7,774 research outputs found
Predator escape tactics in birds: linking ecology and aerodynamics
No full textIn most birds, flight is the most important means of escape from predators. Impaired flight abilities due to increased wing loading may increase vulnerability to predation. To compensate for an increase in wing loading, birds are able to independently decrease body mass (BM) or increase pectoral muscle mass (PMM). Comparing nearshore and farshore foraging shorebird species, we develop a theory as to which of these responses should be the most appropriate. We hypothesize that nearshore foragers should respond to increased predation by increasing their PMM in order to promote speed-based escape. Instead, farshore foragers should decrease BM in order to improve agility for maneuvering escape. Experiments on 2 shorebird species are consistent with these predictions, but on the basis of the theoretical framework for evaluating effect size and biological significance developed here, more experiments are clearly needed. Copyright 2009, Oxford University Press.
Genuine and simulated suicide notes: An analysis of content
No full textThe present study examined genuine and simulated suicide notes aiming to identify the measures of content that best differentiate between the two. Thirty-three genuine and thirty-three simulated suicide notes were content-analysed and data subjected to smallest space analysis (SSA), a Multidimensional Scaling Procedure. The core of all suicide notes was discovered to be constructed with the use of three variables: expressions of love, positive construction of partner and apologies. Furthermore, four different genuine suicide note themes (‘planned escape’, ‘negative affect and self-mitigation’, ‘positive affect and failed relationship’, ‘lack of self-acceptance’) and three simulated suicide note themes (‘escape’, ‘positive affect and self-blame’, ‘purposeless life’) were identified revealing that authentic suicide note themes were more internally consistent and clearer to interpret
Selection of neutralizing antibody escape mutants with type A influenza virus HA-specific polyclonal antisera: possible significance for antigenic drift
No full textTen antisera were produced in rabbits by two or three intravenous injections of inactivated whole influenza type A virions. All contained haemagglutination-inhibition (HI) antibody directed predominantly to an epitope in antigenic site B and, in addition, various amounts of antibodies to an epitope in site A and in site D. The ability of untreated antisera to select neutralization escape mutants was investigated by incubating virus possessing the homologous haemagglutinin with antiserum adjusted to contain anti-B epitope HI titres of 100, 1000 and 10000 HIU/ml. Virus-antiserum mixtures were inoculated into embryonated hen's eggs, and progeny virus examined without further selection. Forty percent of the antisera at a titre of 1000 HIU/ml selected neutralizing antibody escape mutants as defined by their lack of reactivity to Mab HC10 (site B), and unchanged reactivity to other Mabs to site A and site D epitopes. All escape mutant-selecting antisera had a ratio of anti-site B (HC10)-epitope antibody[ratio]other antibodies of [gt-or-equal, slanted]2·0[ratio]1. The antiserum with the highest ratio (7·4[ratio]1) selected escape mutants in all eggs tested in four different experiments. No antiserum used at a titre of 10000 HIU/ml allowed multiplication of any virus. All antisera used at a titre of 100 HIU/ml permitted virus growth, but this was wild-type (wt) virus. We conclude that a predominant epitope-specific antibody response, a titre of [gt-or-equal, slanted]1000 HIU/ml, and a low absolute titre of other antibodies ([less-than-or-eq, slant]500 HIU/ml) are three requirements for the selection of escape mutants. None of the antisera in this study could have selected escape mutants without an appropriate dilution factor, so the occurrence of an escape mutant-selecting antiserum in nature is likely to be a rare event
Severe neurological outcomes after very early bilateral nephrectomies in patients with autosomal recessive polycystic kidney disease (ARPKD)
No full textAbstract To test the association between bilateral nephrectomies in patients with autosomal recessive polycystic kidney disease (ARPKD) and long-term clinical outcome and to identify risk factors for severe outcomes, a dataset comprising 504 patients from the international registry study ARegPKD was analyzed for characteristics and complications of patients with very early (≤ 3 months; VEBNE) and early (4–15 months; EBNE) bilateral nephrectomies. Patients with very early dialysis (VED, onset ≤ 3 months) without bilateral nephrectomies and patients with total kidney volumes (TKV) comparable to VEBNE infants served as additional control groups. We identified 19 children with VEBNE, 9 with EBNE, 12 with VED and 11 in the TKV control group. VEBNE patients suffered more frequently from severe neurological complications in comparison to all control patients. Very early bilateral nephrectomies and documentation of severe hypotensive episodes were independent risk factors for severe neurological complications. Bilateral nephrectomies within the first 3 months of life are associated with a risk of severe neurological complications later in life. Our data support a very cautious indication of very early bilateral nephrectomies in ARPKD, especially in patients with residual kidney function, and emphasize the importance of avoiding severe hypotensive episodes in this at-risk cohort.Universität zu Köln http://dx.doi.org/10.13039/501100008001Marga und Walter Boll-Stiftung http://dx.doi.org/10.13039/501100011566Bundesministerium für Bildung, Wissenschaft und Forschung http://dx.doi.org/10.13039/501100013699Bundesministerium für Bildung und Forschung http://dx.doi.org/10.13039/501100002347European Society for Paediatric NephrologyProjekt DEA
