Effectiveness of Helminth Therapy in the Prevention of Allograft Rejection: A Systematic Review of Allogeneic Transplantation.

Background: The unique immunomodulatory capacity of helminth parasites has been investigated as a novel strategy in the prevention of allograft rejection after transplantation. This review was conducted to fully evaluate the specific effects of helminth therapy on allograft survival reported in published studies of animal models of allogeneic transplantation. Method: Following PRISMA protocol guidelines, a literature search was conducted using PubMed, MEDLINE via OvidSP, along with additional manual searches of selected reference lists. Publications describing helminth intervention within allograft transplantation models were screened for relevance to eligibility criteria. Primary and secondary outcomes were extracted using standardized data collection tables. The SYRCLE risk of bias assessment tool was used for quality assessment. Due to heterogeneity of study designs, meta-analysis could not be performed; rather outcomes are presented as a narrative synthesis with concept mapping. This review was registered in PROSPERO with ID: CRD42018097175. Results: The literature search generated 1,443 publications, which after screening for relevance to the eligibility criteria yielded 15 publications for qualitative analysis. All 15 publications reported improvement to allograft survival as a result of helminth therapy. This prolonged allograft survival was not significantly different when helminth-derived products were used compared to live infection. However, the extent of positive impact on allograft survival was noted to be dependent on study design factors, such as the chronicity of the live helminth infection, allograft type and the species/genus of helminth selected. Conclusion: Both live and product-based helminth therapy have potential applications as novel immune regulators or adjuncts for the prevention of allograft rejection. However, there were differences in efficacy between different worms and preparations of worm-derived products. Therefore, further studies are required to determine the most appropriate worm for a specific allograft, to elucidate the optimal dose and route of administration, and to better understand the modulation of immune responses that can mediate tolerance

El Niño, tropical Atlantic warmth, and Atlantic hurricanes over the past 1500 years

Author Posting. © The Author(s), 2009. This is the author's version of the work. It is posted here by permission of Nature Publishing Group for personal use, not for redistribution. The definitive version was published in Nature 460 (2009): 880-883, doi:10.1038/nature08219.Atlantic Tropical Cyclone (TC) activity, as measured by annual storm counts, reached anomalous levels over the past decade. The short nature of the historical record and potential issues with its reliability in earlier decades, however, has prompted an ongoing debate regarding the reality and significance of the recent rise. Here, we place recent activity in a longer-term context, by comparing two independent estimates of TC activity over the past 1500 years. The first estimate is based on a composite of regional sedimentary evidence of landfalling hurricanes, while the second estimate employs a previously published statistical model of Atlantic TC activity driven by proxy-reconstructions of past climate changes. Both approaches yield consistent evidence of a peak in Atlantic TC activity during Medieval times (around AD 1000) followed by a subsequent lull in activity. The Medieval peak, which rivals or even exceeds (within uncertainties) recent levels of activity, results in the statistical model from a ‘perfect storm’ of La Niña-like climate conditions and relative tropical Atlantic warmth.M.E.M. and Z.Z. acknowledge support from the ATM programme of the National Science Foundation (grant ATM-0542356). J.P.D. acknowledges support from the EAR and OCE programmes of the National Science Foundation (grants EAR-0519118 and OCE-0402746), the Risk Prediction Initiative at the Bermuda Institute for Ocean Sciences, and the Inter-American Institute for Global Change Research

Breaking down automaticity: Case ambiguity and the shift to reflective approaches in clinical reasoning

Context: Two modes of case processing have been shown to underlie diagnostic judgements: analytical and non-analytical reasoning. An optimal form of clinical reasoning is suggested to combine both modes. Conditions leading doctors to shift from the usual mode of non-analytical reasoning to reflective reasoning have not been identified. This paper reports a study aimed at exploring these conditions by investigating the effects of ambiguity of clinical cases on clinical reasoning. Methods: Participants were 16 internal medicine residents in the Brazilian state of Ceará. They were asked to diagnose 20 clinical cases and recall case information. The independent variable was the degree of ambiguity of clinical cases, with 2 levels: straightforward (i.e. non-ambiguous) and ambiguous. Dependent variables were processing time, diagnostic accuracy and proposition per category recalled. Data were analysed using a repeated measures design. Results: Participants processed straightforward cases faster and more accurately than ambiguous ones. The proportion of text propositions recalled was significantly lower (t[15] = 2.29, P = 0.037) in ambiguous cases, and an interaction effect between case version and proposition category was also found (F[5, 75] = 4.52, P = 0.001, d = 0.232, observed power = 0.962). Furthermore, participants recalled significantly more literal propositions from the ambiguous cases than from the straightforward cases (t[15] = 2.28, P = 0.037). Conclusions: Ambiguity of clinical cases was shown to lead residents to switch from automatic to reflective reasoning, as indicated by longer processing time, and more literal propositions recalled in ambiguous cases

