Purification of crude glycerol by employing membrane separation as a mechanism involved in the process had been widely conducted due to its environmentally process and sustainability of energy. Realizing that hybrid membrane has better thermal and mechanical stability as well as better processing flexibility as compared to membrane from pure organic polymer and inorganic material, this research investigated on the use of hybrid membrane as a barrier layer in thin film composite (TFC) for permeation of crude glycerol. In this study, thin film composite membrane consists of polysulfone as base support and hybrid membrane as the barrier layer. In a hybrid membrane formulation, a polymer blend of polyvinyl alcohol with polyethylene glycol was chosen as organic polymer which was cross-linked with tetraethylorthosilicate (TEOS). Glycerol was added as an organic additive to improve the plasticizing effect of hybrid membranes. There were three stages of work involved in the research. The first stage was investigating on base support where suitable concentration of polysulfone had been determined by water flux evaluation and investigation on suitable range of organic polymer, TEOS and glycerol concentrations. The evaluations were carried out through physical and chemical characterization and performance evaluation particularly on thin film composite through separation of crude glycerol solution. Besides good thermal and mechanical stabilities, and high surface hydrophilicity of hybrid membranes as compared to base support and membrane from pure polymer, the incorporation of glycerol had enhanced flexibility of membrane's matrix. These properties had overcome the rigidity of structure and brittleness of ordinary hybrid membranes. Major findings from this stage revealed that the suitable range of total polymer was between 5 to 7 wt.% and TEOS concentrations between 1 to 4 wt.% for formulation of hybrid membranes particularly in permeation process of crude glycerol. The second stage of research involves characterization of crude glycerol and permeation of synthetic crude glycerol which consists of glycerol, water, methanol and NaCl through the fabricated thin film composite. The main purpose was to evaluate the separation pattern of NaCl and glycerol through the TFC. Based on the evaluations, formulation of hybrid membranes with high percentage of polymer and tetraethylorthosilicate had led to high salt rejection but it suffered with low permeation of glycerol. Therefore the best formulations of hybrid membrane particularly in term of polymer and tetraethylorthosilicate concentrations and condition for feed solution that yields high NaCl rejection, high percentage permeation of glycerol and reasonable volume of flux had been determined by using design of experiment. Result showed that the regression equations generated from the experiment were accurate to predict all the responses and the best formulation was achieved at 5 wt.% total polymer with 4 wt.% TEOS, and feed condition with 75 % w/w water addition. The resulted responses were 36% NaCl rejection, 85% permeation of glycerol and 43 L/m.day of flux rate. Permeation of crude glycerol through the fabricated thin film composite, which exhibits a nanofiltration behaviour with a pore flow model as a transport mechanism, has been found as a potential pathway for crude glycerol purification which has some advantages over the existing process that employs membrane such as operation at low pressure and at room temperature.


Engineering is one of the most global professions, with design teams developing technologies for an increasingly interconnected and borderless world. In order for engineering students to be proficient in creating viable solutions to the challenges faced by diverse populations, they must receive an experiential education in rigorous engineering design processes as well as identify the needs of customers living in communities radically different from their own. Acquainting students with the unique context and constraints of developing countries is difficult because of the breadth of pertinent considerations and the time constraints of academic semesters. This article describes a tool called Global Biomedical Device Design, or GloBDD, that facilitates simultaneous instruction in design methodology and global context considerations. GloBDD espouses an example-centric approach to educate students in the user-centered and context-driven design of biomedical devices. The tool employs real-world case studies to help students understand the importance of identifying external considerations early in the design process: issues like anthropometric, contextual, social, economic, and manufacturing considerations amongst many others. This article presents the rationale for the tool, its content and organization, and evaluation results from integration into a junior-level biomedical device design class. Results indicate that the tool engages students in design space exploration, leads them to making sound design decisions, and teaches them how to defend these decisions with a well-informed rationale.


We present the ≲1 kpc resolution 12CO imaging study of 37 optically selected local merger remnants using new and archival interferometric maps obtained with ALMA, CARMA, the Submillimeter Array, and the Plateau de Bure Interferometer. We supplement a sub-sample with single-dish measurements obtained at the Nobeyama Radio Observatory 45 m telescope for estimating the molecular gas mass (107 − 11 M☉) and evaluating the missing flux of the interferometric measurements. Among the sources with robust CO detections, we find that 80% (24/30) of the sample show kinematical signatures of rotating molecular gas disks (including nuclear rings) in their velocity fields, and the sizes of these disks vary significantly from 1.1 kpc to 9.3 kpc. The size of the molecular gas disks in 54% of the sources is more compact than the K-band effective radius. These small gas disks may have formed from a past gas inflow that was triggered by a dynamical instability during a potential merging event. On the other hand, the rest (46%) of the sources have gas disks that are extended relative to the stellar component, possibly forming a late-type galaxy with a central stellar bulge. Our new compilation of observational data suggests that nuclear and extended molecular gas disks are common in the final stages of mergers. This finding is consistent with recent major-merger simulations of gas-rich progenitor disks. Finally, we suggest that some of the rotation-supported turbulent disks observed at high redshifts may result from galaxies that have experienced a recent major merger.


This paper describes a method used to model relative wetness for part of the Antarctic Dry Valleys using Geographic Information Systems (GIS) and remote sensing. The model produces a relative index of liquid water availability using variables that influence the volume and distribution of water. Remote sensing using Moderate Resolution Imaging Spectroradiometer (MODIS) images collected over four years is used to calculate an average index of snow cover and this is combined with other water sources such as glaciers and lakes. This water source model is then used to weight a hydrological flow accumulation model that uses slope derived from Light Detection and Ranging (LIDAR) elevation data. The resulting wetness index is validated using three-dimensional visualization and a comparison with a high-resolution Advanced Land Observing Satellite image that shows drainage channels. This research demonstrates that it is possible to produce a wetness model of Antarctica using data that are becoming widely available.


A prospective analysis of 100 direct laryngoscopic procedures was performed in the department of otolaryngology -al
imamain kadymain hospital- Baghdad –Iraq for the period from December 2013 to December 2014. The patients consisted
of 55% males and 45 % females with an average age of 42.8 years. The most surgical indications for direct laryngoscopy
in this study were hoarsness of voice (77%) and tumor -like masses on direct laryngoscopy (38%).

Most of procedures were performed under general anesthesia. Direct laryngoscopy was done as a diagnostic approach
in 75 % of patients and in 25 % it was performed as a therapeutic procedure. Direct suspension microlaryngoscopy was
further employed in 10 patients for therapeutic purposes. Laryngeal sequamous cell carcinoma was the most common
final diagnosis among malignant cases (41%), where as chronic non-specific laryngitis was the predominant final benign
diagnosis (13%), where as chronic non-specific laryngitis was performed was the predominant final benign diagnosis
(13%).

The result revealed that the diagnostic accuracy of indirect mirror laryngoscopy compared with direct laryngoscopy was 61%
moreover; the diagnostic accuracy was 87% by comparing direct laryngoscopy findings and histological diagnosis. Direct
laryngoscopy was difficult in three patients. The difficulty was generally recognized in patients with short and muscular
neck. The incidence of major complications was at least 4% with minor complications occurring in 7% of patients only.
Moreover, laryngospasm was significantly higher among patients underwent direct laryngoscopy with other procedures
"than those underwent direct laryngoscopy alone.


Suicide is the third leading cause of death of worldwide, and its social ramifications are far-reaching. Due to the stigma associated with suicide, as well as the unique emotional processes that occur during bereavement following this mode of death, suicide bereavement is regarded as different and more intense than other grief experiences. While the effects of suicide on the suicide-bereaved have been welldocumented using objective measures of outcome, the subjective, and often unquantifiable emotional, familial and social consequences of suicide have been largely under-researched. By using an interpretive approach, this study focuses on the subjective experiences of those who have lost a loved one to suicide. Five suicide-bereaved individuals were sampled from a particular community, and their experiences were elicited using semi-structured interviews. The results indicate a number of emotional as well as social processes that occur after suicide, including intense longing for the deceased; rationalisation, disbelief, and denial; feelings of anger, guild, regret, and sadness; a search for answers, meaning and closure; and blaming and social isolation. While these processes cannot be said to occur exclusively in suicide bereavement, they appear to be experienced more intensely during this form of grief.


The air movement within the cylinder of the NACA combustion apparatus was regulated by using shrouded inlet valves and by fairing the inlet passage. Rates of combustion were determined at different inlet-air velocities with the engine speed maintained constant and at different engine speeds with the inlet-air velocity maintained approximately constant. The rate of combustion increased when the engine speed was doubled without changing the inlet-air velocity; the observed increase was about the same as the increase in the rate of combustion obtained by doubling the inlet-air velocity without changing the engine speed. Certain types of directed air movement gave great improvement in the reproducibility of the explosions from cycle to cycle, provided that other variables were controlled. Directing the inlet air past the injection valve during injection increased the rate of burning.


