Single-molecule force spectroscopy of membrane proteins from membranes freely spanning across nanoscopic pores.

Single-molecule force spectroscopy (SMFS) provides detailed insight into the mechanical (un)folding pathways and structural stability of membrane proteins. So far, SMFS could only be applied to membrane proteins embedded in native or synthetic membranes adsorbed to solid supports. This adsorption causes experimental limitations and raises the question to what extent the support influences the results obtained by SMFS. Therefore, we introduce here SMFS from native purple membrane freely spanning across nanopores. We show that correct analysis of the SMFS data requires extending the worm-like chain model, which describes the mechanical stretching of a polypeptide, by the cubic extension model, which describes the bending of a purple membrane exposed to mechanical stress. This new experimental and theoretical approach allows to characterize the stepwise (un)folding of the membrane protein bacteriorhodopsin and to assign the stability of single and grouped secondary structures. The (un)folding and stability of bacteriorhodopsin shows no significant difference between freely spanning and directly supported purple membranes. Importantly, the novel experimental SMFS setup opens an avenue to characterize any protein from freely spanning cellular or synthetic membranes.

Sentinel lymph node biopsy in thick malignant melanoma: A 16-year single unit experience.

BACKGROUND The role of sentinel lymph node biopsy (SLNB) and its benefits in patients with thick melanoma is still controversial. OBJECTIVES We evaluated the clinical effect of SLNB in patients with thick melanoma. METHODS We performed a retrospective cohort review (1996-2012) of thick melanomas. Collected data included the patient and tumour characteristics. Locoregional recurrence, distant metastases, disease free and overall survival were compared between the patients with positive and negative SLNB. RESULTS 126 thick melanomas with a mean age of 64.09 years were included in the study. Positive SLNB were found in 47 (37.3%) patients. Significantly more locoregional recurrence (P = 0.002) and distant metastases (P = 0.030) were detected in the patients with positive SLNB. Furthermore, the patients with negative SLNB showed significantly better disease free survival (P = 0.021). CONCLUSIONS Positive SLNB might be prognostic factor in thick melanoma and aggravates the outcome of thick melanomas.

Expectations and effects of a single yoga session on pain perception

BACKGROUND Several studies show yoga may benefit chronic pain management. We investigated the effect of a single yoga session on the perception of pain, measured by a standardized pain provocation test in healthy yoga participants while also comparing pain perception to participants' own expectations. MATERIALS AND METHODS Ninety yoga participants were recruited at hatha yoga schools in Switzerland. Pain perception was measured with a standardized algometric pain provocation test; i.e., a calibrated peg was applied for 10 seconds after which the participant rated pain intensity on a 0-10 numerical rating scale. The test was applied to the middle finger, ear lobe, and second toe before and after a 60-minute yoga session. RESULTS Sixty out of 90 (66.7%) yoga participants expected a reduced pain perception after the yoga session. However, 36 (40%) participants actually experienced less pain after compared to before the yoga session. But overall, pain perception statistically did not significantly change from before to after the yoga session at any of the three body locations assessed. The expectations and also the previous yoga experience did not significantly influence the participants' pain perception. CONCLUSIONS Regardless of the high positive expectations on the influence of yoga on pain, a single yoga session does not significantly influence pain perception induced by a pain provocation test. Hypoalgesic effects of yoga should be explained otherwise.

Single crowns versus conventional fillings for the restoration of root-filled teeth.