The role of early cytotoxic lymphocyte (CTL) escape in the pathogenesis of HIV-1 subtype C infection
No full textIncludes abstract.Includes bibliographical references.This study investigated the frequency and timing of cytotoxic T-lympthocyte (CTL) escape and its pathogenic consequences on HIV-1 subtype C disease progression
The good parodist: beyond images of escape in the fiction of Doris lessing
No full textIn her earlier fiction, Doris Leasing presents images of escape from what Cohen and Taylor term "everyday life”. These images of escape, such as the vision of the "noble city, set four-square" in Martha Quest and Martha's plunge into the muddy veld pothole in A Proper Marriage, are framed by realism. In positing an escape from 'realism'(understood as both literary form and "everyday reality") they suggest the inadequacy of realism. However, the success of these images is limited as they attempt to posit an "outside", a project which postmodernism has taught us, is bound to fail. Lessing increasingly replaces these images of escape with parody. Parody more fundamentally interrogates realism and allows Lessing to negotiate an escape whilst recognizing her implication in contemporary society. My model of parody takes its lead from Linda Hutcheon's consideration of "serious parody", as marking "the intersection of creation and re-creation, of invention and critique" (A Theory of Parody, 1985). This, I argue, is the intersection of Lessing's political and aesthetic projects. Lessing's use of parody also provides her with a useful strategy for negotiating subjectivity. I argue that whilst she questions the liberal humanist self, she does not completely reject it. She is "post-humanist" rather than "anti-humanist". Lessing's "space fiction" seems to signal a return to the project of positing an "outside" implied by her images of escape. However, I illustrate how her space fiction is equally subject to the problematic politics of parody. Just as parody "installs" a pre-existing text to "subvert" it, so space fiction "installs" the Earth in order to critique it. The "dual-codedness" of parody is, I conclude, perfect for Lessing's multiple projects
Correlates of protective cellular immunity revealed by analysis of population-level immune escape pathways in HIV-1
No full textHLA class I-associated polymorphisms identified at the population level mark viral sites under immune pressure by individual HLA alleles. As such, analysis of their distribution, frequency, location, statistical strength, sequence conservation, and other properties offers a unique perspective from which to identify correlates of protective cellular immunity. We analyzed HLA-associated HIV-1 subtype B polymorphisms in 1,888 treatment-naïve, chronically infected individuals using phylogenetically informed methods and identified characteristics of HLA-associated immune pressures that differentiate protective and nonprotective alleles. Over 2,100 HLA-associated HIV-1 polymorphisms were identified, approximately one-third of which occurred inside or within 3 residues of an optimally defined cytotoxic T-lymphocyte (CTL) epitope. Differential CTL escape patterns between closely related HLA alleles were common and increased with greater evolutionary distance between allele group members. Among 9-mer epitopes, mutations at HLA-specific anchor residues representedthe most frequently detected escape type: these occurred nearly 2-fold more frequently than expected by chance and were computationally predicted to reduce peptide-HLA binding nearly 10-fold on average. Characteristics associated with protective HLA alleles (defined using hazard ratios for progression to AIDS from natural history cohorts) included the potential to mount broad immune selection pressures across all HIV-1 proteins except Nef, the tendency to drive multisite and/or anchor residue escape mutations within known CTL epitopes, and the ability to strongly select mutations in conserved regions within HIV's structural and functional proteins. Thus, the factors defining protective cellular immune responsesmay be more complex than simply targeting conserved viral regions. The results provide new information to guide vaccine design and immunogenicity studies
Effect of Early Surgery vs Endoscopy-First Approach on Pain in Patients With Chronic Pancreatitis The ESCAPE Randomized Clinical Trial
