Shape-induced force fields in optical trapping

Advances in optical tweezers, coupled with the proliferation of two-photon polymerization systems, mean that it is now becoming routine to fabricate and trap non-spherical particles. The shaping of both light beams and particles allows fine control over the flow of momentum from the optical to mechanical regimes. However, understanding and predicting the behaviour of such systems is highly complex in comparison with the traditional optically trapped microsphere. In this Article, we present a conceptually new and simple approach based on the nature of the optical force density. We illustrate the method through the design and fabrication of a shaped particle capable of acting as a passive force clamp, and we demonstrate its use as an optically trapped probe for imaging surface topography. Further applications of the design rules highlighted here may lead to new sensors for probing biomolecule mechanics, as well as to the development of optically actuated micromachines

The utilisation of health research in policy-making: Concepts, examples and methods of assessment

The importance of health research utilisation in policy-making, and of understanding the mechanisms involved, is increasingly recognised. Recent reports calling for more resources to improve health in developing countries, and global pressures for accountability, draw greater attention to research-informed policy-making. Key utilisation issues have been described for at least twenty years, but the growing focus on health research systems creates additional dimensions. The utilisation of health research in policy-making should contribute to policies that may eventually lead to desired outcomes, including health gains. In this article, exploration of these issues is combined with a review of various forms of policy-making. When this is linked to analysis of different types of health research, it assists in building a comprehensive account of the diverse meanings of research utilisation. Previous studies report methods and conceptual frameworks that have been applied, if with varying degrees of success, to record utilisation in policy-making. These studies reveal various examples of research impact within a general picture of underutilisation. Factors potentially enhancing utilisation can be identified by exploration of: priority setting; activities of the health research system at the interface between research and policy-making; and the role of the recipients, or 'receptors', of health research. An interfaces and receptors model provides a framework for analysis. Recommendations about possible methods for assessing health research utilisation follow identification of the purposes of such assessments. Our conclusion is that research utilisation can be better understood, and enhanced, by developing assessment methods informed by conceptual analysis and review of previous studies

Carotid artery calcification at the initiation of hemodialysis is a risk factor for cardiovascular events in patients with end-stage renal disease: a cohort study

<p>Abstract</p> <p>Background</p> <p>Vascular calcification has been recognized as a risk factor for cardiovascular (CV) events in patients with end-stage renal disease (ESRD). However, the association of carotid artery calcification (CAAC) with CV events remains unknown. The aim of this study was to elucidate whether CAAC is associated with composite CV events in ESRD patients.</p> <p>Methods</p> <p>One-hundred thirty-three patients who had been started on hemodialysis between 2004 and 2008 were included in this retrospective cohort study. These patients received multi-detector computed tomography to assess CAAC at the initiation of hemodialysis. Composite CV events, including ischemic heart disease, heart failure, cerebrovascular diseases, and CV deaths after the initiation of hemodialysis, were examined in each patient.</p> <p>Results</p> <p>CAAC was found in 94 patients (71%). At the end of follow-up, composite CV events were seen in 47 patients: ischemic heart disease in 20, heart failure in 8, cerebrovascular disease in 12, and CV deaths in 7. The incidence of CAAC was 87% in patients with CV events, which was significantly higher than the rate (62%) in those without. Kaplan-Meier analysis showed a significant increase in composite CV events in patients with CAAC compared with those without CAAC (p = 0.001, log-rank test). Univariate analysis using a Cox hazards model showed that age, smoking, common carotid artery intima-media thickness and CAAC were risk factors for composite CV events. In multivariate analysis, only CAAC was a significant risk factor for composite CV events (hazard ratio, 2.85; 95% confidence interval, 1.18-8.00; p = 0.02).</p> <p>Conclusions</p> <p>CAAC is an independent risk factor for CV events in ESRD patients. The assessment of CAAC at the initiation of hemodialysis is useful for predicting the prognosis.</p

