There is an urgent need to drive improvements in the efficiency and effectiveness of food chains. The global population is expected to reach at least 9 billion by the year 2050, requiring up to 70% ...more food, and demanding food production systems and the food chain to become fully sustainable. This challenge is complicated by a number of overarching issues, including increasing complexity of food supply chains, environmental constraints, a growing aging population and changing patterns of consumer choice and food consumption. Within this context, food safety must be an enabler and not inhibitor of global food security.
This paper will highlight how recent developments and trends related to food safety will impact the food sector and ultimately the ability of the sector to deliver food security.
Global megatrends including climate change, a growing and aging population, urbanisation, and increased affluence will create food safety challenges and place new demands on producers, manufacturers, marketers, retailers and regulators. Advances in science and technology such as whole genome sequencing, active packaging, developments in tracing and tracking technologies, information computing technology and big data analysis has the potential to help mitigate the challenges and meet demands, but will also create new challenges. Overcoming a number of these challenges will be difficult for developed economies and large food companies, but even greater for small and medium-sized enterprises (SMEs), developing economies and smallholder farmers, noting that each is a critical component in the global food supply.
•There is an urgent need to drive improvements in the efficiency and effectiveness of food chains.•Recent developments and trends related to food safety will impact the food sector and its ability to deliver food security.•Food safety must be an enabler and not inhibitor of global food security.
The sudden resignation of core employees often brings losses to companies in various aspects. Traditional employee turnover theory cannot analyze the unbalanced data of employees comprehensively, ...which leads the company to make wrong decisions. In the face the classification of unbalanced data, the traditional Support Vector Machine (SVM) suffers from insufficient decision plane offset and unbalanced support vector distribution, for which the Synthetic Minority Oversampling Technique (SMOTE) is introduced to improve the balance of generated data. Further, the Fuzzy C-mean (FCM) clustering is improved and combined with the SMOTE (IFCM-SMOTE-SVM) to new synthesized samples with higher accuracy, solving the drawback that the separation data synthesized by SMOTE is too random and easy to generate noisy data. The kernel function is combined with IFCM-SMOTE-SVM and transformed to a high-dimensional space for clustering sampling and classification, and the kernel space-based classification algorithm (KS-IFCM-SMOTE-SVM) is proposed, which improves the effectiveness of the generated data on SVM classification results. Finally, the generalization ability of KS-IFCM-SMOTE-SVM for different types of enterprise data is experimentally demonstrated, and it is verified that the proposed algorithm has stable and accurate performance. This study introduces the SMOTE and FCM clustering, and improves the SVM by combining the data transformation in the kernel space to achieve accurate classification of unbalanced data of employees, which helps enterprises to predict whether employees have the tendency to leave in advance.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Next-generation DNA sequencing promises to revolutionize clinical medicine and basic research. However, while this technology has the capacity to generate hundreds of billions of nucleotides of DNA ...sequence in a single experiment, the error rate of ∼1% results in hundreds of millions of sequencing mistakes. These scattered errors can be tolerated in some applications but become extremely problematic when “deep sequencing” genetically heterogeneous mixtures, such as tumors or mixed microbial populations. To overcome limitations in sequencing accuracy, we have developed a method termed Duplex Sequencing. This approach greatly reduces errors by independently tagging and sequencing each of the two strands of a DNA duplex. As the two strands are complementary, true mutations are found at the same position in both strands. In contrast, PCR or sequencing errors result in mutations in only one strand and can thus be discounted as technical error. We determine that Duplex Sequencing has a theoretical background error rate of less than one artifactual mutation per billion nucleotides sequenced. In addition, we establish that detection of mutations present in only one of the two strands of duplex DNA can be used to identify sites of DNA damage. We apply the method to directly assess the frequency and pattern of random mutations in mitochondrial DNA from human cells.
