Scalable integration of nano-, and microfluidics with hybrid two-photon lithography

Abstract: Nanofluidic devices have great potential for applications in areas ranging from renewable energy to human health. A crucial requirement for the successful operation of nanofluidic devices is the ability to interface them in a scalable manner with the outside world. Here, we demonstrate a hybrid two photon nanolithography approach interfaced with conventional mask whole-wafer UV-photolithography to generate master wafers for the fabrication of integrated micro and nanofluidic devices. Using this approach we demonstrate the fabrication of molds from SU-8 photoresist with nanofluidic features down to 230 nm lateral width and channel heights from micron to sub-100 nm. Scanning electron microscopy and atomic force microscopy were used to characterize the printing capabilities of the system and show the integration of nanofluidic channels into an existing microfluidic chip design. The functionality of the devices was demonstrated through super-resolution microscopy, allowing the observation of features below the diffraction limit of light produced using our approach. Single molecule localization of diffusing dye molecules verified the successful imprint of nanochannels and the spatial confinement of molecules to 200 nm across the nanochannel molded from the master wafer. This approach integrates readily with current microfluidic fabrication methods and allows the combination of microfluidic devices with locally two-photon-written nano-sized functionalities, enabling rapid nanofluidic device fabrication and enhancement of existing microfluidic device architectures with nanofluidic features

Digital Sensing and Molecular Computation by an Enzyme-Free DNA Circuit.

DNA circuits form the basis of programmable molecular systems capable of signal transduction and algorithmic computation. Some classes of molecular programs, such as catalyzed hairpin assembly, enable isothermal, enzyme-free signal amplification. However, current detection limits in DNA amplification circuits are modest, as sensitivity is inhibited by signal leakage resulting from noncatalyzed background reactions inherent to the noncovalent system. Here, we overcome this challenge by optimizing a catalyzed hairpin assembly for single-molecule sensing in a digital droplet assay. Furthermore, we demonstrate digital reporting of DNA computation at the single-molecule level by employing ddCHA as a signal transducer for simple DNA logic gates. By facilitating signal transduction of molecular computation at pM concentration, our approach can improve processing density by a factor of 104 relative to conventional DNA logic gates. More broadly, we believe that digital molecular computing will broaden the scope and efficacy of isothermal amplification circuits within DNA computing, biosensing, and signal amplification in general

Correlation effects in ionic crystals: I. The cohesive energy of MgO

High-level quantum-chemical calculations, using the coupled-cluster approach and extended one-particle basis sets, have been performed for (Mg2+)n (O2-)m clusters embedded in a Madelung potential. The results of these calculations are used for setting up an incremental expansion for the correlation energy of bulk MgO. This way, 96% of the experimental cohesive energy of the MgO crystal is recovered. It is shown that only 60% of the correlation contribution to the cohesive energy is of intra-ionic origin, the remaining part being caused by van der Waals-like inter-ionic excitations.Comment: LaTeX, 20 pages, no figure

<i>In vitro</i> method to quantify dermal absorption of pesticide residues

All pesticides must go through a rigorous risk assessment process in order to show that they are safe for use. With respect to dermal risk assessment for re-entry workers, the absorption value applied to predict systemic dose from this external exposure is obtained by testing liquid forms of the pesticide <i>in vivo</i> and/or <i>in vitro</i>. However, in a real exposure scenario, the worker would be exposed to a dried residue, for which little or no absorption data are available. This study has developed a novel methodology for assessing the dermal absorption of pesticides from dried residues and aims ultimately to use this methodology to obtain more realistic absorption values for the risk assessment

Quantemol Electron Collisions (QEC): An Enhanced Expert System for Performing Electron Molecule Collision Calculations Using the R-Matrix Method