The theory of brain-sign: a physical alternative to consciousness

Consciousness and the mind are prescientific concepts that begin with Greek theorizing. They suppose human rationality and reasoning placed in the human head by (in Christian terms) God, who structured the universe he created with the same kind of underlying characteristics. Descartes' development of the model included scientific objectivity by placing the mind outside the physical universe. In its failure under evidential scrutiny and without physical explanation, this model is destined for terminal decline. Instead, a genuine biological and physical function for the brain phenomenon can be developed. This is the theory of brain-sign. It accepts the causality of the brain as its physical characteristics, already under scientific scrutiny. What is needed is a new neurophysiological mapping language that specifies the relation of the structure and operation of the brain to organismic action in the world. Still what is lacking is an account of how neurophysiologies in different organisms communicate on dynamic, i.e. unpredictable, tasks. It is this evolved capacity that has emerged as brain-sign. Thus rather than mentality being an inner epistemological parallel world suddenly appearing in the head, brain-sign, as the neural sign of the causal status of the brain, facilitates the communicative medium of otherwise isolated organisms. The biogenesis of the phenomenon emerges directly from the account of the physical brain, and functions as a monistic feature of organisms in the physical world. This new paradigm offers disciplinary compatibility, and genuine development in behavioral and brain sciences

Risk factors of one year increment of coronary calcifications and survival in hemodialysis patients

<p>Abstract</p> <p>Background</p> <p>Heart and coronary calcifications in hemodialysis patients are of very common occurrence and linked to cardiovascular events and mortality. Several studies have been published with similar results. Most of them were mainly cross-sectional and some of the prospective protocols were aimed to evaluate the results of the control of altered biochemical parameters of mineral disturbances with special regard to serum calcium, phosphate and CaxP with the use of calcium containing and calcium free phosphate chelating agents. The aim of the present study was to evaluate in hemodialysis patients classic and some non classic risk factors as predictors of calcification changes after one year and to evaluate the impact of progression on survival.</p> <p>Methods</p> <p>81 patients on hemodialysis were studied, with a wide age range and HD vintage. Several classic parameters and some less classic risk factors were studied like fetuin-A, CRP, 25-OHD and leptin. Calcifications, as Agatston scores, were evaluated with Multislice CT basally and after 12-18 months.</p> <p>Results</p> <p>Coronary artery calcifications were observed in 71 of 81 patients. Non parametric correlations between Agatston scores and Age, HD Age, PTH and CRP were significant. Delta increments of Agatston scores correlated also with serum calcium, CaxP, Fetuin-A, triglycerides and serum albumin. Logistic regression analysis showed Age, PTH and serum calcium as important predictors of Delta Agatston scores. LN transformation of the not normally distributed variables restricted the significant correlations to Age, BMI and CRP. Considering the Delta Agatston scores as dependent, significant predictors were Age, PTH and HDL. A strong association was found between basal calcification scores and Delta increment at one year. By logistic analysis, the one year increments in Agatston scores were found to be predictors of mortality. Diabetic and hypertensive patients have significantly higher Delta scores.</p> <p>Conclusions</p> <p>Progression of calcification is of common occurrence, with special regard to elevated basal scores, and is predictive of survival. Higher predictive value of survival is linked to the one year increment of calcification scores. Some classic and non classic risk factors play an important role in progression. Some of them could be controlled with appropriate management with possible improvement of mortality.</p

The NKF-NUS hemodialysis trial protocol - a randomized controlled trial to determine the effectiveness of a self management intervention for hemodialysis patients

