Improving the time resolution in microdialysis coupled to high performance liquid chromatography (HPLC) requires that the volume of the separation system be decreased. A low-volume separation permits smaller microdialysate volumes to be injected without suffering a sensitivity loss from dilution. Thus, improved time resolution can be achieved with offline analysis simply by decreasing the separations system volume. For online (near real-time) analysis, there is a further requirement. The separation speed must be at least as fast as the sampling time. Here, the combined use of high column pressures and temperatures, sub-2-μm stationary phase particles, capillary columns, and sensitive, low dead-volume detection resulted in a retention time for the neurotransmitter serotonin of less than 1 min in a 500 nL dialysate sample volume. Two sensitive detectors, photoluminescence following electron transfer (PFET) and electrochemical, were used for the detection of subnanomolar concentrations of serotonin in brain microdialysate samples. The general principles developed are applicable to a wide range of separations with the additional advantages of increases in sample throughput and decreases in mobile phase usage.


Objective: To determine the frequency and nature of leptomeningeal contrast enhancement in multiple sclerosis (MS) via in vivo 3-tesla postcontrast T2-weighted, fluid-attenuated inversion recovery (FLAIR) MRI and 7-tesla postmortem MRI–pathology correlation. Methods: Brain MRI, using the postcontrast T2-weighted, FLAIR technique, was prospectively collected in 299 MS cases and 37 age-matched neurologically healthy controls. Expert raters evaluated focal gadolinium enhancement in the leptomeningeal compartment. Two progressive MS cases came to autopsy after in vivo MRI characterization. Pathologic and immunohistochemical examination assessed the association of enhancement with leptomeningeal inflammation and adjacent cortical demyelination. Results: Focal contrast enhancement was detected in the leptomeningeal compartment in 74 of 299 MS cases (25%) vs 1 of 37 neurologically healthy controls (2.7%; p = 0.001). Enhancement was nearly twice as frequent (p = 0.009) in progressive MS (39/118 cases, 33%) as in relapsing-remitting MS (35/181, 19%). Enhancing foci generally remained stable throughout the evaluation period (up to 5.5 years). Pathology showed perivascular lymphocytic and mononuclear infiltration in the enhancing areas in association with flanking subpial cortical demyelination. Conclusion: Leptomeningeal contrast enhancement occurs frequently in MS and is a noninvasive, in vivo marker of inflammation and associated subpial demyelination. It might therefore enable testing of new treatments aimed at eliminating this inflammation and potentially arresting progressive MS.


SUMMARY Background: In view of the rise in antibiotic resistance and Clostridium difficile superinfection, close monitoring of antibiotic prescribing practices is essential so that targeted quality assurance measures can be taken. Methods: We analyzed nationwide data from multiple statutory health insurance carriers on prescriptions of systemic antibiotics in the years 2008–2014, with special attention to cephalosporins and fluoroqinolones. Prescribing rates were characterized in terms of defined daily doses (DDD) per 1000 statutory insurees per year and were analyzed separately for each age group and each federal state in Germany. Trends were analyzed with joinpoint regression. Results: Antibiotic prescribing rates for persons aged 15 to 69 increased slightly overall during the period of observation. On the other hand, there was a significant decline in antibiotic prescribing rates for persons under age 15 in all of the German states, with a mean annual decrease of 6.8%. There was also a slight decline in antibiotic prescribing rates for persons aged 70 and above, mainly accounted for by fluoroquinolones. Cephalosporin prescribing rates rose significantly in all states, by an overall average of 7.6% per annum. Cephalo sporin prescribing rates rose significantly in all age groups except persons under age 15, for whom there was a decline that did not reach statistical significance. Conclusion: This study revealed an overall decline in outpatient antibiotic prescriptions for persons under age 15 as well as other major changes in prescribing practices for the types of antibiotics studied. The observed marked rise in cephalosporin prescribing rates in all German states demands special attention because of the associated danger of increased antibiotic resistance and C. difficile superinfection. Oral cephalosporins are not recommended as drugs of first choice in current guidelines.


Didemnum sp. A is a colonial ascidian or "sea squirt" of unknown geographic origin. Colonies of Didemnum sp. A were first documented in U.S. waters in 1993 at Damariscotta River, Maine and San Francisco Bay, California. An alarming number of colonies have since been found at several locations in New England and along the West Coast of the contiguous continental United States. Originally believed to be restricted to artificial structures in nearshore habitats, such as ports and marinas, colonies of Didemnum sp. A have also been discovered on a gravel-pavement habitat on Georges Bank at depths of 40-65m. The wide distribution of Didemnum sp. A, the presence of colonies on an important offshore fishing ground, and the negative economic impacts that other species of noninidigenous ascidians have had on aquaculture operations have raised concerns about the potential impacts of Didemnum sp. A. We reviewed the available information on the biology and ecology of Didemnum sp. A and potentially closely related species to examine the environmental and socioeconomic factors that may have influenced the introduction, establishment and spread of Didemnum sp. A in U.S. waters, the potential impacts of this colonial ascidian on other organisms, aquaculture, and marine fisheries, and the possibility that it will spread to other U.S. waters. In addition, we present and discuss potential management objectives for minimizing the impacts and spread of Didemnum sp. A.

Concern over the potential for Didemnum sp. A to become invasive stems from ecological traits that it shares with other invasive species, including the ability to overgrow benthic organisms, high reproductive and population growth rates, ability to spread by colony fragmentation, tolerance to a wide range of environmental conditions, apparent scarcity of predators, and the ability to survive in human dominated habitats. At relatively small spatial scales, species of Didemnum and other nonindigenous ascidians have been shown to alter the abundance and composition of benthic assemblages. In addition, the Canadian aquaculture industry has reported that heavy infestations of nonindigenous ascidians result in increased handling and processing costs. Offshore fisheries may also suffer where high densities of Didemnum sp. A may alter the access of commercially important fish species to critical spawning grounds, prey items, and refugia. Because colonial ascidian larvae remain viable for only 12–24hrs, the introduction and spread of Didemnum sp. A across large distances is thought to be predominantly human mediated; hull fouling, aquaculture, and ballast water. Recent studies suggest that colony growth rates decline when temperatures exceed 21 oC for 7 consecutive days. Similarly, water temperatures above 8 to 10 oC are necessary for colony growth; however, colonies can survive extended periods of time below this temperature threshold as an unidentified overwintering form.

A qualitative analysis of monthly mean nearshore water temperatures suggest that new colonies of Didemnum will continue to be found in the Northeast U.S., California Current, and Gulf of Alaska LMEs. In contrast, water temperatures become less favorable for colony establishment in subarctic, subtropical, and tropical areas to the north and south of Didemnum's current distribution in cool temperate habitats. We recommend that the Aquatic Nuisance Species Task Force serve as the central management authority to coordinate State and Federal management activities. Five objectives for a Didemnum sp. A management and control program focusing on preventing the spread of Didemnum sp. A to new areas and limiting the impacts of existing populations are discussed. Given the difficulty of eradicating large populations of Didemnum sp. A, developing strategies for limiting the access of Didemnum sp. A to transport vectors and locating newly established colonies are emphasized. (PDF contains 70 pages)


Like its predecessors, this book is a concise volume covering adequately the basic aspects of pharmacology. It is well organized, and except for some minor affectations (such as using plasmatic membrane for plasma membrane, nonsensitive for insensitive and numerous didactic definitions), it is also well written. The unique quality of this book is retained, giving a wealth of historical background on the different branches of pharmacology and many portraits of great men in pharmacology and their important contributions. In the organization of the book, a harmonious compromise seems to have been achieved whereby the importance of pharmacodynamic aspects of drug action has not overshadowed the more frequently used drugs in practice whose mechanisms of actions may not be too well elucidated. Thus the antibiotics are accorded a justifiable priority in the early part of the book. Moreover, drugs acting on the skin, those used on the ears, nose and throat,


BACKGROUND
To evaluate the impact of the treatment with rizatriptan 10 mg (Maxalt) on the return to normal activity and satisfaction with treatment in the general population with migraine.

PATIENTS AND METHOD
We conducted an open, prospective study in patients with migraine (International Headache Society [IHS] criteria) who were followed for up to 3 migraine attacks. We measured the degree of functional disability at 0 and 2 hours after treatment, and satisfaction at 24 hours. Other domains of satisfaction were evaluated after three migraine attacks. The relationship between baseline pain severity, satisfaction after 24 hours and functional disability was analyzed.

RESULTS
2,469 patients were enrolled who experienced 6,323 migraine attacks. A return to normal activity was achieved two hours after treatment in 67% of all attacks treated with rizatriptan 10 mg. The percentage of attacks causing severe functional disability decreased from 39% before therapy to 3.6% two hours after treatment. In more than 90% of moderate or severe attacks, a normal or slightly impaired functional capacity was restored two hours after treatment. In 76.3% of the attacks the patients were fully or very satisfied 24 hours after treatment with rizatriptan 10 mg. After treating three migraine attacks, the proportion of patients fully or very satisfied with rizatriptan was over 79% for all the domains explored.

CONCLUSIONS
The patients were highly satisfied after 24 hours and following three migraine attacks treated with rizatriptan 10 mg. In more than two-thirds of the attacks treated with rizatriptan 10 mg, the patients returned to normal activity two hours after treatment.


Somatic hybridization through protoplast fusion has proven to be a valuable technique in citrus for producing unique allotetraploid breeding parents that combine elite diploid selections. Many citrus somatic hybrids are now flowering and being used in interploid crosses to generate triploid hybrids that produce seedless fruit, a primary objective of citrus breeding programs. Most of the early somatic hybrids produced for mandarin improvement combined sweet oranges with mandarins, because the performance of sweet oranges in tissue/protoplast culture generally exceeds that of most mandarin selections. However, a high percentage of triploid progeny from interploid crosses using sweet orange + mandarin somatic hybrids as the tetraploid parent produce fruit that are difficult to peel. We report nine new allotetraploid somatic hybrids and five new autotetraploids from somatic fusion experiments involving easy-peel mandarin parents. These tetraploids can be used in interploid crosses to increase the percentage of seedless triploid progeny producing easy-to-peel fruit. Ploidy level of the new tetraploids was determined by flow cytometry and their genetic origin by expressed sequence tagsimple sequence repeat marker analysis.