Pilia, G. 2018. Novel Roles of the Ack1 Kinase in Epithelial Biology. Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine 1469. 85 pp. Uppsala: Acta Universitatis Upsaliensis. ISBN 978-91-513-0355-0. Epithelial homeostasis is maintained through integration of diverse signals that regulate cell fate. A strict control of such signals is required to prevent overproliferation and, ultimately, oncogenesis. In this thesis we identify novel roles of Activated Cdc42-associated kinase 1 (Ack1) in maintenance of epithelial homeostasis. Ack1 has been previously linked to cytoskeletal remodeling, signal transduction and gene expression regulation. Interestingly, our work reveals that Ack1 is also important for I) promoting extrinsic apoptosis, II) mediating mechanically-induced inhibition of proliferation and III) attenuating mitogenic signals, fundamental functions to prevent aberrant tissue growth. Apoptosis is a program of regulated cell death that can be triggered by several pathways. Among them, the TNF-related apoptosis-inducing ligand (TRAIL)-induced apoptosis cascade has raised interest for cancer treatment, as many cancer cell lines are susceptible to it. We found that Ack1 increases sensitivity to TRAIL by promoting translocation of ligand-bound TRAILReceptor to lipid rafts. Localisation at the lipid rafts, in turn, favors recruitment of downstream signalling effectors, enhancing the apoptotic response. Yap and Taz are transcriptional co-factors that integrate mechanical and soluble cues to regulate cell proliferation and differentiation. Yap/Taz regulation is mediated by cytoplasmic sequestration and, particularly for Taz, proteasomal degradation via ubiquitination by the E3 ligase β-TrCP. We discovered that Ack1 is activated by mechanical signals and promotes nuclear exclusion of Yap/Taz. Ack1 promotes Yap/Taz interaction with β-TRCP and it is required for efficient degradation of Taz. Consequently, Ack1 limits Yap/Taz-dependent gene expression and cell proliferation. The ErbB family of receptor tyrosine kinases mediates pro-survival and proliferative signals of crucial importance in development and cancer. Among the ErbB family members, ErbB3 has significant oncogenic properties as it potently activates the PI3K/Akt signaling pathway. We observe that Ack1 depletion increases ErbB3 total levels, but not EGFR and ErbB2, and is required for both basal turnover of ErbB3 and its ligand-induced degradation. Consequently, Ack1 attenuates ErbB3-dependent signalling upon Neuregulin-1β treatment. Additionally, Ack1 reduces ErbB3 gene expression both at steady state and upon stimulation, revealing its importance as multi-level regulator of ErbB3. Taken together, our data depict new roles for Ack1 in epithelial cells, highlighting its multifaceted role in maintenance of epithelial homeostasis.


In times of crisis, be them economic or otherwise, the powers that be inevitably look to a scapegoat. They need to be able to shift the focus from their own mistakes to the actions of others so as to take the spotlight off the current crisis and their own shortcomings. It may be no coincidence that during the latest economic crisis, the rhetoric against homosexuals and same-sex marriage has been ratcheted up. While the expected politicians and religious leaders continue the fight against same-sex marriage rights, the more surprising trend has been the success of ballot initiatives against same-sex marriage. With the recent repeal by ballot votes in California and Maine, we have seen the populace shoot down state approved same-sex marriage. Interestingly, public backlash against same-sex marriage comes at a time where support for same-sex marriage rights continues to rise across the country. However, even in the face of polling data which suggests public support, we still see politicians such as those in New York City vote against same-sex marriage rights under the guise of "the will of the public." Where the denial of equal rights comes from may vary from state to state, but whether coming from the legislature or the protesters on Main Street, you are likely to hear the same rationale: Same-sex marriage will ruin the institution of marriage, it will ruin families, it will ruin society, the next step is marrying animals, the list goes on and on. The question becomes: is there a scientific, logical, or legal basis for these arguments? Perhaps more so than with any other social issue, the politics of fear and blame are utilized, often successfully. It is an issue where we see a break from attacks based on science and statistics, with a shift to using hypothetical situations as ammunition. Is there any actual threat to the institution of marriage from the recognition of same-sex marriage, and are these arguments sufficient to justify the denial of equal rights?I argue that the arguments against same-sex marriage rights are fear tactics used against a growing minority to distract the populace. I argue that: (1) data indicates either a strengthening of, or non impact on, familial institutions in nations that granted same-sex marriage or union rights; and (2) the purported state interests in denying same-sex marriage rights do not pass Constitutional muster under any standard of review. I further argue that the recent backlash against homosexuals arises from the politics of fear being implemented by Conservative politicians, leaders, and community members to create a new political underclass that can be focused on in a time of crisis. In short, the current backlash against equal rights of homosexuals is a witch-hunt that uses ballots and pulpits instead of torches and pyres.


Summary

1
Factors that have been considered when deciding how to invest resources in conservation of species include the efficacy and cost of management, the importance of the species, the level of threat, and the timeframe over which results are to be achieved. However, it is unclear how each of these different factors should be weighted and combined when making a decision.

2
We examine how the probabilities of species changing in IUCN Red List categories are influenced by expenditure of resources. We use these relationships to determine optimal investment strategies, using Australian birds as a case study.

3
The optimal level of investment in different species depends critically on whether managers wish to minimize the number of extinct species or a weighted average of all threatened species, and on the available budget. The level of investment should not necessarily reflect the level of threat. In our case study, the timeframe of management had little influence on the investment decision.

4
Our results show that extinctions of Australian birds can be largely avoided over the next 80 years given current expenditure, but greater investment in conservation is required to reduce the number of threatened species.

5
Synthesis and applications. The most efficient allocation of resources to conserve species is difficult to determine intuitively; therefore, this decision demands the use of formal decision theory. The influence of the particular management objective on the optimal decision means that this feature needs careful consideration. Our approach can be used to determine the level of investment that is required to reduce the number of threatened species.


During the last decade, two concerns have been raised about the future of U.S. crop production. These concerns are: A) Will the United States have enough land available in the future that is suitable for crop production? and b) What will future crop yields be? Future U.S. crop production is highly dependent upon both these issues. The real problem may not be the quantity of future crop production, but rather the price of the quantity that is available. The development of a model to answer this question is one of the objectives of this study. The other objective is the projection of prices and quantities for barley, corn, oats, sorghum, soybeans, and wheat for the year 2000 under alternative yield and land availability assumptions.


The Bluenose Schooner forms part of the folk history of Nova Scotia, and is a Canadian icon. Popular assumptions that its name and image formed part of the public domain were put to the test in 2003 when the Bluenose II Preservation Trust Society brought suit against a Halifax business for infringement of its official marks, trademarks and copyrights relating to the ship and its name. The litigation garnered local and national media attention, and the provincial government soon became involved in the dispute.In this article, the author provides some background to the dispute before moving on to consider the merits of the trademark and copyright claims. Because the infringement suit was eventually dropped as part of an agreement between the Trust and the Province of Nova Scotia, the legal issues raised by this case remain unresolved. The author argues that the intellectual property claims of the Trust were largely without merit. She is critical of the official marks regime under the Trade-marks Act, and discusses the boundaries between intellectual property and the public domain.


The recent detection of Earth-sized planets in the habitable zone of Proxima Centauri, Trappist-1, and many other nearby M-type stars has led to speculations whether liquid water and life actually exist on these planets. To a large extent, the answer depends on their yet unknown atmospheres, which may, however, be within observational reach in the near future by JWST, ELT, and other planned telescopes. We consider the habitability of planets of M-type stars in the context of their atmospheric properties, heat transport, and irradiation. Instead of the traditional definition of the habitable zone, we define the biohabitable zone, where liquid water and complex organic molecules can survive on at least part of the planetary surface. The atmospheric impact on the temperature is quantified in terms of the heating factor (a combination of greenhouse heating, stellar irradiation, albedo, etc.) and heat redistribution (horizontal energy transport). We investigate the biohabitable domain (where planets can support surface liquid water and organics) in terms of these two factors. Our results suggest that planets orbiting M-type stars may have life-supporting temperatures, at least on part of their surface, for a wide range of atmospheric properties. We apply this analyses to Proxima Cen b and the Trappist-1 system. Finally, we discuss the implications for the search of biosignatures and demonstrate how they may be used to estimate the abundance of photosynthesis and biotic planets.


The structure of follicle-stimulating hormone bound to the ectodomain of its receptor reveals a possible mechanism for receptor activation. Follicle-stimulating factor (FSH) is a canonical glycoprotein hormone that forms heterodimers consisting of an α subunit common to all glycoprotein hormones and a hormone-specific β subunit. Glycoprotein hormone receptors are G protein–coupled receptors (GPCRs) that have large ectodomains comprising a rigid hormone-binding domain at the N terminus and a "hinge" domain responsible for linking hormone binding to receptor activation. In the FSH receptor, Tyr335 must be sulfated for hormone recognition and signaling. Jiang et al. solved the crystal structure of FSH in complex with the ectodomain of FSH receptor (FSHR), which contained 12 leucine-rich repeats (LRRs) and a protruding hairpin loop. LRR1 through 10 comprised the hormone-binding domain. Contrary to expectation, the authors discovered that the hinge domain was not a separate or disordered domain but comprised LRR11 and 12 along with a protruding hairpin loop in between them that contained Tyr335, which was sulfated in the structure. The presence of three disulfide bonds between the hairpin loop; the CF3 motif, which is common to GPCRs; and hydrophobic interactions that coupled the hinge domain to the hormone-binding domain suggested that large-scale conformational changes upon ligand binding were unlikely. At the hormone-receptor interface, sulfated Tyr335 of the FSHR ectodomain was inserted into a pocket on FSH lined with hydrophobic residues and the positively charged Arg35 of FSH. This microenvironment resulted in a charge-charge interaction between sulfated Tyr335 of FSHR ectodomain and Arg35 of FSH. Comparison with the structure of free FSH revealed that FSH changed conformation to accommodate this interaction. The receptor-binding conformation of FSH was also seen in a structure of FSH in complex with a fragment of the FSHR that only contained the hormone-binding domain, suggesting that the presence of the receptor's sulfated residue was not necessary to induce this change in ligand conformation. Mutation of a residue on FSH below the tyrosine binding pocket from phenylalanine to glutamate, which should alter the interaction with the sulfated Tyr335 of the receptor, enhanced FSHR signaling as measured in a β-arrestin recruitment assay and an estradiol production assay. These structural data suggest that the receptor recruits FSH, inducing conformational changes in FSH that open a binding pocket for sulfated Tyr335 from FSHR. Insertion of the sulfated Tyr335 would then lead to receptor activation and signaling. X. Jiang, H. Liu, X. Chen, P.-H. Chen, D. Fischer, V. Sriraman, H. N. Yu, S. Arkinstall, X. He, Structure of follicle-stimulating hormone in complex with the entire ectodomain of its receptor. Proc. Natl. Acad. Sci. U.S.A. 109, 12491–12496 (2012). [Abstract] [Full Text]


