Evaluation of thermal evaporation conditions used in coating aluminum on near-field fiber-optic probes

This is the published version, also available here: http://dx.doi.org/10.1063/1.1148836.The effects that the thermal evaporation conditions have on the roughness of aluminum-coated near-field fiber-optic probes were investigated using the high-resolution capabilities of atomic force microscopy. The coating conditions studied include the effects of background gas composition, base vacuum pressure, and aluminum evaporation rate. The effects of aging on the aluminum-coated tips were also evaluated. The results from topography measurements of the resulting aluminumfilm indicated that the most dramatic improvements in the tip coatings can be achieved using high aluminum evaporation rates at base vacuum pressures below 10−5 Torr. These results agree with other studies on thin aluminumfilms and reflect a decrease in oxide formation. For demanding applications of near-field microscopy requiring maximal resolution, the results presented here indicate that it may also be necessary to reduce oxygen and/or water from the vacuum chamber prior to coating

A Rediscovered Ancient History of Motivational Interviewing and its Measurement

We wrote this piece for coding teams around the world, hoping to raise some measurement issues, to inspire, and to entertain (perhaps not in that order). This one’s for you, coders and for you, trainers of coders, you who work so hard to measure Motivational Interviewing using the standardized coding systems such as the MISC, MITI, and SCOPE

Probing single molecule orientations in model lipid membranes with near-field scanning optical microscopy

This is the published version, also available here: http://dx.doi.org/10.1063/1.481367.Single molecule near-field fluorescence measurements are utilized to characterize the molecular level structure in Langmuir–Blodgett monolayers of L-α-dipalmitoylphosphatidylcholine (DPPC).Monolayers incorporating 3×10−4 mol % of the fluorescent lipid analog N-(6-tetramethylrhodaminethiocarbamoyl)-1,2-dihexadecanoyl-sn- glycero-3-phosphoethanolamine, triethylammonium salt (TRITC–DHPE) are transferred onto a freshly cleaved mica surface at low (π=8 mN/m) and high (π=30 mN/m)surfacepressures. The near-field fluorescence images exhibit shapes in the single molecule images that are indicative of the lipid analog probe orientation within the films. Modeling the fluorescence patterns yields the single molecule tilt angle distribution in the monolayers which indicates that the majority of the molecules are aligned with their absorption dipole moment pointed approximately normal to the membrane plane. Histograms of the data indicate that the average orientation of the absorption dipole moment is 2.2° (σ=4.8°) in monolayers transferred at π=8 mN/m and 2.4° (σ=5.0°) for monolayers transferred at π=30 mN/m. There is no statistical difference in the mean tilt angle or distribution for the two monolayer conditions studied. The insensitivity of tilt angle to filmsurfacepressure may arise from small chromophore doped domains of trapped liquid-expanded lipid phase remaining at high surfacepressure. There is no evidence in the near-field fluorescence images for probe molecules oriented with their dipole moment aligned parallel with the membrane plane. We do, however, find a small but significant population of probe molecules (∼13%) with tilt angles greater than 16°. Comparison of the simultaneously collected near-field fluorescence and force images suggests that these large angle orientations are not the result of significant defects in the films. Instead, this small population may represent a secondary insertion geometry for the probe molecule into the lipidmonolayer

A Versatile, Portable Intravital Microscopy Platform for Studying Beta-cell Biology In Vivo

The pancreatic islet is a complex micro-organ containing numerous cell types, including endocrine, immune, and endothelial cells. The communication of these systems is lost upon isolation of the islets, and therefore the pathogenesis of diabetes can only be fully understood by studying this organized, multicellular environment in vivo. We have developed several adaptable tools to create a versatile platform to interrogate β-cell function in vivo. Specifically, we developed β-cell-selective virally-encoded fluorescent protein biosensors that can be rapidly and easily introduced into any mouse. We then coupled the use of these biosensors with intravital microscopy, a powerful tool that can be used to collect cellular and subcellular data from living tissues. Together, these approaches allowed the observation of in vivo β-cell-specific ROS dynamics using the Grx1-roGFP2 biosensor and calcium signaling using the GcAMP6s biosensor. Next, we utilized abdominal imaging windows (AIW) to extend our in vivo observations beyond single-point terminal measurements to collect longitudinal physiological and biosensor data through repeated imaging of the same mice over time. This platform represents a significant advancement in our ability to study β-cell structure and signaling in vivo, and its portability for use in virtually any mouse model will enable meaningful studies of β-cell physiology in the endogenous islet niche

Integrin-mediated traction force enhances paxillin molecular associations and adhesion dynamics that increase the invasiveness of tumor cells into a three-dimensional extracellular matrix.