Objectives: Given the limited resources available to conduct clinical trials, it is important to understand how trial sponsorship differs among different therapeutic modalities and cancer types and to consider the ramifications of these differences. Methods: We searched clinicaltrials.gov for a cross-sectional register of active, phase III, randomized controlled trials (RCTs) studying treatment-related endpoints such as survival and recurrence for the 24 most prevalent malignancies. We classified the RCTs into 7 categories of therapeutic modality: (1) chemotherapy/other cancer-directed drugs, (2) targeted therapy, (3) surgery, (4) radiation therapy (RT), (5) RT with other modalities, (6) multimodality therapy without RT, and (7) other. RCTs were categorized as being funded by one or more of the following groups: (1) government, (2) hospital/university, (3) industry, and (4) other. &khgr;2 analysis was performed to detect differences in funding source distribution between modalities and cancer types. Results: The percentage of multimodality trials (5%) and radiation RCTs (4%) funded by industry was less than that for chemotherapy (32%, P<0.01) or targeted therapy (48%, P<0.01). Trials studying targeted therapy were less likely to have hospital/university funding than any of the other modalities (P<0.01 in each comparison). Trials of chemotherapy were more likely to be funded by industry if they also studied targeted therapy (P<0.01). Conclusion: RCTs studying targeted therapies are more likely to be funded by industry than trials studying multimodality therapy or radiation. The impact of industry funding versus institutional or governmental sources of funding for cancer research is unclear and requires further study.


In this work, a corrosion sensor based on an optical time domain reflectometer was presented. The first sensor with a bare tip was used to measure the corrosion process of silica glass fiber. Another sensor with a deposited silver layer was used for monitoring the corrosion process in nitric acid. In both cases, reflectance at the end of the fiber was decreasing with immersion time. Thus we can describe the corrosion stage by the level of fresnel reflectance. The maximum sensitivities of the analyzed sensors were as follows: 0.7dB/min (3% HF solution) 0.15dB/h (5%HNO3 solution) Results showed that the corrosion process in all cases wasn't fully linear, and all reactions began almost instantly after immersing sensors in tested corrosive environments. Full Text: PDF ReferencesC. Elosua, F.J. Arregui et al., "Micro and Nanostructured Materials for the Development of Optical Fibre Sensors", Sensors, 17, 2312 (2017). CrossRef B.H. Lee, Y.H. Kim et al., "Interferometric Fiber Optic Sensors", Sensors, 12, 2467 (2012). CrossRef X. Wang, O.S. Wolfbeis, "Fiber-Optic Chemical Sensors and Biosensors" (2013-2015), Analytical Chemistry, 88, 203 (2016). CrossRef M.A. Butler, "Fiber Optic Sensor for Hydrogen Concentrations near the Explosive Limit", J. Electrochem. Soc., 138, 46 (1991). CrossRef M.A. Butler, "Optical Fiber hydrogen sensor", Appl. Phys. Lett. 45, 1007 (1984). CrossRef S.F. Silva, L. Coelho et al., "A Reviev of Palladium-Based Fiber-Optic Sensors for Molecular Hydrogen Detection", IEEE Sens. J., 12, 93 (2012). CrossRef C. Floridia, F.C. Salgado et al., "Methane leak detection and spectral analysis by using only optical time domain reflectrometry in semidistributed remote optical sensors", IEEE Sens., 2016. CrossRef J.F. Martins-Filho, E. Fontana et al., Fiber-optic-based Corrosion Sensor using OTDR, IEEE SENSORS 2007 Conference (2007). CrossRef E.A. Lima, A.C. Bruno, "Improving the detection of Flaws in Steel Pipes Using SQUID Planar Gradiometers", IEEE Trans. Appl. Supercond. 11, 1299 (2001). CrossRef J. Yin, J. Pineda de Gyvez et al., "Real-Time Full Signature Corrosion Detection of Underground Casing Pipes", IEEE Instrumentation and Measurement Technology Conference (1996). CrossRef H. Park, D. Kim et al., "HF etched glass substrated for improved thin-film solar cells", Heliyon, 4, 10, (2018). CrossRef M. Mozammel, "Kinetics of Silver Dissolution in Nitric Acid from Ag-Au0:04-Cu0:10 and Ag-Cu0:23 Scraps", J. Mater. Sci. Technol., 22, 696 (2006). DirectLink


This study explored the effects of teachers' motivation to students' academic performance in community secondary schools Kinondoni municipality. It investigated the effects of teachers' extrinsic and intrinsic motivation to students' examination performance, significance of the study, limitation and conceptual framework. The study used qualitative approach, using interview, and focus group discussion to obtain data. The study was conducted in Kinondoni municipality, Dar es Salaam region. The sample study was drawn from four community secondary school in Kinondoni municipality whereby head of schools, teachers, students, parents, secondary educational officer and school inspector. Thematic approach was used in data analysis. The finding revealed that extrinsic and intrinsic motivation plays a great role in teaching and learning process. The major findings on students' poor performance in examination were related to teachers' and students' motivation in teaching and learning. It also identifies measures to be taken in order to promote and maintain teachers' motivation in those schools. On the other hand the study showed that teachers work hard, teaching effectively and efficiently when they are motivated, hence, good students' examination performances. Lastly summary, conclusion and recommendation were done.


It is no secret that there is currently an incarceration crisis in America. A Pew Report issued in February of 2008 proved one of our worst fears, as the United States now has the highest rate of incarceration in the world. In fact, according to the report, one in every one hundred adult Americans is presently incarcerated. One has to look no further than the last twenty years to identify the source of the boom in our nation's prison population: Namely, the war on drugs. Of all the communities impacted by the war on drugs, poor African-Americans have arguably experienced the most dramatic and lasting effects of the war. Although African-Americans comprise just 13% of the U.S. population, they are nearly half of those represented in federal and state prisons, largely due to drug-related crime. Notably, a number of incarcerated African-Americans are parents of children under the age of eighteen. In light of the failure of the war on drugs to achieve its goals of reducing access to and the sale of narcotics in the U.S., one must wonder whether a new strategy for addressing the issue of drug trafficking and improving fragile communities is in order. The purpose of this paper is to increase awareness of the devastating effects of the war on drugs on poor African-American children and families in an effort to advocate for change.


: Purpose: The main aim of the research is to present the scale of the number of lost passenger transport as a result of limiting the activity of the aviation industry in Poland in the cross-section of the most important civil airports. Design/Methodology/Approach: An analysis of passenger traffic in the most important airports in Poland was carried out. The methods of regression analysis and forecasting 4 were applied for the analyzes. In order to estimate the impact of restrictions on the operation of the aviation industry on passenger traffic in Poland across individual airports, the parameters of trends in 2011-2019 were estimated. Then, the models for 2020 (March-December) were predicted. As a result, the volume of lost traffic (in thousands of passengers) was obtained and the scale of changes in percent was determined. Linear and nonlinear regression models with index variables were used for the research. Findings: The cause of severe losses is not only the pandemic itself, but it may be the lack of a coherent management system in the COVID-19 crisis. Taking into account the history of the development of passenger air services and the importance they have played for economic development in the most important economies, it should be stated that the crisis of 2020 may be a predictor of significant changes in the management system in the long term. Practical Implications: The introduced restrictions and limitations were poorly coordinated at the national and international levels, which resulted in chaos and a feeling of uncertainty as to the development of the situation, which in turn prevents rational actions by aviation market participants, including airlines. Originality/Value: This article is an original contribution in the study of the impact of pandemic restrictions on passenger air transport in Poland, using regression analysis and forecasting methods.


[Pseudomonas] rubrisubalbicans, a mild plant pathogen. Herbaspirillum seropedicae, and EF group 1 strains (clustered by an immunological method) were investigated by a polyphasic approach with DNA-rRNA and DNA-DNA hybridizations and auxanography on 147 substrates. Our results show that they all belong to the genus Herbaspirillum. In addition to H. seropedicae, two other species are described: Herbaspirillum rubrisubalbicans and a new unnamed species, Herbaspirillum species 3, containing mainly strains of clinical origin. The three species can be differentiated on the basis of their auxanographic features and DNA-DNA similarities. The type strain of H. rubrisubalbicans is NCPPB 1027 (=LMG 2286); representative strains of the third Herbaspirillum species are strains CCUG 189 (=LMG 5523), CCUG 10263 (=LMG 5934), and CCUG 11060 (=LMG 5321). It has been confirmed that H. rubrisubalbicans is an endophytic diazotroph. It colonizes the roots, the stems, and predominantly the leaves of sugarcane (Saccharum spp.), while Herbaspirillum seropedicae colonizes in large numbers many different species of the Gramineae. Both diazotrophic Herbaspirillum species could be differentiated with meso-erythritol and N-acetylglucosamine. Oligonucleotide probes based on partial sequences of the 23S rRNA of H. seropedicae and H. rubrisubalbicans (HS and HR probes, respectively), were constructed and used as diagnostic probes.


Crawling and information extraction is perhaps one of the most extensively studied topics in the web age. Albeit much progress has been made in this area, it is still a page-centric, computation intensive process, and more often than not, it relies on manually crafted templates. But how a web site organizes its data has gone through significant changes since the early days of web, and many web sites, especially e-commerce sites, now support exploratory search, which presents data to the user through an implicit query interface. In this paper, we conduct a comprehensive survey of exploratory web sites, and we show that traditional page-centric crawling is extremely wasteful and the crawled data is seriously incomplete. We propose a query-centric view of web data, and an automatic crawling framework that crawls web sites by queries instead of by pages. In essence, we make queries first class citizens in modeling web data. This allows us to target the right content in crawling, which not only makes crawling more efficient, but also enables us to collect data that is hidden from page views and hence unreachable to traditional crawling methods. We conduct extensive experiments to demonstrate the advantage of the new model, and the performance of our new crawling method.


