The Evidence for a Causal Link Between Disease and Damaging Behavior in Pigs

Damaging behaviors (DB) such as tail and ear biting are prevalent in pig production and reduce welfare and performance. Anecdotal reports suggest that health challenges increase the risk of tail-biting. The prevalence of tail damage and health problems show high correlations across batches within and between farms. There are many common risk factors for tail-biting and health problems, notably respiratory, enteric and locomotory diseases. These include suboptimal thermal climate, hygiene, stocking density and feed quality. The prevalence of tail damage and health problems also show high correlations across batches within and between farms. However, limited evidence supports two likely causal mechanisms for a direct link between DB and health problems. The first is that generalized poor health (e.g., enzootic pneumonia) on farm poses an increased risk of pigs performing DB. Recent studies indicate a possible causal link between an experimental inflammation and an increase in DB, and suggest a link between cytokines and tail-biting. The negative effects of poor health on the ingestion and processing of nutrients means that immune-stimulated pigs may develop specific nutrient deficiencies, increasing DB. The second causal mechanism involves tail-biting causing poor health. Indirectly, pathogens enter the body via the tail lesion and once infected, systemic spread of infection may occur. This occurs mainly via the venous route targeting the lungs, and to a lesser extent via cerebrospinal fluid and the lymphatic system. In carcasses with tail lesions, there is an increase in lung lesions, abscessation, arthritis and osteomyelitis. There is also evidence for the direct spread of pathogens between biters and victims. In summary, the literature supports the association between poor health and DB, particularly tail-biting. However, there is insufficient evidence to confirm causality in either direction. Nevertheless, the limited evidence is compelling enough to suggest that improvements to management and housing to enhance pig health will reduce DB. In the same way, improvements to housing and management designed to address DB, are likely to result in benefits to pig health. While most of the available literature relates to tail-biting, we suggest that similar mechanisms are responsible for links between health and other DB.Peer reviewe

Universities and community-based research in developing countries: community voice and educational provision in rural Tanzania

The main focus of recent research on the community engagement role of universities has been in developed countries, generally in towns and cities and usually conducted from the perspectives of universities rather than the communities with which they engage. The purpose of this paper is to investigate the community engagement role of universities in the rural areas of developing countries, and its potential for strengthening the voice of rural communities. The particular focus is on the provision of primary and secondary education. The paper is based on the assumption that in order for community members to have both the capacity and the confidence to engage in political discourse for improving educational capacity and quality, they need the opportunity to become involved and well-versed in the options available, beyond their own experience. Particular attention is given in the paper to community-based research (CBR). CBR is explored from the perspectives of community members and local leaders in the government-community partnerships which have responsibility for the provision of primary and secondary education in rural Tanzania. The historical and policy background of the partnerships, together with findings from two case studies, provide the context for the paper

A phase II study evaluating neo-/adjuvant EIA chemotherapy, surgical resection and radiotherapy in high-risk soft tissue sarcoma