The adoption of a floating exchange rate system in Kenya was an effort to make it more aligned to the market determined equilibrium rate. However, there is limited empirical evidence that success has since been achieved in realizing the objective for which the foreign exchange market was liberalized. The exports of French beans are one of the leading contributors to foreign exchange earnings in Kenya. Nevertheless, the economic impacts of exchange rate liberalization on French beans exports in Kenya are unclear. This paper evaluates the magnitude and direction of the effects of exchange rate liberalization on French beans exports from Kenya to its major trading partners in the European Union. Monthly data for a fixed exchange regime represented by the period from 1990-1993 and a flexible regime represented by the period from 1994-2011 was used in the estimation of an export demand model. The empirical results show that the liberalization of the exchange rate led to an increase in the French beans export volumes from Kenya to the European Union. The paper recommends that, even if the Kenyan exchange rate system is flexible, exchange rate stability is necessary to avoid adverse effects of exchange rate volatility on French beans exports. Therefore, stability of the exchange rate is needed, not at a fixed level but by controlling exchange rate volatility using the exchange rate target band.


von Willebrand factor (vWF ) in the presence of botrocetin induces p72syk activation, assessed as its autophosphorylated level and in vitro kinase assays, the transient association of p72syk with p60c-src, and the translocation of p60c-src and p54/58lyn to cytoskeletal fractions. Jararaca glycoprotein Ib-binding protein (GPIb-BP), which specifically binds to GPIb, abolished these phenomena, suggesting that they are mediated by the vWF-GPIb interaction. These tyrosine kinase-related events were not inhibited by GRGDS peptide (plus EGTA), indicating that GPIIb/IIIa is not involved in the observed responses. Shc, an adaptor protein, was also tyrosine phosphorylated by the botrocetin-vWF activation. When GPIb was immunoprecipitated with nonfunctional monoclonal antibodies (MoAbs) directed against GPIb, a kinase activity was found to associate with GPIb upon botrocetin-vWF activation. On the other hand, anti-GPIb MoAbs that inhibit the vWF-GPIb interaction did not coprecipitate a kinase activity. Because the recovery of GPIb did not differ significantly, it is suggested that the excessive presence of inhibitory anti-GPIb MoAb dissociated a kinase activity from GPIb. Phosphoamino acid analysis showed that the kinase activity was that of a tyrosine kinase. The identity of the tyrosine kinase and the mode of interaction with the cytoplasmic region of GPIb await to be determined. Our findings suggest that the tyrosine kinase associated with GPIb serves at a most proximal step in the signal transduction pathway involved in the vWF-GPIb-induced platelet activation, which leads to other tyrosine kinase-related intracellular signals.


We consider the problem of creating oscillations of the Furuta pendulum around the open-loop unstable equilibrium. We start with a control transformation shaping the energy of the passive link. Then, a dissipativity-based controller is designed to create oscillations, neglecting the possibility of unbounded motion of the directly actuated link. After that, an auxiliary linear feedback action is added to the control law stabilizing a desired level of the reshaped energy. Parameters of the controller are tuned to approximately keep the originally created oscillations but ensuring bounded motion of both links. The analysis is valid only for oscillations of sufficiently high frequency and is based on higher order averaging technique. The performance of the designed controller is verified using numerical simulations as well as experimentally.


Bacterial proteinaceous filaments termed pili or fimbriae are nonflagellar, hair-like structures protruding from the cell surface that are critical for bacterial virulence and fitness. Present in both Gram-negative and Gram-positive bacteria, pili are involved in many processes such as conjugation, adherence, twitching motility, biofilm formation and immunomodulation. Considerably diverse and complex, Gram-negative pili are formed by noncovalent polymerisation of various pilin subunits; many of these pili require chaperones and usher proteins for their assembly. In contrast, fewer pilus systems have been described for the Gram-positive counterparts; notably well studied are the heterotrimeric or -dimeric pili that are covalently assembled by a transpeptidase enzyme called sortase. Here we review the current knowledge of assembly pathways, structure and function of these pili in Gram-negative and Gram-positive pathogens.

Key Concepts:

Noncovalent pilus polymerisation is a general mechanism of pilus assembly in Gram-negative bacteria, including the chaperon-usher assembly pathway and type IV pilus pathway, which generates noncovalent pilus polymers.

Sortase-mediated pilus assembly is a general mechanism of pilus assembly in Gram-positive bacteria that involves a transpeptidase enzyme named sortase, which cleaves pilin precursors at sorting signals between threonine and glycine and involve the side-chain amino groups of pilin motif sequences to generate covalent links between pilin subunits.

The sorting signal is consisted of an LPXTG motif followed by a hydrophobic domain and a positively charged tail.

The pilin motif is an 11 amino acid sequence of WxxxVxVYPKN located near the N-terminus of major pilin subunits, in which the electron donating lysine residue forms an isopeptide bond with the threonine residue generated from the cleavage of the LPXTG motif of adjacent pilin subunits.

Tissue tropism is referred to as the ability of a pathogen to adhere specifically to some particular epithelial cells.

Phase variation involves switching of surface antigens such as pili that allows a pathogen to evade the host immune system.

Immunomodulation is a process of changing the host's immune system by certain molecules known as immunomodulators including pili that can activate or suppress immune cells.

Dental plaque is one of the most complex bacterial biofilms that is formed by sequential colonisation of initial colonisers such as Actinomyces spp. and oral streptococci and late colonisers; this process involves Actinomyces fimbriae.

Twitching motility mediated by pili allows translocation between mucosal surfaces, colonisation of host tissues and establishment of biofilms by a pathogen.

Keywords:

pili;
fimbriae;
adhesion;
polymerisation;
sortase


A series of intermittent changes in Stephanodiscus (Bacillariophyta) valve morphology was observed in sediment core materials collected from Lake Biwa, Japan. A constant sedimentation rate reveals a continuous but punctuated pattern of morphological evolution. Morphological parameters, including maximum diameter and fascicle number v. diameter ratio (fascicle density), showed long periods of stasis and less than 10 000-year directional changes. Specifically, directional decreases in fascicle density occurred at 200–190 and 160–150 ka, and increases in maximum diameter occurred at 130–120 ka. According to a morphology-based species definition, a non-branching phylogenetic lineage originating from a cosmopolitan ancestor can be presumed from a morphology-based cladistic analysis and the biostratigraphic record. Evolutionary modes were selected from directional change, random walk, stasis and combined models by a statistical test, paleoTS, to clarify that the sequential changes are composed of relatively long stasis modes and short directional change modes. Global climate change was probably an influence during the early stages of the history of Lake Biwa. Supplementary material: Time-series data to discriminate the tempo and mode of morphological evolution are available at http://www.geolsoc.org.uk/SUP18825


Background/introduction Men who have sex with men (MSM) are at risk of HPV-associated genital warts and cancers but are unlikely to benefit from female-oriented HPV vaccination. Aim To examine the attitudes of sexual healthcare professionals (SHCPs) towards HPV vaccination of men in the UK. Methods An e-survey of SHCPs' views was conducted in July–August 2014. Members of UK-based professional sexual health associations were invited to participate by direct email and members' newsletters. Responses to 18 statements, with corresponding Likert scales, were used to examine their views on HPV vaccination. Results Amongst 325 respondents (46% Doctors, 26% Nurses and 15% Health advisors), 14% are already vaccinating men against HPV and 83% would recommend gender-neutral HPV vaccination. While 64% would also recommend targeting MSM, 18% were against this strategy. Only 44% reported having sufficient knowledge about the use of HPV vaccine for MSM and 49% reported having skills to identify MSM likely to benefit from HPV vaccination. While 19% agreed that it is too late to offer HPV vaccine to sexually active MSM, 53% thought all MSM, regardless of their age, should be offered the vaccine. Conclusion SHCPs perceived the need to vaccinate MSM against HPV. Despite insufficient knowledge, a gender-neutral HPV vaccination strategy was favoured over targeted HPV vaccination for MSM. Clear advice and guidelines for SHCPs on HPV vaccine use in men at sexual health clinics are required to ensure equitable opportunities for vaccination. If MSM-targeted HPV vaccination is recommended, SHCPs' attitudes need to be taken into account to achieve optimal uptake.


Multimedia systems are typically monolithic systems that are expensive and challenging to maintain and develop. With the advances of Service Oriented Architecture (SOA) a component-based approach can be applied to multimedia systems development. A complex and large scale multimedia system can be split into smaller and reusable components. These components can be composed in different ways so that the development of multimedia systems can be flexible and the resulting component-based system is more maintainable, reliable and scalable than a monolithic system.
One of the common implementations of SOA is Web services. However the transfer of streaming data, which is a major part of multimedia systems, is not well supported by current Web services standards. To reap the benefits of the component-based approach for multimedia systems development, this thesis proposes a novel extension for multimedia streaming support in the Web services architecture. The proposed extension focuses on three issues: the discoverability of a multimedia Web service, the implementation of streaming data transfer between two Web service endpoints and the efficiency of the streaming data transfer.
First, the discoverability of a Web service relies on a standardized and descriptive metadata for its content. The proposed extension provides a query service so that the description of multimedia content input to and output from a multimedia Web service can be published via an extension of WSDL. Second, the proposed extension implements the streaming data transfer between two service endpoints using two new Message Exchange Patterns (MEPs) and their corresponding HTTP bindings. The implementations use MIME and Message Transmission Optimization Mechanism (MTOM) to transfer streaming multimedia as a stream of SOAP messages. Third, to reduce the transfer overhead introduced by the packaging method, this thesis investigated extensively the application of various compression schemes to the SOAP messages as well as to the packaging of the binary packet data. Experiments show that the proposed extension, coupled with the use of the binary XML encoding scheme, has a significant improvement in performance over current approaches for multimedia streaming transfer.