Arabic news articles in electronic collections are difficult to study. Browsing by category is rarely supported. Although helpful machine‐learning methods have been applied successfully to similar ...situations for English news articles, limited research has been completed to yield suitable solutions for Arabic news. In connection with a Qatar National Research Fund (QNRF)‐funded project to build digital library community and infrastructure in Qatar, we developed software for browsing a collection of about 237,000 Arabic news articles, which should be applicable to other Arabic news collections. We designed a simple taxonomy for Arabic news stories that is suitable for the needs of Qatar and other nations, is compatible with the subject codes of the International Press Telecommunications Council, and was enhanced with the aid of a librarian expert as well as five Arabic‐speaking volunteers. We developed tailored stemming (i.e., a new Arabic light stemmer called P‐Stemmer) and automatic classification methods (the best being binary Support Vector Machines classifiers) to work with the taxonomy. Using evaluation techniques commonly used in the information retrieval community, including 10‐fold cross‐validation and the Wilcoxon signed‐rank test, we showed that our approach to stemming and classification is superior to state‐of‐the‐art techniques.
The accumulation of somatic mitochondrial DNA (mtDNA) mutations is implicated in aging and common diseases of the elderly, including cancer and neurodegenerative disease. However, the mechanisms that ...influence the frequency of somatic mtDNA mutations are poorly understood. To develop a simple invertebrate model system to address this matter, we used the Random Mutation Capture (RMC) assay to characterize the age-dependent frequency and distribution of mtDNA mutations in the fruit fly Drosophila melanogaster. Because oxidative stress is a major suspect in the age-dependent accumulation of somatic mtDNA mutations, we also used the RMC assay to explore the influence of oxidative stress on the somatic mtDNA mutation frequency. We found that many of the features associated with mtDNA mutations in vertebrates are conserved in Drosophila, including a comparable somatic mtDNA mutation frequency (∼10(-5)), an increased frequency of mtDNA mutations with age, and a prevalence of transition mutations. Only a small fraction of the mtDNA mutations detected in young or old animals were G∶C to T∶A transversions, a signature of oxidative damage, and loss-of-function mutations in the mitochondrial superoxide dismutase, Sod2, had no detectable influence on the somatic mtDNA mutation frequency. Moreover, a loss-of-function mutation in Ogg1, which encodes a DNA repair enzyme that removes oxidatively damaged deoxyguanosine residues (8-hydroxy-2'-deoxyguanosine), did not significantly influence the somatic mtDNA mutation frequency of Sod2 mutants. Together, these findings indicate that oxidative stress is not a major cause of somatic mtDNA mutations. Our data instead suggests that somatic mtDNA mutations arise primarily from errors that occur during mtDNA replication. Further studies using Drosophila should aid in the identification of factors that influence the frequency of somatic mtDNA mutations.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
OBJECTIVEThe phase IIIb A Study to Evaluate the Effects of Ocrelizumab on Immune Responses in Participants With Relapsing Forms of Multiple Sclerosis (VELOCE) study (NCT02545868) assessed responses ...to selected vaccines in ocrelizumab (OCR)-treated patients with relapsing multiple sclerosis.
METHODSPatients were randomized 2:1 into the OCR group (n = 68; OCR 600 mg) or control group (n = 34; interferon beta or no disease-modifying therapy). All received tetanus toxoid (TT)-containing vaccine, Pneumovax (23-valent pneumococcal polysaccharide vaccine 23-PPV), and keyhole limpet hemocyanin (KLH). The OCR group was subdivided into OCR1 (n = 33) and OCR2 (n = 35) at randomization. The OCR1 group received Prevnar (13-valent conjugate pneumococcal vaccine) 4 weeks after 23-PPV; the OCR2 and control groups received influenza vaccine. Vaccinations started 12 weeks after OCR initiation (OCR group) or on day 1 (control group).
RESULTSPositive response rate to TT vaccine at 8 weeks was 23.9% in the OCR vs 54.5% in the control group. Positive response rate to ≥5 serotypes in 23-PPV at 4 weeks was 71.6% in the OCR and 100% in the control group. Prevnar did not enhance response to pneumococcal serotypes in common with Pneumovax. Humoral response to KLH was decreased in the OCR vs control group. Seroprotection rates at 4 weeks against 5 influenza strains ranged from 55.6% to 80.0% in the OCR2 group and 75.0% to 97.0% in the control group.
CONCLUSIONPeripherally B-cell–depleted OCR recipients mounted attenuated humoral responses to clinically relevant vaccines and the neoantigen KLH, suggesting that use of standard nonlive vaccines while on OCR treatment remains a consideration. For seasonal influenza vaccines, it is recommended to vaccinate patients on OCR because a potentially protective humoral response, even if attenuated, can be expected.
