Miracle-dz/UniFAR-FTUs huggingface dataset:
Immune Memory in Children Previously Vaccinated With an Experimental Quadrivalent Meningococcal Polysaccharide Diphtheria Toxoid Conjugate Vaccine

Background: In a previous study, a meningococcal diphtheria toxoid conjugate vaccine (MCV-4) triggered robust bactericidal antibody responses against serogroups A, C, Y, and W-135 in 2- to 10-year-old children. A subset of participants, 2 to 3 years of age at the initial vaccination, was evaluated for persistence of antibody, immune memory, and antibody avidity. Methods: Participants were healthy children vaccinated 23 to 36 months earlier with MCV-4 (primed) or newly recruited meningococcal vaccine-naive 4-year-olds. Participants in both groups were alternately allocated to provide sera 8 or 28 days after administration of one tenth of the recommended dose of a meningococcal polysaccharide vaccine (PSV-4). Immune responses were assessed in sera obtained at baseline and either 8 or 28 days after reduced-dose PSV-4 administration. Safety was monitored. Results: Before PSV-4 challenge, serum bactericidal antibody geometric mean titers (SBA GMTs) were higher for all 4 serogroups in the MCV-4-primed group than in the vaccine-naive group. SBA GMTs, geometric mean concentrations of immunoglobulin G (IgG) and geometric mean avidity indices for all 4 serogroups were significantly higher among MCV-4-primed versus vaccine-naive participants in the cohorts evaluated at 8 or 28 days after PSV-4 challenge. Adverse events were generally mild, self-limited, and comparable in all groups of children. Conclusions: Persistence of bactericidal antibody was seen for 23 to 36 months after a primary dose of MCV-4 in young children. Booster responses and avidity maturation were evident after a challenge with reduced-dose polysaccharide vaccine.
The perils of skills: towards a model of integrating graduate attributes into the disciplines

The notion of graduate attributes a surprisingly enduring idea in Australian higher education over the last decade or so has been useful as a way of requiring academics and administrators to reflect seriously on the nexus between university learning and the demands that graduates will face in their subsequent professional lives. A potential danger of this movement however, is that increasingly these attributes will be thought of as discrete skills to be developed on courses, with a concomitant downgrading of the role of disciplinary content. Manifestations of such a trend are the emergence in recent years of a variety of extra-disciplinary courses such as ‘professional writing’ and ‘critical thinking’, as well as a lingering interest in the idea of generic skills testing prior to graduation (e.g., Graduate Skills Assessment test). The main argument of this paper is that if the graduate attributes idea is to continue to be a useful one in the framing of university curricula, it is important that effective ways are found to integrate the development of these attributes within the context of the disciplines. We outline one such method – a possible framework for the analysis and creation of assessment tasks – which, we think, has general applicability to learning in any disciplinary setting. The key element of this framework is the notion of ‘role’ – which can be used to explore with students (and also confer on them) a range of academic and professional identities.
Different anthracycline derivates for reducing cardiotoxicity in cancer patients.

