447 research outputs found
On the Feasibility of Malware Authorship Attribution
There are many occasions in which the security community is interested to
discover the authorship of malware binaries, either for digital forensics
analysis of malware corpora or for thwarting live threats of malware invasion.
Such a discovery of authorship might be possible due to stylistic features
inherent to software codes written by human programmers. Existing studies of
authorship attribution of general purpose software mainly focus on source code,
which is typically based on the style of programs and environment. However,
those features critically depend on the availability of the program source
code, which is usually not the case when dealing with malware binaries. Such
program binaries often do not retain many semantic or stylistic features due to
the compilation process. Therefore, authorship attribution in the domain of
malware binaries based on features and styles that will survive the compilation
process is challenging. This paper provides the state of the art in this
literature. Further, we analyze the features involved in those techniques. By
using a case study, we identify features that can survive the compilation
process. Finally, we analyze existing works on binary authorship attribution
and study their applicability to real malware binaries.Comment: FPS 201
Genome-wide sexually antagonistic variants reveal long-standing constraints on sexual dimorphism in fruit flies
The evolution of sexual dimorphism is constrained by a shared genome, leading to ‘sexual
antagonism’, in which different alleles at given loci are favoured by selection in males and
females. Despite its wide taxonomic incidence, we know little about the identity, genomic
location, and evolutionary dynamics of antagonistic genetic variants. To address these deficits, we use sex-specific fitness data from 202 fully sequenced hemiclonal Drosophila melanogaster fly lines to perform a genome-wide association study (GWAS) of sexual
antagonism. We identify approximately 230 chromosomal clusters of candidate antagonistic
single nucleotide polymorphisms (SNPs). In contradiction to classic theory, we find no clear
evidence that the X chromosome is a hot spot for sexually antagonistic variation. Characterising antagonistic SNPs functionally, we find a large excess of missense variants but little
enrichment in terms of gene function. We also assess the evolutionary persistence of antagonistic variants by examining extant polymorphism in wild D. melanogaster populations and
closely related species. Remarkably, antagonistic variants are associated with multiple signatures of balancing selection across the D. melanogaster distribution range and in their sister species D. simulans, indicating widespread and evolutionarily persistent (about 1 million
years) genomic constraints on the evolution of sexual dimorphism. Based on our results, we
propose that antagonistic variation accumulates because of constraints on the resolution of
sexual conflict over protein coding sequences, thus contributing to the long-term maintenance of heritable fitness variation
Risk factors for delayed presentation and referral of symptomatic cancer: Evidence for common cancers
Background:It has been suggested that the known poorer survival from cancer in the United Kingdom, compared with other European countries, can be attributed to more advanced cancer stage at presentation. There is, therefore, a need to understand the diagnostic process, and to ascertain the risk factors for increased time to presentation.Methods:We report the results from two worldwide systematic reviews of the literature on patient-mediated and practitioner-mediated delays, identifying the factors that may influence these.Results:Across cancer sites, non-recognition of symptom seriousness is the main patient-mediated factor resulting in increased time to presentation. There is strong evidence of an association between older age and patient delay for breast cancer, between lower socio-economic status and delay for upper gastrointestinal and urological cancers and between lower education level and delay for breast and colorectal cancers. Fear of cancer is a contributor to delayed presentation, while sanctioning of help seeking by others can be a powerful mediator of reduced time to presentation. For practitioner delay, ‘misdiagnosis’ occurring either through treating patients symptomatically or relating symptoms to a health problem other than cancer, was an important theme across cancer sites. For some cancers, this could also be linked to inadequate patient examination, use of inappropriate tests or failing to follow-up negative or inconclusive test results.Conclusion:Having sought help for potential cancer symptoms, it is therefore important that practitioners recognise these symptoms, and examine, investigate and refer appropriately. © 2009 Cancer Research UK All rights reserved
Fine sediment reduces vertical migrations of Gammarus pulex (Crustacea: Amphipoda) in response to surface water loss