CLASSIFICATION OF EVIDENCEThis study provides Class II evidence confirming that the humoral response to nonlive vaccines in patients with relapsing multiple sclerosis after OCR treatment is attenuated compared with untreated or interferon beta–treated patients, but they can still be expected to be protective.
CLINICALTRIALS.GOV IDENTIFIERNCT02545868.
Vagal afferents to the gastrointestinal tract are crucial for the regulation of food intake, signaling negative feedback that contributes to satiation and positive feedback that produces appetition ...and reward. Vagal afferents to the small intestinal mucosa contribute to this regulation by sensing luminal stimuli and reporting this information to the brain. These afferents respond to mechanical, chemical, thermal, pH, and osmolar stimuli, as well as to bacterial products and immunogens. Surprisingly, little is known about how these stimuli are transduced by vagal mucosal afferents or how their transduction is organized among these afferents’ terminals. Furthermore, the effects of stimulus concentration ranges or physiological stimuli on vagal activity have not been examined for some of these stimuli. Also, detection of luminal stimuli has rarely been examined in rodents, which are most frequently used for studying small intestinal innervation. Here we review what is known about stimulus detection by vagal mucosal afferents and illustrate the complexity of this detection using nutrients as an exemplar. The accepted model proposes that nutrients bind to taste receptors on enteroendocrine cells (EECs), which excite them, causing the release of hormones that stimulate vagal mucosal afferents. However, evidence reviewed here suggests that although this model accounts for many aspects of vagal signaling about nutrients, it cannot account for all aspects. A major goal of this review is therefore to evaluate what is known about nutrient absorption and detection and, based on this evaluation, identify candidate mucosal cells and structures that could cooperate with EECs and vagal mucosal afferents in stimulus detection.
Summary Background The anti-CD52 monoclonal antibody alemtuzumab reduces disease activity in previously untreated patients with relapsing-remitting multiple sclerosis. We aimed to assess efficacy and ...safety of alemtuzumab compared with interferon beta 1a in patients who have relapsed despite first-line treatment. Methods In our 2 year, rater-masked, randomised controlled phase 3 trial, we enrolled adults aged 18–55 years with relapsing-remitting multiple sclerosis and at least one relapse on interferon beta or glatiramer. Eligible participants were randomly allocated in a 1:2:2 ratio by an interactive voice response system, stratified by site, to receive subcutaneous interferon beta 1a 44 μg, intravenous alemtuzumab 12 mg per day, or intravenous alemtuzumab 24 mg per day. Interferon beta 1a was given three-times per week and alemtuzumab was given once per day for 5 days at baseline and for 3 days at 12 months. The 24 mg per day group was discontinued to aid recruitment, but data are included for safety assessments. Coprimary endpoints were relapse rate and time to 6 month sustained accumulation of disability, comparing alemtuzumab 12 mg and interferon beta 1a in all patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov , number NCT00548405. Findings 202 (87%) of 231 patients randomly allocated interferon beta 1a and 426 (98%) of 436 patients randomly allocated alemtuzumab 12 mg were included in the primary analyses. 104 (51%) patients in the interferon beta 1a group relapsed (201 events) compared with 147 (35%) patients in the alemtuzumab group (236 events; rate ratio 0·51 95% CI 0·39–0·65; p<0·0001), corresponding to a 49·4% improvement with alemtuzumab. 94 (47%) patients in the interferon beta 1a group were relapse-free at 2 years compared with 278 (65%) patients in the alemtuzumab group (p<0·0001). 40 (20%) patients in the interferon beta 1a group had sustained accumulation of disability compared with 54 (13%) in the alemtuzumab group (hazard ratio 0·58 95% CI 0·38–0·87; p=0·008), corresponding to a 42% improvement in the alemtuzumab group. For 435 patients allocated alemtuzumab 12 mg, 393 (90%) had infusion-associated reactions, 334 (77%) had infections (compared with 134 66% of 202 patients in the interferon beta 1a group) that were mostly mild-moderate with none fatal, 69 (16%) had thyroid disorders, and three (1%) had immune thrombocytopenia. Interpretation For patients with first-line treatment-refractory relapsing-remitting multiple sclerosis, alemtuzumab could be used to reduce relapse rates and sustained accumulation of disability. Suitable risk management strategies allow for early identification of alemtuzumab's main adverse effect of secondary autoimmunity. Funding Genzyme (Sanofi) and Bayer Schering Pharma.