Collisions of low energy electrons with molecules are important for understanding many aspects of the environment and technologies. Understanding the processes that occur in these types of collisions can give insights into plasma etching processes, edge effects in fusion plasmas, radiation damage to biological tissues and more. A radical update of the previous expert system for computing observables relevant to these processes, Quantemol-N, is presented. The new Quantemol Electron Collision (QEC) expert system simplifyies the user experience, improving reliability and implements new features. The QEC graphical user interface (GUI) interfaces the Molpro quantum chemistry package for molecular target setups, and the sophisticated UKRmol+ codes to generate accurate and reliable cross-sections. These include elastic cross-sections, super elastic cross-sections between excited states, electron impact dissociation, scattering reaction rates, dissociative electron attachment, differential cross-sections, momentum transfer cross-sections, ionization cross sections, and high energy electron scattering cross-sections. With this new interface we will be implementing dissociative recombination estimations, vibrational excitations for neutrals and ions, and effective core potentials in the near future

Update on the collaborative interventions for circulation and depression (COINCIDE) trial: changes to planned methodology of a cluster randomized controlled trial of collaborative care for depression in people with diabetes and/or coronary heart disease.

Published onlineJournal ArticleRandomized Controlled TrialResearch Support, Non-U.S. Gov'tBACKGROUND: The COINCIDE trial aims to evaluate the effectiveness and cost-effectiveness of a collaborative care intervention for depression in people with diabetes and/or coronary heart disease attending English general practices. DESIGN: This update details changes to the cluster and patient recruitment strategy for the COINCIDE study. The original protocol was published in Trials (http://www.trialsjournal.com/content/pdf/1745-6215-13-139.pdf). Modifications were made to the recruitment targets in response to lower-than-expected patient recruitment at the first ten general practices recruited into the study. In order to boost patient numbers and retain statistical power, the number of general practices recruited was increased from 30 to 36. Follow-up period was shortened from 6 months to 4 months to ensure that patients recruited to the trial could be followed up by the end of the study. RESULTS: Patient recruitment began on the 01/05/2012 and is planned to be completed by the 30/04/2013. Recruitment for general practices was completed on 31/10/2012, by which time the target of 36 practices had been recruited. The main trial results will be published in a peer-reviewed journal. CONCLUSION: The data from the trial will provide evidence on the effectiveness and cost-effectiveness of collaborative care for depression in people with diabetes and/or coronary heart disease. TRIAL REGISTRATION: TRIAL REGISTRATION NUMBER: ISRCTN80309252.NIHR Collaboration for Leadership in Applied Health Research and Care for Greater Mancheste

Collaborative Interventions for Circulation and Depression (COINCIDE): study protocol for a cluster randomized controlled trial of collaborative care for depression in people with diabetes and/or coronary heart disease.

Published onlineJournal ArticleRandomized Controlled TrialResearch Support, Non-U.S. Gov'tBACKGROUND: Depression is up to two to three times as common in people with long-term conditions. It negatively affects medical management of disease and self-care behaviors, and leads to poorer quality of life and high costs in primary care. Screening and treatment of depression is increasingly prioritized, but despite initiatives to improve access and quality of care, depression remains under-detected and under-treated, especially in people with long-term conditions. Collaborative care is known to positively affect the process and outcome of care for people with depression and long-term conditions, but its effectiveness outside the USA is still relatively unknown. Furthermore, collaborative care has yet to be tested in settings that resemble more naturalistic settings that include patient choice and the usual care providers. The aim of this study was to test the effectiveness of a collaborative-care intervention, for people with depression and diabetes/coronary heart disease in National Health Service (NHS) primary care, in which low-intensity psychological treatment services are delivered by the usual care provider - Increasing Access to Psychological Therapies (IAPT) services. The study also aimed to evaluate the cost-effectiveness of the intervention over 6 months, and to assess qualitatively the extent to which collaborative care was implemented in the intervention general practices. METHODS: This is a cluster randomized controlled trial of 30 general practices allocated to either collaborative care or usual care. Fifteen patients per practice will be recruited after a screening exercise to detect patients with recognized depression (≥10 on the nine-symptom Patient Health Questionnaire; PHQ-9). Patients in the collaborative-care arm with recognized depression will be offered a choice of evidence-based low-intensity psychological treatments based on cognitive and behavioral approaches. Patients will be case managed by psychological well-being practitioners employed by IAPT in partnership with a practice nurse and/or general practitioner. The primary outcome will be change in depressive symptoms at 6 months on the 90-item Symptoms Checklist (SCL-90). Secondary outcomes include change in health status, self-care behaviors, and self-efficacy. A qualitative process evaluation will be undertaken with patients and health practitioners to gauge the extent to which the collaborative-care model is implemented, and to explore sustainability beyond the clinical trial. DISCUSSION: COINCIDE will assess whether collaborative care can improve patient-centered outcomes, and evaluate access to and quality of care of co-morbid depression of varying intensity in people with diabetes/coronary heart disease. Additionally, by working with usual care providers such as IAPT, and by identifying and evaluating interventions that are effective and appropriate for routine use in the NHS, the COINCIDE trial offers opportunities to address translational gaps between research and implementation. TRIAL REGISTRATION NUMBER: ISRCTN80309252 TRIAL STATUS: Open.NIHR Collaboration for Leadership in Applied Health Research and Care for Greater Mancheste

