207 research outputs found

    Effects of multiple targeted repelling measures on the behaviour of individually tracked birds in an area of increasing human–wildlife conflict

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    1. Some animal populations are rapidly increasing in numbers and expanding their ranges, leading to intensified human–wildlife conflicts. A wide range of tools has been developed to repel animals from areas where they are suspected to cause damage. For waterfowl, direct comparisons of multiple repelling methods have so far focused only on species´ presence, total numbers, cost effectiveness or subsequent damage assessments, but not on individual behaviour. 2. Here, we investigated the individual responses of free-flying geese to three repelling methods using high-resolution tracking data. In an experimental setup, tracked individuals were repelled by human approach, gunshot sound or handheld lasers. 3. We found that repelling success and return time to the field where the repelling took place increased when individuals were repelled multiple times. Travel distances after the repelling events were longer after human approach and gunshot sound compared to the handheld laser treatments. In spring, the probability to return to the same field was higher after repelling with handheld lasers, but no difference between treatments was evident in autumn. We observed no increase in the probability to visit accommodation fields, where geese were allowed to forage and were not repelled, after the repelling events. 4. Synthesis and applications. We found no strong differences between the three methods regarding the repelling effectiveness and the resulting behaviour of the tracked geese. However, the higher return rates of individuals after repelling with handheld lasers in spring suggest that this method might be less effective in situations with bright sunlight or very large aggregations of geese. Apart from these limitations, we can recommend handheld lasers for repelling as they might reduce energetic losses for the geese and disturbance of non-target wildlife. Since repelling by gunshot sound and handheld lasers was twice as fast as repelling by human approach, those methods will reduce working hours by 50% and therefore be more cost-effective in practice

    Anastrozole and everolimus in advanced gynecologic and breast malignancies: activity and molecular alterations in the PI3K/AKT/mTOR pathway.

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    BackgroundSince PI3K/AKT/mTOR pathway activation diminishes the effects of hormone therapy, combining aromatase inhibitors (anatrozole) with mTOR inhibitors (everolimus) was investigated.Patients and methodsWe evaluated anastrozole and everolimus in 55 patients with metastatic estrogen (ER) and/or progesterone receptor (PR)-positive breast and gynecologic tumors. Endpoints were safety, antitumor activity and molecular correlates.ResultsFull doses of anastrozole (1 mg PO daily) and everolimus (10 mg PO daily) were well tolerated. Twelve of 50 evaluable patients (24%) (median = 3 prior therapies) achieved stable disease (SD) ≥ 6 months/partial response (PR)/complete response (CR) (n = 5 (10%) with PR/CR): 9 of 32 (28%) with breast cancer (n=5 (16%) with PR/CR); 2 of 10 (20%), ovarian cancer; and 1 of 6 (17%), endometrial cancer. Six of 22 patients (27%) with molecular alterations in the PI3K/AKT/mTOR pathway achieved SD ≥ 6 months/PR/CR. Six of 8 patients (75%) with SD ≥ 6 months/PR/CR with molecular testing demonstrated at least one alteration in the PI3K/AKT/mTOR pathway: mutations in PIK3CA (n=3) and AKT1 (n=1) or PTEN loss (n=3). All three responders (CR (n = 1); PR (n=2)) who had next generation sequencing demonstrated additional alterations: amplifications in CCNE1, IRS2, MCL1, CCND1, FGFR1 and MYC and a rearrangement in PRKDC.ConclusionsCombination anastrozole and everolimus is well tolerated at full approved doses, and is active in heavily-pretreated patients with ER and/or PR-positive breast, ovarian and endometrial cancers. Responses were observed in patients with multiple molecular aberrations. CLINICAL TRAILS INCLUDED: NCT01197170

    Can work ability explain the social gradient in sickness absence: a study of a general population in Sweden

