, generally, and the placental P. prolifica, specifically, that appear independent of the general live-bearer lifestyle. Much of the observed patterns of gene expression and positive selection are congruent with the evolution of placentation in fish functionally converging with mammalian placental evolution and with the patterns of rapid evolution facilitated by the teleost-specific whole genome duplication event.


Single-Cell Mass Cytometry Analysis of the Human Endocrine Pancreas.
The human endocrine pancreas consists of multiple cell types and plays a critical role in glucose homeostasis. Here, we apply mass cytometry technology to measure all major islet hormones, proliferative markers, and readouts of signaling pathways involved in proliferation at single-cell resolution. Using this innovative technology, we simultaneously examined baseline proliferation levels of all endocrine cell types from birth through adulthood, as well as in response to the mitogen harmine. High-dimensional analysis of our marker protein expression revealed three major clusters of beta cells within individuals. Proliferating beta cells are confined to two of the clusters.


Processing of temporal unpredictability in human and animal amygdala.
The amygdala has been studied extensively for its critical role in associative fear conditioning in animals and humans. Noxious stimuli, such as those used for fear conditioning, are most effective in eliciting behavioral responses and amygdala activation when experienced in an unpredictable manner. Here, we show, using a translational approach in mice and humans, that unpredictability per se without interaction with motivational information is sufficient to induce sustained neural activity in the amygdala and to elicit anxiety-like behavior. Exposing mice to mere temporal unpredictability within a time series of neutral sound pulses in an otherwise neutral sensory environment increased expression of the immediate-early gene c-fos and prevented rapid habituation of single neuron activity in the basolateral amygdala. At the behavioral level, unpredictable, but not predictable, auditory stimulation induced avoidance and anxiety-like behavior. In humans, functional magnetic resonance imaging revealed that temporal unpredictably causes sustained neural activity in amygdala and anxiety-like behavior as quantified by enhanced attention toward emotional faces. Our findings show that unpredictability per se is an important feature of the sensory environment influencing habituation of neuronal activity in amygdala and emotional behavior and indicate that regulation of amygdala habituation represents an evolutionary-conserved mechanism for adapting behavior in anticipation of temporally unpredictable events.


Risk factors for adjacent segment disease development after lumbar fusion.
Retrospective cohort study. To identify factors which may be important in the occurrence of symptomatic adjacent segment disease (ASD) after lumbar fusion. Many reports have been published about the risk factors for ASD after lumbar fusion. Despite on the great numbers of risk factors identified for ASD development, study results have been inconsistent and there is controversy regarding which are the most important. This study evaluated 120 patients who underwent 360° fusion lumbar surgery from 2007 to 2012. We separated the population into two groups: the first group included 60 patients with long lumbar fusion (three or more levels) and the second group included 60 patients with short lumbar fusion (less than three levels). In the first group, symptomatic ASD was found in 19 cases during the one year follow-up. There were 14 cases with sagittal imbalance and 5 cases at the incipient stage of disc degeneration according to the preoperative magnetic resonance imaging. At the three year follow-up, symptomatic ASD was diagnosed in 31 cases, of which 17 patients had postoperative sagittal balance disturbance. In the second group, 10 patients had ASD at the one year follow-up. Among these cases, preoperative disc degenerative changes were identified in 8 patients. Sagittal imbalance was found only in 2 cases with symptomatic ASD at the one year follow-up. At the three year follow-up, the number of patients with symptomatic ASD increased to 14. Among them, 13 patients had initial preoperative adjacent disc degenerative changes. Patients with postoperative sagittal imbalance have a statistically significant increased risk of developing symptomatic ASD due to an overloading the adjacent segments and limited compensatory capacities due to the large number of fixed mobile segments. In the case of a short fixation, preoperative degenerative changes are more important factors in the development of ASD.