Gymnammodytes oranensis n. sp. (Teleostei, Perciformes, Ammodytidae) is described from upper Miocene marine deposits of Gambetta, near Oran, northwestern Algeria. This species is represented by four articulated but incomplete skeletons. Gymnammodytes oranensis n. sp. differs from Recent species of the genus in possessing a not specialized premaxilla. Gymnammodytes oranensis n. sp. is the earliest known occurrence of the genus Gymnammodytes as skeletal remains. The specimens here described provide unequivocal evidence of the presence of the Ammodytidae in the Miocene of the Mediterranean. RESUME


Enolase, a glycolytic enzyme that catalyzes the dehydration of 2-phospho-d-glycerate (PGA) to form phosphoenolpyruvate (PEP), is a homodimer in all eukaryotes and many prokaryotes. Here, we report the crystal structure of a complex between yeast enolase and an equilibrium mixture of PGA and PEP. The structure has been refined using 29 854 reflections with an F/sigma(F) of >/=3 to an R of 0.137 with average deviations of bond lengths and bond angles from ideal values of 0.013 A and 3.1 degrees , respectively. In this structure, the dimer constitutes the crystallographic asymmetric unit. The two subunits are similar, and their superposition gives a rms distance between Calpha atoms of 0.91 A. The exceptions to this are the catalytic loop Val153-Phe169 where the atomic positions in the two subunits differ by up to 4 A and the loop Ser250-Gln277, which follows the catalytic loop Val153-Phe169. In the first subunit, the imidazole side chain of His159 is in contact with the phosphate group of the substrate/product molecule; in the other it is separated by water molecules. A series of hydrogen bonds leading to a neighboring enolase dimer can be identified as being responsible for ordering and stabilization of the conformationally different subunits in the crystal lattice. The electron density present in the active site suggests that in the active site with the direct ligand-His159 hydrogen bond PGA is predominantly bound while in the active site where water molecules separate His159 from the ligand the binding of PEP dominates. The structure indicates that the water molecule hydrating carbon-3 of PEP in the PEP --> PGA reaction is activated by the carboxylates of Glu168 and Glu211. The crystals are unique because they have resolved two intermediates on the opposite sides of the transition state.


We consider the estimation of multiple time-domain sparse filters from echoic mixtures of several unknown sources, when the sources are sparse in the time-frequency domain. We propose a sparse filter estimation framework consisting of two steps: a) a clustering step to group the time-frequency points of mixtures where only one source is active, for each source; b) a convex optimisation step to estimate the filters based on a time-frequency domain cross-relation. We propose a new wideband formulation of a frequency domain cross-relation, besides the one based on classical narrowband approximation. The solutions of the convex optimisation problem, formed using the cross-relation, are characterised. Numerical evaluation shows the benefit of using the wideband cross-relation for sparse echoic filter estimation. Further, the potential of the proposed framework for blind estimation of sparse echoic filters is demonstrated in a controlled experimental setting where in the proposed approach outperforms the state of the art blind filter estimation techniques, when the filters are suciently sparse.


The widely accepted external incentives model of conditionality (EIM) argues
that the rewards promised by the EU need to be credible for target states to
comply with costly EU conditions. Accordingly, compliance should come to a
halt or decline significantly in countries where the credibility of accession – the
most powerful reward used by the EU – is very low. The case of Turkey appears
therefore to present a puzzle, since the current AKP government is still
complying with costly EU conditions despite the negative signals from the most
powerful member-states and the EU general public. This thesis first establishes
that there is indeed a puzzle. The quantitative and qualitative data gathered on
formal and behavioural compliance demonstrates that credibility is not a
necessary condition for compliance. There are absolutely no signs of decline in
compliance, which challenges the EIM's credibility assumption. The second part
of this thesis moves to consider why the Turkish authorities continue to comply
under diminished credibility. It finds that the AKP makes strategic use of EU
conditionality. Firstly, compliance with EU conditions serves to curb the powers
of the Kemalist/secularist establishment and thereby to secure the party's
continued presence. Secondly, compliance helps the government to appear as a
Western, reformist, moderate and neo-liberal party to the electorate so as to
widen its domestic support. Moreover, lock-in effects of Turkey's already
established pro-European foreign policy, together with issue-specific
costs/benefits, also inform the AKP's decision to comply, albeit to a lesser
extent. Finally, this thesis analyses the role of the EU-related bureaucracy as a
separate, but limited, actor in the compliance process. In contrast to the political
leadership, strong organisational lock-in effects and a high level of social
learning motivate bureaucratic agents' further compliance, which suggests there
is a specific bureaucratic politics of compliance at work in Turkey.


The issue of people smuggling is one of global concern that many states have responded to by introducing a specific criminal offence of people smuggling. In Indonesia, a country that is a key transit point for asylum seekers heading to Australia, new offences have been introduced since 2011 in order to criminalise people smuggling. In this article we analyse the legal framework that has been established to combat people smuggling in Indonesia, both before and after the reforms of 2011. We consider how arrests for people smuggling have been dealt with by the public prosecutor and the judiciary in practice. We argue that the implementation and outcome of the new offences for people smuggling in Indonesia must be considered within the broader social and political context in which courts are situated. We demonstrate that sentencing practices in people smuggling trials are informed by a range of factors in addition to corruption, including judicial discretion and broader social attitudes towards people smugglers.


The pharmaceutical industry may have lost its ability to differentiate prescription drug tablets from generic imitations in light of the Third Circuit's decision in Shire US Inc. v. Barr Laboratories Inc . 1 Traditional trade dress jurisprudence has long recognized a cause of action whereby a national brand-name manufacturer can sue to protect its product's identity from a generically manufactured facsimile. Such an action normally arises when a generic manufacturer copies the appearance of a brand-name product, thereby gaining instant product recognition based on the brand-name manufacturer's established marketing and accumulated goodwill. 2 Trademark common law and the Lanham Act protect brand-name manufacturers from such unfair trade practices. 3 Over-the-counter drugs are packaged in containers bearing manufacturers' names and markings, enabling consumers to differentiate between, for example, Ecotrin™ aspirin and generic CVS store brand aspirin. 4 When a generic manufacturer's label is sufficiently similar to that of an established product, the Lanham Act dictates that the generic manufacturer must cease selling its product. 5 Even when products, i.e., tablets, are physically identical, packaging labels serve as sufficient identification of their source.


Background Adults with intellectual disability (ID) experience inequality in access to healthcare that is considered to extend to end-of-life care. Their experiences of healthcare at the end of life and how these compare with the general population are unknown. Aim To describe the end-of-life care outcomes for adults with ID living in residential care in the UK using the VOICES-SF questionnaire and compare these with the general population. Design Nationwide population-based postbereavement survey. Participants 38 ID care providers took part in the study. The supported over 13 000 people with ID. Over the 18-month period of data collection, 222 deaths were reported. The survey was completed, by care staff, for 157 (70.7%) of those deaths. Results Decedents had complex health, functional and behavioural needs. Death was unanticipated in a high proportion of cases. Quality of care provided across care settings was generally well rated. However, hospital care and care provided at the time of was less well rated, particularly in comparison with the general population. Respondents reported low levels of involvement in care and awareness of approaching death among adults with ID, and lower than in the general population. Conclusions Access to end-of-life care for adults with ID may be constrained by a failure to identify approaching the end of life. The high proportion of unexpected deaths in this population warrants further study. There is a need to increase and support the involvement of adults with ID to be active partners in planning care at the end of their lives.


Optical parametric amplification in type I collinear and one-beam noncritical noncollinear phase-matching (PM) configurations has been investigated. The effects of absorption and walk-off of the interacting beams are fully taken into account, while their divergence, as well as the depletion of the pump, is assumed to be negligible. Numerical results with the organic crystal 3-methyl-4-nitropyridine-l-oxide show that, when the crystal thickness exceeds a certain value, one-beam noncritical noncollinear PM is more efficient than collinear PM owing to the different geometry of the interacting beams. Thus the applications of one-beam noncritical noncollinear type I PM in optical parametric amplification and oscillation experiments are expected to be even more interesting when the beams are focused.


We give a preliminary description of ProppML, an annotation scheme designed to capture all the components of a Proppian-style morphological analysis of narratives. This work represents the first fully complete annotation scheme for Proppian morphologies, going beyond previous annotation schemes such as PftML, ProppOnto, Bod et al., and our own prior work. Using ProppML we have annotated Propp's morphology on fifteen tales (18,862 words) drawn from his original corpus of Russian folktales. This is a significantly larger set of data than annotated in previous studies. This pilot corpus was constructed via double annotation by two highly trained annotators, whose annotations were then combined after discussion with a third highly trained adjudicator, resulting in gold standard data which is appropriate for training machine learning algorithms. Agreement measures calculated between both annotators show very good agreement (F_1>0.75, kappa>0.9 for functions; F_1>0.6 for moves; and F_1>0.8, kappa>0.6 for dramatis personae). This is the first robust demonstration of reliable annotation of Propp's system.


Efficient Disk-Based Techniques for Manipulating Very Large String Databases Amin Mohammad Amin Elsayed Allam Indexing and processing strings are very important topics in database management. Strings can be database records, DNA sequences, protein sequences, or plain text. Various string operations are required for several application categories, such as bioinformatics and entity resolution. When the string count or sizes become very large, several state-of-the-art techniques for indexing and processing such strings may fail or behave very inefficiently. Modifying an existing technique to overcome these issues is not usually straightforward or even possible. A category of string operations can be facilitated by the suffix tree data structure, which basically indexes a long string to enable efficient finding of any substring of the indexed string, and can be used in other operations as well, such as approximate string matching. In this document, we introduce a novel efficient method to construct the suffix tree index for very long strings using parallel architectures, which is a major challenge in this category. Another category of string operations require clustering similar strings in order to perform application-specific processing on the resulting possibly-overlapping clusters. In this document, based on clustering similar strings, we introduce a novel efficient technique for record linkage and entity resolution, and a novel method for correcting errors in a large number of small strings (read sequences) generated by the DNA sequencing machines.


This paper studies a difference operator for stochastic systems whose specifications are represented by Abstract Probabilistic Automata (APAs). In the case refinement fails between two specifications, the target of this operator is to produce a specification APA that represents all witness PAs of this failure. Our contribution is an algorithm that permits to approximate the difference of two deterministic APAs with arbitrary precision. Our technique relies on new quantitative notions of distances between APAs used to assess convergence of the approximations, as well as on an in-depth inspection of the refinement relation for APAs. The procedure is effective and not more complex than refinement checking.