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    <p>Abstract</p> <p>Background</p> <p>Understanding the reasons for the social gradient in sickness absence might provide an opportunity to reduce the general rates of sickness absence. The complete explanation for this social gradient still remains unclear and there is a need for studies using randomized working population samples. The main aim of the present study was to investigate if self-reported work ability could explain the association between low socioeconomic position and belonging to a sample of new cases of sick-listed employees.</p> <p>Methods</p> <p>The two study samples consisted of a randomized working population (n = 2,763) and a sample of new cases of sick-listed employees (n = 3,044), 19-64 years old. Both samples were drawn from the same randomized general population. Socioeconomic status was measured with occupational position and physical and mental work ability was measured with two items extracted from the work ability index.</p> <p>Results</p> <p>There was an association between lower socioeconomic status and belonging to the sick-listed sample among both women and men. In men the crude Odds ratios increased for each downwards step in socioeconomic status, OR 1.32 (95% CI 0.98-1.78), OR 1.53 (1.05-2.24), OR 2.80 (2.11-3.72), and OR 2.98 (2.27-3.90). Among women this gradient was not as pronounced. Physical work ability constituted the strongest explanatory factor explaining the total association between socioeconomic status and being sick-listed in women. However, among men, the association between skilled non-manual, OR 2.07 (1.54-2.78), and non-skilled manual, OR 2.03 (1.53-2.71) positions in relation to being sick-listed remained. The explanatory effect of mental work ability was small. Surprisingly, even in the sick-listed sample most respondents had high mental and physical work ability.</p> <p>Conclusions</p> <p>These results suggest that physical work ability may be an important key in explaining the social gradient in sickness absence, particularly in women. Hence, it is possible that the factors associated with the social gradient in sickness absence may differ, to some extent, between women and men.</p

    Effects of multiple targeted repelling measures on the behaviour of individually tracked birds in an area of increasing human-wildlife conflict

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    1. Some animal populations are rapidly increasing in numbers and expanding their ranges, leading to intensified human-wildlife conflicts. A wide range of tools has been developed to repel animals from areas where they are suspected to cause damage. For waterfowl, direct comparisons of multiple repelling methods have so far focused only on species ' presence, total numbers, cost effectiveness or subsequent damage assessments, but not on individual behaviour. 2. Here, we investigated the individual responses of free-flying geese to three repelling methods using high-resolution tracking data. In an experimental setup, tracked individuals were repelled by human approach, gunshot sound or handheld lasers. 3. We found that repelling success and return time to the field where the repelling took place increased when individuals were repelled multiple times. Travel distances after the repelling events were longer after human approach and gunshot sound compared to the handheld laser treatments. In spring, the probability to return to the same field was higher after repelling with handheld lasers, but no difference between treatments was evident in autumn. We observed no increase in the probability to visit accommodation fields, where geese were allowed to forage and were not repelled, after the repelling events. 4. Synthesis and applications. We found no strong differences between the three methods regarding the repelling effectiveness and the resulting behaviour of the tracked geese. However, the higher return rates of individuals after repelling with handheld lasers in spring suggest that this method might be less effective in situations with bright sunlight or very large aggregations of geese. Apart from these limitations, we can recommend handheld lasers for repelling as they might reduce energetic losses for the geese and disturbance of non-target wildlife. Since repelling by gunshot sound and handheld lasers was twice as fast as repelling by human approach, those methods will reduce working hours by 50% and therefore be more cost-effective in practice.</p

    Mutation-enrichment next-generation sequencing for quantitative detection of KRAS mutations in urine cell-free DNA from patients with advanced cancers

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    Purpose: Tumor-derived cell-free DNA (cfDNA) from urine of patients with cancer offers noninvasive biological material for detection of cancer-related molecular abnormalities such as mutations in Exon 2 of KRASExperimental Design: A quantitative, mutation-enrichment next-generation sequencing test for detecting KRASG12/G13 mutations in urine cfDNA was developed, and results were compared with clinical testing of archival tumor tissue and plasma cfDNA from patients with advanced cancer.Results: With 90 to 110 mL of urine, the KRASG12/G13 cfDNA test had an analytical sensitivity of 0.002% to 0.006% mutant copies in wild-type background. In 71 patients, the concordance between urine cfDNA and tumor was 73% (sensitivity, 63%; specificity, 96%) for all patients and 89% (sensitivity, 80%; specificity, 100%) for patients with urine samples of 90 to 110 mL. Patients had significantly fewer KRASG12/G13 copies in urine cfDNA during systemic therapy than at baseline or disease progression (P = 0.002). Compared with no changes or increases in urine cfDNA KRASG12/G13 copies during therapy, decreases in these measures were associated with longer median time to treatment failure (P = 0.03).Conclusions: A quantitative, mutation-enrichment next-generation sequencing test for detecting KRASG12/G13 mutations in urine cfDNA had good concordance with testing of archival tumor tissue. Changes in mutated urine cfDNA were associated with time to treatment failure

    Performance in Physical Education and Health Impairment 30 Years Later—A Community Based Cohort Study

