An extension of Laplace's method

Asymptotic expansions are obtained for contour integrals of the form $$\int_a^b \exp \left( - zp(t) + z^{\nu /\mu } r(t) \right)q(t)dt,$$ in which $z$ is a large real or complex parameter, $p(t)$, $q(t)$ and $r(t)$ are analytic functions of $t$, and the positive constants $\mu$ and $\nu$ are related to the local behaviour of the functions $p(t)$ and $r(t)$ near the endpoint $a$. Our main theorem includes as special cases several important asymptotic methods for integrals such as those of Laplace, Watson, Erd\'elyi and Olver. Asymptotic expansions similar to ours were derived earlier by Dingle using formal, non-rigorous methods. The results of the paper also serve to place Dingle's investigations on a rigorous mathematical foundation. The new results have potential applications in the asymptotic theory of special functions in transition regions, and we illustrate this by two examples.Comment: 19 pages, 2 figures, revised version, accepted for publication in Constructive Approximatio

The alimentary impact of the hemp seed

Hemp seed and hemp seed oil can supply us with many important substances. Their essential fatty acid compositions are favourable, but they may contain non-psychotropic cannabinoids. Emerging data show that these components can influence the health status of the population beneficially. Some data also showed trace amounts of tetrahydrocannabinol in seed oils, the main psychotropic cannabinoid that is contraindicated.Our aim was to examine cannabinoids and fatty acid composition as well as metal and non-metal element compositions in products, like hemp seed oil and chopped hemp seed capsule.The cannabinoids were separated by thin layer chromatography. Fatty acid composition was determined with gas chromatography, and elements (Al, B, Ba, Ca, Cd, Co, Cr, Cu, Fe, K, Li, Mg, Mn, Mo, Na, Ni, P, Pb, S, Si, Sn, Sr, V, and Zn) were measured by inductively coupled plasma optical emission spectrometric method. Selenium was determined with polarographic analyser.Cannabinoids were not detectable by thin layer chromatography, so hemp seed oil, as well as the capsule, have no psychotropic adverse effect. Our data showed that hemp seed contains essential fatty acids close to the recommended ratio. The B and Se concentrations of the oils and the P concentration of the capsule are also relevant

CT scan screening is associated with increased distress among subjects of the APExS

<p>Abstract</p> <p>Background</p> <p>The aim of this study was to assess the psychological consequences of HRCT scan screening in retired asbestos-exposed workers.</p> <p>Methods</p> <p>A HRCT-scan screening program for asbestos-related diseases was carried out in four regions of France. At baseline (T1), subjects filled in self-administered occupational questionnaires. In two of the regions, subjects also received a validated psychological scale, namely the psychological consequences questionnaire (PCQ). The physician was required to provide the subject with the results of the HRCT scan at a final visit. A second assessment of psychological consequences was performed 6 months after the HRCT-scan examination (T2). PCQ scores were compared quantitatively (t-test, general linear model) and qualitatively (chi²-test, logistic regression) to screening results. Multivariate analyses were adjusted for gender, age, smoking, asbestos exposure and counseling.</p> <p>Results</p> <p>Among the 832 subjects included in this psychological impact study, HRCT-scan screening was associated with a significant increase of the psychological score 6 months after the examination relative to baseline values (8.31 to 10.08, p < 0.0001, t-test). This increase concerned patients with an abnormal HRCT-scan result, regardless of the abnormalities, but also patients with normal HRCT-scans after adjustment for age, gender, smoking status, asbestos exposure and counseling visit. The greatest increase was observed for pleural plaques (+3.60; 95%CI [+2.15;+5.06]), which are benign lesions. Detection of isolated pulmonary nodules was also associated with a less marked but nevertheless significant increase of distress (+1.88; 95%CI [+0.34;+3.42]). However, analyses based on logistic regressions only showed a close to significant increase of the proportion of subjects with abnormal PCQ scores at T2 for patients with asbestosis (OR = 1.92; 95%CI [0.97-3.81]) or with two or more diseases (OR = 2.04; 95%CI [0.95-4.37]).</p> <p>Conclusion</p> <p>This study suggests that HRCT-scan screening may be associated with increased distress in asbestos-exposed subjects. If confirmed, these results may have consequences for HRCT-scan screening recommendations.</p

Impact of identity politics on education in Pakistan: a comparison between Balochistan and Punjab

This research paper examines the impact of ethnic identity based politics on education in Pakistan through in-depth interviews with young professionals from Balochistan and Punjab. Findings suggest that there is the Punjabi-dominated power structure results in an unequal allocation of financial resources, whereby Balochistan lacks the financial resources to invest in education development. In addition, political instability caused by unprecedented ethnic strife contributes towards poor quality education, which, as a result, adversely impacts a Balochi's future course of life. On the other hand, Punjabis are at an advantage in the public arena because of their robust educational foundation

Connectivity and resilience of coral reef metapopulations in marine protected areas : matching empirical efforts to predictive needs