BACKGROUND The use of anthracyclines is limited by the occurrence of cardiotoxicity. In an effort to prevent this cardiotoxicity, different anthracycline derivates have been studied. OBJECTIVES To determine the occurrence of cardiotoxicity with the use of different anthracycline derivates in cancer patients. SEARCH STRATEGY We searched The Cochrane Central Register of Controlled Trials (CENTRAL), (The Cochrane Library, Issue 2, 2009), MEDLINE (1966 to 29 May 2009) and EMBASE (1980 to 2 June 2009). In addition, we searched reference lists of relevant articles, conference proceedings and ongoing-trials-databases. SELECTION CRITERIA Randomised controlled trials (RCTs) in which different anthracycline derivates were compared in cancer patients (children and adults). DATA COLLECTION AND ANALYSIS Two authors independently performed study selection, assessment of risk of bias and data-extraction including adverse effects. MAIN RESULTS We identified five RCTs of varying quality addressing epirubicin versus doxorubicin (1036 patients) with the same dose. The meta-analysis showed no evidence for a significant difference in the occurrence of clinical heart failure between the treatment groups (RR = 0.36, 95% CI 0.12 to 1.11). However, there is some suggestion of a lower rate of clinical heart failure in patients treated with epirubicin.We identified two RCTs with varying quality addressing liposomal-encapsulated doxorubicin versus conventional doxorubicin (521 patients). The meta-analysis showed a significantly lower rate of both clinical heart failure and clinical and subclinical heart failure combined in patients treated with liposomal-encapsulated doxorubicin (RR = 0.20, 95% CI 0.05 to 0.75 and RR = 0.38, 95% CI 0.24 to 0.59 respectively). It should be noted that in one of the studies patients in the liposomal-encapsulated doxorubicin group received a higher cumulative anthracycline dose than patients in the doxorubicin group.For the other possible combinations of different anthracycline derivates only one RCT (epirubicin versus liposomal-encapsulated doxorubicin) or no RCT was identified. AUTHORS' CONCLUSIONS We are not able to favour either epirubicin or doxorubicin when given with the same dose. Based on the currently available evidence on heart failure, we conclude that in adults with a solid tumour liposomal-encapsulated doxorubicin should be favoured over doxorubicin. For both epirubicin versus doxorubicin and liposomal-encapsulated doxorubicin versus conventional doxorubicin no conclusions can be made about the effects of treatment in children treated with anthracyclines and also not in patients diagnosed with leukaemia. More research is needed. For other combinations of anthracycline derivates not enough evidence was available to make definitive conclusions about the occurrence of cardiotoxicity in patients treated with anthracyclines.
Aging in Sub-Saharan Africa: Recommendations for Furthering Research

In sub-Saharan Africa, older people make up a relatively small fraction of the total population and are supported primarily by family and other kinship networks. They have traditionally been viewed as repositories of information and wisdom, and are critical pillars of the community but as the HIV/AIDS pandemic destroys family systems, the elderly increasingly have to deal with the loss of their own support while absorbing the additional responsibilities of caring for their orphaned grandchildren. Aging in Sub-Saharan Africa explores ways to promote U.S. research interests and to augment the sub-Saharan governments' capacity to address the many challenges posed by population aging. Five major themes are explored in the book such as the need for a basic definition of "older person," the need for national governments to invest more in basic research and the coordination of data collection across countries, and the need for improved dialogue between local researchers and policy makers. This book makes three major recommendations: 1) the development of a research agenda 2) enhancing research opportunity and implementation and 3) the translation of research findings.
A randomised study of screening for colorectal cancer using faecal occult blood testing: results after 13 years and seven biennial screening rounds

Background: Three randomised trials have demonstrated reduction in mortality from colorectal cancer (CRC) by repeated screening with faecal occult blood tests, including the trial presented here, which is the only one still in progress. Aims: To evaluate reduction in mortality after seven screening rounds and the possible influence of compliance on mortality from CRC. Methods: At Funen in Denmark, random allocation to biennial screening with Hemoccult-II in 30 967 subjects aged 45–75 years and 30 966 controls was performed in 1985 from a population of 137 485 of the same age. Only participants who completed the first screening round were invited for further screening. Colonoscopy was offered if the test was positive. The primary end point was death from CRC, and the 10 year results were published in 1996. Results: From the beginning of the first screening to the seventh round, mean age increased from 59.8 to 70.0 years in the screening and control groups, and the male/female ratio decreased from 0.92 to 0.81. Those who accepted screening were younger than non-responders. Positivity rates varied from 0.8% to 3.8%, the cumulative ratio of a positive test was 5.1% after seven rounds, and 4.8% of patients had at least one colonoscopy. Mortality from CRC was significantly less in the screening group (relative risk (RR) 0.82 (0.69–0.97)), and the reduction in mortality was most pronounced above the sigmoid colon. After seven rounds, RR was reduced to less than 0.70 compared with controls. Mortality rates from causes other than CRC did not differ. Non-responders had a significantly increased risk of death from CRC compared with those who accepted the full programme. Subjects who accepted the first screening, but not subsequent ones, demonstrated a tendency towards increased risk. Conclusions: The persistent reduction in mortality from CRC in a biennial screening program with Hemoccult-II, and a reduction in RR to less than 0.70 in those adhering to the programme, support attempts to introduce larger scale population screening programmes. The smaller effect on mortality from CRC in the rectum and sigmoid colon suggests evaluation by additional flexible sigmoidoscopy with longer intervals.
Comparison of high-definition oscillometry — a non-invasive technology for arterial blood pressure measurement — with a direct invasive method using radio-telemetry in awake healthy cats

