Variations on Negative Stain Electron Microscopy Methods: Tools for Tackling Challenging Systems.

Negative stain electron microscopy (EM) allows relatively simple and quick observation of macromolecules and macromolecular complexes through the use of contrast enhancing stain reagent. Although limited in resolution to a maximum of ~18 - 20 Å, negative stain EM is useful for a variety of biological problems and also provides a rapid means of assessing samples for cryo-electron microscopy (cryo-EM). The negative stain workflow is straightforward method; the sample is adsorbed onto a substrate, then a stain is applied, blotted, and dried to produce a thin layer of electron dense stain in which the particles are embedded. Individual samples can, however, behave in markedly different ways under varying staining conditions. This has led to the development of a large variety of substrate preparation techniques, negative staining reagents, and grid washing and blotting techniques. Determining the most appropriate technique for each individual sample must be done on a case-by-case basis and a microscopist must have access to a variety of different techniques to achieve the highest-quality negative stain results. Detailed protocols for two different substrate preparation methods and three different blotting techniques are provided, and an example of a sample that shows markedly different results depending on the method used is shown. In addition, the preparation of some common negative staining reagents, and two novel Lanthanide-based stains, is described with discussion regarding the use of each

Incidence and viral aetiologies of acute respiratory illnesses (ARIs) in the United States: a population-based study.

We conducted prospective, community-wide surveillance for acute respiratory illnesses (ARIs) in Rochester, NY and Marshfield, WI during a 3-month period in winter 2011. We estimated the incidence of ARIs in each community, tested for viruses, and determined the proportion of ARIs associated with healthcare visits. We used a rolling cross-sectional design to sample participants, conducted telephone interviews to assess ARI symptoms (defined as a current illness with feverishness or cough within the past 7 days), collected nasal/throat swabs to identify viruses, and extracted healthcare utilization from outpatient/inpatient records. Of 6492 individuals, 321 reported an ARI within 7 days (4·9% total, 5·7% in Rochester, 4·4% in Marshfield); swabs were collected from 208 subjects. The cumulative ARI incidence for the entire 3-month period was 52% in Rochester [95% confidence interval (CI) 42-63] and 35% in Marshfield (95% CI 28-42). A specific virus was identified in 39% of specimens: human coronavirus (13% of samples), rhinovirus (12%), RSV (7%), influenza virus (4%), human metapneumovirus (4%), and adenovirus (1%). Only 39/200 (20%) had a healthcare visit (2/9 individuals with influenza). ARI incidence was ~5% per week during winter

Magnetars and pulsars: a missing link

There is growing evidence that soft gamma-ray repeaters (SGRs) and anomalous X-ray pulsars (AXPs) are isolated neutron stars with superstrong magnetic fields, i.e., magnetars, marking them a distinguished species from the conventional species of spindown-powered isolated neutron stars, i.e., radio pulsars. The current arguments in favor of the magnetar interpretation of SGR/AXP phenomenology will be outlined, and the two energy sources in magnetars, i.e. a magnetic dissipation energy and a spindown energy, will be reviewed. I will then discuss a missing link between magnetars and pulsars, i.e., lack of the observational evidence of the spindown-powered behaviors in known magnetars. Some recent theoretical efforts in studying such behaviors will be reviewed along with some predictions testable in the near future.Comment: Invited talk at the Sixth Pacific Rim Conference on Stellar Astrophysics, a tribute to Helmut A. Abt, July 11-17, 2002, Xi'an. To appear in the proceedings (eds. K. S. Cheng, K. C. Leung & T. P. Li

Magnetic and multiferroic properties of dilute Fe-doped BaTiO3 crystals

Combining and coupling both magnetic and electric properties in one single phase multiferroic material has attracted high interest recently to enable a broad range of novel devices and applications. To evaluate one potential route toward new multiferroics, we have studied 0.5% Fe-doped BaTiO3 single crystals and measured the ferroelectric, magnetic, and multiferroic properties. X-ray absorption spectroscopy shows the presence of Fe3+, and magnetic measurements confirmed that this has a significant impact on the magnetic properties. Doping of iron introduces paramagnetism from lone iron atoms as well as what appears to be a weak ferromagnetism. Multiferroicity and magnetoelectric (ME) coupling were observed in the polarization-electric field hysteresis loops with an applied magnetic field, yet there was no direct evidence that ME coupling persists when the sample was in the defect dipole-aligned state

Patient initiated clinics for patients with chronic or recurrent conditions managed in secondary care: a systematic review of patient reported outcomes and patient and clinician satisfaction