Degree of Postictal Suppression Depends on Seizure Induction Time in Magnetic Seizure Therapy and Electroconvulsive Therapy.
Anesthesia is required for both magnetic seizure therapy (MST) and electroconvulsive therapy (ECT), although it has anticonvulsant properties. In this case, bispectral index (BIS) monitoring, a specific electroencephalogram-derived monitoring, can be used to find the optimal seizure induction time during anesthesia to elicit adequate seizures. A measurement of seizure adequacy in electroencephalogram is the postictal suppression. The purpose of this study was to investigate the influence of seizure induction time on the degree of postictal suppression by comparing BIS versus no-BIS monitoring in MST and ECT. Twenty patients with treatment-resistant depression were randomly assigned to either MST or ECT. Each patient underwent 3 treatments with the determination of seizure induction time by defined prestimulation BIS (BIS condition) and 3 treatments with determination of seizure induction time by controlled clinical trial protocol (no-BIS condition). Statistical analysis was calculated by repeated-measures analysis of variance. The degree of postictal suppression was more pronounced in both MST and ECT, with BIS monitoring. In this connection, no differences between MST and ECT were found. Seizure induction time was significantly later in the BIS condition (181.3 ± 6 seconds) compared with the no-BIS condition (114.3 ± 12 seconds) (P < 0.001). Adequacy of seizures, in the form of the degree of postictal suppression, was superior by determining the seizure induction time with BIS in both MST and ECT. Further research is needed to investigate the correlation between the degree of postictal suppression and treatment response.


[The Kramer osteotomy in the treatment of hallux valgus].
In 1973. J. Kramer published his own technique for the cure of hallux valgus (Orthopädische Praxis Heft 8/1982, 636-645). He corrects bad position of the first bone of the metatarsus with all the consequences which lie in the basis of the deformation. By osteotomy of the first bone of the metatarsus and re-instates functional equipise of the first foot instep in all the components. Having the experience of 550 operated patients he considered that this method has advantages over numerous described method, indicative range is practically wide, respecting the technique it is simply performed, post-operative cure does not require immobilisation, and in comparison with other methods, complications and bad results are practically unknown. On our ward, in the period between 1984 and 1988, we applied Kramer's osteotomy in 98 cases of hallux valgus. The results were satisfying, considerably better than after other methods of hallux valgus treatment.


Nitrogen Fertilizer Management for Enhancing Crop Productivity and Nitrogen Use Efficiency in a Rice-Oilseed Rape Rotation System in China.
The use of efficient rates of nitrogen (N) fertilizer application is important with regard to increasing crop productivity and maintaining environmental sustainability. Rice-oilseed rape rotations are a mainstay of the economy and food security of China. Therefore, a field experiment was carried out during 2011-2013 in Honghu to identify the most appropriate N application rates for enhancing crop productivity and N use efficiency for rice (Oryza sativa L.)-oilseed rape (Brassica napus L.) rotations. Six N fertilizer treatments (RO1, RO2, RO3, RO4, RO5, and RO6) were laid out in a randomized complete block design with three replicates. ROx represented the N fertilizer application rates (kg ha-1) for rice and oilseed rape, respectively. Grain yields from plots receiving N fertilizer were significantly increased by 59-71% (rice) and 109-160% (oilseed rape) during the total rotation (2011-2013), as compared to RO1 (control; no application). Furthermore, a similar trend was observed for N accumulation, ranging from 88 to 125% and 134 to 200% in aerial parts of rice and oilseed rape, respectively. Nitrogen use efficiency (NUE) was significantly higher (38.5%) under RO2 and lower (34.2%) under RO6 while apparent N balance (ANB) was positively lowest under R05 (183.4 kg ha-1) followed by R02 (234.2 kg ha-1) and highest under R06 (344.5 kg ha-1) during the total rotation. The results of grain yield, NUE, and ANB indicated that the R02 rate of N application was superior. This information should help to develop a cost-effective and environment-friendly N management strategy for rice-oilseed rape rotation systems of central China.


Comparing FAMACHA eye color chart and Hemoglobin Color Scale tests for detecting anemia and improving treatment of bovine trypanosomosis in West Africa.
African animal trypanosomosis (AAT) is considered the most important cattle disease in sub-Saharan Africa but its diagnosis in the field is difficult, resulting in inappropriate treatments, excessive delay in treatments and under-treatment. A field study in West Africa investigated the usefulness of anemia in the diagnosis of trypanosomosis. A total of 20,772 cattle blood samples were taken from 121 villages in 3 countries. The average packed cell volume (PCV) of trypanosomosis positive cattle was 23%, versus 28% for negative cattle. In a sub-set of animals, other causes of anemia were investigated showing most of the anemia burden was attributable to trypanosomosis. Anemia was a reasonably accurate indicator of trypanosomosis in the study area, with a sensitivity of 56% and a specificity of 80% and a diagnostic odds ratio of 4.2, the highest of all the signs evaluated (anemia, emaciation, staring coat, lymphadenopathy, fever, lacrimation and salivary or nasal discharge). Having confirmed the usefulness of anemia as a predictor of trypanosomosis, two potential pen-side tests for anemia were evaluated (the first reported trial of their use in cattle), firstly a color chart developed for anemia detection in sheep through visual inspection of conjunctival membranes (FAMACHA) and secondly the Hemoglobin Color Scale (HbCS) developed for assessing hemoglobin levels in human patients by comparing blood drops on filter paper with color standards. In a population of cattle suspected by their owners to be sick with trypanosomosis (n=898) the sensitivity of the HbCS test was 56% and the specificity was 77%, while the sensitivity of the FAMACHA test was 95% and the specificity was 22%. The higher sensitivity but lower specificity suggests the FAMACHA may be useful as a screening test and the HbCS as a confirmatory test. The two tests were also evaluated in cattle randomly selected from the village herd. Using cut-off points to optimize test performance, the HbCS test had a sensitivity of 81% and a specificity of 62% (n=505 cattle), while the FAMACHA had a sensitivity of 92% and a specificity of 30% (n=298 cattle). Recommendations are made for the appropriate use of these tests in the West African region.