Transition probabilities for general birth-death processes with applications in ecology, genetics, and evolution

A birth-death process is a continuous-time Markov chain that counts the number of particles in a system over time. In the general process with $n$ current particles, a new particle is born with instantaneous rate $\lambda_n$ and a particle dies with instantaneous rate $\mu_n$. Currently no robust and efficient method exists to evaluate the finite-time transition probabilities in a general birth-death process with arbitrary birth and death rates. In this paper, we first revisit the theory of continued fractions to obtain expressions for the Laplace transforms of these transition probabilities and make explicit an important derivation connecting transition probabilities and continued fractions. We then develop an efficient algorithm for computing these probabilities that analyzes the error associated with approximations in the method. We demonstrate that this error-controlled method agrees with known solutions and outperforms previous approaches to computing these probabilities. Finally, we apply our novel method to several important problems in ecology, evolution, and genetics

Hurricanes and climate in the Caribbean during the past 3700 years BP

International audienceA multiproxy analysis of lacustrine sediments cored in Grand-Case Pond at Saint-Martin, north of the Lesser Antilles archipelago, reveals three distinct climatic periods for the last 3700 years. From 3700 to ~2500 yr cal. BP and from 1150 yr cal. BP to the present, carbonate mud deposition occurred in connection with pond lowstands. These periods were also punctuated by severe drought events, marked by gypsum laminae, and hurricane landfalls, leading to marine sand inputs into the pond. The intermediate time interval, from 2500 to 1150 yr cal. BP, is typified by black organic mud deposition, suggesting that hypoxic to anoxic conditions prevailed at the pond bottom. These were probably linked with a perennial pond highstand and reflect more uniform and wetter climatic conditions than today. The carbon isotopic composition of the ostracod Perissocytheridea bisulcata shows that the lowest δ13C values are recorded during the hypoxic periods, as a consequence of bacterial recycling of isotopically depleted organic matter. Such a climatic history agrees closely with that documented from other records in the Caribbean area, such as the Cariaco Basin, central coast of Belize or Barbados. By constrast, discrepancies seem to emerge from the comparison between hurricane activity recorded at Saint-Martin on the one hand and Vieques (Puerto Rico) on the other hand. We explain this apparent contradiction by a balance between two distinct storm paths in response to latitudinal shifts of the Intertropical Convergence Zone (ITCZ). Stronger storm activity over the Gulf coast and the inner Caribbean Sea is favoured by a southern position of the ITCZ in connection with dry climatic conditions. Plausible links with the North Atlantic Oscillation (NAO) are also suggested

Revision and Update of the Consensus Definitions of Invasive Fungal Disease From the European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium.

BACKGROUND: Invasive fungal diseases (IFDs) remain important causes of morbidity and mortality. The consensus definitions of the Infectious Diseases Group of the European Organization for Research and Treatment of Cancer and the Mycoses Study Group have been of immense value to researchers who conduct clinical trials of antifungals, assess diagnostic tests, and undertake epidemiologic studies. However, their utility has not extended beyond patients with cancer or recipients of stem cell or solid organ transplants. With newer diagnostic techniques available, it was clear that an update of these definitions was essential. METHODS: To achieve this, 10 working groups looked closely at imaging, laboratory diagnosis, and special populations at risk of IFD. A final version of the manuscript was agreed upon after the groups' findings were presented at a scientific symposium and after a 3-month period for public comment. There were several rounds of discussion before a final version of the manuscript was approved. RESULTS: There is no change in the classifications of "proven," "probable," and "possible" IFD, although the definition of "probable" has been expanded and the scope of the category "possible" has been diminished. The category of proven IFD can apply to any patient, regardless of whether the patient is immunocompromised. The probable and possible categories are proposed for immunocompromised patients only, except for endemic mycoses. CONCLUSIONS: These updated definitions of IFDs should prove applicable in clinical, diagnostic, and epidemiologic research of a broader range of patients at high-risk

18F-FDG PET/CT for diagnosing infectious complications in patients with severe neutropenia after intensive chemotherapy for haematological malignancy or stem cell transplantation