<p>Abstract</p> <p>Background</p> <p>Poor adherence to treatment is common in patients on hemodialysis which may increase risk for poor clinical outcomes and mortality. Self management interventions have been shown to be effective in improving compliance in other chronic populations. The aim of this trial is to evaluate the effectiveness of a recently developed group based self management intervention for hemodialysis patients compared to standard care.</p> <p>Methods/Design</p> <p>This is a multicentre parallel arm block randomized controlled trial (RCT) of a four session group self management intervention for hemodialysis patients delivered by health care professionals compared to standard care. A total of 176 consenting adults maintained on hemodialysis for a minimum of 6 months will be randomized to receive the self management intervention or standard care. Primary outcomes are biochemical markers of clinical status and adherence. Secondary outcomes include general health related quality of life, disease-specific quality of life, mood, self efficacy and self-reported adherence. Outcomes will be measured at baseline, immediately post-intervention and at 3 and 9 months post-intervention by an independent assessor and analysed on intention to treat principles with linear mixed-effects models across all time points. A qualitative component will examine which aspects of program participants found particularly useful and any barriers to change.</p> <p>Discussion</p> <p>The NKF-NUS intervention builds upon previous research emphasizing the importance of empowering patients in taking control of their treatment management. The trial design addresses weaknesses of previous research by use of an adequate sample size to detect clinically significant changes in biochemical markers, recruitment of a sufficiently large representative sample, a theory based intervention and careful assessment of both clinical and psychological endpoints at various follow up points. Inclusion of multiple dependent variables allows us to assess the broader impact on the intervention including both hard end points as well as patient reported outcomes. This program, if found to be effective, has the potential to be implemented within the existing renal services delivery model in Singapore, particularly as this is being delivered by health care professionals already working with hemodialysis patients in these settings who are specifically trained in facilitating self management in renal patients.</p> <p>Trial registration</p> <p>Current Controlled Trials <a href="http://www.controlled-trials.com/ISRTN31434033">ISRTN31434033</a></p

Attainment of clinical performance targets and improvement in clinical outcomes and resource use in hemodialysis care: a prospective cohort study

BACKGROUND: Clinical performance targets are intended to improve patient outcomes in chronic disease through quality improvement, but evidence of an association between multiple target attainment and patient outcomes in routine clinical practice is often lacking. METHODS: In a national prospective cohort study (ESRD Quality, or EQUAL), we examined whether attainment of multiple targets in 668 incident hemodialysis patients from 74 U.S. not-for-profit dialysis clinics was associated with better outcomes. We measured whether the following accepted clinical performance targets were met at 6 months after study enrollment: albumin (≥4.0 g/dl), hemoglobin (≥11 g/dl), calcium-phosphate product (<55 mg(2)/dl(2)), dialysis dose (Kt/V≥1.2), and vascular access type (fistula). Outcomes included mortality, hospital admissions, hospital days, and hospital costs. RESULTS: Attainment of each of the five targets was associated individually with better outcomes; e.g., patients who attained the albumin target had decreased mortality [relative hazard (RH) = 0.55, 95% confidence interval (CI), 0.41–0.75], hospital admissions [incidence rate ratio (IRR) = 0.67, 95% CI, 0.62–0.73], hospital days (IRR = 0.61, 95% CI, 0.58–0.63), and hospital costs (average annual cost reduction = $3,282, P = 0.002), relative to those who did not. Increasing numbers of targets attained were also associated, in a graded fashion, with decreased mortality (P = 0.030), fewer hospital admissions and days (P < 0.001 for both), and lower costs (P = 0.029); these trends remained statistically significant for all outcomes after adjustment (P < 0.001), except cost, which was marginally significant (P = 0.052). CONCLUSION: Attainment of more clinical performance targets, regardless of which targets, was strongly associated with decreased mortality, hospital admissions, and resource use in hemodialysis patients

Comparison of total parathyroidectomy without autotransplantation and without thymectomy versus total parathyroidectomy with autotransplantation and with thymectomy for secondary hyperparathyroidism: TOPAR PILOT-Trial

