Future treatment strategies of aggressive pituitary tumors

While surgery remains the first-line treatment of most aggressive pituitary adenomas, medical therapy is important as second-line or adjunctive therapy in a large proportion of patients. Dopamine agonists (DAs) are the best treatment for prolactinomas, but when DAs are not tolerated, new somatostatin receptor subtype 5 (SSTR5) inhibitors may offer an alternative in the future. Unfortunately, these are unlikely to be effective in DA-resistant prolactinomas. In acromegaly, the existing somatostatin analogs, octreotide and lanreotide, will remain the medical treatment of choice for the foreseeable future. There is an urgent need for medical therapies in Cushing’s disease, and the SSTR5 analogs could offer an effective treatment in a proportion of patients within the next few years. Finally, the medical management options for non-functioning pituitary adenomas are also very limited, and a new chimeric agent with activity towards dopamine receptors, SSTR5 and SSTR2 may help reduce adenoma recurrence in the future

Perceived usefulness of a distributed community-based syndromic surveillance system: a pilot qualitative evaluation study

<p>Abstract</p> <p>Background</p> <p>We conducted a pilot utility evaluation and information needs assessment of the Distribute Project at the 2010 Washington State Public Health Association (WSPHA) Joint Conference. Distribute is a distributed community-based syndromic surveillance system and network for detection of influenza-like illness (ILI). Using qualitative methods, we assessed the perceived usefulness of the Distribute system and explored areas for improvement. Nine state and local public health professionals participated in a focus group (<it>n = 6</it>) and in semi-structured interviews (<it>n = 3</it>). Field notes were taken, summarized and analyzed.</p> <p>Findings</p> <p>Several emergent themes that contribute to the perceived usefulness of system data and the Distribute system were identified: 1) <it>Standardization: </it>a common ILI syndrome definition; 2) <it>Regional Comparability: </it>views that support county-by-county comparisons of syndromic surveillance data; 3) <it>Completeness: </it>complete data for all expected data at a given time; <it>4) Coverage: </it>data coverage of all jurisdictions in WA state; 5) <it>Context: </it>metadata incorporated into the views to provide context for graphed data; 6) <it>Trusted Data</it>: verification that information is valid and timely; and 7) <it>Customization: </it>the ability to customize views as necessary. As a result of the focus group, a new county level health jurisdiction expressed interest in contributing data to the Distribute system.</p> <p>Conclusion</p> <p>The resulting themes from this study can be used to guide future information design efforts for the Distribute system and other syndromic surveillance systems. In addition, this study demonstrates the benefits of conducting a low cost, qualitative evaluation at a professional conference.</p

Does hyperthermia constrain flight duration in a short-distance migrant?

While some migratory birds perform non-stop flights of over 11 000 km, many species only spend around 15% of the day in flight during migration, posing a question as to why flight times for many species are so short. Here, we test the idea that hyperthermia might constrain flight duration (FD) in a short-distance migrant using remote biologging technology to measure heart rate, hydrostatic pressure and body temperature in 19 migrating eider ducks (Somateria mollissima), a short-distance migrant. Our results reveal a stop-and-go migration strategy where migratory flights were frequent (14 flights day(−1)) and short (15.7 min), together with the fact that body temperature increases by 1°C, on average, during such flights, which equates to a rate of heat storage index (HSI) of 4°C h(−1). Furthermore, we could not find any evidence that short flights were limited by heart rate, together with the fact that the numerous stops could not be explained by the need to feed, as the frequency of dives and the time spent feeding were comparatively small during the migratory period. We thus conclude that hyperthermia appears to be the predominant determinant of the observed migration strategy, and suggest that such a physiological limitation to FD may also occur in other species. This article is part of the themed issue ‘Moving in a moving medium: new perspectives on flight’

Towards a Model of Corporate and Social Stakeholder Engagement: Analyzing the Relations Between a French Mutual Bank and Its Members

International audienceThe aim of this article is to develop a new classification of stakeholders based on the concept of corporate and social engagement. Engagement is analyzed as an organizational learning process between the managers of an organization and its stakeholders. It is a necessary condition to improve the organization's impact on its economic, social, and natural environment. Applied to the membership of a French mutual bank in order to identify the members' varying levels of engagement, this new mapping technique may help managers to adapt their practices to the degree of engagement of each identified group of members, and to modify their financial products and communications to foster engagement among as many of these groups as possible

Does an activity based remuneration system attract young doctors to general practice?

