Coping with complexity: working beyond the guidelines for patients with multimorbidities

Primary care physicians believe they are delivering evidence-based care, understanding that adherence to evidence-based clinical guidelines results in tangible benefits in the populations for which they were developed. Unfortunately, most clinical guidelines are based on trial populations which are very different to primary care populations [1], and do not reflect the reality of multimorbidity in general practice [2–6]. Since patients with multimorbidity account for around eight in every 10 primary care consultations [7], it is unsurprising that many primary care physicians find managing these patients challenging. Additionally, current clinical guidelines do not provide guidance on how best to prioritize recommendations for individuals with multimorbidity, and may therefore result in over-treatment and polypharmacy, and a risk of overlooking patient preferences [2,8]. Journal of Comorbidity 2015;5(1):11–1

Return of Aflatoxin Production in Aspergillus flavus and Aspergillus parasiticus after Serial Passaging

Undergraduate Theoretical Proposa

Alva Treadwell interview

Alva Treadwell taught in the business department at Central Washington State College (later Central Washington University), 1937-1971.https://digitalcommons.cwu.edu/cwura_interviews/1086/thumbnail.jp

Calculation of coherent emissions and gain from a prebunched free electron laser

This report advances a theoretical model for the single pass growth of coherent radiation in a prebunched FEL system. The FEL system includes a radio frequency linear accelerator (fr linac) as the injector, a resonator cavity with a wiggler magnet, and two highly reflective plano-concave mirrors, typically 99{percent} of the radiation is reflected inside the resonator. The model is based upon the following assumptions: a) the electron beam is cold, b) a super- electron is a particle with {approximately} 10{sup 8} elementary charges inside a bunch; the bunch length is much smaller than the radiation wavelength and the super-electron scatters with the rf wave in a single pass through the resonator, c) a smooth phase space transition must exist between the rf linac and the resonator, d) the energy gain is low per pass and consequently in the linear gain regime, and e) if condition (b) is satisfied and the bunch is resonant with the FEL beat wave, all electrons lose energy to the wave, in the lowest order approximation. A simple scaling technique is used to calculate the output power given the number of particles in a bunch and the efficiency for retrieving coherent radiation from the resonator. 4 refs., 8 figs., 2 tabs

The Effects of Monetary Policy "News" and "Surprises"

There is substantial agreement in the monetary policy literature over the effects of exogenous monetary policy shocks. The shocks that are investigated, however, almost exclusively represent unanticipated changes in policy, which surprise the private sector and which are typically found to have a delayed and sluggish effect on output. In this paper, we estimate a New Keynesian model that incorporates news about future policies to try to disentangle the anticipated and unanticipated components of policy shocks. The paper shows that the conventional estimates confound two distinct effects on output: an effect due to unanticipated or “surprise” shocks, which is smaller and more short-lived than the response usually obtained in the literature, and a large, delayed, and persistent effect due to anticipated policy shocks or "news." News shocks play a larger role in influencing the business cycle than unanticipated policy shocks, although the overall fraction of economic fluctuations that can be attributed to monetary policy remains limited.Anticipated and unanticipated monetary policy shocks; News shocks; New Keynesian model with news shocks; Effects of monetary policy onoutput

Uniquely human CHRFAM7A gene increases the hematopoietic stem cell reservoir in mice and amplifies their inflammatory response.

A subset of genes in the human genome are uniquely human and not found in other species. One example is CHRFAM7A, a dominant-negative inhibitor of the antiinflammatory α7 nicotinic acetylcholine receptor (α7nAChR/CHRNA7) that is also a neurotransmitter receptor linked to cognitive function, mental health, and neurodegenerative disease. Here we show that CHRFAM7A blocks ligand binding to both mouse and human α7nAChR, and hypothesized that CHRFAM7A-transgenic mice would allow us to study its biological significance in a tractable animal model of human inflammatory disease, namely SIRS, the systemic inflammatory response syndrome that accompanies severe injury and sepsis. We found that CHRFAM7A increased the hematopoietic stem cell (HSC) reservoir in bone marrow and biased HSC differentiation to the monocyte lineage in vitro. We also observed that while the HSC reservoir was depleted in SIRS, HSCs were spared in CHRFAM7A-transgenic mice and that these mice also had increased immune cell mobilization, myeloid cell differentiation, and a shift to inflammatory monocytes from granulocytes in their inflamed lungs. Together, the findings point to a pathophysiological inflammatory consequence to the emergence of CHRFAM7A in the human genome. To this end, it is interesting to speculate that human genes like CHRFAM7A can account for discrepancies between the effectiveness of drugs like α7nAChR agonists in animal models and human clinical trials for inflammatory and neurodegenerative disease. The findings also support the hypothesis that uniquely human genes may be contributing to underrecognized human-specific differences in resiliency/susceptibility to complications of injury, infection, and inflammation, not to mention the onset of neurodegenerative disease

