Extracting human antibody sequences from public databases for antibody humanization: high frequency of species assignment errors

In antibody humanization, complementarity determining regions from a 'donor' antibody are often grafted onto a human framework selected by high sequence identity with the donor. In our own humanization experiments, we have found that species information is often incorrect. Here we take three mouse antibodies and perform BLAST searches against sequences annotated as being human. We find that the first genuine human hits for the six chains appear at Positions 30, 4, 11, 24, 18 and 29 in the hit lists. This illustrates both the need for caution in performing humanization and for improvements in annotation

Precarious lives: exploring lived experiences of the private rented sector in Salford

Research report focusing on the experiences of residents living in the private rented sector in Salford

Communication Channel Preferences of Corn and Soybean Producers

The study reported here sought to identify the types of communication channels Iowa corn and soybean producers prefer for agricultural information. Data were gathered through focus groups and analyzed using theme coding and qualitative data charts. Conclusions included: 1) producers looked to Extension for assistance in evaluating information from other sources rather than acquiring information; 2) producers preferred a variety of communication channels; 3) producers highly preferred consultations highly; 4) producers preferred mass media channels for general information and interpersonal communication channels for specific and applicable information; 5) among mass media channels, producers preferred radio; and 6) among interpersonal channels, producers preferred consultations

Symptomatic spinal metastasis: A systematic literature review of the preoperative prognostic factors for survival, neurological, functional and quality of life in surgically treated patients and methodological recommendations for prognostic studies

PURPOSE: While several clinical prediction rules (CPRs) of survival exist for patients with symptomatic spinal metastasis (SSM), these have variable prognostic ability and there is no recognized CPR for health related quality of life (HRQoL). We undertook a critical appraisal of the literature to identify key preoperative prognostic factors of clinical outcomes in patients with SSM who were treated surgically. The results of this study could be used to modify existing or develop new CPRs. METHODS: Seven electronic databases were searched (1990-2015), without language restriction, to identify studies that performed multivariate analysis of preoperative predictors of survival, neurological, functional and HRQoL outcomes in surgical patients with SSM. Individual studies were assessed for class of evidence. The strength of the overall body of evidence was evaluated using GRADE for each predictor. RESULTS: Among 4,818 unique citations, 17 were included; all were in English, rated Class III and focused on survival, revealing a total of 46 predictors. The strength of the overall body of evidence was very low for 39 and low for 7 predictors. Due to considerable heterogeneity in patient samples and prognostic factors investigated as well as several methodological issues, our results had a moderately high risk of bias and were difficult to interpret. CONCLUSIONS: The quality of evidence for predictors of survival was, at best, low. We failed to identify studies that evaluated preoperative prognostic factors for neurological, functional, or HRQoL outcomes in surgical patients with SSM. We formulated methodological recommendations for prognostic studies to promote acquiring high-quality evidence to better estimate predictor effect sizes to improve patient education, surgical decision-making and development of CPRs

Tuberculosis incidence correlates with sunshine : an ecological 28-year time series study

Birmingham is the largest UK city after London, and central Birmingham has an annual tuberculosis incidence of 80 per 100,000. We examined seasonality and sunlight as drivers of tuberculosis incidence. Hours of sunshine are seasonal, sunshine exposure is necessary for the production of vitamin D by the body and vitamin D plays a role in the host response to tuberculosis. Methods: We performed an ecological study that examined tuberculosis incidence in Birmingham from Dec 1981 to Nov 2009, using publicly-available data from statutory tuberculosis notifications, and related this to the seasons and hours of sunshine (UK Meteorological Office data) using unmeasured component models. Results: There were 9,739 tuberculosis cases over the study period. There was strong evidence for seasonality, with notifications being 24.1% higher in summer than winter (p<0.001). Winter dips in sunshine correlated with peaks in tuberculosis incidence six months later (4.7% increase in incidence for each 100 hours decrease in sunshine, p<0.001). Discussion and Conclusion: A potential mechanism for these associations includes decreased vitamin D levels with consequent impaired host defence arising from reduced sunshine exposure in winter. This is the longest time series of any published study and our use of statutory notifications means this data is essentially complete. We cannot, however, exclude the possibility that another factor closely correlated with the seasons, other than sunshine, is responsible. Furthermore, exposure to sunlight depends not only on total hours of sunshine but also on multiple individual factors. Our results should therefore be considered hypothesis-generating. Confirmation of a potential causal relationship between winter vitamin D deficiency and summer peaks in tuberculosis incidence would require a randomized-controlled trial of the effect of vitamin D supplementation on future tuberculosis incidence

Adaptive latitudinal variation in Common Blackbird Turdus merula nest characteristics

Nest construction is taxonomically widespread, yet our understanding of adaptive intraspecific variation in nest design remains poor. Nest characteristics are expected to vary adaptively in response to predictable variation in spring temperatures over large spatial scales, yet such variation in nest design remains largely overlooked, particularly amongst open-cup-nesting birds. Here, we systematically examined the effects of latitudinal variation in spring temperatures and precipitation on the morphology, volume, composition, and insulatory properties of open-cup-nesting Common Blackbirds’ Turdus merula nests to test the hypothesis that birds living in cooler environments at more northerly latitudes would build better insulated nests than conspecifics living in warmer environments at more southerly latitudes. As spring temperatures increased with decreasing latitude, the external diameter of nests decreased. However, as nest wall thickness also decreased, there was no variation in the diameter of the internal nest cups. Only the mass of dry grasses within nests decreased with warmer temperatures at lower latitudes. The insulatory properties of nests declined with warmer temperatures at lower latitudes and nests containing greater amounts of dry grasses had higher insulatory properties. The insulatory properties of nests decreased with warmer temperatures at lower latitudes, via changes in morphology (wall thickness) and composition (dry grasses). Meanwhile, spring precipitation did not vary with latitude, and none of the nest characteristics varied with spring precipitation. This suggests that Common Blackbirds nesting at higher latitudes were building nests with thicker walls in order to counteract the cooler temperatures. We have provided evidence that the nest construction behavior of open-cup-nesting birds systematically varies in response to large-scale spatial variation in spring temperatures