<p>Abstract</p> <p>Background</p> <p>The role of chemotherapy in high-risk soft tissue sarcoma is controversial. Though many patients undergo initial curative resection, distant metastasis is a frequent event, resulting in 5-year overall survival rates of only 50-60%. Neo-adjuvant and adjuvant chemotherapy (CTX) has been applied to achieve pre-operative cytoreduction, assess chemosensitivity, and to eliminate occult metastasis. Here we report on the results of our non-randomized phase II study on neo-adjuvant treatment for high-risk STS.</p> <p>Method</p> <p>Patients with potentially curative high-risk STS (size ≥ 5 cm, deep/extracompartimental localization, tumor grades II-III [FNCLCC]) were included. The protocol comprised 4 cycles of neo-adjuvant chemotherapy (EIA, etoposide 125 mg/m²iv days 1 and 4, ifosfamide 1500 mg/m²iv days 1 - 4, doxorubicin 50 mg/m²day 1, pegfilgrastim 6 mg sc day 5), definitive surgery with intra-operative radiotherapy, adjuvant radiotherapy and 4 adjuvant cycles of EIA.</p> <p>Result</p> <p>Between 06/2005 and 03/2010 a total of 50 subjects (male = 33, female = 17, median age 50.1 years) were enrolled. Median follow-up was 30.5 months. The majority of primary tumors were located in the extremities or trunk (92%), 6% originated in the abdomen/retroperitoneum. Response by RECIST criteria to neo-adjuvant CTX was 6% CR (n = 3), 24% PR (n = 12), 62% SD (n = 31) and 8% PD (n = 4). Local recurrence occurred in 3 subjects (6%). Distant metastasis was observed in 12 patients (24%). Overall survival (OS) and disease-free survival (DFS) at 2 years was 83% and 68%, respectively. Multivariate analysis failed to prove influence of resection status or grade of histological necrosis on OS or DFS. Severe toxicities included neutropenic fever (4/50), cardiac toxicity (2/50), and CNS toxicity (4/50) leading to CTX dose reductions in 4 subjects. No cases of secondary leukemias were observed so far.</p> <p>Conclusion</p> <p>The current protocol is feasible for achieving local control rates, as well as OS and DFS comparable to previously published data on neo-/adjuvant chemotherapy in this setting. However, the definitive role of chemotherapy remains unclear in the absence of large, randomized trials. Therefore, the current regimen can only be recommended within a clinical study, and a possibly increased risk of secondary leukemias has to be taken into account.</p> <p>Trial registration</p> <p>ClinicalTrials.gov <a href="http://www.clinicaltrials.gov/ct2/show/NCT01382030">NCT01382030</a>, EudraCT 2004-002501-72</p

ParadisEO-MOEO: A Software Framework for Evolutionary Multi-Objective Optimization

This chapter presents ParadisEO-MOEO, a white-box object-oriented software framework dedicated to the flexible design of metaheuristics for multi-objective optimization. This paradigm-free software proposes a unified view for major evolutionary multi-objective metaheuristics. It embeds some features and techniques for multi-objective resolution and aims to provide a set of classes allowing to ease and speed up the development of computationally efficient programs. It is based on a clear conceptual distinction between the solution methods and the problems they are intended to solve. This separation confers a maximum design and code reuse. This general-purpose framework provides a broad range of fitness assignment strategies, the most common diversity preservation mechanisms, some elitistrelated features as well as statistical tools. Furthermore, a number of state-of-the-art search methods, including NSGA-II, SPEA2 and IBEA, have been implemented in a user-friendly way, based on the fine-grained ParadisEO-MOEO components

Cirrhotic livers reveal genetic changes in the MDM2-P14ARF system of cell cycle regulators

The genesis of hepatocellular carcinoma is promoted by changes in the regulatory MDM2-P14ARF system. The incidence of such changes has to date not been analysed in non-tumourous livers showing regenerative proliferation. In the present study, 24 cirrhotic livers of alcohol-, autoimmue disorder- or HCV-caused genesis were screened for MDM2-P14ARF alterations at the level of protein, DNA and mRNA. Using confocal laser scanning microscopy, the absence of MDM2 and P14ARF expression was detected in all samples except three HCV-infected livers (four livers) which contained hepatocytes overexpressing MDM2 (P14ARF) protein. In two of the samples lacking P14ARF expression, laser microdissection and PCR demonstrated deletion of the P14ARF gene. The P14ARF gene amplified from other specimens did not carry mutations. MDM2 splicing variants were present in tissues from alcohol- and autoimmune disorder-induced cirrhoses. Sequencing of full-size mRNA revealed a MDM2 mis-sense mutation in an alcohol-induced cirrhosis. One sample contained regenerative nodules with genetic instability occurring at MDM2 locus D12S83 according to the data of automatic PCR fragment analysis. In summary, this study gives first evidence for different types of MDM2 and P14ARF alterations in cirrhotic livers. We suggest that the changes impair the regulatory MDM2-P14ARF system, thus possibly favouring regenerative proliferation and transformation

A case study of a mother's intertwining experiences with incest and postpartum depression