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    Objective: A main purpose of physical education (PE) in school is to promote future health. However, there is very limited evidence of the effects of PE on the adult health. We hypothesized that a low performance in PE was associated with an increased risk of health impairment by middle age. Methods: We performed a cohort study in a community-based setting in Sweden spanning over three decades. We followed up on 1712 of 2225 students (76.9%) who in 1974–1976 graduated with a grade in PE after 9 years of education (mean subject age 16 years). The grade in PE (compulsory subject) was retrieved from municipal archives. We defined three proxies for health impairment: total number of visits to primary care physicians in 2003–2007, having been hospitalized 2003–2007, and total number of days with sick leave in 2004–2007. Using binomial regression models, we adjusted the risk estimates for level of education and occupation. Subjects with an average grade in PE served as reference category. Results: In both the crude and adjusted model, women with a low grade in PE had more physician visits (adjusted IRR 1.30, 95 % confidence interval 1.06–1.60) and an increased number of days with sick leave (adjusted IRR 1.44, 1.05–1.95). An increased, although not significant, risk was also observed for having received in-patient care (adjusted RR 1.26; 0.88–1.80). No significant results or similar pattern were observed in men. Conclusion: Women with a low grade in PE in adolescence seem to have an increased risk of health impairment by middl

    The Evolution of Extracellular Fibrillins and Their Functional Domains

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    Fibrillins constitute the major backbone of multifunctional microfibrils in elastic and non-elastic extracellular matrices, and are known to interact with several binding partners including tropoelastin and integrins. Here, we study the evolution of fibrillin proteins. Following sequence collection from 39 organisms representative of the major evolutionary groups, molecular evolutionary genetics and phylogeny inference software were used to generate a series of evolutionary trees using distance-based and maximum likelihood methods. The resulting trees support the concept of gene duplication as a means of generating the three vertebrate fibrillins. Beginning with a single fibrillin sequence found in invertebrates and jawless fish, a gene duplication event, which coincides with the appearance of elastin, led to the creation of two genes. One of the genes significantly evolved to become the gene for present-day fibrillin-1, while the other underwent evolutionary changes, including a second duplication, to produce present-day fibrillin-2 and fibrillin-3. Detailed analysis of several sequences and domains within the fibrillins reveals distinct similarities and differences across various species. The RGD integrin-binding site in TB4 of all fibrillins is conserved in cephalochordates and vertebrates, while the integrin-binding site within cbEGF18 of fibrillin-3 is a recent evolutionary change. The proline-rich domain in fibrillin-1, glycine-rich domain in fibrillin-2 and proline-/glycine-rich domain in fibrillin-3 are found in all analyzed tetrapod species, whereas it is completely replaced with an EGF-like domain in cnidarians, arthropods, molluscs and urochordates. All collected sequences contain the first 9-cysteine hybrid domain, and the second 8-cysteine hybrid domain with exception of arthropods containing an atypical 10-cysteine hybrid domain 2. Furin cleavage sites within the N- and C-terminal unique domains were found for all analyzed fibrillin sequences, indicating an essential role for processing of the fibrillin pro-proteins. The four cysteines in the unique N-terminus and the two cysteines in the unique C-terminus are also highly conserved

    Landscape homogenization due to agricultural intensification disrupts the relationship between reproductive success and main prey abundance in an avian predator

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    Selecting high-quality habitat and the optimal time to reproduce can increase individual fitness and is a strong evolutionary factor shaping animal populations. However, few studies have investigated the interplay between land cover heterogeneity, limitation in food resources, individual quality and spatial variation in fitness parameters. Here, we explore how individuals of different quality respond to possible mismatches between a cue for prey availability (land cover heterogeneity) and the actual fluctuating prey abundance.Peer reviewe

    Allele-Specific HLA Loss and Immune Escape in Lung Cancer Evolution

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    Immune evasion is a hallmark of cancer. Losing the ability to present neoantigens through human leukocyte antigen (HLA) loss may facilitate immune evasion. However, the polymorphic nature of the locus has precluded accurate HLA copy-number analysis. Here, we present loss of heterozygosity in human leukocyte antigen (LOHHLA), a computational tool to determine HLA allele-specific copy number from sequencing data. Using LOHHLA, we find that HLA LOH occurs in 40% of non-small-cell lung cancers (NSCLCs) and is associated with a high subclonal neoantigen burden, APOBEC-mediated mutagenesis, upregulation of cytolytic activity, and PD-L1 positivity. The focal nature of HLA LOH alterations, their subclonal frequencies, enrichment in metastatic sites, and occurrence as parallel events suggests that HLA LOH is an immune escape mechanism that is subject to strong microenvironmental selection pressures later in tumor evolution. Characterizing HLA LOH with LOHHLA refines neoantigen prediction and may have implications for our understanding of resistance mechanisms and immunotherapeutic approaches targeting neoantigens. Video Abstract [Figure presented] Development of the bioinformatics tool LOHHLA allows precise measurement of allele-specific HLA copy number, improves the accuracy in neoantigen prediction, and uncovers insights into how immune escape contributes to tumor evolution in non-small-cell lung cancer
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