This study compared indirect blood pressure measurements using a non-invasive method, high-definition oscillometry (HDO), with direct measurements using a radio-telemetry device in awake cats. Paired measurements partitioned to five sub-ranges were collected in six cats using both methods. The results were analysed for assessment of correlation and agreement between the two methods, taking into account all pressure ranges, and with data separated in three sub-groups, low, normal and high ranges of systolic (SBP) and diastolic (DBP) blood pressure. SBP data displayed a mean correlation coefficient of 0.92 ± 0.02 that was reduced for low SBP. The agreement level evaluated from the whole data set was high and slightly reduced for low SBP values. The mean correlation coefficient of DBP was lower than for SBP (ie, 0.81 ± 0.02). The bias for DBP between the two methods was 22.3 ± 1.6 mmHg, suggesting that HDO produced lower values than telemetry. These results suggest that HDO met the validation criteria defined by the American College of Veterinary Internal Medicine consensus panel and provided a faithful measurement of SBP in conscious cats. For DBP, results suggest that HDO tended to underestimate DBP. This finding is clearly inconsistent with the good agreement reported in dogs, but is similar to outcomes achieved in marmosets and cynomolgus monkeys, suggesting that this is not related to HDO but is species related. The data support that the HDO is the first and only validated non-invasive blood pressure device and, as such, it is the only non-invasive reference technique that should be used in future validation studies.
Conference on ‘ Dietary strategies for the management of cardiovascular risk ’ Reappraisal of SFA and cardiovascular risk

This review reappraises dietary advice to reduce and replace SFA for the prevention of CVD. In the 1970s, SFA accounted for about 18% UK food energy, by 2001 it had fallen to 13% and continues to be above the <11% target. Compared with carbohydrates, C12–C16 SFA raise serum total cholesterol (TC), LDL-cholesterol (LDL-C) and HDL-cholesterol (HDL-C) without affecting the TC:HDL-C ratio; other SFA have neutral effects on the fasting lipid profile. Replacing 3% dietary SFA with MUFA or PUFA lowers LDL-C by 2% and TC:HDL-C ratio by 0·03. No other specific adverse effects of SFA compared with MUFA on risk CVD factors have been proven. Meta-analyses of prospective cohort studies report the relative risks (95% CI) of high v. low intakes of SFA to be 1·07 (0·96, 1·19) for CHD, 0·81 (0·62, 1·05) for stroke and 1·00 (0·89, 1·11) for CVD mortality and were not statistically significant. Exchanging 5% energy SFA for PUFA or carbohydrates found hazard ratios (95% CI) for CHD death to be 26% (−23, −3) and 4% (−18, 12; NS) lower, respectively. Meta-analysis of randomised controlled trials with clinical endpoints reports mean reductions (95% CI) of 14% (4, 23) in CHD incidence and 6% (−25, 4; NS) in mortality in trials, where SFA was lowered by decreasing and/or modifying dietary fat. In conclusion, SFA intakes are now close to guideline amounts and further reductions may only have a minor impact on CVD.
Getting to the Bottom Line: How Using Evaluation Results to Enhance Extension Programs Can Lead to Greater Levels of Accountability.