Local institutional and structural (meso) factors can play a role in mediating the returns to a macro-social policy. I focus on the Brazilian cash-transfer-programme Bolsa Familia and check how contextual features influence the returns to transfers. Building on Amartya Sen's work, I assess the return to the policy in terms of non-monetary achievement indicators in the dimensions of education, health and employment quality. I use the extensive CadUnico of the Brazilian Ministry for Social Development comprising all beneficiaries of Bolsa Familia, and a meso-level dataset containing information on economic structure, socio-demographic and institutional characteristics of Brazil's 5565 municipalities in a random coefficients (multilevel) model. First results confirm that a number of contextual factors play a role in increasing the conversion of transfers into human development.


Abstract The soil fertilization in ecological agriculture is done mostly using organic fertilizers. Some of them are prepared as compost from waste, but other haven't, until now, any recycling possibility. In this context, for the preparation of new types of compost, we used three type of waste: sewage sludge from waste water treatment, marine algae and farmyard manure. We have made four different composting variants, each consisting of different proportions of the three waste: equal parts (33.33%) of each waste, 50% of each of the three wastes separately, the difference being made up in equal amounts (25%) of the other two wastes. Composting process was performed in Könemann silos (cubs with side by 1.20m) and lasted 60 days, from July 19 until September 16, when the composted material has passed the stages of reduction and oxidation. During composting process, in the reductive stage the material has reached a temperature up to 63°C Celsius, enough heat for its sterilization. Initial material, semi composted and final composted material were been chemical analyzed, especially in terms of macro- and microelements, analytical results revealing high and normal content of such chemicals. Therefore the achieved compost could be used in organic farming systems.


Improved access to better seeds and other inputs, as well as to market and financing, provides greater harvest security for smallholder farmers in Africa, boosting their incomes and increasing food security. Since 2015, a variety of agronomic measures have been introduced and adopted by smallholder farmers under a program led by the United Nations' World Food Program (WFP) called the Patient Procurement Platform (PPP). Here, we integrate a variety of agronomic measures proposed by the PPP to more than 20,000 smallholder farmers in Tanzania into 18 management strategies. We apply these across the country through grid-based crop model (DSSAT) simulations in order to quantify their benefits and risk to regional food security and smallholder farmers' livelihoods. The simulation demonstrates current maize yields are far below potential yields in the country. Simulated yields across the nation were slightly higher than the mean of reported values from 1984 to 2014. Periodic droughts delayed farmers' sowing and reduced maize yield, leading to high risk and low sustainability of maize production in most of the maize areas of the country. Better agronomic management strategies, particularly the combination of long-maturity, drought tolerance cultivars, with high fertilizer input, can potentially increase national maize production by up to five times, promoting Tanzania as a regional breadbasket. Our study provides detailed spatial and temporal information of the yield responses and their spatial variations, facilitating the adoption of various management options for stakeholders.


This paper examines whether EU membership enhances or diminishes the UK's financial sector stability, and therefore its prominence in global finance. The UK is host to the largest share of financial services in the EU, despite being outside of the Eurozone. An important reason is that, as a member of the EU, the UK has direct access to the Eurozone's financial infrastructure. If the UK leaves the EU (and EEA) banks and other financial services firms may continue to have access to the Single Market, but they are unlikely to have direct access to the Eurozone's infrastructure. Banks in the UK will no longer be direct members the Eurozone's payments system. The swap arrangement between the European Central Bank and Bank of England would have no legal enforcement mechanism. Resolution of cross-border banks would be more challenging with less incentive for a cooperative outcome. While some may welcome the reduced size of the financial system, not without reason, this could be achieved more effectively with domestic regulation than by leaving the EU. Given the uncertainty that would follow a vote to leave, there is a risk of capital flight.


Since the initial publication of this classic text, motivational interviewing (MI) has been used by countless clinicians in diverse settings. Theory and methods have evolved apace, reflecting new knowledge on the process of behavior change, a growing body of outcome research, and the development of new applications within and beyond the addictions field. Including 25 nearly all-new chapters, this revised and expanded second edition now brings MI practitioners and trainees fully up to date. William R. Miller and Stephen Rollnick explain how to work through ambivalence to facilitate change, present detailed guidelines for using their approach with a variety of clinical populations, and reflect on the process of learning MI. Chapters contributed by other leading experts then address such special topics as MI and the stages-of-change model; using the approach with groups, couples, and adolescents; and applications to general medical care, health promotion, and criminal justice settings.


People often do not know where things are and have to look for them. This thesis presents a formal model suitable for reasoning about how to find things and acting to find them, which I will call "search behavior". Since not knowing location of something can prevent an agent from reaching his desired goal, the ability to plan and conduct a search will be argued to increase the variety of situations in which an agent can succeed at his chosen task. Searching for things is a natural problem that arises when the blocks world assumptions (which have been the problem setting for most planning research) are modified by providing the agent only partial knowledge of his environment. Since the agent does not know the total world state, actions may appear to have nondeterministic effects. The significant aspects of the search problem which differ from previously studied planning problems are the acquisition of information and iteration of similar actions while exploring a search space. Since introduction of the situation calculus [MH69], various systems have been proposed for representing and reasoning about actions which involve knowledge acquisition and iteration, including Moore's work on the interaction between knowledge and action [Moo80]. Such systems can be used to infer properties of plans which have already been constructed, but do not themselves construct plans for complex actions. My concern with searching has to do with a sense that Moore's knowledge preconditions are overly restrictive. Morgenstern [Mor88] examined ways to weaken knowledge preconditions for an individual agent by relying on the knowledge and abilities of other agents. Lesperance's research [Lesgl] on indexical knowledge is another way of weakening the knowledge preconditions. I am trying to reduce the amount of information an agent must know (provided he can search a known search space). If you dial the right combination to a safe it will open, whether or not you knew in advance that it was the right combination. Search is a way to guarantee you will eventually dial the right combination. So what I am exploring is how to systematically construct a search that will use available knowledge to accomplish something the agent does not currently know enough to do directly. I claim it is possible for automated agents to engage in search behavior. Engaging in search behavior consists in recognizing the need for a search, constructing an effective plan, and then carrying out that plan. Expressing such a plan and reasoning about its effectiveness requires a representation language. I will select a representation language based on criteria derived from analyzing the search planning problem. Each of the three components of a system for engaging in search behavior will be designed and implemented to demonstrate that an automated agent can find things when he needs to. Comments University of Pennsylvania Department of Computer and Information Science Technical Report No. MSCIS-93-56. This technical report is available at ScholarlyCommons: http://repository.upenn.edu/cis_reports/254 Search Plans (Dissertation Proposal) MS-CIS-93-56 LINC LAB 250


In this work we have executed a comprehensive review of green energy consumers to predict the market behavior and discussed some inputs for financial modeling. We have proposed a model based on different input parameters and linked them to form a structure that can be used for financial analysis to forecast future prospectus of green energy. Impact of various scenarios are considered and discussed in detail, and their effects on the market of alternative energy are explained. Demand, sales, decision making, simulations, extreme events are discussed and modeling options are explored. Importance of forming parity, random movements, and equilibriums are scrutinized so that they can be modified for making financial engineering models for green energy.


This paper explores how a certain country is described on official tourist sites whose main aim is to achieve more tourists (formal communication sources) and in informal tourists comments, who want to exchange their opinions. It shows that the difference in aims impacts the construction of country image as a set of different items reflecting real aspects of a certain country. The semantic and contextual analyses of Russian and German formal and informal tourism related sources shows the predominance of cognitive items (compared with affective ones) in both sources types, but cultural items colored positively prevail in formal sources (and thus an elaborated image is developed) whereas different cognitive and affective items are common for informal sources.


Eighteen diabetic patients representing a spectrum from hyperlabile to stable forms of this disease were investigated under metabolic ward conditions. Hyperlabile patients had the greatest daily and hourly variation in glycosuria and the most marked ketonuria. In our hyperlabile patients, multiple daily injections of short-acting insulin proved to be the only therapeutic measure that provided significant improvement in diabetic regulation when dietary and general health measures were already optimal. In more stable patients, longer acting insulin injected less frequently was found to be satisfactory therapy if careful adjustments to individual needs were made. Blood glucose and serum ketone-body and free fatty acid concentrations as well as qualitative estimates of glucose and ketone bodies in small samples of freshly voided urine were found to be suitable indicators of the immediate state of metabolic regulation. These parameters correlated with one another to a satisfactory degree, but they proved to be poorly correlated with measurements of urinary glucose and ketone bodies during periods of five to twenty-four hours. Quantitative analysis of individual blood samples or qualitative estimates of glucose or ketone bodies in freshly voided urine specimens proved to be unreliable indices of the patients' long-term metabolic compensation except in the most stable patients. Quantitations of urinary glucose and ketone bodiesin five, nine, and twenty-four-hour collections of urine, on the other hand, give satisfactory data to assess diabetic regulation, both as to accuracy of compensation and stability.