Abstract. The area lies in arid zone of western Rajasthan having very scanty rains and very low ground water reserves. Some of the other problems that are faced by the area are disposal of industrial effluent posing threat to its sustainability of water resource. Textiles, dyeing and printing industries, various mechanical process and chemical/synthetic dyes are used and considerable wastewater discharged from these textile units contains about high amount of the dyes into the adjoining drainages. This has caused degradation of water quality in this water scarce semi-arid region of the country. Pali city is located South-West, 70 Kms from Jodhpur in western Rajasthan (India). There are four Common Effluent Treatment Plant (CETP) treating wastewater to meet the pollutant level permissible to river discharge, a huge amount of effluent water of these factories directly meets the into the river Bandi – a tributary of river Luni. In order to monitor the impact of industrial effluents on the environment, identifying the extent of the degradation and evolving possible means of minimizing the impacts studies on quality of effluents, polluted river water and water of adjoining wells, the contamination migration of the pollutants from the river to ground water were studied. Remote sensing analysis has been carried out using Resourcesat −1 multispectral satellite data along with DEM derived from IRS P5 stereo pair. GIS database generated of various thematic layers viz. base layer – inventorying all waterbodies in the vicinity, transport network and village layer, drainage, geomorphology, structure, land use. Analysis of spatial distribution of the features and change detection in land use/cover carried out. GIS maps have been used to help factor in spatial location of source and hydro-geomorphological settings. DEM & elevation contour helped in delineation of watershed and identifying flow modelling boundaries. Litholog data analysis carried out for aquifer boundaries using specialized software. Establishment of other boundary conditions was based on well data. Calibration and validation of was done using ground water modelling software. Change detection analysis indicated areas of impact on land use/ cover particularly, agriculture activity. Normalised difference vegetation index found to have negative correlation with pollution level. Population dynamics have been studied and it is found to be poorly correlated with land degradation. Water levels do not show significant variations in past twenty years baring normal seasonal fluctuation. Chemical analysis of ground water samples studies in time series. The water quality studied through various parameters shows concentration in mid-reach of the Bandi river. Analysis of litholog data shows three unconfined aquifers. Pump test and resistivity survey was carried out for initial aquifer properties in local water levels. Modelling contaminant migration helped in prediction of the extent of the adversity. Surface flow is checked allowing more water but it is proving to be accumulation point in absence of good rainfall & flow in the river. Hotspots of dumping /active contamination were identified with certain remediation efforts and supply of solid waste to cement industry in addition to bio-filter for heavy metals.


The advent of wide-field galaxy surveys with high quality imaging provides an opportunity to map the dark matter distribution in large parts of the visible Universe. However, the available probes of the large-scale structure have distinct properties. In particular, galaxies are a high resolution but biased tracer of mass, while weak lensing avoids such biases but, due to low signal-to-noise ratio, has poor resolution.
After reviewing the applications of maps in cosmology, I investigate the relation between the Fourier phases of cosmological fields. By considering Gaussian random fields, I take some steps in describing the statistics of phase difference. Then I consider some simple models of realistic cosmological fields galaxies and weak gravitational lensing. I find that a linear bias evolving in redshift leads to a scale independent phase difference, whereas shot noise and stochasticity lead to a scale dependent phase difference.
I investigate reconstructing the projected density field using the complementarity of weak lensing and galaxy positions. I propose a maximum probability reconstruction of the 2D lensing convergence with a likelihood term for shear data and a prior on the Fourier phases constructed from the galaxy positions. By considering only the phases of the galaxy field, the method evades the unknown value of the bias and allows it to be calibrated by lensing on a mode-by-mode basis.


Introduction: DREEM stands for Dundee Ready Education Environment Measure is an internationally accepted checklist for assessment of educational status in medical schools. Objective: To find out the reliability of DREEM scale and its different domains like  Students' Perceptions of Learning (SPL), Students' Perceptions of Atmosphere (SPA), Students' Perceptions of Teachers (SPT), Students' Academic Self- Perceptions (SASP), and Students' Social Self-Perceptions (SSSP). Methods: The study was conducted at IQ City Medical College, Durgapur, West Bengal from April–September, 2018 among 407 students with a response rate of 72.5%. Reliability analysis was evaluated by the Cronbach's alpha, corrected item total correlation and Cronbach's alpha if item deleted values by SPSS software. Results: Overall DREEM scale had excellent reliability with Cronbach's α value 0.905. Regarding different sub domains SPL, SPT and SPA had acceptable reliability with a score more than 0.7 and less than 0.8. SASP had questionable reliability with a value of 0.674 and SSSP had poor reliability with a score of 0.518. Apart from the DREEM questionnaires following are the suggestions from the students' - more practical exposures, patient exposure, integrated teaching, more interactive sessions, seminars, workshops, quizzes, increased number of academic cases in the college, good canteen facilities, recreational environment for relaxation, good senior – junior interaction, more attention to mediocre & slow students, extra doubt clearing classes, correct way of writing answers to get good marks in examinations etc. Conclusion: Although overall reliability of the scale was excellent but different domains was not found to be consistent as other studies, which needs revisiting. Keywords: DREEM, educational environment, reliability, Cronbach's α


Archaeotrogons have long been known from late Eocene and Oligocene localities in France, where limb bones are abundantly represented. The phylogenetic affinities of these birds, however, have remained elusive. Although archaeotrogons are now considered to be representatives of the Strisores, the clade including 'caprimulgiform' and apodiform birds, their exact position in this clade is unresolved. Here, a partial skeleton of a new species of the Archaeotrogonidae is described from the early Eocene London Clay of Walton‐on‐the‐Naze (Essex, UK). In addition, a new specimen of the archaeotrogon Hassiavis from the latest early or earliest middle Eocene of the Messel fossil site in Germany is reported, which is the best preserved skeleton of this species. Archaeodromus anglicus gen. et sp. nov. from the London Clay is the earliest archaeotrogon known to date, and the holotype shows previously unknown skeletal characteristics of archaeotrogons that bear on the phylogenetic affinities of these birds. The quadrate in particular exhibits a distinctive morphology and shows derived morphological characteristics of the Strisores. Although the primary analysis did not conclusively resolve the affinities of archaeotrogons, analyses constrained to a molecular scaffold resulted in a sister group relationship to the Caprimulgidae (nightjars). The evolutionary history of this most species‐rich group of nocturnal Strisores is virtually unknown, and recognition of archaeotrogons as archaic stem group representatives of the Caprimulgidae would fill a striking gap in the fossil record.


Farmers' response to price has usually been measured by acreage response. Changes in yield were regarded largely as a consequence of weather. Accordingly, the inclusion of such changes would tend to obscure the underlying production-price responses of farmers. Weather has played a much less important role as a determinant of yields during World War II and the postwar period, and the notion of a yield response to price has become a logical assumption in the statistical measurement of supply response. The effects of weather were not analyzed in this particular study. In this paper, relationships between supply of potatoes (as measured by acreage and yield response) and expected "normal" price are studied. This price differs from previous year's price. Farmers are believed to gage the prospective price for the current crop from an evaluation of past prices to form some sort of "normal" price. The prospective or expected price is modified each year by the knowledge gained from actual price. Two objects are sought: (1) To obtain total elasticity of supply measures from elasticity of acreage and elasticity of yield, and (2) to evaluate farmers' response to expected "normal" price as contrasted with previous year's price. The study provides for a single yearly adjustment to price and therefore does not consider projected adjustments that might occur over long periods. For valuable assistance given the author wishes to express his appreciation to Anthony S. Rojko, Frederick V. Waugh, Will M. Simmons, and James P. C avin of the Agricultural Marketing Service, and Richard J. Foote, formerly of AMS. The paper was developed from research under authority of the Agricultural Marketing Act of 1946 (RMA, Title II).


All aerobic cells and organisms must synthesize heme from the amino acid glycine and the tricarboxylic acid cycle intermediate succinyl CoA for incorporation into hemoproteins, such as the cytochromes needed for oxidative phosphorylation. Most studies on heme regulation have been done in erythroid cells or hepatocytes; however, much less is known about heme metabolism in other cell types. The feline leukemia virus subgroup C receptor (FLVCR) is a 12-transmembrane domain surface protein that exports heme from cells, and it was shown to be required for erythroid development. In this article, we show that deletion of Flvcr in murine hematopoietic precursors caused a complete block in ab T cell development at the CD4 + CD8 + double-positive stage, although other lymphoid lineages were not affected. Moreover, FLVCR was required for the proliferation and survival of peripheral CD4 + and CD8 + T cells. These studies identify a novel and unexpected role for FLVCR, a major facilitator superfamily metabolite transporter, in T cell development and suggest that heme metabolism is particularly important in the T lineage. The Journal of Immunology , 2015, 194: 000–000.


OBJECTIVE : To investigate the chemosensory function and food attribute preferences of individuals with Prader-Willi Syndrome. DESIGN : Cross-sectional, matched-groups comparison. SUBJECTS : Fifteen (eight female and seven male) individuals with Prader-Willi Syndrome and an age- and sex-matched non-affected sample. MEASUREMENTS : Intensity ratings of taste and odor stimuli and hedonic ranking of 20 foods varying in sensory attributes (e.g. taste familiarity). RESULTS : Sensory test performance was comparable in the PWS and control groups. In addition, individuals with Prader-Willi Syndrome showed a pattern of food preferences that was similar to their non-affected counterparts. CONCLUSION : Abnormal chemosensory function does not underlie the ingestive behavior of individuals with Prader-Willi Syndrome.


A new rubber.-HALL and GOODSPEED,Io in connection with the war demand, have investigated a possible native source of rubber, studying especially Chrysothamnus. They found rubber of high grade in C. nauseosus, and adopted the name "chrysil" for this particular kind or rubber. This species includes 22 recognized varieties, which have been taxonomically presented by HALL." Of these varieties, I2 were examined and all found to contain rubber. The shrub grows readily from seed and matures in 6-8 years. The largest stands occur in Colorado, Nevada, and Utah; and it is estimated that the total amount of rubber present in wild shrub is over 300,000,000 lbs. Chrysil is not a latex rubber, but occurs in individual cells. The results of i8o chemical analyses and 8o microscopical examinations are tabulated. The rubber occurs in the plants in greatest abundance about the soil line, being present in the root in only the upper parts, and occurring in small amounts in young twigs and leaves. The best varieties for rubber are those growing in alkaline soils, so that the culture of this rubber-yielding plant could be developed extensively in alkaline regions unsuitable for other crop plants. The authorsl2 also give an account of the occurrence of rubber in other species of Chrysothamnus and in Haplopappus. They also append a long list of species, chiefly Compositae, in which no rubber was found.-J. M. C.