Summary Background The anti-CD52 monoclonal antibody alemtuzumab reduced disease activity in a phase 2 trial of previously untreated patients with relapsing-remitting multiple sclerosis. We aimed to ...assess efficacy and safety of first-line alemtuzumab compared with interferon beta 1a in a phase 3 trial. Methods In our 2 year, rater-masked, randomised controlled phase 3 trial, we enrolled adults aged 18–50 years with previously untreated relapsing-remitting multiple sclerosis. Eligible participants were randomly allocated in a 2:1 ratio by an interactive voice response system, stratified by site, to receive intravenous alemtuzumab 12 mg per day or subcutaneous interferon beta 1a 44 μg. Interferon beta 1a was given three-times per week and alemtuzumab was given once per day for 5 days at baseline and once per day for 3 days at 12 months. Coprimary endpoints were relapse rate and time to 6 month sustained accumulation of disability in all patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov , number NCT00530348. Findings 187 (96%) of 195 patients randomly allocated interferon beta 1a and 376 (97%) of 386 patients randomly allocated alemtuzumab were included in the primary analyses. 75 (40%) patients in the interferon beta 1a group relapsed (122 events) compared with 82 (22%) patients in the alemtuzumab group (119 events; rate ratio 0·45 95% CI 0·32–0·63; p<0.0001), corresponding to a 54·9% improvement with alemtuzumab. Based on Kaplan-Meier estimates, 59% of patients in the interferon beta 1a group were relapse-free at 2 years compared with 78% of patients in the alemtuzumab group (p<0·0001). 20 (11%) of patients in the interferon beta 1a group had sustained accumulation of disability compared with 30 (8%) in the alemtuzumab group (hazard ratio 0·70 95% CI 0·40–1·23; p=0·22). 338 (90%) of patients in the alemtuzumab group had infusion-associated reactions; 12 (3%) of which were regarded as serious. Infections, predominantly of mild or moderate severity, occurred in 253 (67%) patients treated with alemtuzumab versus 85 (45%) patients treated with interferon beta 1a. 62 (16%) patients treated with alemtuzumab had herpes infections (predominantly cutaneous) compared with three (2%) patients treated with interferon beta 1a. By 24 months, 68 (18%) patients in the alemtuzumab group had thyroid-associated adverse events compared with 12 (6%) in the interferon beta 1a group, and three (1%) had immune thrombocytopenia compared with none in the interferon beta 1a group. Two patients in the alemtuzumab group developed thyroid papillary carcinoma. Interpretation Alemtuzumab's consistent safety profile and benefit in terms of reductions of relapse support its use for patients with previously untreated relapsing-remitting multiple sclerosis; however, benefit in terms of disability endpoints noted in previous trials was not observed here. Funding Genzyme (Sanofi) and Bayer Schering Pharma.
Social media and online services with user-generated content (e.g., Twitter, Facebook, Flickr, YouTube) have made a staggering amount of information (and misinformation) available. Government ...officials seek to leverage these resources to improve services and communication with citizens. Significant potential exists to identify issues in real time, so emergency managers can monitor and respond to issues concerning public safety. Yet, the sheer volume of social data streams generates substantial noise that must be filtered in order to detect meaningful patterns and trends. Important events can then be identified as spikes in activity, while event meaning and consequences can be deciphered by tracking changes in content and public sentiment. This paper presents findings from a exploratory study we conducted between June and December 2010 with government officials in Arlington, VA (and the greater National Capitol Region around Washington, D.C.), with the broad goal of understanding social media use by government officials as well as community organizations, businesses, and the public at large. A key objective was also to understand social media use specifically for managing crisis situations from the routine (e.g., traffic, weather crises) to the critical (e.g., earthquakes, floods).
► Organizational and information factors affect social media adoption by government. ► Social media are rich, but overwhelming sources of information in crisis situations. ► Visualizations and data mining techniques help users make sense of social media.
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