Water dispersible microbicidal cellulose acetate phthalate film

BACKGROUND: Cellulose acetate phthalate (CAP) has been used for several decades in the pharmaceutical industry for enteric film coating of oral tablets and capsules. Micronized CAP, available commercially as "Aquateric" and containing additional ingredients required for micronization, used for tablet coating from water dispersions, was shown to adsorb and inactivate the human immunodeficiency virus (HIV-1), herpesviruses (HSV) and other sexually transmitted disease (STD) pathogens. Earlier studies indicate that a gel formulation of micronized CAP has a potential as a topical microbicide for prevention of STDs including the acquired immunodeficiency syndrome (AIDS). The objective of endeavors described here was to develop a water dispersible CAP film amenable to inexpensive industrial mass production. METHODS: CAP and hydroxypropyl cellulose (HPC) were dissolved in different organic solvent mixtures, poured into dishes, and the solvents evaporated. Graded quantities of a resulting selected film were mixed for 5 min at 37°C with HIV-1, HSV and other STD pathogens, respectively. Residual infectivity of the treated viruses and bacteria was determined. RESULTS: The prerequisites for producing CAP films which are soft, flexible and dispersible in water, resulting in smooth gels, are combining CAP with HPC (other cellulose derivatives are unsuitable), and casting from organic solvent mixtures containing ≈50 to ≈65% ethanol (EtOH). The films are ≈100 µ thick and have a textured surface with alternating protrusions and depressions revealed by scanning electron microscopy. The films, before complete conversion into a gel, rapidly inactivated HIV-1 and HSV and reduced the infectivity of non-viral STD pathogens >1,000-fold. CONCLUSIONS: Soft pliable CAP-HPC composite films can be generated by casting from organic solvent mixtures containing EtOH. The films rapidly reduce the infectivity of several STD pathogens, including HIV-1. They are converted into gels and thus do not have to be removed following application and use. In addition to their potential as topical microbicides, the films have promise for mucosal delivery of pharmaceuticals other than CAP

Mothers’ work–family conflict and enrichment:associations with parenting quality and couple relationship

Background Employment participation of mothers of young children has steadily increased in developed nations. Combining work and family roles can create conflicts with family life, but can also bring enrichment.Work–family conflict and enrichment experienced by mothers may also impact children’s home environments via parenting behaviour and the couple relationship, particularly in the early years of parenting when the care demands for young children is high. Methods In order to examine these associations, while adjusting for a wide range of known covariates of parenting and relationship quality, regression models using survey data from 2151 working mothers of 4- to 5-year-old children are reported. Results/Conclusion Results provided partial support for the predicted independent relationships between work–family conflict, enrichment and indicators of the quality of parenting and the couple relationship

Core vs. diet -associated and postprandial bacterial communities of the rainbow trout (Oncorhynchus mykiss) midgut and feaces

ACKNOWLEDGMENTS: Eleni Mente was awarded a visiting fellowship by Marine Alliance for Science and Technology Scotland (MASTS). Part of Eleni’s Nikouli’s work in this paper was carried out under the program “Scholarships of IKY in the Marine and Inland Management of Water Resources” and was co-funded by EEA grants– Financial Mechanism 2009-2014 (85%) and the General Secretariat for Investments and Development (15%). The authors declare no competing interests.Peer reviewedPublisher PD

Aqueous outflow imaging techniques and what they tell us about intraocular pressure regulation.

Recent advances in the medical and surgical management of open-angle glaucoma have increased the number of treatment options available. Several new intraocular pressure (IOP)-lowering treatments target the conventional aqueous outflow (AO) system. However, success rates are variable and outcomes in individual patients are often difficult to predict. Variable treatment responses remain unexplained and highlight deficiencies in our current understanding of AO regulation and IOP homeostasis. Imaging is often relied upon to confirm diagnoses and monitor treatment responses in other ocular and systemic pathologies. As yet no suitable AO imaging tool has been developed to fulfil this role in glaucoma. A variety of imaging techniques have been used to study the AO tracts of humans and animals in ex vivo and in vivo eyes. In this review, results from novel imaging techniques that assess aqueous drainage through the episcleral venous system are considered and we argue these provide new insights into AO regulation. We suggest that the ability to objectively measure AO responses to interventions would be a significant clinical advance, and we have demonstrated that this can be achieved with direct visualisation of aqueous drainage. We predict that the evolution of AO imaging technology will continue to reveal critical components of AO and IOP regulation, and that personalised IOP-lowering treatment in glaucoma care may well become a reality in the near future.1. A core support grant from the Wellcome Trust and MRC to the Wellcome Trust – Medical Research Council Cambridge Stem Cell Institute 2. Haemoglobin Video Imaging facilities funded by Sydney Eye Hospital Foundation, Carl Zeiss Meditec, and Glaukos Corporatio