Imaging local genetic influences on cortical folding

Recent progress in deciphering mechanisms of human brain cortical folding leave unexplained whether spatially patterned genetic influences contribute to this folding. High-resolution in vivo brain MRI can be used to estimate genetic correlations (covariability due to shared genetic factors) in interregional cortical thickness, and biomechanical studies predict an influence of cortical thickness on folding patterns. However, progress has been hampered because shared genetic influences related to folding patterns likely operate at a scale that is much more local (cm) than that addressed in prior imaging studies. Here, we develop methodological approaches to examine local genetic influences on cortical thickness and apply these methods to two large, independent samples. We find that such influences are markedly heterogeneous in strength, and in some cortical areas are notably stronger in specific orientations relative to gyri or sulci. The overall, phenotypic local correlation has a significant basis in shared genetic factors and is highly symmetric between left and right cortical hemispheres. Furthermore, the degree of local cortical folding relates systematically with the strength of local correlations, which tends to be higher in gyral crests and lower in sulcal fundi. The relationship between folding and local correlations is stronger in primary sensorimotor areas and weaker in association areas such as prefrontal cortex, consistent with reduced genetic constraints on the structural topology of association cortex. Collectively, our results suggest that patterned genetic influences on cortical thickness, measurable at the scale of in vivo MRI, may be a causal factor in the development of cortical folding

Human resources for health at the district level in Indonesia: the smoke and mirrors of decentralization

<p>Abstract</p> <p>Background</p> <p>In 2001 Indonesia embarked on a rapid decentralization of government finances and functions to district governments. One of the results is that government has less information about its most valuable resource, the people who provide the services. The objective of the work reported here is to determine the stock of human resources for health in 15 districts, their service status and primary place of work. It also assesses the effect of decentralization on management of human resources and the implications for the future.</p> <p>Methods</p> <p>We enumerated all health care providers (doctors, nurses and midwives), including information on their employment status and primary place of work, in each of 15 districts in Java. Data were collected by three teams, one for each province.</p> <p>Results</p> <p>Provider density (number of doctors, nurses and midwives/1000 population) was low by international standards – 11 out of 15 districts had provider densities less than 1.0. Approximately half of all three professional groups were permanent public servants. Contractual employment was also important for both nurses and midwives. The private sector as the primary source of employment is most important for doctors (37% overall) and increasingly so for midwives (10%). For those employed in the public sector, two-thirds of doctors and nurses work in health centres, while most midwives are located at village-level health facilities.</p> <p>Conclusion</p> <p>In the health system established after Independence, the facilities established were staffed through a period of obligatory service for all new graduates in medicine, nursing and midwifery. The last elements of that staffing system ended in 2007 and the government has not been able to replace it. The private sector is expanding and, despite the fact that it will be of increasing importance in the coming decades, government information about providers in private practice is decreasing. Despite the promise of decentralization to increase sectoral "decision space" at the district level, the central government now has control over essentially all public sector health staff at the district level, marking a return to the situation of 20 years ago. At the same time, Indonesia has changed dramatically. The challenge now is to envision a new health system that takes account of these changes. Envisioning the new system is a crucial first step for development of a human resources policy which, in turn, will require more information about health care providers, public and private, and increased capacity for human resource planning.</p