This is the final version of the article. Available from BioMed Central via the DOI in this record.BACKGROUND: The cost to the NHS of missed or inappropriate hospital appointments is considerable. Alternative methods of appointment scheduling might be more flexible to patients' needs without jeopardising health and service quality. The objective was to systematically review evidence of patient initiated clinics in secondary care on patient reported outcomes among patients with chronic/recurrent conditions. METHODS: Seven databases were searched from inception to June 2013. Hand searching of included studies references was also conducted. Studies comparing the effects of patient initiated clinics with traditional consultant led clinics in secondary care for patients with long term chronic or recurrent diseases on health related quality of life and/or patient satisfaction were included. Data was extracted by one reviewer and checked by a second. Results were synthesised narratively. RESULTS: Seven studies were included in the review, these covered a total of 1,655 participants across three conditions: breast cancer, inflammatory bowel disease and rheumatoid arthritis. Quality of reporting was variable. Results showed no significant differences between the intervention and control groups for psychological and health related quality of life outcomes indicating no evidence of harm. Some patients reported significantly more satisfaction using patient-initiated clinics than usual care (p < 0.001). CONCLUSIONS: The results show potential for patient initiated clinics to result in greater patient and clinician satisfaction. The patient-consultant relationship appeared to play an important part in patient satisfaction and should be considered an important area of future research as should the presence or absence of a guidebook to aid self-management. Patient initiated clinics fit the models of care suggested by policy makers and so further research into long term outcomes for patients and service use in this area of practice is both relevant and timely.This systematic review was funded by the National Institute of Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care (CLAHRC) for the South West. The views expressed in this publication are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health

Protocol for a randomized controlled trial examining multilevel prediction of response to behavioral activation and exposure-based therapy for generalized anxiety disorder.

BACKGROUND:Only 40-60% of patients with generalized anxiety disorder experience long-lasting improvement with gold standard psychosocial interventions. Identifying neurobehavioral factors that predict treatment success might provide specific targets for more individualized interventions, fostering more optimal outcomes and bringing us closer to the goal of "personalized medicine." Research suggests that reward and threat processing (approach/avoidance behavior) and cognitive control may be important for understanding anxiety and comorbid depressive disorders and may have relevance to treatment outcomes. This study was designed to determine whether approach-avoidance behaviors and associated neural responses moderate treatment response to exposure-based versus behavioral activation therapy for generalized anxiety disorder. METHODS/DESIGN:We are conducting a randomized controlled trial involving two 10-week group-based interventions: exposure-based therapy or behavioral activation therapy. These interventions focus on specific and unique aspects of threat and reward processing, respectively. Prior to and after treatment, participants are interviewed and undergo behavioral, biomarker, and neuroimaging assessments, with a focus on approach and avoidance processing and decision-making. Primary analyses will use mixed models to examine whether hypothesized approach, avoidance, and conflict arbitration behaviors and associated neural responses at baseline moderate symptom change with treatment, as assessed using the Generalized Anxiety Disorder-7 item scale. Exploratory analyses will examine additional potential treatment moderators and use data reduction and machine learning methods. DISCUSSION:This protocol provides a framework for how studies may be designed to move the field toward neuroscience-informed and personalized psychosocial treatments. The results of this trial will have implications for approach-avoidance processing in generalized anxiety disorder, relationships between levels of analysis (i.e., behavioral, neural), and predictors of behavioral therapy outcome. TRIAL REGISTRATION:The study was retrospectively registered within 21 days of first participant enrollment in accordance with FDAAA 801 with ClinicalTrials.gov, NCT02807480. Registered on June 21, 2016, before results

Influenza transmission in a cohort of households with children: 2010-2011

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The impacting cantilever: modal non-convergence and the importance of stiffness matching.

The problem of an Euler-Bernoulli cantilever beam whose free end impacts with a point constraint is revisited from the point of view of modal analysis. It is shown that there is non-uniqueness of consistent impact laws for a given modal truncation. Moreover, taking an N-mode compliant, bilinear formulation and passing to the rigid limit leads to a sequence of impact models that does not converge as N--> ∞. The dynamics of such truncated models are studied numerically and found to give rise to quite different dynamics depending on the number of degrees of freedom taken. The simulations are compared with results from simple experiments that show a propensity for multiple-tap dynamics, in which higher-order modes lead to rapidly cycling intermittent contact. The conclusion reached is that, to derive an accurate model, one needs to avoid the impact limit altogether, and take sufficiently many modes in the formulation to match the actual stiffness of the constraining stop