Antimicrobial Susceptibility of Udder Pathogens Isolated from Dairy Herds in the West Littoral Region of Uruguay

A total of 522 strains belonging to streptococci, enterococci and staphylococci isolated from sub-clinical and clinical cases of bovine mastitis from the west littoral region of Uruguay were analysed for their susceptibility to several antimicrobial agents. The susceptibility patterns were studied by agar disk diffusion methods (ADDM) and broth micro-dilution to determine the minimum inhibitory concentration (MIC). The concentration that inhibits 90% (MIC(90)) of the analysed strains reported in micrograms per millilitre, for Staphylococcus aureus were > 8, 8, ≤ 0.5, ≤ 4, ≤ 1, ≤ 0.5, > 64, ≤ 0.25, 0.5, ≤ 1 and ≤ 1 to penicillin, ampicillin, oxacillin, cephalotin, gentamicin, erythromycin, oxitetracycline, enrofloxacin, trimethoprim/sulfamethoxazole, neomycin, and clindamycin, respectively. Coagulase-negative staphylococci (CNS) had different values for penicillin (4) and ampicillin (2), while the other antimicrobial agents had the same MIC(90 )values as reported for S. aureus. The MIC(90 )values for streptococci were 0.12, 0.25, ≤ 4, 16, ≤ 0.25, 0.5, 0.25 for penicillin, ampicillin, cephalotin, gentamicin, erythromycin, oxytetracycline and trimethoprim-sulfamethoxazole, whereas MIC(90 )for enterococci were 4, 4, 4, ≤ 0.5, 2, > 8 for penicillin, ampicillin, gentamicin, erythromycin, oxytetracycline and trimethoprim-sulfamethoxazole, respectively. Of 336 strains of S. aureus, 160 (47.6%) were resistant to penicillin. For 41 CNS strains, 10 (27%) presented penicillin-resistance. All the streptococcal strains were susceptible to penicillin, while 3 (7%) of the 43 enteroccocal strains were resistant. Non significant statistical differences were found between the results obtained by ADDM and broth micro-dilution for classifying bacterial isolates as susceptible or resistant according to the National Committee of Clinical Laboratory Standards

Optimised configuration of sensors for fault tolerant control of an electro-magnetic suspension system

For any given system the number and location of sensors can affect the closed-loop performance as well as the reliability of the system. Hence, one problem in control system design is the selection of the sensors in some optimum sense that considers both the system performance and reliability. Although some methods have been proposed that deal with some of the aforementioned aspects, in this work, a design framework dealing with both control and reliability aspects is presented. The proposed framework is able to identify the best sensor set for which optimum performance is achieved even under single or multiple sensor failures with minimum sensor redundancy. The proposed systematic framework combines linear quadratic Gaussian control, fault tolerant control and multiobjective optimisation. The efficacy of the proposed framework is shown via appropriate simulations on an electro-magnetic suspension system

The anti-fibrotic effect of inhibition of TGFβ-ALK5 signalling in experimental pulmonary fibrosis in mice is attenuated in the presence of concurrent γ-herpesvirus infection.

Journal ArticleTGFβ-ALK5 pro-fibrotic signalling and herpesvirus infections have been implicated in the pathogenesis and exacerbation of pulmonary fibrosis. In this study we addressed the role of TGFβ-ALK5 signalling during the progression of fibrosis in a two-hit mouse model of murine γ-herpesvirus 68 (MHV-68) infection on the background of pre-existing bleomycin-induced pulmonary fibrosis. Assessment of total lung collagen levels in combination with ex vivo micro-computed tomography (µCT) analysis of whole lungs demonstrated that MHV-68 infection did not enhance lung collagen deposition in this two-hit model but led to a persistent and exacerbated inflammatory response. Moreover, µCT reconstruction and analysis of the two-hit model revealed distinguishing features of diffuse ground-glass opacities and consolidation superimposed on pre-existing fibrosis that were reminiscent of those observed in acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF). Virally-infected murine fibrotic lungs further displayed evidence of extensive inflammatory cell infiltration and increased levels of CCL2, TNFα, IL-1β and IL-10. Blockade of TGFβ-ALK5 signalling attenuated lung collagen accumulation in bleomycin-alone injured mice, but this anti-fibrotic effect was reduced in the presence of concomitant viral infection. In contrast, inhibition of TGFβ-ALK5 signalling in virally-infected fibrotic lungs was associated with reduced inflammatory cell aggregates and increased levels of the antiviral cytokine IFNγ. These data reveal newly identified intricacies for the TGFβ-ALK5 signalling axis in experimental lung fibrosis, with different outcomes in response to ALK5 inhibition depending on the presence of viral infection. These findings raise important considerations for the targeting of TGFβ signalling responses in the context of pulmonary fibrosis.MRCNovartis CASE studentshi