Reliability of a consensus-based ultrasound score for tenosynovitis in rheumatoid arthritis.
To produce consensus-based scoring systems for ultrasound (US) tenosynovitis and to assess the intraobserver and interobserver reliability of these scoring systems in rheumatoid arthritis (RA). We undertook a Delphi process on US-defined tenosynovitis and US scoring system of tenosynovitis in RA among 35 rheumatologists, experts in musculoskeletal US (MSUS), from 16 countries. Then, we assessed the intraobserver and interobserver reliability of US in scoring tenosynovitis on B-mode and with a power Doppler (PD) technique. Ten patients with RA with symptoms in the hands or feet were recruited. Ten rheumatologists expert in MSUS blindly, independently and consecutively scored for tenosynovitis in B-mode and PD mode three wrist extensor compartments, two finger flexor tendons and two ankle tendons of each patient in two rounds in a blinded fashion. Intraobserver reliability was assessed by Cohen's κ. Interobserver reliability was assessed by Light's κ. Weighted κ coefficients with absolute weighting were computed for B-mode and PD signal. Four-grade semiquantitative scoring systems were agreed upon for scoring tenosynovitis in B-mode and for scoring pathological peritendinous Doppler signal within the synovial sheath. The intraobserver reliability for tenosynovitis scoring on B-mode and PD mode was good (κ value 0.72 for B-mode; κ value 0.78 for PD mode). Interobserver reliability assessment showed good κ values for PD tenosynovitis scoring (first round, 0.64; second round, 0.65) and moderate κ values for B-mode tenosynovitis scoring (first round, 0.47; second round, 0.45). US appears to be a reproducible tool for evaluating and monitoring tenosynovitis in RA.


Quantum process tomography with unsupervised learning and tensor networks.
The impressive pace of advance of quantum technology calls for robust and scalable techniques for the characterization and validation of quantum hardware. Quantum process tomography, the reconstruction of an unknown quantum channel from measurement data, remains the quintessential primitive to completely characterize quantum devices. However, due to the exponential scaling of the required data and classical post-processing, its range of applicability is typically restricted to one- and two-qubit gates. Here, we present a technique for performing quantum process tomography that addresses these issues by combining a tensor network representation of the channel with a data-driven optimization inspired by unsupervised machine learning. We demonstrate our technique through synthetically generated data for ideal one- and two-dimensional random quantum circuits of up to 10 qubits, and a noisy 5-qubit circuit, reaching process fidelities above 0.99 using several orders of magnitude fewer (single-qubit) measurement shots than traditional tomographic techniques. Our results go far beyond state-of-the-art, providing a practical and timely tool for benchmarking quantum circuits in current and near-term quantum computers.


Therapeutic effects of statins drugs use and continuous nursing on patients with chronic obstructive pulmonary disease and the influence of life quality.
Chronic obstructive pulmonary disease (COPD) is able to be treated and delayed. Many interventions include smoking cessation and daily maintenance of drug therapy. In clinical practice, although respiratory physicians have given optimal drug treatment to patients, there is no treatment for etiological factors in these treatments, and they have little effect on the long-term prognosis of COPD. Therefore, this paper puts forward a method of continuing care. Through Meta analysis of the therapeutic effects of statins, it is shown that statins have a positive impact on the treatment of chronic obstructive pulmonary disease. On the other hand, the study shows that continuing care can reduce the SGRQ (St George's respiratory questionnaire) score of the patient, thereby improving the patient's quality of life. Therefore, both drug therapy and continuing care are effective methods for the treatment of chronic obstructive pulmonary disease, which can be effectively combined.