© 2009 The Authors. This is an open-access article distributed under the terms of the Creative Commons Attribution Noncommercial License. The definitive version was published in Coral Reefs 28 (2009): 327-337, doi:10.1007/s00338-009-0466-z.Design and decision-making for marine protected areas (MPAs) on coral reefs require prediction of MPA effects with population models. Modeling of MPAs has shown how the persistence of metapopulations in systems of MPAs depends on the size and spacing of MPAs, and levels of fishing outside the MPAs. However, the pattern of demographic connectivity produced by larval dispersal is a key uncertainty in those modeling studies. The information required to assess population persistence is a dispersal matrix containing the fraction of larvae traveling to each location from each location, not just the current number of larvae exchanged among locations. Recent metapopulation modeling research with hypothetical dispersal matrices has shown how the spatial scale of dispersal, degree of advection versus diffusion, total larval output, and temporal and spatial variability in dispersal influence population persistence. Recent empirical studies using population genetics, parentage analysis, and geochemical and artificial marks in calcified structures have improved the understanding of dispersal. However, many such studies report current self-recruitment (locally produced settlement/settlement from elsewhere), which is not as directly useful as local retention (locally produced settlement/total locally released), which is a component of the dispersal matrix. Modeling of biophysical circulation with larval particle tracking can provide the required elements of dispersal matrices and assess their sensitivity to flows and larval behavior, but it requires more assumptions than direct empirical methods. To make rapid progress in understanding the scales and patterns of connectivity, greater communication between empiricists and population modelers will be needed. Empiricists need to focus more on identifying the characteristics of the dispersal matrix, while population modelers need to track and assimilate evolving empirical results.Work by CB Paris was supported by the National Science Foundation grant NSF-OCE 0550732. Work by M-A Coffroth and SR Thorrold was supported by the National Science Foundation grant NSF-OCE 0424688. Work by TL Shearer was supported by an International Cooperative Biodiversity Group grant R21 TW006662-01 from the Fogarty International Center at the National Institutes of Health

Cathepsin B-like and cell death in the unicellular human pathogen Leishmania

In several studies reporting cell death (CD) in lower eukaryotes and in the human protozoan parasite Leishmania, proteolytic activity was revealed using pan-caspase substrates or inhibitors such as carbobenzoxy-valyl-alanyl-aspartyl-[O-methyl]-fluoromethylketone (Z-VAD-FMK). However, most of the lower eukaryotes do not encode caspase(s) but MCA, which differs from caspase(s) in its substrate specificity and cannot be accountable for the recognition of Z-VAD-FMK. In the present study, we were interested in identifying which enzyme was capturing the Z-VAD substrate. We show that heat shock (HS) induces Leishmania CD and leads to the intracellular binding of Z-VAD-FMK. We excluded binding and inhibition of Z-VAD-FMK to Leishmania major metacaspase (LmjMCA), and identified cysteine proteinase C (LmjCPC), a cathepsin B-like (CPC) enzyme, as the Z-VAD-FMK binding enzyme. We confirmed the specific interaction of Z-VAD-FMK with CPC by showing that Z-VAD binding is absent in a Leishmania mexicana strain in which the cpc gene was deleted. We also show that parasites exposed to various stress conditions release CPC into a soluble fraction. Finally, we confirmed the role of CPC in Leishmania CD by showing that, when exposed to the oxidizing agent hydrogen peroxide (H2O2), cpc knockout parasites survived better than wild-type parasites (WT). In conclusion, this study identified CPC as the substrate of Z-VAD-FMK in Leishmania and as a potential additional executioner protease in the CD cascade of Leishmania and possibly in other lower eukaryotes

Relevance of the Diversity among Members of the Trypanosoma Cruzi Trans-Sialidase Family Analyzed with Camelids Single-Domain Antibodies

The sialic acid present in the protective surface mucin coat of Trypanosoma cruzi is added by a membrane anchored trans-sialidase (TcTS), a modified sialidase that is expressed from a large gene family. In this work, we analyzed single domain camelid antibodies produced against trans-sialidase. Llamas were immunized with a recombinant trans-sialidase and inhibitory single-domain antibody fragments were obtained by phage display selection, taking advantage of a screening strategy using an inhibition test instead of the classic binding assay. Four single domain antibodies displaying strong trans-sialidase inhibition activity against the recombinant enzyme were identified. They share the same complementarity-determining region 3 length (17 residues) and have very similar sequences. This result indicates that they likely derived from a unique clone. Probably there is only one structural solution for tight binding inhibitory antibodies against the TcTS used for immunization. To our surprise, this single domain antibody that inhibits the recombinant TcTS, failed to inhibit the enzymatic activity present in parasite extracts. Analysis of individual recombinant trans-sialidases showed that enzymes expressed from different genes were inhibited to different extents (from 8 to 98%) by the llama antibodies. Amino acid changes at key positions are likely to be responsible for the differences in inhibition found among the recombinant enzymes. These results suggest that the presence of a large and diverse trans-sialidase family might be required to prevent the inhibitory response against this essential enzyme and might thus constitute a novel strategy of T. cruzi to evade the host immune system