This paper presents a laboratory session of an advanced programming course to introduce students to the technology involved with the Java programming language. In this special lab session the educational software tool VisualJVM is used, providing a graphical front-end to a Java virtual machine (JVM). This tool helps students learn about JVM architecture, learn how JVM works, and consequently, to understand why a Java program is platform independent. The student reaction to this experience was very positive and the authors are planning to use the tool in other contexts.


Purpose This study was performed to determine if there is a sex-based bias in referral practices, complexity of disease, surgical treatment, or outcomes in patients undergoing mitral valve surgery at our institution. Methods Data were collected from the Cardiovascular Research Database of the Clinical Trial Unit of the Bluhm Cardiovascular Institute at Northwestern Memorial Hospital and they were defined according to the Society of Thoracic Surgeons National Database (www.sts.org). All patients who had mitral valve replacement, mitral valve repair with annuloplasty ring placement, and mitral valve annuloplasty alone were evaluated, including patients who underwent concomitant tricuspid valve surgery, atrial fibrillation ablation, patent foramen ovale closure, and coronary artery bypass grafting. An unmatched comparison was made between the 836 men and 600 women in the entire cohort (N = 1436) and propensity score-matching was performed in 423 pairs of men and women. Additional propensity score-matching for 219 pairs of men and women with Type II mitral valve functional class and no coronary artery disease and for 68 pairs of men and women with Type 1 or Type IIIb mitral valve functional class. Propensity score matching was used to compare sex differences involving a greedy algorithm with a caliper of size 0.1 logit propensity score standard deviation units. Results Between 1 April 2004 and 30 June 2017, 1436 patients (41.8% women, mean age 61.1 ± 12.6 years (men), 62.9 ± 13.3 years (women)) underwent mitral valve surgery. The unmatched comparison for the entire cohort showed that, on average, at the time of surgery, women had higher Society of Thoracic Surgery risk scores, were older and had more heart failure, coronary artery disease, and mitral stenosis than men. Women received proportionately fewer mitral repairs and more atrial fibrillation ablation, and tricuspid valve surgery. Women had longer intensive care unit and hospital stays, required more dialysis, and suffered more transient ischemic attacks and cardiac arrests postoperatively, and 30-day mortality rate was higher for women. However, propensity score-matching of 846 of the patients (423 men; 423 women) indicated that both the surgical approaches and surgical outcomes were comparable for men and women who had similar levels of disease and co-morbidities. Additional propensity score-matching of only those patients with degenerative mitral regurgitation (DMR) (219 men; 219 women) and those with Type 1 or Type III mitral valve disease showed no differences in the surgical procedures performed or in 30-day mortality rates. Conclusions Women appear to be referred for mitral valve surgery later in the course of their disease, which could possibly be on the basis of sex bias, but they may also have a more aggressive form of mitral valve disease than men. Regardless of the reasons for the later referral of women for mitral valve surgery, the clinical outcomes are dependent upon the severity of the mitral disease and associated co-morbidities at the time of surgery, not on the basis of sex bias.


In this paper, a course on applied superconductivity is described. The course structure is outlined and the learning objectives and the learning activities are described. The teaching was multidisciplinary given by four departments each contributing with their expertise. Being applied superconductivity, the focus was on an application, which could benefit from using superconductors. The application used in this course was superconducting generators for direct drive wind turbines. As part of the course, the students built a small-scale superconducting machine and set up FE (finite element) models of that machine as well as large-scale wind turbine generators with superconductors and PM (permanent magnet) generators, too. The course was assessed by a conference contribution and reports from the students. The quality of the course was evaluated by interviewing the students after the course had finished. The students were very pleased with the course and gave suggestions of how the course could be improved further.


The report highlights the close linkages between child labor and broader development objectives, and the consequent need to address child labor as an important component of national development strategies. It also illustrates the wide array of factors contributing to child labor, and the resulting importance of a broad, integrated policy response to it. Finally, the report underscores the importance of concerted action by international development agencies in support of Government efforts in the fight against child labor. International development agencies have a support role to play both in the development of integrated national strategies against child labor, and in the implementation of such strategies, in accordance with the relative strengths of each agency.


Lanthanum aluminate powders were prepared via a polymer complexing method by using PEG as complexing agent. The LaAlO3 powder was characterized by XRD and SEM. The influence of processing parameters such as molar ratio of PEG monomers to metal cations (PEG:Men+) and aging process on the phase purity and powder morphology were investigated. The calcined powder with the PEG:Men+ ratio larger than 2:1 may contain the secondary phase, namely La2O3. The formation of phase pure LaAlO3 powder occurs when the PEG:Men+ ratio is 1:1 or enough gelation time is involved. Although the phase pure powder is obtained by this PEG method, all the single phase LaAlO3 powders are found to have seriously aggregated particles. The weakly agglomerated powder morphology is only found in the powders which contain La2O3.


Objective: Neurofibromatosis (NF) is the most common autosomal dominantly inherited neurocutaneous syndrome. The characteristic features of NF type 1 (NF-1) are café au lait spots, axillary and inguinal freckling, peripheral neurofibromas, optic pathway glioma, and Lisch nodules. The present study aimed to analyze the clinical features of children with NF-1. Materials and Methods: In this study, the children with NF-1 diagnosed and followed-up in our center between 2000 and 2020 were retrospectively evaluated. Demographic and clinical features of patients were defined. Results: The study group consisted of 52 patients. Of those, 25 were boys and 27 were girls. The children's median age at diagnosis was 5.9 years (1-15.8). Café au lait (CAL) spots and axillary/inguinal freckling were observed in 50 and 24 patients, respectively. Neurofibroma was present in 22 cases. Ten of the cohort had optic gliomas, and 39 of them had cranial hamartomas. Orthopedic complications such as scoliosis, tibial pseudoarthrosis, and osteoporosis were observed in 13 patients. Eleven children had neurocognitive disorders. Conclusions: Early diagnosis is important in neurofibromatosis to prevent the complications of the disease. Also, neurological development and secondary malignancy follow-up should be done carefully in this group of patients.


The city walls go beyond their physical aspect towards the perception that invisible walls divide society and generate significant impacts. This theme was part of the fieldwork for high school students from public schools in Campinas-SP (Brazil) in the context of the Anhumas River in the School Project (ARS). The fieldwork Walls was developed by a multidisciplinary group of teachers through face-to-face meetings and online activities in the TelEduc learning virtual environment. This work focuses on how online mediation with face-to-face interaction allowed the construction of the fieldwork, making participants think critically about social and spatial organization. To analyze this process, the mediated action theory was used, admitting "agents-acting-with-cultural-tools" and statements as units of analysis. A method was developed to analyze the online forum and its relations, together with other TelEduc data and interviews. The results indicate a strong relationship between online and face-to-face discussions, although at an early stage of the use of digital technology, highlighting the possibility of an independent access schedule. The analysis of semantic flows in the forums indicated the route for the construction of the concept of walls, starting with concrete / physical walls and proceeding to the abstract and the consequences for the use and occupation of space. The enhancement of the work was expected from the use of digital technologies, which actually happened, though culturally there remains a difficulty in online collaborative work, which highlights the use of email regarding the diversity of tools, requiring a deeper process of digital enculturation.


Analysis of commercial strains of two edible mushrooms, Pleurotus ostreatus and Agaricus bisporus, using PCR and isozyme electrophoresis techniques allowed us to differentiate groups of genetically similar and distant strains. Among the commercial strains of P. ostreatus, the level of genetic variation was higher suggesting a broader genetic basis employed in breeding of this mushroom. The cultivars and hybrids of, A. bisporus, showed a higher level of homology. The isozyme markers (nonspecific esterase, leucinaminopeptidase, and phosphoglucoisomerase) are recommended for identification of the commercial strains of edible mushrooms.


Aim Breaking bad news to patients is difficult for healthcare professionals. As part of my reflections and learning from studying Loss and Grief (University module) at the hospice I wanted to explore how we might improve this. Method Within the day unit we identified a need to support patients throughout this time. I drew inspiration from Wor-den ' s Tasks of Mourning (1982) along with an awareness of the social context of loss and grief. I gathered ideas about how we might enhance practice and have been piloting a new approach to delivering bad news to patients. Results This new approach focuses on a celebration of life, bringing all patients together in a safe environment where they are told about the loss. An ' I remember ' discussion (led by day unit staff with support from volunteers, spiritual and social care teams) is held, which is a positive interaction to share memories through reminiscence. Throughout suggestions are made about how to celebrate the memory of the deceased, which includes music, singing and lighting candles. Conclusion Initial results suggest that patients are not left low in mood. In fact, their memories bring positive emotions such as laughter. We believe that by encouraging patients to communicate after loss will enable them to speak more freely about their own diagnosis and wishes.


While many recent observers have accused American judges - especially Supreme Court justices - of being too driven by politics and ideology, others have argued that judges are justified in using their positions to advance personal views. Advocating a different approach - one that eschews ideology but still values personal perspective - H. Jefferson Powell makes a compelling case for the centrality of individual conscience in constitutional decision making.Powell argues that almost every controversial decision has more than one constitutionally defensible resolution. In such cases, he goes on to contend, the language and ideals of the Constitution require judges to decide in good faith, exercising what Powell calls the constitutional virtues: candor, intellectual honesty, humility about the limits of constitutional adjudication, and willingness to admit that they do not have all the answers. "Constitutional Conscience" concludes that the need for these qualities in judges - as well as lawyers and citizens - is implicit in our constitutional practices, and that without them judicial review would forfeit both its own integrity and the credibility of the courts themselves.


Power systems' operators have the task of maintaining the balance between the demand and generation of electric power. Much research and attention is being given to find more environmental friendly sources of power generation. Naturally, more power is required when the load is at its peak value, and this tends to be when the most non environmentally friendly sources of power generation are used. This paper proposes a new controller for peak load shaving by intelligently scheduling power consumption of domestic electric water heater using binary particle swarm optimization. Past studies show that similar demand side management programs were not successful because the impact that the load control has on the end users' comfort. In this study, Binary Particle Swarm Optimization (BPSO) finds the optimal load demand schedule for minimizing the peak load demand while maximizing customer comfort level. A simulation in Matlab is used to test the performance of the demand response program using field data gathered by smart meters from 200 households. The direct load control is shown to be an effective tool for peak shaving of load demand, shifting the loads to valleys and reducing the aggregated load of electricity without compromising customer satisfaction.