Surface and subsurface sediments in river ecosystems are recognized as refuges that may promote invertebrate survival during disturbances such as floods and streambed drying. Refuge use is spatiotemporally variable, with environmental factors including substrate composition, in particular the proportion of fine sediment (FS), affecting the ability of organisms to move through interstitial spaces. We conducted a laboratory experiment to examine the effects of FS on the movement of Gammarus pulex Linnaeus (Crustacea: Amphipoda) into subsurface sediments in response to surface water loss. We hypothesized that increasing volumes of FS would impede and ultimately prevent individuals from migrating into the sediments. To test this hypothesis, the proportion of FS (1–2 mm diameter) present within an open gravel matrix (4–16 mm diameter) was varied from 10 to 20% by volume in 2.5% increments. Under control conditions (0% FS), 93% of individuals moved into subsurface sediments as the water level was reduced. The proportion of individuals moving into the subsurface decreased to 74% at 10% FS, and at 20% FS no individuals entered the sediments, supporting our hypothesis. These results demonstrate the importance of reducing FS inputs into river ecosystems and restoring FS-clogged riverbeds, to promote refuge use during increasingly common instream disturbances
The predictive role of serum and bronchoalveolar lavage cytokines and adhesion molecules for acute respiratory distress syndrome development and outcome
BACKGROUND: The predictive role of many cytokines and adhesion molecules has not been studied systematically in acute respiratory distress syndrome (ARDS). METHODS: We measured prospectively tumour necrosis factor alpha (TNF-α), interleukin (IL)-1, soluble vascular adhesion molecule-1 (VCAM-1) and soluble intercellular adhesion molecule-1 (ICAM-1) in serum and bronchoalveolar lavage fluid (BALF) within 2 hours following admission, in 65 patients. The patients were divided into: those fulfilling the criteria for ARDS (n = 23, group A), those who were pre-ARDS and who developed ARDS within 24 hours (n = 14, group B), and those on pre-ARDS but who never developed ARDS (n = 28, group C). RESULTS: All the measured molecules were only found at higher levels in the serum of patients that died either with or without ARDS (P < 0.05 – P < 0.0001). Patients at risk exhibited a good negative predictive value (NPV) of the measured molecules for ARDS development both in their serum (89 to 95%) and BALF (86 to 92%) levels. In contrast to BALF, serum levels of IL-1 and adhesion molecules exhibited a good NPV (68 to 96%), sensitivity (60 to 88%) and survival specificity (74 to 96%) in all groups. All molecules in serum and BALF IL-1 were correlated with the APACHE II (P < 0.05 – P < 0.0001). Serum and BALF IL-1 as well as BALF TNF-α were negatively correlated to PaO(2)/FiO(2) (all P < 0.05). CONCLUSIONS: The studied molecules have good NPV for ARDS development both in serum and BALF. Serum rather than BALF levels seem to be related to outcome
Preoperative bi-fractionated accelerated radiation therapy for combined treatment of locally advanced rectal cancer in a consectutive series of unselected patients
Background: although preoperative RT (Radiation Therapy) is becoming the preferred approach for combined treatment of locally advanced rectal adenocarcinoma, no regimen can be now considered as a standard. Since the toxicity of preoperative RT isn't yet completely known, and the advantages of preoperative RT could be counterbalanced by increased postoperative morbidity and mortality, a monocentre series of preoperative bifractionated accelerated RT was retrospectively reviewed to clarify toxicity and outcomes after a prolonged follow up. Methods: patients were screened following these eligibility criteria: histology-proven adenocarcinoma of the rectum; distal tumour extent at 12 cm or less from the anal verge; clinical stage T3-4/anyN, or anyT/ N1-2; ECOG Performance Status 0-2. A total dose of 41.6 Gy (26 twice daily fractions of 1.6 Gy) was delivered. Surgery was carried out 17 \ub1 2 days after RT completion, adopting the total mesorectal excision technique. Results: 24 men and 23 women were enrolled; median age was 55 years (r.: 39-77). Twenty-eight patients were stage II and 19 stage III. 9 patients suffered from a recurrent tumour. 2 patients experienced a severe grade 4 gastrointestinal toxicity (a colo-vaginal fistula and an intestinal obstruction, both successfully treated). Operative mortality was nil; postoperative early complications occurred in 13 cases; mean length of hospital stay was 15 days. After a mean follow up of 44 months (r.: 18-84) 8 patients had deceased for recurrent disease, 15 were alive with a disease progression (2 pelvic recurrences and 13 pure distant deposits) and 24 were alive, without disease. The 5-year actuarial overall survival was 74.2%, the disease-free survival 62.9% and the regional control rate 84.7%. Long-term complications included 1 case of radiation enteritis requiring surgery, 2 cases of anastomotic stricture and 3 cases of bladder incontinence. Conclusion: bifractionated accelerated RT administered in the preoperative setting to patients bearing locally advanced rectal cancer is reliable and safe, as its immediate and late toxicity (mainly infectious) is acceptably low and long-term survivals are achievable. These findings support the increasing use of preoperative RT for treatment of this malignancy in experienced centres. Ongoing multicentric trials are expected to address still unsolved issues, including the benefit of CT adjunct to preoperative RT
Prospective functional classification of all possible missense variants in PPARG.