Item does not contain fulltextPURPOSE: Between 30 and 50% of febrile neutropenic episodes are accounted for by infection. C-reactive protein (CRP) is a nonspecific parameter for infection and inflammation but might be employed as a trigger for diagnosis. The aim of the study was to evaluate whether (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT can be used to detect inflammatory foci in neutropenic patients with elevated CRP and whether it helps to direct treatment. METHODS: Twenty-eight consecutive patients with neutropenia as a result of intensive chemotherapy for haematological malignancies or myeloablative therapy for haematopoietic stem cell transplantation were prospectively included. (18)F-FDG PET/CT was added to the regular diagnostic workup once the CRP level rose above 50 mg/l. RESULTS: Pathological FDG uptake was found in 26 of 28 cases despite peripheral neutrophil counts less than 0.1 x 10(-9)/l in 26 patients: in the digestive tract in 18 cases, around the tract of the central venous catheter (CVC) in 9 and in the lungs in 7 cases. FDG uptake in the CVC tract was associated with coagulase-negative staphylococcal bacteraemia (p < 0.001) and deep venous thrombosis (p = 0.002). The number of patients having Streptococcus mitis bacteraemia appeared to be higher in patients with grade 3 oesophageal FDG uptake (p = 0.08). Pulmonary FDG uptake was associated with the presence of invasive fungal disease (p = 0.04). CONCLUSION: (18)F-FDG PET/CT scanning during chemotherapy-induced febrile neutropenia and increased CRP is able to detect localized foci of infection and inflammation despite the absence of circulating neutrophils. Besides its potential role in detecting CVC-related infection during febrile neutropenia, the high negative predictive value of (18)F-FDG PET/CT is important for avoiding unnecessary diagnostic tests and therapy.1 januari 201

Anaesthetic considerations of adults with Morquio's syndrome - a case report

<p>Abstract</p> <p>Background</p> <p>The anaesthetic management of patients with Morquio syndrome is complicated by a number of factors including odontoid hypoplasia, atlantoaxial instability, thoracic kyphosis, and deposition of mucopolysaccharides in the soft tissue of the oropharnyx.</p> <p>Case presentation</p> <p>Herein we describe the anaesthetic considerations and management of a 26 year old adult with Morquio syndrome, who presented for an elective hip replacement.</p> <p>Conclusion</p> <p>This report details an awake fiberoptic intubation in an adult with Morquio syndrome. We recommend that this approach be considered in patients with Morquio syndrome undergoing general anaesthesia.</p

Evolutionary patterns of two major reproduction candidate genes (Zp2 and Zp3) reveal no contribution to reproductive isolation between bovine species

<p>Abstract</p> <p>Background</p> <p>It has been established that mammalian egg zona pellucida (ZP) glycoproteins are responsible for species-restricted binding of sperm to unfertilized eggs, inducing the sperm acrosome reaction, and preventing polyspermy. In mammals, ZP apparently represents a barrier to heterospecific fertilization and thus probably contributes to reproductive isolation between species. The evolutionary relationships between some members of the tribe Bovini are complex and highly debatable, particularly, those involving <it>Bos </it>and <it>Bison </it>species for which interspecific hybridization is extensively documented. Because reproductive isolation is known to be a major precursor of species divergence, testing evolutionary patterns of ZP glycoproteins may shed some light into the speciation process of these species. To this end, we have examined intraspecific and interspecific genetic variation of two ZP genes (<it>Zp2 </it>and <it>Zp3</it>) for seven representative species (111 individuals) from the Bovini tribe, including five species from <it>Bos </it>and <it>Bison</it>, and two species each from genera <it>Bubalus </it>and <it>Syncerus</it>.</p> <p>Results</p> <p>A pattern of low levels of intraspecific polymorphism and interspecific divergence was detected for the two sequenced fragments each for <it>Zp2 </it>and <it>Zp3</it>. At intraspecific level, none of neutrality tests detected deviations from neutral equilibrium expectations for the two genes. Several haplotypes in both genes were shared by multiple species from <it>Bos </it>and <it>Bison</it>.</p> <p>Conclusions</p> <p>Here we argue that neither ancestral polymorphism nor introgressive hybridization alone can fully account for haplotype sharing among species from <it>Bos </it>and <it>Bison</it>, and that both scenarios have contributed to such a pattern of haplotype sharing observed here. Additionally, codon-based tests revealed strong evidence for purifying selection in the <it>Zp3 </it>coding haplotype sequences and weak evidence for purifying selection in the <it>Zp2 </it>coding haplotype sequences. Contrary to a general genetic pattern that genes or genomic regions contributing to reproductive isolation between species often evolve rapidly and show little or no gene flow between species, these results demonstrate that, particularly, those sequenced exons of the <it>Zp2 </it>and the <it>Zp3 </it>did not show any contribution to reproductive isolation between the bovine species studied here.</p