Metastasis requires tumor cells to navigate through a stiff stroma and squeeze through confined microenvironments. Whether tumors exploit unique biophysical properties to metastasize remains unclear. Data show that invading mammary tumor cells, when cultured in a stiffened three-dimensional extracellular matrix that recapitulates the primary tumor stroma, adopt a basal-like phenotype. Metastatic tumor cells and basal-like tumor cells exert higher integrin-mediated traction forces at the bulk and molecular levels, consistent with a motor-clutch model in which motors and clutches are both increased. Basal-like nonmalignant mammary epithelial cells also display an altered integrin adhesion molecular organization at the nanoscale and recruit a suite of paxillin-associated proteins implicated in invasion and metastasis. Phosphorylation of paxillin by Src family kinases, which regulates adhesion turnover, is similarly enhanced in the metastatic and basal-like tumor cells, fostered by a stiff matrix, and critical for tumor cell invasion in our assays. Bioinformatics reveals an unappreciated relationship between Src kinases, paxillin, and survival of breast cancer patients. Thus adoption of the basal-like adhesion phenotype may favor the recruitment of molecules that facilitate tumor metastasis to integrin-based adhesions. Analysis of the physical properties of tumor cells and integrin adhesion composition in biopsies may be predictive of patient outcome

Prosocial Spending and Well-Being: Cross-Cultural Evidence for a Psychological Universal

This research provides the first support for a possible psychological universal: human beings around the world derive emotional benefits from using their financial resources to help others (prosocial spending). Analyzing survey data from 136 countries, we show that prosocial spending is consistently associated with greater happiness. To test for causality, we conduct experiments within two very different countries (Canada and Uganda) and show that spending money on others has a consistent, causal impact on happiness. In contrast to traditional economic thought—which places self-interest as the guiding principle of human motivation—our findings suggest that the reward experienced from helping others may be deeply ingrained in human nature, emerging in diverse cultural and economic contexts.

ELIXIR-UK role in bioinformatics training at the national level and across ELIXIR

ELIXIR-UK is the UK node of ELIXIR, the European infrastructure for life science data. Since its foundation in 2014, ELIXIR-UK has played a leading role in training both within the UK and in the ELIXIR Training Platform, which coordinates and delivers training across all ELIXIR members. ELIXIR-UK contributes to the Training Platform’s coordination and supports the development of training to address key skill gaps amongst UK scientists. As part of this work it acts as a conduit for nationally-important bioinformatics training resources to promote their activities to the ELIXIR community. ELIXIR-UK also leads ELIXIR’s flagship Training Portal, TeSS, which collects information about a diverse range of training and makes it easily accessible to the community. ELIXIR-UK also works with others to provide key digital skills training, partnering with the Software Sustainability Institute to provide Software Carpentry training to the ELIXIR community and to establish the Data Carpentry initiative, and taking a lead role amongst national stakeholders to deliver the StaTS project – a coordinated effort to drive engagement with training in statistics

Comparing Breast Cancer Multiparameter Tests in the OPTIMA Prelim Trial: No Test Is More Equal Than the Others