Use of Self-Selected Postures to Regulate Multi-Joint Stiffness During Unconstrained Tasks

The human motor system is highly redundant, having more kinematic degrees of freedom than necessary to complete a given task. Understanding how kinematic redundancies are utilized in different tasks remains a fundamental question in motor control. One possibility is that they can be used to tune the mechanical properties of a limb to the specific requirements of a task. For example, many tasks such as tool usage compromise arm stability along specific directions. These tasks only can be completed if the nervous system adapts the mechanical properties of the arm such that the arm, coupled to the tool, remains stable. The purpose of this study was to determine if posture selection is a critical component of endpoint stiffness regulation during unconstrained tasks.Three-dimensional (3D) estimates of endpoint stiffness were used to quantify limb mechanics. Most previous studies examining endpoint stiffness adaptation were completed in 2D using constrained postures to maintain a non-redundant mapping between joint angles and hand location. Our hypothesis was that during unconstrained conditions, subjects would select arm postures that matched endpoint stiffness to the functional requirements of the task. The hypothesis was tested during endpoint tracking tasks in which subjects interacted with unstable haptic environments, simulated using a 3D robotic manipulator. We found that arm posture had a significant effect on endpoint tracking accuracy and that subjects selected postures that improved tracking performance. For environments in which arm posture had a large effect on tracking accuracy, the self-selected postures oriented the direction of maximal endpoint stiffness towards the direction of the unstable haptic environment.These results demonstrate how changes in arm posture can have a dramatic effect on task performance and suggest that postural selection is a fundamental mechanism by which kinematic redundancies can be exploited to regulate arm stiffness in unconstrained tasks

Mini-laparoscopic versus laparoscopic approach to appendectomy

BACKGROUND: The purpose of this clinical study is to evaluate the feasibility of using 2-mm laparoscopic instruments to perform an appendectomy in patients with clinically suspected acute appendicitis and compare the outcome of this mini-laparoscopic or "needlescopic" approach to the conventional laparoscopic appendectomy. METHODS: Two groups of patients undergoing appendectomy over 24 months were studied. In the first group, needlescopic appendectomy was performed in 15 patients by surgeons specializing in advanced laparoscopy. These patients were compared with the second or control group that included 21 consecutive patients who underwent laparoscopic appendectomy. We compared the patients' demographic data, operative findings, complications, postoperative pain medicine requirements, length of hospital stay, and recovery variables. Differences were considered statistically significant at a p-value < 0.05. RESULTS: Patient demographics, history of previous abdominal surgery, and operative findings were similar in both groups. There was no conversion to open appendectomy in either group. No postoperative morbidity or mortality occurred in either group. The needlescopic group had a significantly shorter mean operative time (p = 0.02), reduced postoperative narcotics requirements (p = 0.05), shorter hospital stay (p = 0.04), and quicker return to work (p = 0.03) when compared with the laparoscopic group. CONCLUSIONS: We conclude that the needlescopic technique is a safe and effective approach to appendectomy. When performed by experienced laparoscopic surgeons, the needlescopic technique results in significantly shorter postoperative convalescence and a prompt recovery

Evolution favors protein mutational robustness in sufficiently large populations

BACKGROUND: An important question is whether evolution favors properties such as mutational robustness or evolvability that do not directly benefit any individual, but can influence the course of future evolution. Functionally similar proteins can differ substantially in their robustness to mutations and capacity to evolve new functions, but it has remained unclear whether any of these differences might be due to evolutionary selection for these properties. RESULTS: Here we use laboratory experiments to demonstrate that evolution favors protein mutational robustness if the evolving population is sufficiently large. We neutrally evolve cytochrome P450 proteins under identical selection pressures and mutation rates in populations of different sizes, and show that proteins from the larger and thus more polymorphic population tend towards higher mutational robustness. Proteins from the larger population also evolve greater stability, a biophysical property that is known to enhance both mutational robustness and evolvability. The excess mutational robustness and stability is well described by existing mathematical theories, and can be quantitatively related to the way that the proteins occupy their neutral network. CONCLUSIONS: Our work is the first experimental demonstration of the general tendency of evolution to favor mutational robustness and protein stability in highly polymorphic populations. We suggest that this phenomenon may contribute to the mutational robustness and evolvability of viruses and bacteria that exist in large populations