List of Contributors. Preface. A Personal Foreword. Part One Prodrug Design and Intellectual Property. 1 Prodrug Strategies in Drug Design (Jarkko Rautio). 1.1 Prodrug Concept. 1.2 Basics of Prodrug Design. 1.3 Rationale for Prodrug Design. 1.4 History of Prodrug Design. 1.5 Recently Marketed Prodrugs. 1.6 Concluding Remarks. References. 2 The Molecular Design of Prodrugs by Functional Group (Victor R. Guarino). 2.1 Introduction. 2.2 The Prodrug Concept and Basics of Design. 2.3 Common Functional Group Approaches in Prodrug Design. 2.4 Conclusions. References. 3 Intellectual Property Primer on Pharmaceutical Patents with a Special Emphasis on Prodrugs and Metabolites (Eyal H. Barash). 3.1 Introduction. 3.2 Patents and FDA Approval Process. 3.3 Obtaining a Patent. 3.4 Conclusion. Part Two Prodrugs Addressing ADMET Issues. 4 Increasing Lipophilicity for Oral Drug Delivery (Majid Y. Moridani). 4.1 Introduction. 4.2 pKa, Degree of Ionization, Partition Coefficient, and Distribution Coefficient. 4.3 Prodrug Strategies to Enhance Lipid Solubility. 4.4 Prodrug Examples for Antibiotics. 4.5 Antiviral Related Prodrugs. 4.6 Cardiovascular Related Prodrugs. 4.7 Lipophilic Prodrugs of Benzamidine Drugs. 4.8 Miscellaneous Examples. 4.9 Summary and Conclusion. References. 5 Modulating Solubility Through Prodrugs for Oral and IV Drug Delivery (Victor R. Guarino). 5.1 Introduction. 5.2 Basics of Solubility and Oral/IV Drug Delivery. 5.3 Prodrug Applications for Enhanced Aqueous Solubility. 5.4 Challenges with Solubilizing Prodrugs of Insoluble Drugs. 5.5 Additional Applications of Prodrugs for Modulating Solubility. 5.6 Parallel Exploration of Analogues and Prodrugs in Drug Discovery (Commentary). 5.7 Conclusions. References. 6 Prodrugs Designed to Target Transporters for Oral Drug Delivery (Mark S. Warren and Jarkko Rautio). 6.1 Introduction. 6.2 Serendipity: An Actively Transported Prodrug. 6.3 Requirements for Actively Transported Prodrugs. 6.4 Peptide Transporters: PEPT1 and PEPT2. 6.5 Monocarboxylate Transporters. 6.6 Bile Acid Transporters. 6.7 Conclusions. References. 7 Topical and Transdermal Delivery Using Prodrugs: Mechanism of Enhancement (Kenneth Sloan, Scott C. Wasdo, and Susruta Majumdar). 7.1 Introduction. 7.2 Arrangement of Water in the Stratum Corneum. 7.3 A New Model for Diffusion Through the Stratum Corneum: The Biphasic Solubility Model. 7.4 Equations for Quantifying Effects of Solubility on Diffusion Through the Stratum Corneum. 7.5 Design of Prodrugs for Topical and Transdermal Delivery Based on the Biphasic Solubility Model. 7.6 Comparison of Human and Mouse Skin Experiments. 7.7 Summary. References. 8 Ocular Delivery Using Prodrugs (Deep Kwatra, Ravi Vaishya, Ripal Gaudana, Jwala Jwala, and Ashim K. Mitra). 8.1 Introduction. 8.2 Criteria for an Ideal Ophthalmic Prodrug. 8.3 Anatomy and Physiology of the Eye. 8.4 Barriers to Ocular Drug Delivery. 8.5 Influx and Efflux Transporters on the Eye. 8.6 Transporter-Targeted Prodrug Approach. 8.7 Drug Disposition in Ocular Delivery. 8.8 Effect of Physiochemical Factors on Drug Disposition in Eye. 8.9 Prodrug Strategy to Improve Ocular Bioavailability (Nontransporter-Targeted Approach). 8.10 Recent Patents and Marketed Ocular Prodrugs. 8.11 Novel Formulation Approaches for Sustained Delivery of Prodrugs. 8.12 Conclusion. References. 9 Reducing Presystemic Drug Metabolism (Majid Y. Moridani). 9.1 Introduction. 9.2 Presystemic Metabolic Barriers. 9.3 Prodrug Approaches to Reduce Presystemic Drug Metabolism. 9.4 Targeting Colon. 9.5 Targeting Lymphatic Route. 9.6 Conclusion. References. 10 Enzyme-Activated Prodrug Strategies for Site-Selective Drug Delivery (Krista Laine and Kristiina Huttunen). 10.1 Introduction. 10.2 General Requirements for Enzyme-Activated Targeted Prodrug Strategy. 10.3 Examples of Targeted Prodrug Strategies. 10.4 Summary. References. 11 Prodrug Approaches for Central Nervous System Delivery (Quentin R. Smith and Paul R. Lockman). 11.1 Blood Brain Barrier in CNS Drug Development. 11.2 Prodrug Strategies. 11.3 Prodrug Strategies Based Upon BBB Nutrient Transporters. 11.4 Prodrug Strategies Based Upon BBB Receptors. 11.5 CNS Prodrug Summary. References. 12 Directed Enzyme Prodrug Therapies (Dan Niculescu-Duvaz, Gabriel Negoita-Giras, Ion Niculescu-Duvaz, Douglas Hedley, and Caroline J. Springer). 12.1 Introduction. 12.2 Theoretical Background of DEPT. 12.3 Comparison of ADEPT and GDEPT. 12.4 Enzymes in ADEPT and GDEPT. 12.5 Design of Prodrugs. 12.6 Strategies Used for the Improvement of DEPT Systems. 12.7 Biological Data for ADEPT and GDEPT. 12.8 Conclusions. References. Part Three Codrugs and Soft Drugs. 13 Improving the Use of Drug Combinations Through the Codrug Approach (Peter A. Crooks, Harpreet K. Dhooper, and Ujjwal Chakraborty). 13.1 Codrugs and Codrug Strategy. 13.2 Ideal Codrug Characteristics. 13.3 Examples of Marketed Codrugs. 13.4 Topical Codrug Therapy for the Treatment of Ophthalmic Diseases. 13.5 Codrugs for Transdermal Delivery. 13.6 Codrugs of L-DOPA for the Treatment of Parkinson.s Disease. 13.7 Analgesic Codrugs Containing Nonsteroidal Anti-Inflammatory Agents. 13.8 Analgesic Codrugs of Opioids and Cannabinoids. 13.9 Codrugs Containing Anti-HIV Drugs. References. 14 Soft Drugs (Paul W. Erhardt and Michael D. Reese). 14.1 Introduction. 14.2 Indications. 14.3 Design Considerations. 14.4 Case Study: The Discovery of Esmolol. 14.5 Summary. References. Part Four Preclinical and Clinical Consideration for Prodrugs. 15 Pharmacokinetic and Biopharmaceutical Considerations in Prodrug Discovery and Development (John P. O.Donnell). 15.1 Introduction. 15.2 Understanding Pharmacokinetic/Pharmacodynamic Relationships. 15.3 Pharmacokinetics. 15.4 Tools for the Prodrug Scientist. 15.5 Enzymes Involved with Prodrug Conversion. 15.6 Use of the Caco-2 System for Permeability and Active Transport Evaluation. 15.7 XP13512: Improving PK Performance by Targeting Active Transport. 15.8 Prodrug Absorption: Transport/Metabolic Conversion Interplay. 15.9 Preabsorptive Degradation. 15.10 Biopharmaceutical-Based PK Modeling for Prodrug Design. 15.11 Conclusions. References. 16 The Impact of Pharmacogenetics on the Clinical Outcomes of Prodrugs (Jane P.F. Bai, Mike Pacanowski, Atiqur Rahman, and Lawrence L. Lesko). 16.1 Introduction. 16.2 Clopidogrel and CYP2C19. 16.3 Codeine and CYP2D6. 16.4 Tamoxifen and CYP2D6. 16.5 Fluorouracil Prodrugs and Carboxylesterase. 16.6 Irinotecan and Carboxylesterase 2. 16.7 Others. 16.8 Drug Development Implication. 16.9 Conclusions. References. Index.


Quasi-continuous-wave generation at 589 nm in periodically poled KTP was achieved by sum-frequency mixing of synchronized mode-locked pulses emitted at 1064 and 1319 nm from two mode-locked Nd:YAG lasers. As acousto-optic mode lockers operated by the same frequency were used for mode locking, pulse trains were well synchronized with phase control of the radio frequency. The maximum output power at 589 nm was 260 mW mixing 1.9 W at 1064 nm and 0.88 W at 1319 nm. Conversion efficiency was reached to 14%, even for single-pass pumping using 5-mm-long periodically poled KTP.


Successful integration entails that refugees engage in both intra-ethnic social bonding and inter-ethnic social bridging. The settlement house model as an intervention has potential to increase social bonding and bridging amongst newly resettled refugees; however, little is known about the social interactions that occur within this model. This focused ethnography examined the social engagement patterns of refugees residing within a local settlement house. Nearly 100 hours of observation were conducted and 36 refugee residents, settlement house staff and volunteers, and apartment management formally interviewed. Eligible participants spoke English, French, Vietnamese, Burmese, Chin or Karen and were at least eighteen years old. Thorough descriptions of the research environment were recorded. Themes were extracted from the data using a priori and emergent codes and constant comparison analysis was then conducted. Etic interpretations were applied to the data through memo writing and co-author feedback. Results represent a co-construction of events informed by both emic and etic perspectives. Due to unforeseen circumstances, the settlement house unexpectedly closed halfway through the study. We found three primary types of social engagement occurring within a local settlement house--functional, communal, and exploratory engagement; the combination of all three is necessary for successful integration. The settlement house fostered inter-ethnic social bridging through functional and exploratory engagement and intra-ethnic social bonding through communal engagement. When the settlement house closed, refugee residents lost access to all onsite exploratory engagement opportunities and many functional engagement services. Communal engagement persisted amongst refugee residents despite the closing. The loss of exploratory and functional engagement opportunities affected refugee residents differently due to contextual and cultural distinctions. Factors contributing to the decline of the settlement including communications challenges, low rapport, passive management styles, and ill-defined role delineations will also be discussed.


Over the last three decades there has been an increasing interest in acupuncture treatment of substance abuse around the world. Three important steps can be identified in this field. Dr. H. L. Wen of Hong Kong was the first (1973) to report that acupuncture at 4 body points and 2 ear points combined with electrical stimulation can relieve opiate withdrawal signs in the addicts. The second major step was made by Dr. M. Smith in New York, the head of the National Acupuncture Detoxification Association (NADA) of the U.S.A., who finalized a protocol (1985), using only ear points without electrical stimulation for the treatment of drug abuse. The recent advance in this field was made by Prof. J. S. Han and his colleagues in Neuroscience Research Institute of the Peking University, Beijing, who characterized a protocol (1992- ), using electrical stimulation of identified frequencies on body points to ameliorate heroin withdrawal signs and prevent relapse to heroin use. In this review, the efficacy of acupuncture and related techniques for the treatment of drug dependence in experimental settings and clinical practice will be reviewed, and the possible mechanisms underlying this effect be discussed.