Blogs bother me : social media, journalism and the curriculum

This paper grew out of the authors&rsquo; interest in updating the journalism curriculum at AUT (Aukland University of Technology) to better reflect the impact of online media, including social media, on the work of journalists. The challenge for journalism educators is to remain relevant in rapidly changing news and education environments. Our study suggests that while the vast majority of students have some engagement with social media, particularly social networking, and are aware that it can be a powerful tool for journalists, they are still not entirely comfortable with its techniques and they are not experimenting with social media as a production platform as much as we first thought. In short, it appears that they do not have command of professional fluency with social media tools. In response to these findings we have begun to introduce some social media tools and processes directly into the units we teach, in particular: digital story-telling techniques; the use of Twitter and location-based applications; encouraging the ethical use of Facebook etc. for sourcing stories and talent for interviews; podcasting, soundslides and video for the Web, Dreamweaver, InDesign and PHP-based content management systems. We do not see the work to date as the end-point of the changes that we know are necessary, but we are acutely aware of the limitations (structural, institutional and financial) that suggest we should continue with this small-steps approach for the foreseeable future.<br /

Impact of elosulfase alfa in patients with morquio A syndrome who have limited ambulation: An open-label, phase 2 study.

Efficacy and safety of elosulfase alfa enzyme replacement therapy (ERT) were assessed in an open-label, phase 2, multi-national study in Morquio A patients aged ≥5 years unable to walk ≥30 meters in the 6-min walk test. Patients received elosulfase alfa 2.0 mg/kg/week intravenously for 48 weeks. Efficacy measures were functional dexterity, pinch/grip strength, mobility in a modified timed 25-foot walk, pain, quality of life, respiratory function, and urine keratan sulfate (KS). Safety/tolerability was also assessed. Fifteen patients received elosulfase alfa, three patients discontinued ERT due to adverse events (two were grade 3 drug-related adverse events, the other was not drug-related), and two patients missed &gt;20% of planned infusions; 10 completed treatment through 48 weeks and received ≥80% of planned infusions (Modified Per Protocol [MPP] population). The study population had more advanced disease than that enrolled in other trials. From baseline to week 48, MPP data showed biochemical efficacy (urine KS decreased 52.4%). The remaining efficacy results were highly variable due to challenges in test execution because of severe skeletal and joint abnormalities, small sample sizes, and clinical heterogeneity among patients. Eight patients showed improvements in one or more outcome measures; several patients indicated improvements not captured by the study assessments (e.g., increased energy, functional ability). The nature of adverse events was similar to other elosulfase alfa studies. This study illustrates the considerable challenges in objectively measuring impact of ERT in very disabled Morquio A patients and highlights the need to examine results on an individual basis. © 2016 The Authors. American Journal of Medical Genetics Part A Published by Wiley Periodicals, Inc

The effect of therapeutic glucocorticoids on the adrenal response in a randomized controlled trial in patients with rheumatoid arthritis

Objective. To measure the effect of low-dose systemic glucocorticoid treatment on the adrenal response to adrenocorticotropic hormone (ACTH) in patients with rheumatoid arthritis (RA). Methods. Patients with RA who took part in a randomized double-blind placebo-controlled trial of budesonide (3 mg/day and 9 mg/day) and prednisolone (7.5 mg/day) underwent a short (60-minute) test with injection of ACTH (tetracosactide hexaacetate) at baseline and the day after completing the 3-month treatment program. Plasma cortisol measurements at baseline and 3 months were compared within and between the treatment groups. Individual patients were classified as normal responders to ACTH or as abnormal responders if changes were > 2 SD below the pretreatment value in the entire group of study patients. Results. Short tests with ACTH injection were performed on 139 patients before beginning the study medication and on 134 patients after cessation of the medication. There were no changes in the placebo group. Mean plasma cortisol levels following treatment were reduced in all active treatment groups. In addition, mean values were significantly reduced for the 30-minute and 60-minute responses to ACTH. The maximum reduction (35%) occurred in the prednisolone group at 60 minutes. Following treatment, 34% of patients taking budesonide 9 mg and 46% of those taking prednisolone 7.5 mg failed to reach the normal maximum cortisol response to ACTH. Four patients failed to achieve the normal percentage increase in cortisol levels, but only 1 patient failed to meet both criteria. Conclusion. Low doses of a glucocorticoid resulted in depression of baseline and ACTH-stimulated cortisol levels after 12 weeks of therapy. Although the responsiveness of the hypothalamic-pituitary-adrenal axis in individual patients generally remained within the normal range, these changes should be investigated further