Extension has enhanced the lives of U.S. citizens through adult education in a myriad of ways. However, as budgets get tighter, accountability becomes increasingly more important. Over the years, Extension has reported low level impacts rather than the long–term successes that those working within the system know are occurring. Without enhanced evaluation–driven environments, Extension systems will continue to inadequately report programmatic successes, resulting in a lower perceived public value of Extension programs. The use of evaluation can create an atmosphere which encourages organizational thinking resulting in the types of accountability reports which are adequate for decision making. This study examined how Extension professionals’ perceptions of evaluation use related to their evaluation behaviors. The findings suggest a substantial percentage of Extension professionals are doing just enough evaluation to complete mandatory reports. It also showed that Extension professionals who valued their own personal use, but not necessarily organizational use of their evaluations, were more likely to conduct in–depth evaluations. Recommendations for enhancing evaluation driven work environments include clearer communication from administration demonstrating the value of evaluation beyond the role it plays in accountability and working directly with Extension professionals to promote evaluation–oriented conversations rather than just delivering state–led in–service trainings.
Morphologic features of chronic hepatitis associated with primary sclerosing cholangitis and chronic ulcerative colitis

Histologic, ultrastructural, chemical, and statistical methods were used to study liver biopsy and autopsy specimens from 43 patients who had primary sclerosing cholangitis (PSC), with or without chronic ulcerative colitis (CUC), and from 19 patients who had CUC without PSC. In all study groups, essentially the same abnormalities were found in the hepatic parenchyma outside the major bile ducts, although nondiagnostic tissue samples were observed also. Specimens from patients with extrahepatic PSC were indistinguishable from those from patients with combined extra‐ and intrahepatic PSC. Common findings included periductal fibrosis and inflammation, portal edema and fibrosis, focal proliferation of bile ducts and ductules, focal bile duct obliteration and loss of bile ducts, copper deposition, and cholestasis. Proliferation of bile ducts in some portal tracts and obliteration or absence of bile duct in others were the most characteristic changes. In most specimens, inflammatory changes appeared mild, yet biliary cirrhosis had developed in 34% of the patients. Specimens from patients with PSC, with or without CUC, more often contained bile and strikingly increased stainable copper (Grades 2 and 3) than did specimens from patients with CUC without PSC. Hepatic copper contents, measured by atomic absorption spectrophotometry, also were higher in specimens from patients with PSC. Study of PCS specimens by transmission electron microscopy and by energy‐dispersive X‐ray microanalysis revealed that most copper was sequestered in lipolysosomes. The recognition of strikingly similar morphologic features in many liver specimens from patients with either PSC or CUC or both suggests that the causes of these conditions are closely related.
Factor or Industry Cleavages in Trade Policy? An Empirical Analysis of the Stolper-Samuelson Theorem

If factors of production are mobile between industries, the Stolper-Samuelson Theorem predicts that cleavages over trade policy will form along factor lines. Conversely, if factors are immobile, cleavages will form along industry lines. These two hypotheses are empirically examined using micro-data from a survey conducted during the 1988 Canadian federal election - a de facto referendum on free trade. Factors of production are found to be important determinants of preferences on trade policy. However, the industry of employment also helps determine preferences on trade policy. These results are consistent with partial factor mobility.
'Thank you for Smoking!': a multi-level study on the policy impact of anti-tobacco movements, tobacco industry's countermovements and political opportunity structure on tobacco control policies in 22 European countries