<p>Abstract</p> <p>Background</p> <p>Secondary hyperparathyroidism (sHPT) is common in patients with chronic renal failure. Despite the initiation of new therapeutic agents, several patients will require parathyroidectomy (PTX). Total PTX with autotransplantation of parathyroid tissue (TPTX+AT) and subtotal parathyroidectomy (SPTX) are currently considered as standard surgical procedures in the treatment of sHPT. Recurrencerates after TPTX+AT or SPTX are between 10% and 12% (median follow up: 36 months).</p> <p>Recent retrospective studies demonstrated a lower rate of recurrent sHPT of 0–4% after PTX without autotransplantation and thymectomy (TPTX) with no higher morbidity when compared to the standard procedures. The observed superiority of TPTX is flawed due to different definitions of outcomes, varying follow up periods and different surgical treatment strategies (with and without thymectomy).</p> <p>Methods/Design</p> <p>Patients with sHPT (intact parathyroid hormone > 10 times above the upper limit of normal) on long term dialysis (>12 months) will be randomized either to TPTX or TPTX+AT and followed for 36 months. Outcome parameters are recurrence rates of sHPT, frequencies of reoperations due to refractory hypoparathyroidism or recurrent/persistent hyperparathyroidism, postoperative morbidity and mortality and quality of life. 50 patients per group will be randomized in order to obtain relevant frequencies of outcome parameters that will form the basis for a large scale confirmatory multicentred randomized controlled trial.</p> <p>Discussion</p> <p>sHPT is a disease with a high incidence in patients with chronic renal failure. Even a small difference in outcomes will be of clinical relevance. To assess sufficient data about the rate of recurrent sHPT after both methods, a multicentred, randomized controlled trial (MRCT) under standardized conditions is mandatory.</p> <p>Due to the existing uncertainties the calculated number of patients necessary in each treatment arm (n > 4000) makes it impossible to perform this study as a confirmatory trial. Therefore estimates of different outcomes are performed using a pilot MRCT comparing 50 versus 50 randomized patients in order to establish a hypothesis that can be tested thereafter.</p> <p>If TPTX proves to have a lower rate of recurrent sHPT, no relevant disadvantages and no higher morbidity than TPTX+AT, current surgical practice may be changed.</p> <p>Trial registration</p> <p>International Standard Randomized Controlled Trial Number Registration (ISRCTN86202793)</p

Modulation of Experimental Herpes Encephalitis-Associated Neurotoxicity through Sulforaphane Treatment

Reactive oxygen species (ROS) produced by brain-infiltrating macrophages and neutrophils, as well as resident microglia, are pivotal to pathogen clearance during viral brain infection. However, unchecked free radical generation is also responsible for damage to and cytotoxicity of critical host tissue bystander to primary infection. These unwanted effects of excessive ROS are combated by local cellular production of antioxidant enzymes, including heme oxygenase-1 (HO-1) and glutathione peroxidase 1 (Gpx1). In this study, we showed that experimental murine herpes encephalitis triggered robust ROS production, as well as an opposing upregulation of the antioxidants HO-1 and Gpx1. This antioxidant response was insufficient to prevent tissue damage, neurotoxicity, and mortality associated with viral brain infection. Previous studies corroborate our data supporting astrocytes as the major antioxidant producer in brain cell cultures exposed to HSV-1 stimulated microglia. We hypothesized that stimulating opposing antioxidative responses in astrocytes, as well as neurons, would mitigate the effects of ROS-mediated neurotoxicity both in vitro and during viral brain infection in vivo. Here, we demonstrate that the addition of sulforaphane, a potent stimulator of antioxidant responses, enhanced HO-1 and Gpx1 expression in astrocytes through the activation of nuclear factor-E2-related factor 2 (Nrf2). Additionally, sulforaphane treatment was found to be effective in reducing neurotoxicity associated with HSV-stimulated microglial ROS production. Finally, intraperitoneal injections of sulforaphane into mice during active HSV infection reduced neuroinflammation via a decrease in brain-infiltrating leukocytes, macrophage- and neutrophil-produced ROS, and MHCII-positive, activated microglia. These data support a key role for astrocyte-produced antioxidants in modulating oxidative stress and neuronal damage in response to viral infection

Yes, research can inform health policy; but can we bridge the 'Do-Knowing It's Been Done' gap?

Copyright @ 2011 Hanney and Gonzalez.Provisional Abstract: This editorial introduces a new Supplement in Health Research Policy and Systems and highlighs the importance of assessing the impact of health research by examining whether we can move from 'Know-Do' to 'Do-Knowing It's Been Done'This article is made available through the Brunel Open Access publishing fund