<p>Abstract</p> <p>Background</p> <p>The use of increasingly complex payment schemes in primary care may represent a barrier to recruiting general practitioners (GP). The existing Norwegian remuneration system is fully activity based - 2/3 fee-for-service and 1/3 capitation. Given that the system has been designed and revised in close collaborations with the medical association, it is likely to correspond - at least to some degree - with the preferences of <it>current </it>GPs (men in majority). The objective of this paper was to study which preferences that young doctors (women in majority), who are the <it>potential entrants </it>to general practice have for activity based vs. salary based payment systems.</p> <p>Methods</p> <p>In November-December 2010 all last year medical students and all interns in Norway (n = 1.562) were invited to participate in an online survey. The respondents were asked their opinion on systems of remuneration for GPs; inclination to work as a GP; risk attitude; income preferences; work pace tolerance. The data was analysed using one-way ANOVA and multinomial logistic regression analysis.</p> <p>Results</p> <p>A total of 831 (53%) responded. Nearly half the sample (47%) did not consider the remuneration system to be important for their inclination to work as GP; 36% considered the current system to make general practice <it>more </it>attractive, while 17% considered it to make general practice <it>less </it>attractive. Those who are attracted by the existing system were men and those who think high income is important, while those who are deterred by the system are risk averse and less happy with a high work pace. On the question of preferred remuneration system, half the sample preferred a mix of salary and activity based remuneration (the median respondent would prefer a 50/50 mix). Only 20% preferred a fully activity based system like the existing one. A salary system was preferred by women, and those less concerned with high income, while a fully activity based system was preferred by men, and those happy with a high work pace.</p> <p>Conclusions</p> <p>Given a concern about low recruitment to general practice in Norway, and the fact that an increasing share of medical students is women, we were interested in the extent to which the current Norwegian remuneration system correspond with the preferences of potential GPs. This study suggests that an existing remuneration mechanism has a selection effect on who would like to become a GP. Those most attracted are income motivated men. Those deterred are risk averse, and less happy with a high work pace. More research is needed on the extent to which experienced GPs differ along the questions we asked potential GPs, as well as studying the relative importance of other attributes than payment schemes.</p

The evolutionary demography of duplicate genes

Key words: gene duplication, genome evolution, genome size Although gene duplication has generally been viewed as a necessary source of material for the origin of evolu-tionary novelties, the rates of origin, loss, and preservation of gene duplicates are not well understood. Applying steady-state demographic techniques to the age distributions of duplicate genes censused in seven completely sequenced genomes, we estimate the average rate of duplication of a eukaryotic gene to be on the order of 0.01/ gene/million years, which is of the same order of magnitude as the mutation rate per nucleotide site. However, the average half-life of duplicate genes is relatively small, on the order of 4.0 million years. Significant inter-specific variation in these rates appears to be responsible for differences in species-specific genome sizes that arise as a consequence of a quasi-equilibrium birth-death process. Most duplicated genes experience a brief period of relaxed selection early in their history and a minority exhibit the signature of directional selection, but those that survive more than a few million years eventually experience strong purifying selection. Thus, although most theoretical work on the gene-duplication process has focused on issues related to adaptive evolution, the origin of a new function appears to be a very rare fate for a duplicate gene. A more significant role of the duplication process may be the generation of microchromosomal rearrangements through reciprocal silencing of alternativ