Purpose
In contrast to the reflective approach of service quality measurement, this paper aims to propose and validate a parsimonious multidimensional second-order formatively measured model of service quality for primary health-care services provided by hospital outpatient departments. The index's empirical validity is examined by investigating the strength of its relationship with certain behavioral responses such as patient satisfaction and behavioral intentions.

Design/methodology/approach
Data were collected through a stratified random sampling from eight hospital outpatient departments in Greece. Covariance-based structural equation modeling techniques were used to validate the proposed service quality index and further investigate its effect on patient satisfaction and behavioral intention.

Findings
The data analysis indicated that the proposed formative index is fully functional with medical care being the factor and mostly contributes to service quality perception, followed by administrative service and staff performance, and facilities condition and nursing care. It, further, confirmed the partial mediating role of satisfaction, as it enhances the high impact of service quality on behavioral intentions.

Research limitations/implications
The relationships among hospital outpatient departments service quality, patient satisfaction and behavioral intentions were validated with data from one country and a health-care system which is state driven and funded.

Practical implications
An understanding of hospital primary health-care service quality formation is important to health-care decision makers because it offers them the opportunity to consider patients' needs and wants, and takes the appropriate actions for improving the relevant underling procedures in a more efficient manner to achieve favorable behavioral responses.

Originality/value
The paper manages to propose and empirically evaluate a formatively measured approach of service quality and investigate the effects of the proposed index on patient satisfaction and behavioral intention, especially in the hospital outpatient services context in Greece.


Modeling sediment transport processes by means of numerical approach often poses severe challenges. In this way, a number of techniques have been suggested to solve flow and sediment equations in decoupled, semi-coupled or fully coupled forms. Furthermore, in order to capture flow discontinuities, a number of techniques, like artificial viscosity and shock fitting, have been proposed for solving these equations which are mostly required careful calibration processes. In this research, a numerical scheme for solving shallow water and Exner equations in fully coupled form is presented. First-Order Centered scheme is applied for producing required numerical fluxes and the reconstruction process is carried out toward using Monotonic Upstream Scheme for Conservation Laws to achieve a high order scheme. In order to satisfy C-property of the scheme in presence of bed topography, Surface Gradient Method is proposed. Combining the presented scheme with fourth order Runge-Kutta algorithm for time integration yields a competent numerical scheme. In addition, to handle non-prismatic channels problems, Cartesian Cut Cell Method is employed. A trained MultiLayer Perceptron Artificial Neural Network which is of Feed Forward Back Propagation (FFBP) type estimates sediment flow discharge in the model rather than usual empirical formulas. Hydrodynamic part of the model is tested for showing its capability in simulation of flow discontinuities, transcritical flows, wetting/drying conditions and non-prismatic channel flows. In this end, dam-break flow onto a locally non-prismatic convergingdiverging channel with initially dry bed conditions is modeled. The morphodynamic part of the model is verified simulating dam break on a dry movable bed and bed level variations in an alluvial junction. The results show that the model is capable in capturing the flow discontinuities, solving wetting/drying problems even in nonprismatic channels and presenting proper results for movable bed situations. It can also be deducted that applying Artificial Neural Network, instead of common empirical formulas for estimating sediment flow discharge, leads to more accurate results. Keywords—Artificial neural network, morphodynamic model, sediment continuity equation, shallow water equations.


Research on longevity is important to both prolong lifespan and support healthy aging. Natural products are widely being utilized and used as new resources for drug molecules. Caenorhabditis elegans is an advantageous organism for longevity research and age-related diseases. In this study, we tested a number of plant extracts for their effects on C. elegans longevity. In lifespan assays, agesynchronized wild-type C. elegans specimens were treated with different concentrations of plant extracts. Plant extracts were prepared as either infusions or decoctions, similar to their traditional utilization. Hedera helix L. (Araliaceae) extended lifespan in worms in a concentration-dependent manner. The mean survival rates in the H. helix-treated groups were significantly higher, by 23.7% when applied at 1000 µg/mL, 16% when applied at 500 µg/mL, and 16% when applied at 250 µg/mL, compared to the control group. HPLC analysis identified chlorogenic acid as the major component of H. helix. Salvia verticillata L. (Lamiaceae) and Myrtus communis L. (Myrtaceae) treatments resulted in median lifespan extension. Maximum lifespan was extended in worms by Rubus sanctus Schreb. (Rosaceae) treatment. This study provided the first evidence demonstrating the possible lifespan-extending effects of a group of Turkish medicinal plants in an in vivo model, C. elegans.


Background: The burden of cancer among indigenous people in Canada has been understudied due to a lack of ethnic identifiers in cancer registries. We compared cancer survival among First Nations to that among non-Aboriginal adults in Canada in the first national study of its kind to date. Methods: A population-based cohort of approximately 2 million respondents to the 1991 Canadian Long Form Census was followed for cancer diagnoses and deaths using probabilistic linkage to cancer and death registries until 2009. Excess mortality rate ratios (EMRR) and 5-year age-standardized relative survival rates were calculated for 15 cancers using age, sex, ethnicity, and calendar-time–specific life tables derived from the cohort at large. Results: First Nations diagnosed with cancers of the colon and rectum, lung and bronchus, breast, prostate, oral cavity and pharynx, cervix, ovary, or with non-Hodgkin lymphoma and leukemia all had significantly poorer 5-year survival than their non-Aboriginal peers. For colorectal cancer, a significant disparity was only present between 2001 and 2009 (EMRR: 1.52; 95% CI, 1.28–1.80). For prostate cancer, a significant disparity was only present between 1992 and 2000 (EMRR: 2.76; 95% CI, 1.81–4.21). Adjusting for income and rurality had little impact on the EMRRs. Conclusions: Compared with non-Aboriginals, First Nations people had poorer survival for 14 of 15 of the most common cancers, and disparities could not be explained by income and rurality. Impact: The results of this study can serve as a benchmark for monitoring progress toward narrowing the gap in survival. Cancer Epidemiol Biomarkers Prev; 26(1); 145–51. ©2016 AACR.


UNLABELLED
Cardiac morbidity and mortality remain the major operative risk following aortic reconstruction (AR) performed for aneurysmal and occlusive disease. We reviewed the preoperative cardiac evaluation and outcome in 209 patients who had AR between 1987 and 1992. Dipyridamole-thallium stress test (DTST) was performed in 147 (70.3%) patients. Fifty-six of these patients had a normal DTST and only 1 (1.8%) had a perioperative myocardial infarction (MI). Forty-six patients had a fixed defect on their DTST and 3 (6.5%) had perioperative MI. Forty-five patients had reversible defects on their DTST and 2 (4.4%) had perioperative MI with 1 cardiac death. Following DTST, 29 coronary catheterizations were performed. Ten catheterizations were normal or had minimal one-vessel coronary artery disease with an associated postoperative death in 1 patient due to cardiac dysrhythmia. Nineteen patients had abnormal coronary angiography, 1 of whom had a perioperative myocardial infarction and 5 of whom underwent coronary artery revascularization (CABG) (3) or percutaneous transluminal angioplasty (2) prior to AR without subsequent cardiac events. Forty-three (20.6%) had either no cardiac symptoms (40) or prior CABG (3) precluding invasive cardiac evaluation. There was one fatal perioperative myocardial infarction (2.3%), resulting in a cardiac mortality of 2.3% in this group. The remaining 19 patients who did not have a DTST (9.1%) had coronary angiography based on evidence of significant cardiac disease resulting in one CABG and one percutaneous transluminal angioplasty. There was one (5.3%) perioperative myocardial infarction in this group and no cardiac deaths. Thirty-day mortality was 3.8%, perioperative MI rate was 3.8%, and perioperative cardiac mortality was 1.0%. During the follow-up period (median, 18 months; range, 1-89), there were 19 deaths (10%) and the 5-year cumulative survival was 76%.

CONCLUSION
Selective use of DTST can direct further evaluation, intervention, and subsequent perioperative care. This algorithm has enabled us to perform AR even in patients with defined perfusion abnormalities with acceptable morbidity. The true sensitivity, specificity, and predictive value of DTST can only be determined by a prospective trial.


Problem statement: In this study, we considered the application of a genetic algorithm to vehicle routing problem with time windows where a set of vehicles with limits on capacity and travel time are available to service a set of customers with demands and earliest and latest time for serving. The objective is to find routes for the vehicles to service all the customers at a minimal cost without violating the capacity and travel time constraints of the vehicles and the time window constraints set by the customers. Approach: We proposed a genetic algorithm using an optimized crossover operator designed by a complete undirected bipartite graph that finds an optimal set of delivery routes satisfying the requirements and giving minimal total cost. Various techniques have also been introduced into the proposed algorithm to further enhance the solutions quality. Results: We tested our algorithm with benchmark instances and compared it with some other heuristics in the literature. The results showed that the proposed algorithm is competitive in terms of the quality of the solutions found. Conclusion/Recommendations: This study presented a genetic algorithm for solving vehicle routing problem with time windows using an optimized crossover operator. From the results, it can be concluded that the proposed algorithm is competitive when compared with other heuristics in the literature.


In recent years, international organizations have concluded that standard principles of Public Finance Management (PFM) are equally applicable to all areas of the national budget, including the security sector. In many cases long-term external assistance may be required for the security sector, generating severe trade-offs with other priority sectors which also require long-term external support. Overcoming the legacy of a fiscally unsustainable and poorly managed security sector calls for full application of PFM principles to support the establishment of checks and balances required to establish a wholly accountable security sector. The recent World Bank PFM review of Afghanistan, perhaps the first example of such a review, provides a number of lessons, summarized in this note. Some of these include: security in post-conflict situations is a key condition for a return to political normalcy and conversely, development is also needed for security; PFM practices can take into consideration the most complex and confidential issues without undermining the application of the fundamental principles of accountability to elected civil authorities; and reviewing security reform through a PFM lens reduces risks and costs to both the country concerned and donors.


