Descriptive Epidemiology of Bovine Tuberculosis in Michigan (1975–2010): Lessons Learned

Despite ongoing eradication efforts, bovine tuberculosis (BTB) remains a challenge in Michigan livestock and wildlife. The objectives of this study were to (1) review the epidemiology of BTB in Michigan cattle, privately owned cervids, and wildlife between 1975 and 2010 and (2) identify important lessons learned from the review and eradication strategies. BTB information was accessed from the Michigan BTB Eradication Project agencies. Cattle herds (49), privately owned deer herds (4), and wild white-tailed deer (668) were found infected with BTB during the review period. BTB has occurred primarily in counties located at the northern portion of the state's Lower Peninsula. Currently used BTB eradication strategies have successfully controlled BTB spread. However additional changes in BTB surveillance, prevention, and eradication strategies could improve eradication efforts

Quantum Fields in Hyperbolic Space-Times with Finite Spatial Volume

The one-loop effective action for a massive self-interacting scalar field is investigated in $4$-dimensional ultrastatic space-time $R \times H^3/\Gamma$, $H^3/\Gamma$ being a non-compact hyperbolic manifold with finite volume. Making use of the Selberg trace formula, the $\zeta$-function related to the small disturbance operator is constructed. For an arbitrary gravitational coupling, it is found that $\zeta(s)$ has a simple pole at $s=0$. The one-loop effective action is analysed by means of proper-time regularisations and the one-loop divergences are explicitly found. It is pointed out that, in this special case, also $\zeta$-function regularisation requires a divergent counterterm, which however is not necessary in the free massless conformal invariant coupling case. Finite temperature effects are studied and the high-temperature expansion is presented. A possible application to the problem of the divergences of the entanglement entropy for a free massless scalar field in a Rindler-like space-time is briefly discussed.Comment: 13 pages, LaTex. The contribution of hyperbolic elements has been added. Other minor corrections and reference

Rationale and design of PROSPECT-CONKO 004: a prospective, randomized trial of simultaneous pancreatic cancer treatment with enoxaparin and chemotherapy

BACKGROUND: Advanced pancreatic cancer, in addition to its high mortality, is characterized by one of the highest rates of venous thromboembolic events (VTE) as compared to other types of cancer. Enoxaparin, a low molecular weight heparin (LMWH), has proven to be effective for the prevention and treatment of VTE in surgical and general medical patients. Results of some small studies suggest that this benefit might extend to patients with cancer, however, enoxaparin is not currently indicated for this use. This phase IIb study was designed to analyze the efficacy of enoxaparin in patients with locally advanced or metastatic pancreatic cancer undergoing systemic chemotherapy. METHODS: The aim of this prospective multicenter trial is to compare concomitant treatment with enoxaparin to no anticoagulation in 540 patients. Primary endpoint is the incidence of clinically relevant VTE (symptomatic deep venous thrombosis (DVT) of the leg and / or pelvic and / or pulmonary embolism (PE)) within the first 3 months. Secondary endpoints include the incidence of symptomatic and asymptomatic VTE after 6, 9 and 12 months as well as remission at 3, 6, 9 and 12 months, overall survival and bleeding. Trial registration: isrctn.org identifier CCT-NAPN-16752, controlled-trials.com identifier: ISRCTN02140505. RESULTS: An interim analysis for safety performed after inclusion of 152 patients revealed no increased risk of bleeding (5 pts vs. 6 pts, Chi2: 0.763). CONCLUSIONS: PROSPECT is a pivotal study in elucidating the role of low molecular weight heparins in advanced pancreatic cancer. Its results will lead to a new understanding of the role of heparins in the prevention of venous thromboembolism and of their effect on survival, remission rates and toxicity of chemotherapeutic regimens