Event-based knowledge elicitation of operating room management decision-making using scenarios adapted from information systems data

<p>Abstract</p> <p>Background</p> <p>No systematic process has previously been described for a needs assessment that identifies the operating room (OR) management decisions made by the anesthesiologists and nurse managers at a facility that do not maximize the efficiency of use of OR time. We evaluated whether event-based knowledge elicitation can be used practically for rapid assessment of OR management decision-making at facilities, whether scenarios can be adapted automatically from information systems data, and the usefulness of the approach.</p> <p>Methods</p> <p>A process of event-based knowledge elicitation was developed to assess OR management decision-making that may reduce the efficiency of use of OR time. Hypothetical scenarios addressing every OR management decision influencing OR efficiency were created from published examples. Scenarios are adapted, so that cues about conditions are accurate and appropriate for each facility (e.g., if OR 1 is used as an example in a scenario, the listed procedure is a type of procedure performed at the facility in OR 1). Adaptation is performed automatically using the facility's OR information system or anesthesia information management system (AIMS) data for most scenarios (43 of 45). Performing the needs assessment takes approximately 1 hour of local managers' time while they decide if their decisions are consistent with the described scenarios. A table of contents of the indexed scenarios is created automatically, providing a simple version of problem solving using case-based reasoning. For example, a new OR manager wanting to know the best way to decide whether to move a case can look in the chapter on "Moving Cases on the Day of Surgery" to find a scenario that describes the situation being encountered.</p> <p>Results</p> <p>Scenarios have been adapted and used at 22 hospitals. Few changes in decisions were needed to increase the efficiency of use of OR time. The few changes were heterogeneous among hospitals, showing the usefulness of individualized assessments.</p> <p>Conclusions</p> <p>Our technical advance is the development and use of automated event-based knowledge elicitation to identify suboptimal OR management decisions that decrease the efficiency of use of OR time. The adapted scenarios can be used in future decision-making.</p

Bayesian perspectives on mathematical practice

Mathematicians often speak of conjectures as being confirmed by evidence that falls short of proof. For their own conjectures, evidence justifies further work in looking for a proof. Those conjectures of mathematics that have long resisted proof, such as the Riemann hypothesis, have had to be considered in terms of the evidence for and against them. In recent decades, massive increases in computer power have permitted the gathering of huge amounts of numerical evidence, both for conjectures in pure mathematics and for the behavior of complex applied mathematical models and statistical algorithms. Mathematics has therefore become (among other things) an experimental science (though that has not diminished the importance of proof in the traditional style). We examine how the evaluation of evidence for conjectures works in mathematical practice. We explain the (objective) Bayesian view of probability, which gives a theoretical framework for unifying evidence evaluation in science and law as well as in mathematics. Numerical evidence in mathematics is related to the problem of induction; the occurrence of straightforward inductive reasoning in the purely logical material of pure mathematics casts light on the nature of induction as well as of mathematical reasoning

Direct intra-tumoral injection of zinc-acetate halts tumor growth in a xenograft model of prostate cancer

Intracellular levels of zinc have shown a strong inverse correlation to growth and malignancy of prostate cancer. To date, studies of zinc supplementation in prostate cancer have been equivocal and have not accounted for bioavailability of zinc. Therefore, we hypothesized that direct intra-tumoral injection of zinc could impact prostate cancer growth. In this study, we evaluated the cytotoxic properties of the pH neutral salt zinc acetate on the prostate cancer cell lines PC3, DU145 and LNCaP. Zinc acetate killed prostate cancer cell lines in vitro, independent of androgen sensitivity, in a dose-dependent manner in a range between 200 and 600 μM. Cell death occurred rapidly with 50% cell death by six hours and maximal cell death by 18 hours. We next established a xenograft model of prostate cancer and tested an experimental treatment protocol of direct intra-tumoral injection of zinc acetate. We found that zinc treatments halted the growth of the prostate cancer tumors and substantially extended the survival of the animals, whilst causing no detectable cytoxicity to other tissues. Thus, our studies form a solid proof-of-concept that direct intra-tumoral injection of zinc acetate could be a safe and effective treatment strategy for prostate cancer