The association between childhood sexual abuse (CSA) and major depression disorder (MDD) gives reason to suspect that many mothers with postpartum depression (PPD) have a history of CSA. However, few studies have investigated how CSA and PPD are related. In this case study we explore how the experience of incest intertwines with the experience of postpartum depression. We focus on participant subject “Nina,” who has experienced both. We interviewed her three times and we analysed the interviews with Giorgi's phenomenological descriptive method to arrive at a contextualised meaning structure. Nina's intruding fantasies of men who abuse her children merge with her recollections of her own incest experiences. She may succeed in forcing these fantasies out of her consciousness, but they still alter her perceptions, thoughts, and emotions. She feels overwhelmed and succumbs to sadness, while she also is drawn towards information about CSA, which in turn feeds her fantasies. The psychodynamic concepts of repetition compulsion, transference, and projection may provide some explanation of Nina's actions, thoughts, and emotions through her past experiences. With our phenomenological stance, we aim to acknowledge Nina's descriptions of her everyday life here and now. With reference to Husserl, Heidegger, Merleau-Ponty, and Minkowski, we show that Nina's past is not a dated memory; rather it determines the structure of her consciousness that constitutes her past as her true present and future. Incest dominates Nina's world, and her possibilities for action are restricted by this perceived world. Any suspension of action implies anguish, and she resolves this by incest-structured action that in turn feeds and colours her expectations. Thus anxiety and depression are intertwined in the structure of this experience

Activation and deactivation steps in the tryptophan breakdown pathway in major depressive disorder: A link to the monocyte inflammatory state of patients

It is unclear how the tryptophan (TRP) breakdown pathway relates to the activated inflammatory state of patients with major depressive disorder (MDD). We determined in two different cohorts of patients with MDD (n = 281) and healthy controls (HCs) (n = 206) collected for the EU-MOODINFLAME project: a.) the monocyte expression levels of 5 key pro-inflammatory cytokine/chemokine genes (ICCGs), 5 type I interferon stimulated genes (ISGs), and 4 kynurenine pathway (KP) enzyme genes (i.e. IDO-1, KMO, CCBL1/KAT II and CCBL2/KAT III) by standard q-PCR, b.) serum levels of TRP, 5-HTrp, 5-HIAA, KYN, KYNA, 3-HK, XA, PIC, and QUIN by LC-MS/MS and/or HPLC, and calculated various TRP/KP metabolism ratios. We then correlated outcomes to each other, and to the clinical characteristics of patients. Both cohorts of patients differed clinically; patients of the Munich cohort (n = 50) were less overweight, less medicated, were less in the current episode and showed a higher HAM-D 17 score as compared with patients of the Muenster cohort (n = 231). An increased expression of ICCGs was found in the circulating monocytes of patients of both cohorts; this was in particular evident in the Munich cohort. In contrast, ISGs monocyte expression levels tended to be reduced (both cohorts). TRP serum levels were linked to the pro-inflammatory (ICCGs) monocyte state of patients; a decrease in TRP serum levels was found in the Munich cohort; TRP levels correlated negatively to patient's HAM-D 17 score. Contrary to what expected, KYN serum levels were not increased in patients (both cohorts); and an increased KYN/TRP ratio was only found in the Munich patients (who showed the lowest TRP serum levels). IDO-1 monocyte expression levels were decreased in patients (both cohorts) and negatively associated to their pro-inflammatory (ICCGs) monocyte state. Thus, a depletion of TRP via an ICCGs-inflammatory IDO activation is not likely in MDD. Downstream from KYN, and regarding compounds influencing glutamate receptors (GR), reduced serum levels of KYNA (NMDA-R antagonist), 3-HK (NMDA-R agonist), and XA (mGlu2/3 agonist) were found in patients of both cohorts; PIC serum levels (NMDA-R antagonist) were increased in patients of both cohorts. Reduced QUIN serum levels (NMDA-R agonist) were found in patients of the Muenster cohort,only. 3-HK levels correlated to the monocyte inflammatory ICCG state of patients. The ultimate effect on brain glutamate receptor triggering of this altered equilibrium between peripheral agonists and antagonists remains to be elucidated