Meta-Analysis on the Effects of Octreotide on Tumor Mass in Acromegaly

<div><h3>Background</h3><p>The long-acting somatostatin analogue octreotide is used either as an adjuvant or primary therapy to lower growth hormone (GH) levels in patients with acromegaly and may also induce pituitary tumor shrinkage.</p> <h3>Objective</h3><p>We performed a meta-analysis to accurately assess the effect of octreotide on pituitary tumor shrinkage.</p> <h3>Data Sources</h3><p>A computerized Medline and Embase search was undertaken to identify potentially eligible studies.</p> <h3>Study Eligibility Criteria</h3><p>Eligibility criteria included treatment with octreotide, availability of numerical metrics on tumor shrinkage and clear definition of a clinically relevant reduction in tumor size. Primary endpoints included the proportion of patients with tumor shrinkage and mean percentage reduction in tumor volume.</p> <h3>Data Extraction and Analysis</h3><p>The electronic search identified 2202 articles. Of these, 41 studies fulfilling the eligibility criteria were selected for data extraction and analysis. In total, 1685 patients were included, ranging from 6 to 189 patients per trial. For the analysis of the effect of octreotide on pituitary tumor shrinkage a random effect model was used to account for differences in both effect size and sampling error.</p> <h3>Results</h3><p>Octreotide was shown to induce tumor shrinkage in 53.0% [95% CI: 45.0%–61.0%] of treated patients. In patients treated with the LAR formulation of octreotide, this increased to 66.0%, [95% CI: 57.0%–74.0%). In the nine studies in which tumor shrinkage was quantified, the overall weighted mean percentage reduction in tumor size was 37.4% [95% CI: 22.4%–52.4%], rising to 50.6% [95% CI: 42.7%–58.4%] with octreotide LAR.</p> <h3>Limitations</h3><p>Most trials examined were open-label and had no control group.</p> <h3>Conclusions</h3><p>Octreotide LAR induces clinically relevant tumor shrinkage in more than half of patients with acromegaly.</p> </div

A Search for Dark Higgs Bosons

Recent astrophysical and terrestrial experiments have motivated the proposal of a dark sector with GeV-scale gauge boson force carriers and new Higgs bosons. We present a search for a dark Higgs boson using 516 fb-1 of data collected with the BABAR detector. We do not observe a significant signal and we set 90% confidence level upper limits on the product of the Standard Model-dark sector mixing angle and the dark sector coupling constant.Comment: 7 pages, 5 postscript figures, published version with improved plots for b/w printin

Study of CP violation in Dalitz-plot analyses of B0 --> K+K-KS, B+ --> K+K-K+, and B+ --> KSKSK+

We perform amplitude analyses of the decays $B^0 \to K^+K^-K^0_S$, $B^+ \rightarrow K^+K^-K^+$, and $B^+ \to K^0_S K^0_S K^+$, and measure CP-violating parameters and partial branching fractions. The results are based on a data sample of approximately $470\times 10^6$ $B\bar{B}$ decays, collected with the BABAR detector at the PEP-II asymmetric-energy $B$ factory at the SLAC National Accelerator Laboratory. For $B^+ \to K^+K^-K^+$, we find a direct CP asymmetry in $B^+ \to \phi(1020)K^+$ of $A_{CP}= (12.8\pm 4.4 \pm 1.3)$, which differs from zero by $2.8 \sigma$. For $B^0 \to K^+K^-K^0_S$, we measure the CP-violating phase $\beta_{\rm eff} (\phi(1020)K^0_S) = (21\pm 6 \pm 2)^\circ$. For $B^+ \to K^0_S K^0_S K^+$, we measure an overall direct CP asymmetry of $A_{CP} = (4 ^{+4}_{-5} \pm 2)$. We also perform an angular-moment analysis of the three channels, and determine that the $f_X(1500)$ state can be described well by the sum of the resonances $f_0(1500)$, $f_2^{\prime}(1525)$, and $f_0(1710)$.Comment: 35 pages, 68 postscript figures. v3 - minor modifications to agree with published versio

Search for rare quark-annihilation decays, B --> Ds(*) Phi

We report on searches for B- --> Ds- Phi and B- --> Ds*- Phi. In the context of the Standard Model, these decays are expected to be highly suppressed since they proceed through annihilation of the b and u-bar quarks in the B- meson. Our results are based on 234 million Upsilon(4S) --> B Bbar decays collected with the BABAR detector at SLAC. We find no evidence for these decays, and we set Bayesian 90% confidence level upper limits on the branching fractions BF(B- --> Ds- Phi) Ds*- Phi)<1.2x10^(-5). These results are consistent with Standard Model expectations.Comment: 8 pages, 3 postscript figues, submitted to Phys. Rev. D (Rapid Communications