New functional and structural insights from updated mutational databases for complement factor H, Factor I, membrane cofactor protein and C3

aHUS (atypical haemolytic uraemic syndrome), AMD (age-related macular degeneration) and other diseases are associated with defective AP (alternative pathway) regulation. CFH (complement factor H), CFI (complement factor I), MCP (membrane cofactor protein) and C3 exhibited the most disease-associated genetic alterations in the AP. Our interactive structural database for these was updated with a total of 324 genetic alterations. A consensus structure for the SCR (short complement regulator) domain showed that the majority (37%) of SCR mutations occurred at its hypervariable loop and its four conserved Cys residues. Mapping 113 missense mutations onto the CFH structure showed that over half occurred in the C-terminal domains SCR-15 to -20. In particular, SCR-20 with the highest total of affected residues is associated with binding to C3d and heparin-like oligosaccharides. No clustering of 49 missense mutations in CFI was seen. In MCP, SCR-3 was the most affected by 23 missense mutations. In C3, the neighbouring thioester and MG (macroglobulin) domains exhibited most of 47 missense mutations. The mutations in the regulators CFH, CFI and MCP involve loss-of-function, whereas those for C3 involve gain-of-function. This combined update emphasizes the importance of the complement AP in inflammatory disease, clarifies the functionally important regions in these proteins, and will facilitate diagnosis and therapy

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

The handbook for standardized field and laboratory measurements in terrestrial climate change experiments and observational studies (ClimEx)

1. Climate change is a world‐wide threat to biodiversity and ecosystem structure, functioning and services. To understand the underlying drivers and mechanisms, and to predict the consequences for nature and people, we urgently need better understanding of the direction and magnitude of climate change impacts across the soil–plant–atmosphere continuum. An increasing number of climate change studies are creating new opportunities for meaningful and high‐quality generalizations and improved process understanding. However, significant challenges exist related to data availability and/or compatibility across studies, compromising opportunities for data re‐use, synthesis and upscaling. Many of these challenges relate to a lack of an established ‘best practice’ for measuring key impacts and responses. This restrains our current understanding of complex processes and mechanisms in terrestrial ecosystems related to climate change. 2. To overcome these challenges, we collected best‐practice methods emerging from major ecological research networks and experiments, as synthesized by 115 experts from across a wide range of scientific disciplines. Our handbook contains guidance on the selection of response variables for different purposes, protocols for standardized measurements of 66 such response variables and advice on data management. Specifically, we recommend a minimum subset of variables that should be collected in all climate change studies to allow data re‐use and synthesis, and give guidance on additional variables critical for different types of synthesis and upscaling. The goal of this community effort is to facilitate awareness of the importance and broader application of standardized methods to promote data re‐use, availability, compatibility and transparency. We envision improved research practices that will increase returns on investments in individual research projects, facilitate second‐order research outputs and create opportunities for collaboration across scientific communities. Ultimately, this should significantly improve the quality and impact of the science, which is required to fulfil society's needs in a changing world

Using mobile phones to examine and enhance perceptions of control in mildly depressed and nondepressed volunteers: intervention study