Background: Previous reports identifying discordance between multiparameter tests at the individual patient level have been largely attributed to methodological shortcomings of multiple in silico studies. Comparisons between tests, when performed using actual diagnostic assays, have been predicted to demonstrate high degrees of concordance. OPTIMA prelim compared predicted risk stratification and subtype classification of different multiparameter tests performed directly on the same population. Methods: Three hundred thirteen women with early breast cancer were randomized to standard (chemotherapy and endocrine therapy) or test-directed (chemotherapy if Oncotype DX recurrence score >25) treatment. Risk stratification was also determined with Prosigna (PAM50), MammaPrint, MammaTyper, NexCourse Breast (IHC4-AQUA), and conventional IHC4 (IHC4). Subtype classification was provided by Blueprint, MammaTyper, and Prosigna. Results: Oncotype DX predicted a higher proportion of tumors as low risk (82.1%, 95% confidence interval [CI] = 77.8% to 86.4%) than were predicted low/intermediate risk using Prosigna (65.5%, 95% CI = 60.1% to 70.9%), IHC4 (72.0%, 95% CI = 66.5% to 77.5%), MammaPrint (61.4%, 95% CI = 55.9% to 66.9%), or NexCourse Breast (61.6%, 95% CI = 55.8% to 67.4%). Strikingly, the five tests showed only modest agreement when dichotomizing results between high vs low/intermediate risk. Only 119 (39.4%) tumors were classified uniformly as either low/intermediate risk or high risk, and 183 (60.6%) were assigned to different risk categories by different tests, although 94 (31.1%) showed agreement between four of five tests. All three subtype tests assigned 59.5% to 62.4% of tumors to luminal A subtype, but only 121 (40.1%) were classified as luminal A by all three tests and only 58 (19.2%) were uniformly assigned as nonluminal A. Discordant subtyping was observed in 123 (40.7%) tumors. Conclusions: Existing evidence on the comparative prognostic information provided by different tests suggests that current multiparameter tests provide broadly equivalent risk information for the population of women with estrogen receptor (ER)–positive breast cancers. However, for the individual patient, tests may provide differing risk categorization and subtype information

Esophageal sphincter device for gastroesophageal reflux disease

BACKGROUND Patients with gastroesophageal reflux disease who have a partial response to proton-pump inhibitors often seek alternative therapy. We evaluated the safety and effectiveness of a new magnetic device to augment the lower esophageal sphincter. METHODS We prospectively assessed 100 patients with gastroesophageal reflux disease before and after sphincter augmentation. The study did not include a concurrent control group. The primary outcome measure was normalization of esophageal acid exposure or a 50% or greater reduction in exposure at 1 year. Secondary outcomes were 50% or greater improvement in quality of life related to gastroesophageal reflux disease and a 50% or greater reduction in the use of proton-pump inhibitors at 1 year. For each outcome, the prespecified definition of successful treatment was achievement of the outcome in at least 60% of the patients. The 3-year results of a 5-year study are reported. RESULTS The primary outcome was achieved in 64% of patients (95% confidence interval [CI], 54 to 73). For the secondary outcomes, a reduction of 50% or more in the use of proton-pump inhibitors occurred in 93% of patients, and there was improvement of 50% or more in quality-of-life scores in 92%, as compared with scores for patients assessed at baseline while they were not taking proton-pump inhibitors. The most frequent adverse event was dysphagia (in 68% of patients postoperatively, in 11% at 1 year, and in 4% at 3 years). Serious adverse events occurred in six patients, and in six patients the device was removed. CONCLUSIONS In this single-group evaluation of 100 patients before and after sphincter augmentation with a magnetic device, exposure to esophageal acid decreased, reflux symptoms improved, and use of proton-pump inhibitors decreased. Follow-up studies are needed to assess long-term safety. (Funded by Torax Medical; ClinicalTrials.gov number, NCT00776997.

30 days wild: development and evaluation of a large-scale nature engagement campaign to improve well-being

There is a need to increase people’s engagement with and connection to nature, both for human well-being and the conservation of nature itself. In order to suggest ways for people to engage with nature and create a wider social context to normalise nature engagement, The Wildlife Trusts developed a mass engagement campaign, 30 Days Wild. The campaign asked people to engage with nature every day for a month. 12,400 people signed up for 30 Days Wild via an online sign-up with an estimated 18,500 taking part overall, resulting in an estimated 300,000 engagements with nature by participants. Samples of those taking part were found to have sustained increases in happiness, health, connection to nature and pro-nature behaviours. With the improvement in health being predicted by the improvement in happiness, this relationship was mediated by the change in connection to nature