Clinical exome sequencing routinely identifies missense variants in disease-related genes, but functional characterization is rarely undertaken, leading to diagnostic uncertainty. For example, mutations in PPARG cause Mendelian lipodystrophy and increase risk of type 2 diabetes (T2D). Although approximately 1 in 500 people harbor missense variants in PPARG, most are of unknown consequence. To prospectively characterize PPARγ variants, we used highly parallel oligonucleotide synthesis to construct a library encoding all 9,595 possible single-amino acid substitutions. We developed a pooled functional assay in human macrophages, experimentally evaluated all protein variants, and used the experimental data to train a variant classifier by supervised machine learning. When applied to 55 new missense variants identified in population-based and clinical sequencing, the classifier annotated 6 variants as pathogenic; these were subsequently validated by single-variant assays. Saturation mutagenesis and prospective experimental characterization can support immediate diagnostic interpretation of newly discovered missense variants in disease-related genes.This work was supported by grants from the National Institute of Diabetes and Digestive and Kidney Diseases (1K08DK102877-01, to A.R.M.; 1R01DK097768-01, to D.A.), NIH/Harvard Catalyst (1KL2TR001100-01, to A.R.M.), the Broad Institute (SPARC award, to A.R.M. and T.M.), and the Wellcome Trust (095564, to K.C.; 107064, to D.B.S.).This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/ng.370
Analgesic management of an eight-year-old Springer Spaniel after amputation of a thoracic limb
Analgesic agents were administered perioperatively to an eight-year-old Springer Spaniel undergoing amputation of its right thoracic limb. The amputation was carried out due to a painful, infiltrative and poorly differentiated sarcoma involving the nerves of the brachial plexus. A combination of pre-emptive and multimodal perioperative analgesic strategies was used; including intravenous (IV) infusions of fentanyl, morphine, lidocaine and ketamine
Determining the interviewer effect on CQ Index outcomes: a multilevel approach
<p>Abstract</p> <p>Background</p> <p>The CQ Index for the elderly, a quality-of-care questionnaire administered by conducting interviews, is used to assess clients' experiences in Dutch nursing homes and homes for the elderly. This article describes whether inter-interviewer differences influence the perceived quality of healthcare services reported by residents, the size of this interviewer effect and the influence of the interviewer characteristics on CQ Index dimensions for public reporting.</p> <p>Methods</p> <p>Data from 4345 questionnaires was used. Correlations were calculated, reliability analyses were performed, and a multilevel analysis was used to calculate the degree of correlation between two interviewers within one health care institution. Five models were constructed and the Intra Class Correlation (ICC) was calculated. Healthcare institutions were given 1-5 stars on every quality dimensions (1 = worst and 5 = best), adjusted for resident and interviewer characteristics. The effect of these characteristics on the assignment of the stars was investigated.</p> <p>Results</p> <p>In a multilevel approach, the ICC showed a significant amount of variance on five quality dimensions. Of the interviewer characteristics, only previous interviewing experience, the reason of interviewing and general knowledge of health care had a significant effect on the quality dimensions. Adjusting for interviewer characteristics did not affect the overall star assignment to the institutions regarding 7 of 12 quality dimensions. For the other five dimensions (Shared decision-making, Meals, Professional competency, Autonomy, and Availability of personnel) a minor effect was found.</p> <p>Conclusions</p> <p>We have shown that training, the use of experienced interviewers, written instructions, supervision and educational meetings do not automatically prevent interviewer effects. While the results of this study can be used to improve the quality of services provided by these institutions, several CQ index dimensions should be interpreted with caution for external purposes (accountability and transparency).</p
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