No full textImportance: For patients with painful chronic pancreatitis, surgical treatment is postponed until medical and endoscopic treatment have failed. Observational studies have suggested that earlier surgery could mitigate disease progression, providing better pain control and preserving pancreatic function. Objective: To determine whether early surgery is more effective than the endoscopy-first approach in terms of clinical outcomes. Design, Setting, and Participants: The ESCAPE trial was an unblinded, multicenter, randomized clinical superiority trial involving 30 Dutch hospitals participating in the Dutch Pancreatitis Study Group. From April 2011 until September 2016, a total of 88 patients with chronic pancreatitis, a dilated main pancreatic duct, and who only recently started using prescribed opioids for severe pain (strong opioids for ≤2 months or weak opioids for ≤6 months) were included. The 18-month follow-up period ended in March 2018. Interventions: There were 44 patients randomized to the early surgery group who underwent pancreatic drainage surgery within 6 weeks after randomization and 44 patients randomized to the endoscopy-first approach group who underwent medical treatment, endoscopy including lithotripsy if needed, and surgery if needed. Main Outcomes and Measures: The primary outcome was pain, measured on the Izbicki pain score and integrated over 18 months (range, 0-100 [increasing score indicates more pain severity]). Secondary outcomes were pain relief at the end of follow-up; number of interventions, complications, hospital admissions; pancreatic function; quality of life (measured on the 36-Item Short Form Health Survey [SF-36]); and mortality. Results: Among 88 patients who were randomized (mean age, 52 years; 21 (24%) women), 85 (97%) completed the trial. During 18 months of follow-up, patients in the early surgery group had a lower Izbicki pain score than patients in the group randomized to receive the endoscopy-first approach group (37 vs 49; between-group difference, -12 points [95% CI, -22 to -2]; P = .02). Complete or partial pain relief at end of follow-up was achieved in 23 of 40 patients (58%) in the early surgery vs 16 of 41 (39%)in the endoscopy-first approach group (P = .10). The total number of interventions was lower in the early surgery group (median, 1 vs 3; P < .001). Treatment complications (27% vs 25%), mortality (0% vs 0%), hospital admissions, pancreatic function, and quality of life were not significantly different between early surgery and the endoscopy-first approach. Conclusions and Relevance: Among patients with chronic pancreatitis, early surgery compared with an endoscopy-first approach resulted in lower pain scores when integrated over 18 months. However, further research is needed to assess persistence of differences over time and to replicate the study findings. Trial Registration: ISRCTN Identifier: ISRCTN45877994
Kramers Escape Rate in Nonlinear Diffusive Media
No full textIn this paper, we study nonlinear Kramers problem by investigating overdamped systems ruled by the one-dimensional nonlinear Fokker-Planck equation. We obtain an analytic expression for the Kramers escape rate under quasistationary conditions by employingIn this paper, we study nonlinear Kramers problem by investigating overdamped systems ruled by the one-dimensional nonlinear Fokker-Planck equation. We obtain an analytic expression for the Kramers escape rate under quasistationary conditions by employing a metastable potential and its predictions are in excellent agreement with numerical simulations. The results exhibit the anomalies due to the nonlinearity in W that the escape rate grows with D and drops as mu becomes large at a fixed D. Indeed, particles in the subdiffusive media (mu>1) can escape over the barrier only when D is above a critical value, while this confinement does not exist in the superdiffusive media (mu < 1)
Human monoclonal antibody combination against SARS coronavirus : synergy and coverage of escape mutants
No full textBackground: Experimental animal data show that protection against severe acute respiratory syndrome coronavirus (SARS-CoV) infection with human monoclonal antibodies (mAbs) is feasible. For an effective immune prophylaxis in humans, broad coverage of different strains of SARS-CoV and control of potential neutralization escape variants will be required. Combinations of virus-neutralizing, noncompeting mAbs may have these properties. Methods and Findings: Human mAb CR3014 has been shown to completely prevent lung pathology and abolish pharyngeal shedding of SARS-CoV in infected ferrets. We generated in vitro SARS-CoV variants escaping neutralization by CR3014, which all had a single P462L mutation in the glycoprotein spike (S) of the escape virus. In vitro experiments confirmed that binding of CR3014 to a recombinant S fragment (amino acid residues 318–510) harboring this mutation was abolished. We therefore screened an antibody-phage library derived from blood of a convalescent SARS patient for antibodies complementary to CR3014. A novel mAb, CR3022, was identified that neutralized CR3014 escape viruses, did not compete with CR3014 for binding to recombinant S1 fragments, and bound to S1 fragments derived from the civet cat SARS-CoV-like strain SZ3. No escape variants could be generated with CR3022. The mixture of both mAbs showed neutralization of SARS-CoV in a synergistic fashion by recognizing different epitopes on the receptor-binding domain. Dose reduction indices of 4.5 and 20.5 were observed for CR3014 and CR3022, respectively, at 100% neutralization. Because enhancement of SARS-CoV infection by subneutralizing antibody concentrations is of concern, we show here that anti-SARS-CoV antibodies do not convert the abortive infection of primary human macrophages by SARS-CoV into a productive one. Conclusions: The combination of two noncompeting human mAbs CR3014 and CR3022 potentially controls immune escape and extends the breadth of protection. At the same time, synergy between CR3014 and CR3022 may allow for a lower total antibody dose to be administered for passive immune prophylaxis of SARS-CoV infection
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