Outcome of crisis intervention for borderline personality disorder and post traumatic stress disorder: a model for modification of the mechanism of disorder in complex post traumatic syndromes

<p>Abstract</p> <p>Background</p> <p>This study investigates the outcome of crisis intervention for chronic post traumatic disorders with a model based on the theory that such crises manifest trauma in the present. The sufferer's behavior is in response to the current perception of dependency and entrapment in a mistrusted relationship. The mechanism of disorder is the sufferer's activity, which aims to either prove or disprove the perception of entrapment, but, instead, elicits more semblances of it in a circular manner. Patients have reasons to keep such activity private from therapy and are barely aware of it as the source of their symptoms.</p> <p>Methods</p> <p>The hypothesis is that the experimental intervention will reduce symptoms broadly within 8 to 24 h from initiation of treatment, compared to treatment as usual. The experimental intervention sidesteps other symptoms to engage patients in testing the trustworthiness of the troubled relationship with closure, thus ending the circularity of their own ways. The study compares 32 experimental subjects with 26 controls at similar crisis stabilization units.</p> <p>Results</p> <p>The results of the Brief Psychiatric Rating Scale (BPRS) supported the hypothesis (both in total score and for four of five subscales), as did results with Client Observation, a pilot instrument designed specifically for the circular behavior targeted by the experimental intervention. Results were mostly non-significant from two instruments of patient self-observation, which provided retrospective pretreatment scores.</p> <p>Conclusions</p> <p>The discussion envisions further steps to ascertain that this broad reduction of symptoms ensues from the singular correction that distinguishes the experimental intervention.</p> <p>Trial registration</p> <p>Protocol Registration System NCT00269139. The PRS URL is <url>https://register.clinicaltrials.gov</url></p

Health equity issues at the local level: Socio-geography, access, and health outcomes in the service area of the Hôpital Albert Schweitzer-Haiti

<p>Abstract</p> <p>Background</p> <p>Although health equity issues at regional, national and international levels are receiving increasing attention, health equity issues at the local level have been virtually overlooked. Here, we describe here a comprehensive equity assessment carried out by the Hôpital Albert Schweitzer-Haiti (HAS) in 2003. HAS has been operating health and development programs in the Artibonite Valley of Haiti for 50 years.</p> <p>Methods</p> <p>We reviewed all available information arising from a comprehensive evaluation of the programs of HAS carried out in 1999 and 2000. As part of this evaluation, two demographic and health surveys were carried out. We carried out exit interviews with clients receiving primary health care, observations within health facilities, interviews with households related to quality of care, and focus group discussions with community-based health workers. A special study was carried out in 2003 to assess factors determining the use of prenatal care services. Finally, selected findings were obtained from the HAS information system.</p> <p>Results</p> <p>We found markedly reduced access to health services in the peripheral mountainous areas compared to the central plains. The quality of services was more deficient and the coverage of key services was lower in the mountains. Finally, health status, as measured by under-five mortality rates and levels of childhood malnutrition, was also worse in the mountains.</p> <p>Conclusion</p> <p>These findings indicate that local health programs need to give attention to monitoring the health status as well as the quality and coverage of basic services among marginalized groups within the program service area. Health inequities will not be overcome until such monitoring occurs and leaders of health programs ensure that inequities identified are addressed in the local programming of activities. It is quite likely that, within relatively small geographic areas in resource-poor settings around the world, similar, if not even greater, levels of health inequities exist. These inequities need to be measured and addressed in order for health programs to achieve equity and maximum improvement in health status within the population.</p

Aspergillus fumigatus Stimulates the NLRP3 Inflammasome through a Pathway Requiring ROS Production and the Syk Tyrosine Kinase

Invasive aspergillosis (IA) is a life-threatening disease that occurs in immunodepressed patients when infected with Aspergillus fumigatus. This fungus is the second most-common causative agent of fungal disease after Candida albicans. Nevertheless, much remains to be learned about the mechanisms by which A. fulmigatus activates the innate immune system. We investigated the inflammatory response to conidia and hyphae of A. fumigatus and specifically, their capacity to trigger activation of an inflammasome. Our results show that in contrast to conidia, hyphal fragments induce NLRP3 inflammasome assembly, caspase-1 activation and IL-1β release from a human monocyte cell line. The ability of Aspergillus hyphae to activate the NLRP3 inflammasome in the monocytes requires K+ efflux and ROS production. In addition, our data show that NLRP3 inflammasome activation as well as pro-IL-1β expression relies on the Syk tyrosine kinase, which is downstream from the pathogen recognition receptor Dectin-1, reinforcing the importance of Dectin-1 in the innate immune response against fungal infection. Furthermore, we show that treatment of monocytes with corticosteroids inhibits transcription of the gene encoding IL-1β. Thus, our data demonstrate that the innate immune response against A. fumigatus infection involves a two step activation process, with a first signal promoting expression and synthesis of pro-IL-1β; and a second signal, involving Syk-induced activation of the NLRP3 inflammasome and caspase-1, allowing processing and secretion of the mature cytokine