BACKGROUND Endodontic treatment involves removal of the dental pulp and its replacement by a root canal filling. Restoration of root filled teeth can be challenging due to structural differences between vital and non-vital root-filled teeth. Direct restoration involves placement of a restorative material e.g. amalgam or composite, directly into the tooth. Indirect restorations consist of cast metal or ceramic (porcelain) crowns. The choice of restoration depends on the amount of remaining tooth, and may influence durability and cost. The decision to use a post and core in addition to the crown is clinician driven. The comparative clinical performance of crowns or conventional fillings used to restore root-filled teeth is unknown. This review updates the original, which was published in 2012. OBJECTIVES To assess the effects of restoration of endodontically treated teeth (with or without post and core) by crowns versus conventional filling materials. SEARCH METHODS We searched the following databases: the Cochrane Oral Health Group's Trials Register, CENTRAL, MEDLINE via OVID, EMBASE via OVID, CINAHL via EBSCO, LILACS via BIREME. We also searched the reference lists of articles and ongoing trials registries.There were no restrictions regarding language or date of publication. The search is up-to-date as of 26 March 2015. SELECTION CRITERIA Randomised controlled trials (RCTs) or quasi-randomised controlled trials in participants with permanent teeth that have undergone endodontic treatment. Single full coverage crowns compared with any type of filling materials for direct restoration or indirect partial restorations (e.g. inlays and onlays). Comparisons considered the type of post and core used (cast or prefabricated post), if any. DATA COLLECTION AND ANALYSIS Two review authors independently extracted data from the included trial and assessed its risk of bias. We carried out data analysis using the 'treatment as allocated' patient population, expressing estimates of intervention effect for dichotomous data as risk ratios, with 95% confidence intervals (CI). MAIN RESULTS We included one trial, which was judged to be at high risk of performance, detection and attrition bias. The 117 participants with a root-filled, premolar tooth restored with a carbon fibre post, were randomised to either a full coverage metal-ceramic crown or direct adhesive composite restoration. None experienced a catastrophic failure (i.e. when the restoration cannot be repaired), although only 104 teeth were included in the final, three-year assessment. There was no clear difference between the crown and composite group and the composite only group for non-catastrophic failures of the restoration (1/54 versus 3/53; RR 0.33; 95% CI 0.04 to 3.05) or failures of the post (2/54 versus 1/53; RR 1.96; 95% CI 0.18 to 21.01) at three years. The quality of the evidence for these outcomes is very low. There was no evidence available for any of our secondary outcomes: patient satisfaction and quality of life, incidence or recurrence of caries, periodontal health status, and costs. AUTHORS' CONCLUSIONS There is insufficient evidence to assess the effects of crowns compared to conventional fillings for the restoration of root-filled teeth. Until more evidence becomes available, clinicians should continue to base decisions about how to restore root-filled teeth on their own clinical experience, whilst taking into consideration the individual circumstances and preferences of their patients.

Single-center experience in the management of spontaneous isolated abdominal aortic dissection

OBJECTIVE This study aims to report the management of patients with spontaneous isolated dissection of the abdominal aorta (sIAAD). METHODS A cohort of 18 consecutive patients (12 male, mean age 58 years) with sIAAD was treated between 1990 and 2009. Dissection was asymptomatic in ten and symptomatic in eight patients. Retrospective data analysis from patient charts was performed. Follow-up included clinical examination, ultrasound, and/or CT-angiography. Mean follow-up was 54 months (range 1-211). RESULTS In total, eight out of 18 received invasive treatment. All asymptomatic patients initially underwent conservative treatment and surveillance. Spontaneous false lumen thrombosis occurred in four (40 %), and three patients showed relevant aneurysmatic progression and underwent elective invasive treatment (open n = 2, endovascular n = 1), representing a crossover rate of 30 %. Late mortality was 20 % (n = 2) in this group. In symptomatic patients, five underwent urgent treatment due to persistent abdominal or back pain (n = 4) or contained rupture (n = 1); one was treated for claudication. The remaining two patients presented with irreversible spinal cord ischemia and were treated conservatively. Three patients were treated by open surgery and three by endovascular interventions (two stentgrafts, one Palmaz XXL stent). Early and late morbidity and mortality was 0 % in this group. There were no reinterventions CONCLUSION: The majority of patients with sIADD require invasive treatment, with EVAR being the preferable treatment option today. In asymptomatic IADD, primary surveillance is justifiable, but close surveillance due to expansion is necessary.

Rituximab Maintenance for a Maximum of 5 Years After Single-Agent Rituximab Induction in Follicular Lymphoma: Results of the Randomized Controlled Phase III Trial SAKK 35/03.