Naturally Occurring Tuberculosis in White-Tailed Deer

Objective—To determine the distribution of lesions and extent of tissues infected with Mycobacterium bovis in a captive population of white-tailed deer. Design—Cross-sectional study. Animals—116 captive white-tailed deer. Procedure—Deer were euthanatized, and postmortem examinations were performed. Tissues with gross lesions suggestive of tuberculosis were collected for microscopic analysis and bacteriologic culture. Tissues from the head, thorax, and abdomen of deer with no gross lesions were pooled for bacteriologic culture. Tonsillar, nasal, oral, and rectal swab specimens, fecal samples, and samples of hay and pelleted feed, soil around feeding sites, and water from 2 natural ponds were collected for bacteriologic culture. Results—Mycobacterium bovis was isolated from 14 of 116 (12%) deer; however, only 9 of 14 had lesions consistent with tuberculosis. Most commonly affected tissues included the medial retropharyngeal lymph node and lung. Five of 14 tuberculous deer had no gross lesions; however,M bovis was isolated from pooled tissue specimens from the heads of each of these deer. Bacteriologic culture of tonsillar swab specimens from 2 of the infected deer yielded M bovis. Mean (± SEM) age of tuberculous deer was 2.5 ± 0.3 years (range, 0.5 to 6 years). Mycobacterium bovis was not isolated from feed, soil, water, or fecal samples. Conclusions and Clinical Relevance—Examination of hunter-killed white-tailed deer for tuberculosis commonly includes only the lymph nodes of the head. Results of such examinations may underestimate disease prevalence by as much as 57%. Such discrepancy should be considered when estimating disease prevalence

Tamoxifen enhances the cytotoxic effects of nelfinavir in breast cancer cells

Introduction: The HIV protease inhibitor nelfinavir is currently under investigation as a new anti-cancer drug. Several studies have shown that nelfinavir induces cell cycle arrest, endoplasmic reticulum stress, autophagy, and apoptosis in cancer cells. In the present article, the effect of nelfinavir on human breast cancer cells is examined and potential combination treatments are investigated. Methods: The effects of nelfinavir and tamoxifen on the human breast cancer cell lines MCF7, T47 D, MDA-MB-453, and MDA-MB-435 were tested by analysing their influence on cell viability (via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay), apoptosis (annexin binding, poly(ADP-ribose) polymerase cleavage), autophagy (autophagy marker light chain 3B expression), endoplasmic reticulum stress (binding protein and activating transcription factor 3 expression), and the occurrence of oxidative stress (intracellular glutathione level). Results: Nelfinavir induced apoptosis in all four breast cancer cell lines tested, although the extent of autophagy and endoplasmic reticulum stress varied among the cell lines. The concentration of nelfinavir needed for an efficient induction of apoptosis in breast cancer cells could be reduced from 15 mu g/ml to 6 mu g/ml when combined with tamoxifen. At a concentration of 6 mu g/ml, tamoxifen substantially enhanced the endoplasmic reticulum stress reaction in those cell lines that responded to nelfinavir with binding protein (BiP) upregulation (MCF7, T47D), and enhanced autophagy in cell lines that responded to nelfinavir treatment with autophagy marker light chain 3B upregulation (MDA-MB-453). Although tamoxifen has been described to be able to induce oxidative stress at concentrations similar to those applied in this study (6 mu g/ml), we observed that nelfinavir but not tamoxifen reduced the intracellular glutathione level of breast cancer cells within hours of application by up to 32%, suggesting the induction of oxidative stress was an early event and an additional cause of the apoptosis induced by nelfinavir. Conclusions: The results demonstrate that nelfinavir may be an effective drug against breast cancer and could be combined with tamoxifen to enhance its efficacy against breast cancer cells. Moreover, the cytotoxic effect of a tamoxifen and nelfinavir combination was independent of the oestrogen receptor status of the analysed breast cancer cells, suggesting a potential benefit of a combination of these two drugs even in patients with no hormone-responsive tumours. We therefore recommend that clinical studies on nelfinavir with breast cancer patients should include this drug combination to analyse the therapeutic efficacy as well as the safety and tolerability of this potential treatment option

θ13\theta_{13}, δ\delta and the neutrino mass hierarchy at a γ=350\gamma=350 double baseline Li/B β\beta-Beam

We consider a $\beta$-Beam facility where $^8$Li and $^8$B ions are accelerated at $\gamma = 350$, accumulated in a 10 Km storage ring and let decay, so as to produce intense $\bar \nu_e$ and $\nu_e$ beams. These beams illuminate two iron detectors located at $L \simeq 2000$ Km and $L \simeq 7000$ Km, respectively. The physics potential of this setup is analysed in full detail as a function of the flux. We find that, for the highest flux ($10 \times 10^{18}$ ion decays per year per baseline), the sensitivity to $\theta_{13}$ reaches $\sin^2 2 \theta_{13} \geq 2 \times10^{-4}$; the sign of the atmospheric mass difference can be identified, regardless of the true hierarchy, for $\sin^2 2 \theta_{13} \geq 4\times10^{-4}$; and, CP-violation can be discovered in 70% of the $\delta$-parameter space for $\sin^2 2 \theta_{13} \geq 10^{-3}$, having some sensitivity to CP-violation down to $\sin^2 2 \theta_{13} \geq 10^{-4}$ for $|\delta| \sim 90^\circ$.Comment: 35 pages, 20 figures. Minor changes, matches the published versio