The Autistic Brain-Temple Grandin 2014 WINNER OF 'BEST NON FICTION' IN THE GOODREADS CHOICE AWARDS 2013 It's estimated that one in almost a hundred people are diagnosed as being on the autistic spectrum but there is far more hope for them today than ever before thanks to groundbreaking new research. In this fascinating and highly readable book, Temple Grandin offers her own experience as an autistic person alongside remarkable new discoveries about the autistic brain, as well as genetic research. She also highlights long-ignored sensory problems as well as the need to treat autism symptom by symptom, rather than with an umbrella diagnosis. Most exciting of all, she argues that raising and educating children on the autistic spectrum needs to be less about focusing on their weaknesses, and more about fostering their unique contributions.


Abstract High rates of comorbidity are observed between internalizing and externalizing problems, yet the developmental dynamics of comorbid symptom presentations are not yet well understood. This study explored the developmental course of latent profiles of internalizing and externalizing symptoms across kindergarten, first grade, and second grade. The sample consisted of 336 children from an urban, low-income community, selected based on relatively high (61%) or low (39%) aggressive/oppositional behavior problems at school entry (64% male; 70% African American, 20% Hispanic). Teachers reported on children's symptoms in each year. An exploratory latent profile analysis of children's scores on aggression/oppositionality, hyperactivity/inattention, anxiety, and social withdrawal symptom factors revealed four latent symptom profiles: comorbid (48% of the sample in each year), internalizing (19%–23%), externalizing (21%–22%), and well-adjusted (7%–11%). The developmental course of these symptom profiles was examined using a latent transition analysis, which revealed remarkably high continuity in the comorbid symptom profile (89% from one year to the next) and moderately high continuity in both the internalizing and externalizing profiles (80% and 71%, respectively). Internalizing children had a 20% probability of remitting to the well-adjusted profile by the following year, whereas externalizing children had a 25% probability of transitioning to the comorbid profile. These results are consistent with the hypothesis that a common vulnerability factor contributes to developmentally stable internalizing–externalizing comorbidity, while also suggesting that some children with externalizing symptoms are at risk for subsequently accumulating internalizing symptoms.


Personal communication devices are increasingly equipped with sensors for passive monitoring of encounters and surroundings. We envision the emergence of services that enable a community of mobile users carrying such resource-limited devices to query such information at remote locations in the field in which they collectively roam. One approach to implement such a service is directed placement and retrieval (DPR), whereby readings/queries about a specific location are routed to a node responsible for that location. In a mobile, potentially sparse setting, where end-to-end paths are unavailable, DPR is not an attractive solution as it would require the use of delay-tolerant (flooding-based store-carry-forward) routing of both readings and queries, which is inappropriate for applications with data freshness constraints, and which is incompatible with stringent device power/memory constraints. Alternatively, we propose the use of amorphous placement and retrieval (APR), in which routing and field monitoring are integrated through the use of a cache management scheme coupled with an informed exchange of cached samples to diffuse sensory data throughout the network, in such a way that a query answer is likely to be found close to the query origin. We argue that knowledge of the distribution of query targets could be used effectively by an informed cache management policy to maximize the utility of collective storage of all devices. Using a simple analytical model, we show that the use of informed cache management is particularly important when the mobility model results in a non-uniform distribution of users over the field. We present results from extensive simulations which show that in sparsely-connected networks, APR is more cost-effective than DPR, that it provides extra resilience to node failure and packet losses, and that its use of informed cache management yields superior performance.


Although social exclusion has become a key issue on the European
policy agenda in recent years, both the social phenomena the term refers to and
the best way to monitor these remain unclear. In response to this, we developed
a conceptual model for social exclusion and a methodology for its empirical
assessment. Social exclusion is conceived as a multidimensional concept. It is
operationalized as a combination of  material deprivation, insufficient
access to social rights, a low degree of social participation and a lack of
normative integration.
 In a survey among 860 Dutch households we found a valid scale which expresses
the degree of social exclusion in a single figure. This measure indicates that
about 11% of the adult population may be regarded as socially excluded.
 A causal analysis subsequently showed that having bad health is the most
important risk factor. Other main determinants of social exclusion are a
low income, benefit dependency, limited Dutch language skills, and living in a
single-parent household.
 The outcomes suggest that it is worthwhile to strive for a specific
measurement of social exclusion as such, and that the concept should not be
equated with shortfalls in income and labour participation, as the current
European policy debate tends to do.


Equity in a home can serve as an important source of supplemental income in retirement. Reverse mortgages allow seniors to draw down equity without selling their home, and without a monthly mortgage payment. The most widely used reverse mortgage product is offered by Federal Housing Administration's Home Equity Conversion Mortgage (HECM) program.The Aging in Place study is a multi-phase research project being conducted by researchers at The Ohio State University, in partnership with the certified reverse mortgage counseling agency, ClearPoint Credit Counseling Solutions, with funding from The MacArthur Foundation and The U.S. Department of Housing and Urban Development (HUD). Before obtaining a HECM loan, prospective borrowers are required to complete counseling with a certified counseling agency. The study combines administrative data from households who have been counseled for reverse mortgages, HUD loan data for households who borrowed HECM loans, and survey data collected on households three to nine years after receiving counseling for a reverse mortgage. The goal of the study is to provide a better understanding of the relationships between borrowing through a reverse mortgage and financial security, well-being and independence in older age. This report summarizes the results of the Aging in Place study's survey of counseled households, administered in phases from January, 2014 through July, 2015. The sample population includes seniors who had been counseled for a reverse mortgage by ClearPoint Credit Counseling Solutions from 2006 to 2011, including (1) those who decided not to take out a reverse mortgage; (2) those who took out a reverse mortgage and retained it as of the survey date; (3) and those who took out and then terminated their reverse mortgage as of the survey date. The survey asks people about their experiences with reverse mortgages, as well as general questions on household financial well-being, living conditions and personal health.


SUMMARY In the course of electrophysiological evaluation of six patients with sick sinus syndrome, two patients with chronic conduction system disease and four patients with paroxysmal supraventricular tachycardia or atrial flutter-fibrillation, the phenomenon of concealed conduction within the atrium (At) was repeatedly observed. One pair of intracardiac electrodes was used to deliver electrical stimulus (St) to the high right At and two additional pairs of electrodes were utilized to record high right and low septal right atrial electrograms. The interelectrode distances were 10 mm apart. In all 12 patients, high right atrial capture could be accomplished at a pacing rate of > 200 beats/min. Concealed intra-atrial conduction was evident when the intra-atrial conduction time of the propagated St during 2: 1 St-At block was more than 40 msec longer than that during 1: 1 St-At conduction at half the St frequency. This indicated that the nonpropagated St during 2: 1 St-At block partially penetrated the At and in turn, delayed conduction of the subsequently propagated St. Further observations revealed that a gradual increase in the St frequency resulted in a progressive prolongation of the intra-atrial conduction time and a shifting of 2:1 to 3:1 St-At block (alternating Wenckebach periodicity in the At) in five patients. These findings clearly demonstrate the occurrence of concealed conduction in the human At.


uberculosis (TB), an infection obtained from Mycobacterium, is the fourth leading cause of death in the Philippines. It remains to be a problem especially in developing countries, even after following guidelines and achieving some of the targets set by the World Health Organization (WHO) for TB elimination. Inspired by the TB transmission model developed by Trauer et al. (2014), we propose a model for TB transmission in the Philippines and validated it using Philippine-based data for TB incidence and prevalence rates in 2003-2013 (WHO, 2014). Using the Theorem of van den Driessche & Watmough (2002) we show that our proposed Philippine TB model has a locally asymptotically stable endemic equilibrium, with basic reproduction number R0 = 0.4516 and an unstable free-disease equilibrium, with R0 = 3.8896. Moreover, our projected simulations show that improving partial immunity, treatment success, treatment duration and case detection in the Philippines will significantly reduce the TB incidence and prevalence rates. Interestingly, we found that improving vaccine coverage would not significantly reduce the projected TB incidence and prevalence rates. These results can help the Philippines in improving its TB programs and develop new strategies to eliminate tuberculosis in the country. KEYWORDS


In Roberts v. United States Jaycees, the Supreme Court reversed Judge Richard S. Arnold's decision for the Court of Appeals and held - without dissent - that the First Amendment did not shield the Jaycees' men-only membership policy from the non-discrimination requirements of the Minnesota Human Rights Act. The claim in this essay is that Judge Arnold's position and decision in the Jaycees case deserved, and still deserve, more thoughtful and sympathetic treatment. Even some of Judge Arnold's many friends and fans tend to treat as something of an embarrassing lapse or anomalous error his conclusion in that case that, because "the First Amendment . . . must[,] on occasion, protect the association of which we disapprove, the Constitution therefore protected the Jaycees' right not to admit women to full membership". In fact, though, it was precisely Judge Arnold's civil-libertarian commitments prompted him to cast a skeptical eye on the efforts of government to pursue its own or the majority's agenda at the expense of constitutionally protected rights. For Judge Arnold, governments constrained by our First Amendment and by a respect for the freedom of speech are limited to persuasion, not coercion, when trying to influence and shape the beliefs and expression of citizens and associations. In his view, the same democratic values that underlie our constitutional commitment to equal protection of the laws are the basis for a no-less-fundamental commitment to limited government and a free civil society. Justice Brennan himself - the author of the Court's opinion in Jaycees and Judge Arnold's former boss - recognized that Judge Arnold has consistently vindicated the First Amendment guarantees of freedom of the press and freedom of speech, even in cases in which the protected expression was controversial, distasteful, or hateful. Judge Arnold's ruling and reasoning in Jaycees, it seems to me, is of a piece with this commendable legacy.