PURPOSE Rituximab maintenance therapy has been shown to improve progression-free survival in patients with follicular lymphoma; however, the optimal duration of maintenance treatment remains unknown. PATIENTS AND METHODS Two hundred seventy patients with untreated, relapsed, stable, or chemotherapy-resistant follicular lymphoma were treated with four doses of rituximab monotherapy in weekly intervals (375 mg/m(2)). Patients achieving at least a partial response were randomly assigned to receive maintenance therapy with one infusion of rituximab every 2 months, either on a short-term schedule (four administrations) or a long-term schedule (maximum of 5 years or until disease progression or unacceptable toxicity). The primary end point was event-free survival (EFS). Progression-free survival, overall survival (OS), and toxicity were secondary end points. Comparisons between the two arms were performed using the log-rank test for survival end points. RESULTS One hundred sixty-five patients were randomly assigned to the short-term (n = 82) or long-term (n = 83) maintenance arms. Because of the low event rate, the final analysis was performed after 95 events had occurred, which was before the targeted event number of 99 had been reached. At a median follow-up period of 6.4 years, the median EFS was 3.4 years (95% CI, 2.1 to 5.3) in the short-term arm and 5.3 years (95% CI, 3.5 to not available) in the long-term arm (P = .14). Patients in the long-term arm experienced more adverse effects than did those in the short-term arm, with 76% v 50% of patients with at least one adverse event (P < .001), five versus one patient with grade 3 and 4 infections, and three versus zero patients discontinuing treatment because of unacceptable toxicity, respectively. There was no difference in OS between the two groups. CONCLUSION Long-term rituximab maintenance therapy does not improve EFS, which was the primary end point of this trial, or OS, and was associated with increased toxicity.

Radiation dose in pneumatic reduction of ileo-colic intussusceptions--results from a single-institution study

BACKGROUND Air enema under fluoroscopy is a well-accepted procedure for the treatment of childhood intussusception. However, the reported radiation doses of pneumatic reduction with conventional fluoroscopy units have been high in decades past. OBJECTIVE To compare current radiation doses at our institution to past doses reported by others for fluoroscopic-guided pneumatic reduction of ileo-colic intussusception in children. MATERIALS AND METHODS Since 2007 radiologists and residents in our department who perform reduction of intussusceptions have received a radiation risk training. We retrospectively analyzed the data of 45 children (5 months-8 years) who underwent a total of 48 pneumatic reductions of ileo-colic intussusception between 2008 and 2012. We analyzed data for screening time and dose area product (DAP) and compared these data to those reported up to and including the year 2000. RESULTS Our mean screening time measured by the DAP-meter was 53.8 s (range 1-320 s, median 33.0 s). The mean DAP was 11.4 cGy ∙ cm(2) (range 1-145 cGy ∙ cm(2), median 5.45 cGy ∙ cm(2)). There was one bowel perforation, in a 1-year-old boy requiring surgical revision. Only three studies in the literature presented radiation exposure results on children who received pneumatic or hydrostatic reduction of intussusception under fluoroscopy. Screening times and dose area products in those studies, which were published in the 1990 s and in the year 2000, were substantially higher than those in our sample. CONCLUSION Low-frequency pulsed fluoroscopy and other dose-saving keys as well as the radiation risk training might have helped to improve the quality of the procedure in terms of radiation exposure.

SOP: Parallel surrogate global optimization with Pareto center selection for computationally expensive single objective problems

This paper presents a parallel surrogate-based global optimization method for computationally expensive objective functions that is more effective for larger numbers of processors. To reach this goal, we integrated concepts from multi-objective optimization and tabu search into, single objective, surrogate optimization. Our proposed derivative-free algorithm, called SOP, uses non-dominated sorting of points for which the expensive function has been previously evaluated. The two objectives are the expensive function value of the point and the minimum distance of the point to previously evaluated points. Based on the results of non-dominated sorting, P points from the sorted fronts are selected as centers from which many candidate points are generated by random perturbations. Based on surrogate approximation, the best candidate point is subsequently selected for expensive evaluation for each of the P centers, with simultaneous computation on P processors. Centers that previously did not generate good solutions are tabu with a given tenure. We show almost sure convergence of this algorithm under some conditions. The performance of SOP is compared with two RBF based methods. The test results show that SOP is an efficient method that can reduce time required to find a good near optimal solution. In a number of cases the efficiency of SOP is so good that SOP with 8 processors found an accurate answer in less wall-clock time than the other algorithms did with 32 processors.