Abstract Background: Perceived control is strongly linked to healthy outcomes, mental healthiness, and psychological well-being. This is particularly important when people have little control over things that are happening to them. Perceived control studies have been performed extensively in laboratory settings and show that perceived control can be increased by experimental manipulations. Although these studies suggest that it may be possible to improve people’s mental health by increasing their perceived control, there is very little evidence to date to suggest that perceived control can also be influenced in the real world. Objective: The first aim of this study was to test for evidence of a link between noncontrol situations and psychological well-being in the real world using a mobile phone app. The second and arguably more important aim of the study was to test whether a simple instructional intervention on the nature of alternative causes would enhance people’s perceptions of their own control in these noncontrol situations. Methods: We implemented a behavioral action-outcome contingency judgment task using a mobile phone app. An opportunity sample of 106 healthy volunteers scoring low (n=56, no depression) or high (n=50, mild depression) on a depression scale participated. They were given no control over the occurrence of a low- or high-frequency stimulus that was embedded in everyday phone interactions during a typical day lasting 8 hours. The intervention involved instructions that either described a consistent alternative cause against which to assess their own control, or dynamic alternative causes of the outcome. Throughout the day, participants rated their own control over the stimulus using a quantitative judgment scale. Results: Participants with no evidence of depression overestimated their control, whereas those who were most depressed were more accurate in their control ratings. Instructions given to all participants about the nature of alternative causes significantly affected the pattern of perceived control ratings. Instructions describing discrete alternative causes enhanced perceived control for all participants, whereas dynamic alternative causes were linked to less perceived control. Conclusions: Perceptions of external causes are important to perceived control and can be used to enhance people’s perceptions. Theoretically motivated interventions can be used to enhance perceived control using mobile phone apps. This is the first study to do so in a real-world setting

Management of Nephrolithiasis in Pregnancy: Multi-Disciplinary Guidelines From an Academic Medical Center

Introduction: The management of nephrolithiasis during pregnancy can be stressful for urologists due to concerns for investigations and treatments that may pose risk of fetal harm, and unfamiliarity with optimal management of these complex patients. In response, we created multi-disciplinary evidence-based guidelines to standardize the care for obstetric patients presenting with flank pain and suspicion for nephrolithiasis. Methods: A multi-disciplinary team involving Urology, Obstetric Anesthesiology, Obstetrics and Gynecology, Diagnostic Radiology, and Interventional Radiology from a single academic medical center was assembled. A PubMed search was performed using keywords of pregnancy/antepartum, nephrolithiasis/calculi/kidney stones, ureteroscopy, non-obstetric surgery, complications, preterm delivery, MRI, computerized tomography, renal bladder ultrasound (RBUS), and anesthesia to identify relevant articles. Team members reviewed their respective areas to create a comprehensive set of guidelines. One invited external expert reviewed the guidelines for validation purposes. Results: A total of 54 articles were reviewed for evidence synthesis. Four guideline statements were constructed to guide diagnosis and imaging, and seven statements to guide intervention. Guidelines were then used to create a diagnostic and intervention flowchart for ease of use. In summary, RBUS should be the initial diagnostic study. If diagnostic uncertainty still exists, a non-contrast CT scan should be obtained. For obstetric patients presenting with a septic obstructing stone, urgent decompression should be achieved. We recommend ureteral stent placement as the preferred intervention if local factors allow. Conclusions: We present a standardized care pathway for the management of nephrolithiasis during pregnancy. Our aim is to standardize and simplify the clinical management of these complex scenarios for urologists

Predictors of parents' intention to limit children's television viewing

Background Scientific evidence demonstrates a link between viewing time and several poor health outcomes. We use a reasoned action approach to identify the determinants and beliefs associated with parents' intention to limit their children's television viewing. Methods We surveyed a random sample of 516 caregivers to children ages 3-16 in a large Northeastern city. Multiple regression analyses were used to test a reasoned action model and examine the differences across demographic groups. Results The intention to limit viewing (−3 to 3) was low among parents of adolescents (M: 0.05) compared with parents of 3-6 year olds (M: 1.49) and 7-12 year olds (M: 1.16). Attitudes were the strongest determinant of intention (β = 0.43) across all demographic groups and normative pressure was also significantly related to intention (β = 0.20), except among parents of adolescents. Relevant beliefs associated with intention to limit viewing included: limiting television would be associated with the child exercising more, doing better in school, talking to family more and having less exposure to inappropriate content. Conclusions Attitudes and normative pressure play an important role in determining parents' intention to limit their child's television viewing. The beliefs that were associated with parents' intention to limit should be emphasized by health professionals and in health communication campaigns

Äldres rehabiliteringsbehov i hemmiljö

Upprättat; 2001; 20131113 (andbra