Based on a cross- national study of 22 European countries, we conducted a multi-level assessment of the impact of societal, political and industry factors on the strictness of tobacco control legislation for the period 1980-2012. Specifically we framed tobacco control policy processes as taken place in the realm of the triad formed by the state on top and anti-tobacco movement and tobacco industry’s countermovement on both base corners. Our main question concerns the separate influence of these parties in tobacco policy processes and its resulting consequences in terms of policy outcomes. We draw on political opportunity structure (POS) theory and policy diffusion theory to assess the possibilities a political system provides for grassroots participation in policy processes. Corporate Political Action (CPA) theory is used to evaluate tobacco industry’s countemobilization efforts to impede policy reform. Finally, we draw on resource mobilization (RM) theory to indicate anti-tobacco movements abilities to impact policy processes. We found that a population’s likeliness to participate in politics negatively relates to the strictness of tobacco control policies. Potentially because policymaking processes become more complex as a multitude of grassroots interests are released on policymakers which constrains more radical policy decision-making. In accordance, we found that state’s repression of grassroots participation in politics, is positively related to the strictness of tobacco control legislation. In such case, state public health concerns or international legislative pressure, outweigh grassroots interests in policy decisions. No evidence was found that POS, and specifically the openness of political systems and the presence of allies, enabled the anti-tobacco movement and tobacco industry’s countermovement, to impact policy outcomes. Moreover, we found no evidence that tobacco industry’s countermovements impacted domestic tobacco control policies. Our main contribution are integrating state, social movement and corporate countermovement in one framework and study these parties influence on policy processes in a simultaneously manner. Moreover policy processes are complex and could only partly be explained by the multi-level factors included in our study. Clustering our data within countries, revealed that there are unobserved characteristic nested within countries that do impact the strictness of tobacco control policies but we did not control for. We encourage researchers to include more factors in our suggested triad framework and test their impact on policy processes, in order to further unravel the complex phenomena policy processes are.
TH17 (and TH1) signatures of intestinal biopsies of CD patients in response to gliadin

Celiac disease (CD) is an immunological disorder caused by intolerance to ingested gliadin and other cereal prolamins that has been included in the TH1-dominated group of diseases, where IL-12 induced IFNγ is the major proinflamatory signal. Recently, another linage of T cells has been described, namely TH17, characterized by production of IL-17, that differentiate in response to TGFβ and IL-6 and participate in the pathogenesis of several autoimmune diseases. Using RT-PCR analysis of gene expression, we analyzed the presence of TH1 (IL-12 and IFNγ) and TH17 (TGFβ, IL-6, IL-17A, IL-17F and IL-23) related cytokines in intestinal biopsies from CD patients with active disease compared to remission and from treated patients after acute, in vitro re-exposure to gliadin. Potent TH1 and TH17 responses were present in the active stage of the disease, whereas short incubation of normalized biopsies with gliadin did not increase the expression of the effector cytokines, although a tendency of upregulation for both TH1 and TH17 promoting factors was observed, suggestive of a reactivation of proinflammatory pathways. These results place CD into the group of autoimmune disorders in which TH17 cells also participate, although the relative importance of each T cell response and their role in the initial events of the disease need further investigation.
PPARbeta/delta regulates paneth cell differentiation via controlling the hedgehog signaling pathway.

BACKGROUND & AIMS All 4 differentiated epithelial cell types found in the intestinal epithelium derive from the intestinal epithelial stem cells present in the crypt unit, in a process whose molecular clues are intensely scrutinized. Peroxisome proliferator-activated receptor beta (PPARbeta) is a nuclear hormone receptor activated by fatty acids and is highly expressed in the digestive tract. However, its function in intestinal epithelium homeostasis is understood poorly. METHODS To assess the role of PPARbeta in the small intestinal epithelium, we combined various cellular and molecular approaches in wild-type and PPARbeta-mutant mice. RESULTS We show that the expression of PPARbeta is particularly remarkable at the bottom of the crypt of the small intestine where Paneth cells reside. These cells, which have an important role in the innate immunity, are strikingly affected in PPARbeta-null mice. We then show that Indian hedgehog (Ihh) is a signal sent by mature Paneth cells to their precursors, negatively regulating their differentiation. Importantly, PPARbeta acts on Paneth cell homeostasis by down-regulating the expression of Ihh, an effect that can be mimicked by cyclopamine, a known inhibitor of the hedgehog signaling pathway. CONCLUSIONS We unraveled the Ihh-dependent regulatory loop that controls mature Paneth cell homeostasis and its modulation by PPARbeta. PPARbeta currently is being assessed as a drug target for metabolic diseases; these results reveal some important clues with respect to the signals controlling epithelial cell fate in the small intestine.