Medical errors and patient safety have become increasingly important in the area of medical research in the recent years. World health Organization and other international committees have long been recommending the early integration of education about errors and patient safety in undergraduate and graduate medical education. To integrate patient safety education into existing curriculum views of the doctors towards patient safety education is an important issue. This descriptive type of cross sectional study was carried out to explore the views of intern doctors regarding medical error and patient safety education in undergraduate medical education of Bangladesh. The study was carried out in seven (three public and four private) medical colleges of Bangladesh over a period from July 2014 to June 2015. Study population was 400 intern doctors. Data were collected by self-administered structured questionnaire. The existing curriculum was also reviewed to find out patient safety issues. The study revealed that the topic medical error and patient safety were mostly neglected in the curriculum. But the intern doctors had positive attitude towards patient safety education. A total of 84.8% of the intern doctors with a high average score of 4.24 agreed that teaching students about patient safety should be a priority in medical students training while 87.8% agreed that learning about patient safety before graduation from medical colleges would produce more effective doctors. Among the respondents 76.6% expected more training on patient safety. Almost half of the participants (52.3%) reported that they had been assigned to tasks for which they were not trained or where medical errors could have happened easily (57.5 %). From this study it can be concluded that, there was a distinct need for more education and training in the field of medical error and patient safety among the intern doctors.


When and why are codified constitutions efficacious? Answering these key and apparently straightforward questions turns out to be extremely challenging. The road to responding to them is paved with conceptual, theoretical, and empirical difficulties. In this article, I make a modest, but nevertheless hopefully useful, claim: that overlooking certain conceptual difficulties is detrimental to the advancement of the theoretical and empirical agenda on constitutional efficacy. In other words, I posit that empirical and theoretical research linked to these questions can benefit from a clear conceptualization of constitutional (or more broadly formal) efficacy that is consistent with their research objectives. It is not uncommon for social and political science research in this area to overlook the question "how should constitutional efficacy be conceptualized?" A close analysis of academic sources makes it clear that even specialized literature on questions related to constitutional (or more broadly formal) efficacy have assumed conceptualizations that are theoretically problematic given their research objectives, potentially leading to theoretical inconsistencies or inaccurate empirical conclusions. To exemplify this point, I analyze the conceptualization of constitutional efficacy used in two influential political science texts: Barry Weingast's "The Political Foundations of Democracy and the Rule of Law" and Gretchen Helmke and Steven Levitsky's Informal Institutions and Democracy. I argue that the conceptualizations of constitutional (or more broadly formal) efficacy used in their theoretical proposals are not adequately suited to their own research objectives, and that this conceptual misfit affects the theoretical consistency and empirical applicability of their conclusions.


Large quantities of ground water have been pumped for many years in Texas from formations of Cretaceous, Eocene, Miocene, Pliocene, and Pleistocene age. Declines in water levels have resulted and investigations have been made by the Geological Survey in cooperation with the Texas Board of Water Engineers to determine the capacities of the formations to yield water to wells. The most reliable index of the quantity of water that a formation will yield has heretofore been considered to be the empirical correlation of pumpage and water levels in wells. Studies of recharge, laboratory studies of permeability and specific yield of water-bearing materials, and measurements of specific capacities of wells have also proven valuable.With the development of new methods, pumping tests have recently come into use. A pumping test and the use of its results are essentially a process of obtaining for the formation under investigation the equation of a water-level drawdown curve for a short period of time and extending the curve over a longer period by means of the equation. Predictions may thus be made of drawdowns caused by given rates of pumping. In making the predictions computed drawdowns must be adjusted for boundaries and changes in character of the formation not taken into account by the equation determined with the pumping test. Pumping tests have been made at Houston, Lufkin, Camp Swift, South Camp Hood, North Camp Hood, and Sweeny. The methods of making the tests, the results, and the use of the results are briefly described in this paper.


On 14 February 2018 the Draft of the Criminal Code (RKUHP) was adjourned until an undetermined time, several articles deemed to be problematic. One of them is a criminal act of fornication. A new article will convict a denial-men who promises woman he has intercoursed with. Eventhough that article is meant to protect women, on the other hand, it can also be a factor to victimize women as perpetrator. This paper examines the position of women among the articles which will protect women's rights as well as those which criminalize them. This paper is a normative juridical study by using literature review and aims to find the problem and also intend solving it. The result, victimized-women protection Article in RKUHP should carefully be formulated in order not to allow victim women to be criminalized.


The I.O.D.E. as we currently know it today was founded in 1900 by Margaret Polson Murray of Montreal, who recognized a need for loyal support of Canadians departing to fight in the Boer War with the Empire forces in South Africa. She encouraged the formation of a federation of women to promote patriotism, loyalty and service to others. The first chapter was formed in Fredericton, New Brunswick on January 15th 1900. Primary chapters were formed in quick succession across Canada. In 1901, Edith Boulton Nordheimer was elected the first national president, the location of the head office became Toronto, Ontario and the federation was incorporated as Imperial Order Daughters of the Empire and Children of the Empire Junior Branch. The Earl Mountbatten Chapter was formed in 1947 and is continuing to be a functioning chapter at the time of writing this finding aid. During the 1970's the name I.O.D.E. was officially adopted. It is a federally chartered not-for-profit, charitable organization. Structured to report under the jurisdiction of the National chapter are the Provincial chapters, the Municipal chapters and the Primary chapters. The I.O.D.E. is associated with the Victory League in England and Daughters of the British Empire in the United States and it is proud of its heritage and traditions. Queen Elizabeth II is the current patron of the organization and although chapters sometimes disband there are always new chapters forming, including e-chapters that meet through 21st century electronics.


Developing and maintaining life requires a lot of computation. This is done by gene regulatory networks. But we have little understanding of how this computation is organized. I show that there is a direct correspondence between the structural and functional building blocks of regulatory networks, which I call regulatory motifs. I derive a simple bound on the range of function that these motifs can perform, in terms of the local network structure. I prove that this range is a small fraction of all possible functions, which severely constrains global network behavior. Part of this restriction is due to redundancy in the function that regulatory motifs can achieve - there are many ways to perform the same task. Regulatory motifs help us understanding how genetic computation is organized and what it can achieve.


Recombinant adeno-associated virus (rAAV) has been widely used as an efficient transgenic vector in biomedical research, as well as gene therapy. Serotype-associated transduction efficiency, tissue- or cell-type tropism and immunological profile are major considerations in the various applications of rAAVs. There are increasing needs for different serotypes of rAAV, either naturally isolated or artificially engineered. However, affordable and scalable production of a desired serotype of rAAV remains very difficult, especially for researchers lacking relevant experience. On the basis of our previously established single recombinant baculovirus expression vector (BEV)-derived OneBac system, we have optimized the process and expanded the rAAV production range to the full range of serotypes rAAV1-13. Firstly, the AAV Cap gene was optimized to translate by ribosome leaky scanning and the gene of interest (GOI) was cloned into the pFD/Cap-(ITR-GOI)-Rep2 shutte plasmid. Following the classical Bac-to-Bac method, sufficient BEV stock containing all rAAV packaging elements can be quickly obtained. Finally, we can repeatedly scale up production of rAAVs in one week by using a single BEV to infect suspension-cultured Sf9 cells. The rAAV1-13 show relatively high yields ranging from 5×104 to 4×105 VG/cell. More than 1×1015 VG purified rAAVs can be easily obtained from 5 L suspension-cultured Sf9 cells. As expected, rAAV serotypes 1-13 show different potencies for in vitro transduction and cell-type tropisms. In summary, the single BEV-derived OneBac system should prove popular for laboratory scaling-up production of any serotype of rAAV.


From the mid 1980"s to 2004, golden apple (Spondias cytherea Sonn.) was one of the most important non-traditional fruit crops exported from Grenada. In 1995, some 617, 637 kg of the fruit was exported earning EC$1, 439,789.11. Golden apple accounted for 36% of all non-traditional fruit exports. Because the trees are very tall (up to 14 m), harvesting is difficult and, therefore, an estimated 30% of the fruits are damaged during the harvesting process. A methodology was, therefore, developed to get low growing trees which can be easily harvested from the ground level. If golden apple growers adopt this method one can expect an increase in the quantity of fruits exported and marketed locally. Farmers will have greater control over harvesting and marketing of their fruits allowing them to access more profitable marketing arrangements. On the other hand, praedial larceny of golden apple fruits may become a factor impacting farmers.


Between February 1995 and August 1997, 11 children (eight males, three females) aged 4-16 years (median 7 years) underwent allogeneic PBPC transplantation for treatment of hematological disorders. Seven patients with acute leukemia (n = 5 ALL, n = 1 AML) or lymphoma (n = 1) received primary allogeneic PBPC transplantation, four patients received a second allotransplantation for graft failure (n = 1 AML, n = 1 sickle cell anemia) or disease recurrence (n = 1 ALL, n = 1 MDS). Five donors were HLA-identical siblings, five were 0-1 antigen mismatched family members and one was a matched unrelated donor. Donors received G-CSF 10-12 microg/kg/day for 3-7 days, and underwent one or two leukaphereses. The median cell yield per donor expressed per kg of recipient body weight was as follows: mononucleated cells 10.8 x 10(8)/kg (range 4.7-21.2); CD34+ cells 8.6 x 10(6)/kg (range 3.2-22); CD3+ cells 3.7 x 10(8)/kg (range 2.7-7.5). All patients achieved an ANC >0.5 x 10(9)/l after a median of 12 days (11-18). An unsupported platelet count >50 x 10(9)/l was reached 15 days (13-21) after PBPC transplantation; four patients failed to reach this threshold. Acute GVHD (aGVHD) grades II to IV occurred in eight (73%) patients: seven of them experienced grade III-IV aGVHD. Seven patients evaluable for chronic GVHD (cGVHD) were scored as absent in five, limited in one and extensive in one patient. As of September 1997, six patients (55 %) were alive between 60 and 938 days post-transplant (median follow-up 274 days); four patients with malignancy were alive in CR after primary allotransplantation, two patients were alive after a second PBPC transplant. Five patients have died with the main causes of death being aGVHD (n = 3), ARDS (n = 1), relapse of the underlying disease (n = 1). In conclusion, despite the limited number of patients, these preliminary results indicate that PBPC may be considered as an alternative to bone marrow for allografting also in children.