Detecting single-target changes in multiple object tracking: The case of peripheral vision

In the current study it is investigated whether peripheral vision can be used to monitor multi-ple moving objects and to detect single-target changes. For this purpose, in Experiment 1, a modified MOT setup with a large projection and a constant-position centroid phase had to be checked first. Classical findings regarding the use of a virtual centroid to track multiple ob-jects and the dependency of tracking accuracy on target speed could be successfully replicat-ed. Thereafter, the main experimental variations regarding the manipulation of to-be-detected target changes could be introduced in Experiment 2. In addition to a button press used for the detection task, gaze behavior was assessed using an integrated eye-tracking system. The anal-ysis of saccadic reaction times in relation to the motor response shows that peripheral vision is naturally used to detect motion and form changes in MOT because the saccade to the target occurred after target-change offset. Furthermore, for changes of comparable task difficulties, motion changes are detected better by peripheral vision than form changes. Findings indicate that capabilities of the visual system (e.g., visual acuity) affect change detection rates and that covert-attention processes may be affected by vision-related aspects like spatial uncertainty. Moreover, it is argued that a centroid-MOT strategy might reduce the amount of saccade-related costs and that eye-tracking seems to be generally valuable to test predictions derived from theories on MOT. Finally, implications for testing covert attention in applied settings are proposed.

Motion-insensitive determination of B1+ amplitudes based on the bloch-siegert shift in single voxels of moving organs including the human heart.

PURPOSE To reliably determine the amplitude of the transmit radiofrequency ( B1+) field in moving organs like the liver and heart, where most current techniques are usually not feasible. METHODS B1+ field measurement based on the Bloch-Siegert shift induced by a pair of Fermi pulses in a double-triggered modified Point RESolved Spectroscopy (PRESS) sequence with motion-compensated crusher gradients has been developed. Performance of the sequence was tested in moving phantoms and in muscle, liver, and heart of six healthy volunteers each, using different arrangements of transmit/receive coils. RESULTS B1+ determination in a moving phantom was almost independent of type and amplitude of the motion and agreed well with theory. In vivo, repeated measurements led to very small coefficients of variance (CV) if the amplitude of the Fermi pulse was chosen above an appropriate level (CV in muscle 0.6%, liver 1.6%, heart 2.3% with moderate amplitude of the Fermi pulses and 1.2% with stronger Fermi pulses). CONCLUSION The proposed sequence shows a very robust determination of B1+ in a single voxel even under challenging conditions (transmission with a surface coil or measurements in the heart without breath-hold). Magn Reson Med, 2015. © 2015 Wiley Periodicals, Inc.

Prevention of ischemic complications during aneurysm surgery

Ischemic complications during aneurysm surgery are a frequent cause of postoperative infarctions and new neurological deficits. In this article, we discuss imaging and neurophysiological tools that may help the surgeon to detect intraoperative ischemia. The strength of intraoperative digital subtraction angiography (DSA) is the full view of the arterial and venous vessel. DSA is the gold standard in complex and giant aneurysms, but due to certain disadvantages, it cannot be considered standard of care. Microvascular Doppler sonography is probably the fastest diagnostic tool and can quickly aid diagnosis of large vessel occlusions. Intraoperative indocyanine green videoangiography is the best tool to assess flow in perforating and larger arteries, as well as occlusion of the aneurysm sac. Intraoperative neurophysiological monitoring with somatosensory and motor evoked potentials indirectly measures blood flow by recording neuronal function. It covers all causes of intraoperative ischemia, provided that ischemia occurs in the brain areas under surveillance. However, every method has advantages and disadvantages. No single method is superior to the others in every aspect. Therefore, it is very important for the neurosurgeon to know the strengths and weaknesses of each tool in order to have them available, to know how to use them for each individual situation, and to be ready to apply them within the time window for reversible cerebral ischemia.

An improved single-plaquette gauge action

We describe and test a nonperturbatively improved single-plaquette lattice action for 4-d SU(2) and SU(3) pure gauge theory, which suppresses large fluctuations of the plaquette, without requiring the naive continuum limit for smooth fields. We tune the action parameters based on torelon masses in moderate cubic physical volumes, and investigate the size of cut-off effects in other physical quantities, including torelon masses in asymmetric spatial volumes, the static quark potential, and gradient flow observables. In 2-d O(N) models similarly constructed nearest-neighbor actions have led to a drastic reduction of cut-off effects, down to the permille level, in a wide variety of physical quantities. In the gauge theories, we find significant reduction of lattice artifacts, and for some observables, the coarsest lattice result is very close to the continuum value. We estimate an improvement factor of 40 compared to using the Wilson gauge action to achieve the same statistical accuracy and suppression of cut-off effects.

