Concepts and characteristics of the 'COST Reference Microplasma Jet'

Biomedical applications of non-equilibrium atmospheric pressure plasmas have attracted intense interest in the past few years. Many plasma sources of diverse design have been proposed for these applications, but the relationship between source characteristics and application performance is not well-understood, and indeed many sources are poorly characterized. This circumstance is an impediment to progress in application development. A reference source with well-understood and highly reproducible characteristics may be an important tool in this context. Researchers around the world should be able to compare the characteristics of their own sources and also their results with this device. In this paper, we describe such a reference source, developed from the simple and robust micro-scaled atmospheric pressure plasma jet (μ-APPJ) concept. This development occurred under the auspices of COST Action MP1101 'Biomedical Applications of Atmospheric Pressure Plasmas'. Gas contamination and power measurement are shown to be major causes of irreproducible results in earlier source designs. These problems are resolved in the reference source by refinement of the mechanical and electrical design and by specifying an operating protocol. These measures are shown to be absolutely necessary for reproducible operation. They include the integration of current and voltage probes into the jet. The usual combination of matching unit and power supply is replaced by an integrated LC power coupling circuit and a 5 W single frequency generator. The design specification and operating protocol for the reference source are being made freely available

Geriatric pharmacotherapy : optimisation through integrated approach in the hospital setting

Since older patients are more vulnerable to adverse drug-related events, there is a need to ensure appropriate prescribing in these patients in order to prevent misuse, overuse and underuse of drugs. Different tools and strategies have been developed to reduce inappropriate prescribing; the available measures can be divided into medication assessment tools, and specific interventions to reduce inappropriate prescribing. Implicit criteria of inappropriate prescribing focus on appropriate dosing, search for drug-drug interactions, and increase adherence. Explicit criteria are consensus-based standards focusing on drugs and diseases and include lists of drugs to avoid in general or lists combining drugs with clinical data. These criteria take into consideration differences between patients, and stand for a medication review, by using a systematic approach. Different types of interventions exist in order to reduce inappropriate prescribing in older patients, such as: educational interventions, computerized decision support systems, pharmacist-based interventions, and geriatric assessment. The effects of these interventions have been studied, sometimes in a multifaceted approach combining different techniques, and all types seem to have positive effects on appropriateness of prescribing. Interdisciplinary teamwork within the integrative pharmaceutical care is important for improving of outcomes and safety of drug therapy. The pharmaceutical care process consists offour steps, which are cyclic for an individual patient. These steps are pharmaceutical anamnesis, medication review, design and follow-up of a pharmaceutical care plan. A standardized approach is necessary for the adequate detection and evaluation of drug-related problems. Furthermore, it is clear that drug therapy should be reviewed in-depth, by having full access to medical records, laboratory values and nursing notes. Although clinical pharmacists perform the pharmaceutical care process to manage the patient’s drug therapy in every day clinical practice, the physician takes the ultimate responsibility for the care of the patient in close collaboration with nurses

Development and internal validation of a machine learning prediction model for low back pain non-recovery in patients with an acute episode consulting a physiotherapist in primary care

BACKGROUND: While low back pain occurs in nearly everybody and is the leading cause of disability worldwide, we lack instruments to accurately predict persistence of acute low back pain. We aimed to develop and internally validate a machine learning model predicting non-recovery in acute low back pain and to compare this with current practice and 'traditional' prediction modeling. METHODS: Prognostic cohort-study in primary care physiotherapy. Patients (n = 247) with acute low back pain (≤ one month) consulting physiotherapists were included. Candidate predictors were assessed by questionnaire at baseline and (to capture early recovery) after one and two weeks. Primary outcome was non-recovery after three months, defined as at least mild pain (Numeric Rating Scale > 2/10). Machine learning models to predict non-recovery were developed and internally validated, and compared with two current practices in physiotherapy (STarT Back tool and physiotherapists' expectation) and 'traditional' logistic regression analysis. RESULTS: Forty-seven percent of the participants did not recover at three months. The best performing machine learning model showed acceptable predictive performance (area under the curve: 0.66). Although this was no better than a'traditional' logistic regression model, it outperformed current practice. CONCLUSIONS: We developed two prognostic models containing partially different predictors, with acceptable performance for predicting (non-)recovery in patients with acute LBP, which was better than current practice. Our prognostic models have the potential of integration in a clinical decision support system to facilitate data-driven, personalized treatment of acute low back pain, but needs external validation first

Structural basis for CRISPR RNA-guided DNA recognition by Cascade

The CRISPR (clustered regularly interspaced short palindromic repeats) immune system in prokaryotes uses small guide RNAs to neutralize invading viruses and plasmids. In Escherichia coli, immunity depends on a ribonucleoprotein complex called Cascade. Here we present the composition and low-resolution structure of Cascade and show how it recognizes double-stranded DNA (dsDNA) targets in a sequence-specific manner. Cascade is a 405-kDa complex comprising five functionally essential CRISPR-associated (Cas) proteins (CasA1B2C6D1E1) and a 61-nucleotide CRISPR RNA (crRNA) with 5′-hydroxyl and 2′,3′-cyclic phosphate termini. The crRNA guides Cascade to dsDNA target sequences by forming base pairs with the complementary DNA strand while displacing the noncomplementary strand to form an R-loop. Cascade recognizes target DNA without consuming ATP, which suggests that continuous invader DNA surveillance takes place without energy investment. The structure of Cascade shows an unusual seahorse shape that undergoes conformational changes when it binds target DNA.

Is manipulative therapy more effective than sham manipulation in adults?: A systematic review and meta-analysis

Background: Manipulative therapy is widely used in the treatment of spinal disorders. Manipulative techniques are under debate because of the possibility of adverse events. To date, the efficacy of manipulations compared to sham manipulations is unclear. The purpose of the study is: to assess the efficacy of manipulative therapy compared to sham in adults with a variety of complaints.Study design: Systematic review and meta-analysis.Methods: Bibliographic databases (PubMed, EMBASE, CINAHL, PEDro, Central) along with a hand search of selected bibliographies were searched from inception up to April 2012.Two reviewers independently selected randomized clinical trials (RCTs) that evaluated manipulative therapy compared to sham manipulative therapy in adults, assessed risk of bias and extracted data concerning participants, intervention, kind of sham, outcome measures, duration of follow-up, profession, data on efficacy and adverse events. Pooled (standardized) mean differences or risk differences were calculated were possible using a random effects model. The primary outcomes were pain, disability, and perceived recovery. The overall quality of the body of evidence was evaluated using GRADE.Results: In total 965 references were screened for eligibility and 19 RCTs (n = 1080) met the selection criteria. Eight studies were considered of low risk of bias. There is moderate level of evidence that manipulative therapy has a significant effect in adults on pain relief immediately after treatment (standardized mean difference [SMD] - 0.68, 95% confidence interval (-1.06 to -0.31). There is low level of evidence that manipulative therapy has a significant effect in adults on pain relief (SMD - 0.37, -0.69 to -0.04) at short- term follow-up. In patients with musculoskeletal disorders, we found moderate level of evidence for pain relief (SMD - 0.73, -1.21 to -0.25) immediate after treatment and low level of evidence for pain relief (SMD - 0.52, -0.87 to -0.17) at short term-follow-up. We found very low level of evidence that manipulative therapy has no statistically significant effect on disability and perceived (asthma) recovery. Sensitivity analyses did not change the main findings. No serious adverse events were reported in the manipulative therapy or sham group.Conclusions: Manipulative therapy has a clinical relevant effect on pain, but not on disability or perceived (asthma) recovery. Clinicians can refer patients for manipulative therapy to reduce pain