Abstract The purpose of this study was to compare the reliability of passive stiffness, passive torque, range of motion (ROM), and electromyography (EMG) of the biceps femoris during passive thigh flexion motions intended to assess the ROM of the posterior muscles of the hip and thigh during manual versus automated assessment techniques. Eleven healthy men (mean ± s age = 22 ± 4 years; mass = 85 ± 12 kg; and height = 178 ± 4 cm) and nine healthy women (age = 19 ± 1 years; mass = 66 ± 15 kg; and height = 164 ± 5 cm) completed four randomly ordered passive straight-legged ROM assessments. Two ROM assessments were performed using a manual technique, which consisted of the primary investigator applying slow passive resistance against a load cell attached to the heel while the foot was moved toward the head. Two automated ROM assessments were also performed using a Biodex System 3 isokinetic dynamometer programmed in passive mode to move the foot toward the head at 0.087 rad · s−1. The intraclass correlation coefficients (ICCs) for passive stiffness measured with the manual technique ranged from 0.81–0.86, while for the automated technique they were 0.72–0.92. Standard error of measurement (SEM) values for passive stiffness expressed as a percentage of the mean ranged from 15.5–21.7% for the manual and 17.8–23.7% for the automated technique. Both techniques (manual and automated) were comparably reliable across the three trials, which suggested that the manual technique could be applied outside the laboratory.


Floating matrix tablets were designed and evaluated. Theophylline was used as a model drug. The system was prepared by mixing drug, matrix-forming polymer (hydroxypropyl methylcellulose, HPMC) and fillers together. The blended powder was compressed by hydraulic press. The effect of formulation variables such as type of matrix forming polymer (HPMC K100LV, HPMC K4M, HPMC K100M), amount of effervescent agent (0, 20, 30, 40% w/w) and compression force (0.5, 1 ton) on floating properties and drug release of floating matrix tablets were investigated. The results demonstrated that type of polymer affected floating properties of the floating matrix tablets. The floating matrix tablets prepared from lower viscosity HPMC (HPMC K100LV) showed faster drug release than those prepared from higher viscosity HPMC (HPMC K4M, HPMC K100M). Increasing amount of effervescent agent decreased time to float and increased drug release from the floating matrix tablets. Higher compression force did not affect time to float but decreased drug release from the floating matrix tablets. According to these results, floating properties and drug release of the floating matrix tablets could be modified by formulation variables. Some floating tablet formulations developed in this study showed good floating properties (time to float less than 15 minutes, floating time more than 8 hours) with sustained release as required. The system is promising as a carrier for gastroretentive drug delivery systems.


An experiment with soybeans . Glycine max (L .) Merrill, was planted at Cidra . Puerto Rico , on May 23, 1973, on a Torres clay, an Ultisol (Orthoxic Palehumults, clayey, mixed , isohyperthermic) . The experiment was one of a series "designed to study the relative efficiency of banded vs. broadcast P and of its residual effects on various successive crops . This was the fourth in the series after two corn and one rice experiments cropped in the same field in the seasons immediately preceding its installation. The identity of the plots was maintained throughout the whole series. There was no grain response to the broadcast or banded P, whether limed or unlimed, which had been applied to the previo us crops, although soil analyses by both the Olsen and the Bray No.2 method indicated deficiency of available P. However, a field-wide grain average of 3698 kg/ha, equivalent to 55 bu/acre, was obtained. The Bray No.2 extractable P content had fallen to less than 20 p/m 2 years after applying 359 kg/ha or less fertilizer P. This yield is almost twice that of the average commercial 1973 U.S. yield and demonstrates the potential for growing soybeans on Ultisols of the humid tropics.


There is a high level of comorbidity between depression and alcohol use disorder. Subanesthetic doses of ketamine induce short-acting and enduring antidepressant effects after a single or a few administrations. Considering such comorbidity, we assessed, in Swiss male mice, if ketamine-induced antidepressant-like effects would alter ethanol's rewarding effects; and, if ethanol pretreatment would alter the rewarding and antidepressant effects of ketamine. The role of the brain-derived neurotrophic factor (BDNF) and its high and low affinity receptors TrkB and p75NTR, respectively, in both reward and depression-related behaviors is well established. The present study assessed, in outbred Swiss male mice, the expression of these proteins in the prefrontal cortex and hippocampus. Ketamine did not alter the development of ethanol-induced conditioned place preference (CPP), yet ethanol inhibited the expression of CPP induced by 50 mg/kg ketamine. The antidepressant action of 50 mg/kg ketamine was attenuated after repeated treatment (i.e., developed tolerance), an effect blocked by ethanol preexposure; ethanol also inhibited the antidepressant effect of 30 mg/kg ketamine. Ketamine (50 mg/kg) and Ethanol-Ketamine (50 mg/kg) groups showed lower levels of 145 kDa TrkB in the hippocampus than Saline-treated group. Ethanol-Ketamine (50 mg/kg) decreased the hippocampal expression of p75NTR compared to Saline-Saline and Saline-Ethanol groups. Ketamine (50 mg/kg) induced hippocampal downregulation of 145 kDa TrkB may contribute to ketamine-induced antidepressant tolerance. Likewise, a relationship between low hippocampal levels of p75NTR in the Ethanol-Ketamine (50 mg/kg) and ketamine-induced CPP blockade may be considered. The findings underscore potential ethanol-ketamine interactions likely to undermine ketamine putative antidepressant effects.


OBJECTIVE: To investigate tympanic membrane healing process and biocompatibility of pressure-equalizing (PE) tubes, made of a novel biodegradable, absorbable material, in an animal model. BACKGROUND: Myringotomy and pressure-equalizing tube insertion is a frequent otologic procedure in children. However, results may vary because of the unpredictable extrusion rate of tubes. Furthermore, tubes that are no longer required need a surgical procedure to be removed. The ideal pressure-equalizing tube should remain in place for the time selected by the otologist, with no need for subsequent removal. This objective could be met with pressure-equalizing tubes made from a self-disintegrating material. METHODS: Pressure-equalizing tubes, made of poly-bis(ethylalanate)phosphazene, were inserted in 55 ears of 28 Hartley guinea pigs, with survival times of 10, 30, and 60 days after tube insertion. In vivo reactions between the poly-bis(ethylalanate)phosphazene pressure-equalizing tubes and the tympanic membrane were studied. Tympanic membranes, middle ears, and tubes were examined by scanning electron microscopy. RESULTS: There was neither infection nor inflammatory reaction to the tube in any animal. The healing process of tympanic membranes revealed neither residual perforation nor inward spread of skin epithelium into the middle ear cavity. At 30 days, 53% of the tubes had disintegrated. At 60 days, tubes were functioning in 25% of ears. CONCLUSION: These new poly-bis(ethylalanate)phosphazene pressure-equalizing tubes are promising. The healing process of tympanic membranes is excellent, with no complications. The tube disintegration rate can be controlled by varying the formulation of the polymer, obtaining tubes with predictable resorption rates, to adapt treatment to the needs of each single patient.


The thrust surface of W615 engine is remanufactured by plasma transferred arc (PTA) powder surfacing technology. The Ni15 Nickle-based alloy powder is selected as deposited metal. By optimizing the welding procedure, the coating is free of crack and pore. The microstructure characteristics of deposition layer are investigated by metallographic microscope, and the microhardness of the overlay is measured by vickers hardness tester. It is found that the heat affected zone is narrow, the rate of dilution is low and the microhardness of deposition layer is about HV130 which is close to that of base metal. Furthermore, the hardness of welding surface can meet the needs of the engine.


IntroductionStudies of the health of prisoners have proliferated in the past decade. However, relatively few studies have examined health outcomes after release from custody. As such, although >30 million people are released from prison globally each year, the health and health service experiences of this population remain poorly understood.
Objectives and ApproachWell-powered longitudinal studies are essential for answering these questions but are expensive and difficult to conduct. Internationally, few such studies have been undertaken, and most suffer from either substantial and biased attrition, or recruitment bias. Cross-sectoral linkage of health and justice data circumvents some of these problems but presents its own ethical and methodological challenges. Large longitudinal studies, combining rich survey and clinical data with prospective data linkage, provide unique opportunities to examine and understand health outcomes for these highly marginalised individuals.
ResultsThis presentation will describe the process and challenges of establishing the world's largest (N=2,702) prospective study of adults released from prison: the Health After Release from Prison (HARP) cohort study. The cohort spans two Australian states and includes 538 women and 1,002 Indigenous Australians. An overview of the data collected through face-to-face surveys, medical record review, and prospective linkage with State-based health and correctional records, national Medicare and pharmaceutical records, and the National Death Index, will be provided. Some examples of how these data have been used to answer novel public health questions will be presented. The strengths and limitations of the cohort, and the applicability of this research design for other inclusion health populations, will be discussed.
Conclusion/ImplicationsGiven their extreme vulnerability, understanding the health of people who cycle through prisons is important to addressing health inequalities at the population level. Novel research designs that combine prospective data linkage with other data sources provide new opportunities to examine the health of socially excluded populations.


The American Journal of International Law welcomes short communications from its readers. It reserves the right to determine which letters should be published and to edit any letters printed. Letters should conform to the same format requirements as other manuscripts.