A Single-blinded, Randomized Clinical Trial of How to Implement an Evidence-based Treatment for Generalized Anxiety Disorder [IMPLEMENT] — Effects of Three Different Strategies of Implementation

BACKGROUND: Despite long-standing calls to disseminate evidence-based treatments for generalized anxiety (GAD), modest progress has been made in the study of how such treatments should be implemented. The primary objective of this study was to test three competing strategies on how to implement a cognitive behavioral treatment (CBT) for out-patients with GAD (i.e., comparison of one compensation vs. two capitalization models). METHODS: For our three-arm, single-blinded, randomized controlled trial (implementation of CBT for GAD [IMPLEMENT]), we recruited adults with GAD using advertisements in high-circulation newspapers to participate in a 14-session cognitive behavioral treatment (Mastery of your Anxiety and Worry, MAW-packet). We randomly assigned eligible patients using a full randomization procedure (1:1:1) to three different conditions of implementation: adherence priming (compensation model), which had a systematized focus on patients' individual GAD symptoms and how to compensate for these symptoms within the MAW-packet, and resource priming and supportive resource priming (capitalization model), which had systematized focuses on patients' strengths and abilities and how these strengths can be capitalized within the same packet. In the intention-to-treat population an outcome composite of primary and secondary symptoms-related self-report questionnaires was analyzed based on a hierarchical linear growth model from intake to 6-month follow-up assessment. This trial is registered at ClinicalTrials.gov (identifier: NCT02039193) and is closed to new participants. FINDINGS: From June 2012 to Nov. 2014, from 411 participants that were screened, 57 eligible participants were recruited and randomly assigned to three conditions. Forty-nine patients (86%) provided outcome data at post-assessment (14% dropout rate). All three conditions showed a highly significant reduction of symptoms over time. However, compared with the adherence priming condition, both resource priming conditions indicated faster symptom reduction. The observer ratings of a sub-sample of recorded videos (n = 100) showed that the therapists in the resource priming conditions conducted more strength-oriented interventions in comparison with the adherence priming condition. No patients died or attempted suicide. INTERPRETATION: To our knowledge, this is the first trial that focuses on capitalization and compensation models during the implementation of one prescriptive treatment packet for GAD. We have shown that GAD related symptoms were significantly faster reduced by the resource priming conditions, although the limitations of our study included a well-educated population. If replicated, our results suggest that therapists who implement a mental health treatment for GAD might profit from a systematized focus on capitalization models. FUNDING: Swiss Science National Foundation (SNSF-Nr. PZ00P1_136937/1) awarded to CF. KEYWORDS: Cognitive behavioral therapy; Evidence-based treatment; Implementation strategies; Randomized controlled trial

Feasibility study of a single-blind randomised controlled trial of an occupational therapy intervention.

BACKGROUND Several factors facilitate or hinder efficacy research in occupational therapy. Strategies are needed, therefore, to support the successful implementation of trials. AIM To assess the feasibility of conducting a randomised controlled trial (RCT). The main feasibility objectives of this study were to assess the process, resources, management, and scientific basis of a trial RCT. MATERIAL AND METHODS A total of 10 occupational therapists, between the ages of 30 and 55 (M 43.4; SD 8.3) with seven to 26 years' (M 14.3; SD 6.1) experience, participated in this study. Qualitative data collected included minutes of meetings, reports, and field notes. The data were analysed based on the principles of content analysis, using feasibility objectives as the main categories. RESULTS Data analysis revealed strengths in relation to retention and inclusion criteria of participants, the study protocol, study organisation, and the competence of researchers. Weaknesses were found related to recruitment, randomisation, data collection, time for training and communication, commitment, and design. CONCLUSION The findings indicated that there are several factors which had a considerable impact on the implementation of an RCT in practice. However, it was useful to assess methods and procedures of the trial RCT as a basis to refine research plans.