Hormonal Signal Amplification Mediates Environmental Conditions during Development and Controls an Irreversible Commitment to Adulthood

Many animals can choose between different developmental fates to maximize fitness. Despite the complexity of environmental cues and life history, different developmental fates are executed in a robust fashion. The nematode Caenorhabditis elegans serves as a powerful model to examine this phenomenon because it can adopt one of two developmental fates (adulthood or diapause) depending on environmental conditions. The steroid hormone dafachronic acid (DA) directs development to adulthood by regulating the transcriptional activity of the nuclear hormone receptor DAF-12. The known role of DA suggests that it may be the molecular mediator of environmental condition effects on the developmental fate decision, although the mechanism is yet unknown. We used a combination of physiological and molecular biology techniques to demonstrate that commitment to reproductive adult development occurs when DA levels, produced in the neuroendocrine XXX cells, exceed a threshold. Furthermore, imaging and cell ablation experiments demonstrate that the XXX cells act as a source of DA, which, upon commitment to adult development, is amplified and propagated in the epidermis in a DAF-12 dependent manner. This positive feedback loop increases DA levels and drives adult programs in the gonad and epidermis, thus conferring the irreversibility of the decision. We show that the positive feedback loop canalizes development by ensuring that sufficient amounts of DA are dispersed throughout the body and serves as a robust fate-locking mechanism to enforce an organism-wide binary decision, despite noisy and complex environmental cues. These mechanisms are not only relevant to C. elegans but may be extended to other hormonal-based decision-making mechanisms in insects and mammals

Uncertainty estimation for operational ocean forecast products-a multi-model ensemble for the North Sea and the Baltic Sea

Multi-model ensembles for sea surface temperature (SST), sea surface salinity (SSS), sea surface currents (SSC), and water transports have been developed for the North Sea and the Baltic Sea using outputs from several operational ocean forecasting models provided by different institutes. The individual models differ in model code, resolution, boundary conditions, atmospheric forcing, and data assimilation. The ensembles are produced on a daily basis. Daily statistics are calculated for each parameter giving information about the spread of the forecasts with standard deviation, ensemble mean and median, and coefficient of variation. High forecast uncertainty, i.e., for SSS and SSC, was found in the Skagerrak, Kattegat (Transition Area between North Sea and Baltic Sea), and the Norwegian Channel. Based on the data collected, longer-term statistical analyses have been done, such as a comparison with satellite data for SST and evaluation of the deviation between forecasts in temporal and spatial scale. Regions of high forecast uncertainty for SSS and SSC have been detected in the Transition Area and the Norwegian Channel where a large spread between the models might evolve due to differences in simulating the frontal structures and their movements. A distinct seasonal pattern could be distinguished for SST with high uncertainty between the forecasts during summer. Forecasts with relatively high deviation from the multi-model ensemble (MME) products or the other individual forecasts were detected for each region and each parameter. The comparison with satellite data showed that the error of the MME products is lowest compared to those of the ensemble members

Boundary relations and generalized resolvents of symmetric operators

The Kre\u{\i}n-Naimark formula provides a parametrization of all selfadjoint exit space extensions of a, not necessarily densely defined, symmetric operator, in terms of maximal dissipative (in \dC_+) holomorphic linear relations on the parameter space (the so-called Nevanlinna families). The new notion of a boundary relation makes it possible to interpret these parameter families as Weyl families of boundary relations and to establish a simple coupling method to construct the generalized resolvents from the given parameter family. The general version of the coupling method is introduced and the role of boundary relations and their Weyl families for the Kre\u{\i}n-Naimark formula is investigated and explained.Comment: 47 page

Two Regional Mental Health Treatment Facilities

One of the major social programs of the 1960s was the development of community mental health centers. As with most early attempts at evaluation, the results were pessimistic. This article reanalyzes one of the earliest, and best-known, evaluations of a community-based treatment facility. Following the conceptual framework of Campbell and his associates, it was found that the various threats to the validity of the findings indicate a consistent and systematic bias against detecting a positive effect for the new mental health center. In light of recent federal legislation mandating formal evaluations, appropriate procedures are discussed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68090/2/10.1177_0193841X7900300403.pd