Background and Aim Hyponatremia is common in patients with chronic kidney disease and is associated with increased mortality in hemodialysis patients. However, few studies have addressed this issue in peritoneal dialysis (PD) patients. Methods This prospective observational study included a total of 441 incident patients who started PD between January 2000 and December 2005. Using time-averaged serum sodium (TA-Na) levels, we aimed to investigate whether hyponatremia can predict mortality in these patients. Results Among the baseline parameters, serum sodium level was positively associated with serum albumin (β = 0.145; p = 0.003) and residual renal function (RRF) (β = 0.130; p = 0.018) and inversely associated with PD ultrafiltration (β = −0.114; p = 0.024) in a multivariable linear regression analysis. During a median follow-up of 34.8 months, 149 deaths were recorded. All-cause death occurred in 81 (55.9%) patients in the lowest tertile compared to 37 (25.0%) and 31 (20.9%) patients in the middle and highest tertiles, respectively. After adjusting for multiple potentially confounding covariates, increased TA-Na level was associated with a significantly decreased risk of all-cause (HR per 1 mEq/L increase, 0.79; 95% CI, 0.73–0.86; p<0.001) and infection-related (HR per 1 mEq/L increase, 0.77; 95% CI, 0.70–0.85; p<0.001) deaths. Conclusions This study showed that hyponatremia is an independent predictor of mortality in PD patients. Nevertheless, whether correcting hyponatremia improves patient survival is unknown. Future interventional studies should address this question more appropriately.


This celebrated book provides entertaining, easy-to-use lesson plans for teaching labor history. "Most school teachers are drowned in paper, but here is one book I want to recommend to them. It is a way of getting American teenagers not just interested, but excited and passionate about their history - modern American labor history." - Pete Seeger


Cricotracheal separation (CTS) is an uncommon injury, with a high index of suspicion required to establish the diagnosis. Computerized tomography (CT) plays a role in diagnosis but cannot necessarily be relied upon. Bilateral recurrent laryngeal nerve (RLN) palsies are usually associated with this type of injury. We recently treated a patient with CTS in whom one RLN was intact from the time of the injury and the other nerve recovered within three months. Computed tomography was inconclusive. Early open repair of the injury and frequent follow-up examinations led to successful decannulation after six weeks and excellent short-term voice and airway outcomes. A detailed discussion of this unusual case is followed by a review of the current literature on CTS, with particular emphasis on significant management dilemmas and controversies. Clinical suspicion remains more sensitive than investigations in diagnosing CTS. Permanent bilateral RLN palsies are not inevitable following these injuries.


Abstract Lower Triassic carbonate sedimentary rocks exhibit fabrics and facies indicative of reduced bioturbation and reduced abundance of skeletal animals and algae relative to their Permian counterparts. Widespread microbial mounds are one widely cited example. Micritic spheroids of probable microbial origin occur at a few horizons in the Spathian (uppermost Lower Triassic) Virgin Limestone Member of the Moenkopi Formation, exposed in southern Nevada. These spheroids (3–12 mm) consist of an irregular framework of micrite clots up to 100 μm in diameter and micrite-walled filaments ∼10 μm wide and <500 μm long. Based upon their microstructure, we suggest that these microbial spheroids formed through the rapid microbial precipitation of calcium carbonate from seawater. As such, they probably represent unattached analogues of Early Triassic microbial mounds. The microbial spheroids formed and lithified rapidly in shallow-water, high-energy settings. Their presence, in concert with other carbonate microbialites from the Moenkopi, is consistent with the observation that microbially mediated precipitation was an important carbonate depositional mode in the aftermath of the end-Permian mass extinction.


Salmon is a nutritious fish food high in omega-3 fatty acids and is highly sought for its unique sensory attributes. Long term frozen storage allows the widespread distribution of salmon to improve the economic situation of this industry and avail a greater population to the nutritional benefits of salmon. The purpose of this research was to determine the quality changes in Atlantic Salmon stored at different freezer temperatures over 12 months. Fresh and pre-frozen salmon were placed in five different freezers set at 7°C, -12°C, -18°C, -29°C and -77°C and evaluated for quality at 90, 180, 270 and 360 days of storage. In general, quality was retained to a greater extent in salmon held at -29°C and -77°C for 360 days compared to other storage temperatures. No significant difference between freezer -29°C and 77°C was found in weight loss at days 180, 270 and 360, pore size at days 270 and 360, and for water holding capacity, texture and TBARS, at days 90, 180, 270 and 360. The predicted shelf life of freshly frozen Atlantic Salmon was calculated based on the zero-order reaction model which was 268.82 days-7°C; 297.61 days-12°C; 355.78 days-18°C; 438.02 days-29°C, and 424 days-77°C. While the shelf life of pre-frozen Atlantic Salmon was 271.28 days- 7°C; 281.77 days-12°C; 351.33 days-18°C; 392.59 days-29°C; and 402.99 days-77°C. Based on several quality parameters having minimal variation between 4 to 9 months at home freezer temperatures, energy savings could be realized by use of higher freezer temperatures for storage of salmon.


Recognition accuracy and response time are both critically essential ahead of building practical electroencephalography (EEG) based brain-computer interface (BCI). Recent approaches, however, have either compromised in the classification accuracy or responding time. This paper presents a novel deep learning approach designed towards remarkably accurate and responsive motor imagery (MI) recognition based on scalp EEG. Bidirectional Long Short-term Memory (BiLSTM) with the Attention mechanism manages to derive relevant features from raw EEG signals. The connected graph convolutional neural network (GCN) promotes the decoding performance by cooperating with the topological structure of features, which are estimated from the overall data. The 0.4-second detection framework has shown effective and efficient prediction based on individual and group-wise training, with 98.81% and 94.64% accuracy, respectively, which outperformed all the state-of-the-art studies. The introduced deep feature mining approach can precisely recognize human motion intents from raw EEG signals, which paves the road to translate the EEG based MI recognition to practical BCI systems.


Chemical vapor deposition (CVD) diamond thin films are widely used in modern industries. However, due to the nature of polycrystalline, thin films are required to be polished in the final process to increase its surface quality. Thermal-chemical polishing is known for its less processing time and low cost. In this paper, the experiments are carried out to observe the effect of processing conditions such as temperature, rotational speed, polishing pressure, and substrate material on the surface roughness and on the material removal rate of the chemical vapor deposition diamond (CVDD). At the same time, the processing mechanism for this thermal-chemical polishing is investigated, and a polishing model is built for comparison with the experiment results. The results show that the material removal rate is affected mainly by the diffusing rate in the Fe-C polishing system. By using the model, the approximate value of material removal rate can be calculated according to the polishing temperature.


Endometriosis is pathologically defined as the presence of endometrial tissue in ectopic locations. Currently, there are no specific, non-invasive biomarkers and no cure for endometriosis. Non-human primates (NHP), including Macaca mulatta (rhesus macaques), have been highlighted as appropriate models to study endometriosis due to genetic, physiological, and anatomical similarities to humans. Research shows endometriosis might be associated with molecular deviations in human peritoneal endometriosis, such as increased levels of estrogen receptors and decreased levels of progesterone receptors. The aim of this study is to determine protein expression of steroid receptors in five endometriotic lesions of rhesus macaques. We propose that lesions of rhesus macaques will express elevated estrogen receptors and diminished progesterone receptors, similar to human endometriotic lesions. Endometriotic lesions of rhesus macaques were obtained at time of surgery from different locations, and steroid receptor expression was determined by immunohistochemistry. This study was able to determine the expression of steroid receptors in endometriotic lesions of rhesus macaques; however the results were not able to support our hypothesis. Results did not observe significant differences between estrogen and progesterone receptor protein expressions in glandular and stromal compartments of the endometriotic lesions. Still, this animal model represents a valuable tool to study endometriosis since they do develop spontaneous endometriosis. Future studies should match the location of lesions and classify the severity of endometriosis in the rhesus macaques.


Human topoisomerase I (top1) is the molecular target of a diverse set of anticancer compounds, including the camptothecins, indolocarbazoles, and indenoisoquinolines. These compounds bind to a transient top1-DNA covalent complex and inhibit the resealing of a single-strand nick that the enzyme creates to relieve superhelical tension in duplex DNA. (Hertzberg, R. P.; et al. Biochem. 1989, 28, 4629-4638. Hsiang, Y. H.; et al. J. Biol. Chem 1985, 260, 14873-14878. Champoux, J. J. Annu. Rev. Biochem. 2001, 70, 369-413. Stewart, L.; et al. Science 1998, 729, 1534-1541.) We report the X-ray crystal structures of the human top1-DNA complex bound with camptothecin and representative members of the indenoisoquinoline and indolocarbazole classes of top1 poisons. The planar nature of all three structurally diverse classes allows them to intercalate between DNA base pairs at the site of single-strand cleavage. All three classes of compounds have a free electron pair near Arg364, a residue that if mutated confers resistance to all three classes of drugs. The common intercalative binding mode is augmented by unexpected chemotype-specific contacts with amino acid residues Asn352 and Glu356, which adopt alternative side-chain conformations to accommodate the bound compounds. These new X-ray structures explain how very different molecules can stabilize top1-DNA covalent complexes and will aid the rational design of completely novel structural classes of anticancer drugs.


The Earth's polar regions are low rates of inter- and intraspecific diversification. An extreme mammalian example is the Arctic ringed seal (Pusa hispida hispida), which is assumed to be panmictic across its circumpolar Arctic range. Yet, local Inuit communities in Greenland and Canada recognize several regional variants; a finding supported by scientific studies of body size variation. It is however unclear whether this phenotypic variation reflects plasticity, morphs or distinct ecotypes. Here, we combine genomic, biologging and survey data, to document the existence of a unique ringed seal ecotype in the Ilulissat Icefjord (locally 'Kangia'), Greenland; a UNESCO World Heritage site, which is home to the most productive marine-terminating glacier in the Arctic. Genomic analyses reveal a divergence of Kangia ringed seals from other Arctic ringed seals about 240 kya, followed by secondary contact since the Last Glacial Maximum. Despite ongoing gene flow, multiple genomic regions appear under strong selection in Kangia ringed seals, including candidate genes associated with pelage coloration, growth and osmoregulation, potentially explaining the Kangia seal's phenotypic and behavioural uniqueness. The description of 'hidden' diversity and adaptations in yet another Arctic species merits a reassessment of the evolutionary processes that have shaped Arctic diversity and the traditional view of this region as an evolutionary freezer. Our study highlights the value of indigenous knowledge in guiding science and calls for efforts to identify distinct populations or ecotypes to understand how these might respond differently to environmental change.


The cellular fatty acid compositions and ubiquinone contents of 182 Legionella strains representing 23 species were determined by capillary gas-liquid chromatography and reverse-phase high-performance liquid chromatography, respectively. Except for the type strain of Legionella erythra (ATCC 35303T), all Legionella species contained large (40 to 90%) amounts of branched-chain fatty acids and only trace to small (less than 0.5 to 5%) amounts of ester-linked hydroxy acids. The 23 species were placed in three major fatty acid groups on the basis of differences in the relative amounts of 14-methylpentadecanoic (Ci16:0), hexadecanoic (C16:1), and 12-methyltetradecanoic (Ca15:0) acids. All Legionella species contained ubiquinones with 9 to 14 isoprene units in the side chains and were divided into five different ubiquinone groups. The species were further differentiated into 16 groups on the basis of qualitative and quantitative differences in their fatty acid compositions and ubiquinone contents. Both of these chemical characteristics can be used to distinguish Legionella species from other gram-negative bacteria and rapidly and accurately identify suspected isolates before serologic and other tests are done.


Acute otitis media, inflammation of the middle ear, is the most common bacterial infection in children and as a consequence is the most common reason for antimicrobial prescription to this age group. There is currently no effective vaccine for the principal pathogen involved, non-typeable Haemophilus influenzae (NTHi). The most frequently used and widely accepted experimental animal model of middle ear infection is in chinchillas, but mice and gerbils have also been used. We have established a robust model of middle ear infection by NTHi in the Junbo mouse, a mutant mouse line that spontaneously develops chronic middle ear inflammation under specific pathogen free conditions. The heterozygote Junbo mouse ( Jbo/ +) bears a mutation in a gene (Evi1, also known as Mecom) that plays a role in host innate immune regulation; pre-existing middle ear inflammation promotes NTHi middle ear infection. A single intranasal inoculation with NTHi produces high rates (up to 90%) of middle ear infection and bacterial titers (10 4 to 10 5 CFU/μl) in bulla fluids. Bacteria are cleared from the majority of middle ears between day 21 and 35 post-inoculation but remain in approximately 20% of middle ears at least up to day 56 post-infection. The expression of TLR-dependent response cytokine genes is elevated in the middle ear of the Jbo /+ mouse following NTHi infection. The translational potential of the Junbo model for studying antimicrobial intervention regimens was shown using a 3-day course of Azithromycin to clear NTHi infection, and its potential use in vaccine development studies by demonstrating protection in mice immunized with killed homologous, but not heterologous, NTHi bacteria.


The growing interest in named entity recognition (NER) in various domains has led to the creation of different benchmark datasets, often with slightly different annotation guidelines. To better understand the different NER benchmark datasets for the domain of English literature and their impact on the evaluation of NER tools, we analyse two existing annotated datasets and create two additional gold standard datasets. Following on from this, we evaluate the performance of two NER tools, one domain-specific and one general-purpose NER tool, using the four gold standards, and analyse the sources for the differences in the measured performance. Our results show that the performance of the two tools varies significantly depending on the gold standard used for the individual evaluations.


Background Current smokers have an increased cardiovascular disease (CVD) risk compared to ex-smokers due to reversible as well as irreversible effects of smoking. We investigated if current smokers remain to have an increased CVD risk compared to ex-smokers in subjects with a long and intense smoking history. We in addition studied if the effect of smoking continuation on CVD risk is independent of or modified by the presence of cardiovascular calcifications. Methods The cohort used comprised a sample of 3559 male lung cancer screening trial participants. We conducted a case-cohort study using all CVD cases and a random sample of 10% (n = 341) from the baseline cohort (subcohort). A weighted Cox proportional hazards model was used to estimate the hazard ratios for current smoking status in relation to CVD events. Results During a median follow-up of 2.6 years (max. 3.7 years), 263 fatal and non-fatal cardiovascular events (cases) were identified. Age, packyears and cardiovascular calcification adjusted hazard ratio of current smokers compared to former smokers was 1.33 (95% confidence interval 1.00–1.77). In additional analyses that incorporated multiplicative interaction terms, neither coronary nor aortic calcifications modified the association between smoking status and cardiovascular risk (P = 0.08). Conclusions Current smokers have an increased CVD risk compared to former smokers even in subjects with a long and intense smoking history. Smoking exerts its hazardous effects on CVD risk by pathways partly independent of cardiovascular calcifications.


It is inevitable that the incidence of pelvic organ prolapse will increase with the rapid rise of the aging population in the modern era. This book is a surgical video atlas dedicated to pelvic organ prolapse. From anatomy to complication management, the book covers the whole spectrum involving the evaluation and surgical treatment of this complicated condition. Moreover, it also includes controversial topics such as mesh augmentation and route of surgery. The original illustrations are clear and thoughtfully laid out with numerous video clips further helping the reader understand in a 3 dimensional manner. This is a truly comprehensive surgical atlas that will help any surgeon involved in the correction of the prolapsed female pelvic organ.


An employer that sets up a defined benefit pension plan promises to periodically pay a certain sum to each participant starting at some future date and continuing until death. Although both the future beneficiary and the employer can be asked to finance the plan throughout the beneficiary's career, any shortcoming of funds in the future is often the employer's responsibility. It is therefore essential for the employer to be able to predict with a high degree of confidence the total amount that will be required to cover its future pension obligations. Applying mortality forecasting models to the case of the Royal Canadian Mounted Police pension plan, we illustrate the importance of mortality forecasting to value a pension fund's actuarial liabilities. As future survival rates are uncertain, pensioners may live longer than expected. We find that such longevity risk represents approximately 2.8 percent of the total liability ascribable to retired pensioners (as measured by the relative value at risk at the 95th percentile) and 2.5 percent of the total liabilities ascribable to current regular contributors. Longevity risk compounds the model risk associated with not knowing what is the true mortality model, and we estimate that model risk represents approximately 3.2 percent of total liabilities. The compounded longevity risk therefore represents almost 6 percent of the pension plan's total liabilities.


Introduction: Myeloproliferative neoplasms (MPN) are clonal hematopoietic stem cell (HSC) disorders characterized by overproduction of mature blood cells and increased risk of transformation to myelofibrosis (MF) and acute myeloid leukemia (AML), although molecular mechanisms driving disease progression remain elusive. While most patients who acquire a JAK2V617F mutation in CD34+ cells present with chronic, indolent Polycythemia Vera (PV), ~25% will progress to MF or AML. High Mobility Group A1/2 (HMGA1/2) genes encode oncogenic chromatin remodeling proteins which are overexpressed in aggressive leukemia where they portend adverse outcomes. In murine models, Hmga1/2 overexpression drives clonal expansion and uncontrolled proliferation. HMGA1/2 genes are also overexpressed in MPN with disease progression. We therefore sought to: 1) test the hypothesis that HMGA proteins are required for leukemic transformation and rational therapeutic targets in MPN progression, and, 2) identify mechanisms mediated by HMGA1/2 during disease progression.
 Methods: We measured HMGA1/2 in JAK2V617F mutant human AML cell lines from MPN patients (DAMI, SET-2), CD34+ cells from PV patients during chronic and transformation phases, and JAK2V617F transgenic murine models of PV (transgenic JAK2V617F) and PV-AML (transgenic JAK2V617F/MPLSV; Blood 2015;126:484). To elucidate HMGA1/2 function, we silenced HMGA1 or HMGA2 via short hairpin RNA in human MPN-AML cell lines (DAMI, SET-2) and assessed proliferation, colony formation, and leukemic engraftment in immunodeficient mice. To further assess Hmga1 function in vivo, we crossed mice with heterozygous Hmga1 deficiency onto murine models of PV and PV-AML. Finally, to dissect molecular mechanisms underlying HMGA1, we compared RNA-Seq from MPN-AML cell lines (DAMI, SET-2) after silencing HMGA1/2 to that of controls and applied Ingenuity Pathway Analysis.
 Results: HMGA1/2 mRNA are up-regulated in all JAK2V617F-positive contexts, including primary human PV CD34+ cells and total bone marrow from JAK2V617F mouse models for PV compared to controls. Further, there is a marked up-regulation in both HMGA1/2 in CD34+ cells from PV patients after transformation to MF or AML and in leukemic blasts from our PV-AML mouse model compared to PV mice. Overexpression of HMGA1/2 also correlates with clonal dominance of human JAK2V617F-homozygous stem cells and additional mutations of epigenetic regulators (EZH2, SETBP1). Silencing HMGA1 or HMGA2 in human MPN-AML cell lines (DAMI, SET-2) dramatically halts proliferation, disrupts clonogenicity, and prevents leukemic engraftment in mice. Further, heterozygous Hmga1 deficiency decreases splenic enlargement in PV mouse models with advancing age. Moreover, heterozygous Hmga1 deficiency prolongs survival in the transgenic PV-AML murine model with fulminant leukemia and early mortality. PV-AML mice survived a median of 5 weeks whereas PV-AML mice with heterozygous Hmga1 deficiency survive a median of 12 weeks (P< 0.002). The leukemic burden was also decreased in mice with Hmga1 deficiency. Preliminary RNA-Seq analyses from DAMI and SET-2 cells show that HMGA1 drives pathways involved in Th1/Th2 activation, chemotaxis, cell-cell signaling, myeloid cell accumulation and other immune cell trafficking, inflammation, and injury, suggesting that HMGA1 co-opts immune and inflammatory networks to drive tumor progression. Surprisingly, atherosclerosis pathways are also induced by HMGA1.
 Conclusions: HMGA1/2 genes are overexpressed in MPN with highest levels in more advanced disease (MF, AML) both in primary human tumors and murine models. Strikingly, silencing HMGA1 or HMGA2 halts proliferation and clonogenicity in vitro and prevents leukemic engraftment in vivo. Further, heterozygous Hmga1 deficiency prolongs survival in a murine model of fulminant MPN AML and decreases tumor burdens. Finally, preliminary RNA-Seq analyses suggest that HMGA1 amplifies transcriptional networks involved in immune cell trafficking and inflammation to drive tumor progression. Unexpectedly, HMGA1 also regulates pathways involved in atherosclerosis, implicating HMGA1 as a novel link between clonal hematopoiesis and cardiovascular disease. Our findings further highlight HMGA1/2 as a key molecular switch for leukemic transformation in MPN and opens the door to novel therapeutic approaches to prevent disease progression.

 No relevant conflicts of interest to declare.