Entanglement model of antibody viscosity

Antibody solutions are typically much more viscous than solutions of globular proteins at equivalent volume fraction. Here we propose that this is due to molecular entanglements that are caused by the elongated shape and intrinsic flexibility of antibody molecules. We present a simple theory in which the antibodies are modeled as linear polymers that can grow via reversible bonds between the antigen binding domains. This mechanism explains the observation that relatively subtle changes to the interparticle interaction can lead to large changes in the viscosity. The theory explains the presence of distinct power law regimes in the concentration dependence of the viscosity as well as the correlation between the viscosity and the charge on the variable domain in our anti-streptavidin IgG1 model system

Rapid Mapping of Zebrafish Mutations With SNPs and Oligonucleotide Microarrays

Large-scale genetic screens in zebrafish have identified thousands of mutations in hundreds of essential genes. The genetic mapping of these mutations is necessary to link DNA sequences to the gene functions defined by mutant phenotypes.Here, we report two advances that will accelerate the mapping of zebrafish mutations: (1) The construction of a first generation single nucleotide polymorphism (SNP) map of the zebrafish genome comprising 2035 SNPs and 178 small insertions/deletions, and (2) the development of a method for mapping mutations in which hundreds of SNPs can be scored in parallel with an oligonucleotide microarray.We have demonstrated the utility of the microarray technique in crosses with haploid and diploid embryos by mapping two known mutations to their previously identified locations.We have also used this approach to localize four previously unmapped mutations.We expect that mapping with SNPs and oligonucleotide microarrays will accelerate the molecular analysis of zebrafish mutations

Developing the content of two behavioural interventions : using theory-based interventions to promote GP management of upper respiratory tract infection without prescribing antibiotics #1

Background: Evidence shows that antibiotics have limited effectiveness in the management of upper respiratory tract infection (URTI) yet GPs continue to prescribe antibiotics. Implementation research does not currently provide a strong evidence base to guide the choice of interventions to promote the uptake of such evidence-based practice by health professionals. While systematic reviews demonstrate that interventions to change clinical practice can be effective, heterogeneity between studies hinders generalisation to routine practice. Psychological models of behaviour change that have been used successfully to predict variation in behaviour in the general population can also predict the clinical behaviour of healthcare professionals. The purpose of this study was to design two theoretically-based interventions to promote the management of upper respiratory tract infection (URTI) without prescribing antibiotics. Method: Interventions were developed using a systematic, empirically informed approach in which we: selected theoretical frameworks; identified modifiable behavioural antecedents that predicted GPs intended and actual management of URTI; mapped these target antecedents on to evidence-based behaviour change techniques; and operationalised intervention components in a format suitable for delivery by postal questionnaire. Results: We identified two psychological constructs that predicted GP management of URTI: "Self-efficacy," representing belief in one's capabilities, and "Anticipated consequences," representing beliefs about the consequences of one's actions. Behavioural techniques known to be effective in changing these beliefs were used in the design of two paper-based, interactive interventions. Intervention 1 targeted self-efficacy and required GPs to consider progressively more difficult situations in a "graded task" and to develop an "action plan" of what to do when next presented with one of these situations. Intervention 2 targeted anticipated consequences and required GPs to respond to a "persuasive communication" containing a series of pictures representing the consequences of managing URTI with and without antibiotics. Conclusion: It is feasible to systematically develop theoretically-based interventions to change professional practice. Two interventions were designed that differentially target generalisable constructs predictive of GP management of URTI. Our detailed and scientific rationale for the choice and design of our interventions will provide a basis for understanding any effects identified in their evaluation. Trial registration: Clinicaltrials.gov NCT00376142This study is funded by the European Commission Research Directorate as part of a multi-partner program: Research Based Education and Quality Improvement (ReBEQI): A Framework and tools to develop effective quality improvement programs in European healthcare. (Proposal No: QLRT-2001-00657)

Second-generation bio-based plastics are becoming a reality - Non-renewable energy and greenhouse gas (GHG) balance of succinic acid-based plastic end products made from lignocellulosic biomass:NREU and GHG balance of succinic acid-based PBS products made from lignocellulosic biomass

Bio-based and bio-degradable plastics such as polybutylene succinate (PBS) have the potential to become sustainable alternatives to petrochemical-based plastics. Polybutylene succinate can be produced from bio-based succinic acid and 1,4-butanediol using first-generation (1G) or second-generation (2G) sugars. A cradle-to-grave environmental assessment was performed for PBS products in Europe to investigate the non-renewable energy use (NREU) and greenhouse gas (GHG) impacts. The products investigated are single-use trays and agricultural film, with incineration, industrial composting and degradation on agricultural land as end-of-life scenarios. Both end products manufactured from fully bio-based PBS and from partly bio-based PBS (made from bio-based succinic acid and fossil fuel-based 1,4 butanediol) were analysed. We examine corn (1G) as well as corn stover, wheat straw, miscanthus and hardwood as 2G feedstocks. For the cradle-to-grave system, 1G fully bio-based PBS plastic products were found to have environmental impacts comparable with their petrochemical incumbents, while 2G fully bio-based PBS plastic products allow to reduce NREU and GHG by around one third under the condition of avoidance of concentration of sugars and energy integration of the pretreatment process with monomer production. Without energy integration and with concentration of sugars (i.e., separate production), the impacts of 2G fully bio-based PBS products are approximately 15–20% lower than those of 1G fully bio-based PBS products. The environmental analysis of PBS products supports the value proposition related to PBS products while also pointing out areas requiring further research and development

Translating clinicians' beliefs into implementation interventions (TRACII) : a protocol for an intervention modeling experiment to change clinicians' intentions to implement evidence-based practice

Background: Biomedical research constantly produces new findings, but these are not routinely incorporated into health care practice. Currently, a range of interventions to promote the uptake of emerging evidence are available. While their effectiveness has been tested in pragmatic trials, these do not form a basis from which to generalise to routine care settings. Implementation research is the scientific study of methods to promote the uptake of research findings, and hence to reduce inappropriate care. As clinical practice is a form of human behaviour, theories of human behaviour that have proved to be useful in other settings offer a basis for developing a scientific rationale for the choice of interventions. Aims: The aims of this protocol are 1) to develop interventions to change beliefs that have already been identified as antecedents to antibiotic prescribing for sore throats, and 2) to experimentally evaluate these interventions to identify those that have the largest impact on behavioural intention and behavioural simulation. Design: The clinical focus for this work will be the management of uncomplicated sore throat in general practice. Symptoms of upper respiratory tract infections are common presenting features in primary care. They are frequently treated with antibiotics, and research evidence is clear that antibiotic treatment offers little or no benefit to otherwise healthy adult patients. Reducing antibiotic prescribing in the community by the "prudent" use of antibiotics is seen as one way to slow the rise in antibiotic resistance, and appears safe, at least in children. However, our understanding of how to do this is limited. Participants will be general medical practitioners. Two theory-based interventions will be designed to address the discriminant beliefs in the prescribing of antibiotics for sore throat, using empirically derived resources. The interventions will be evaluated in a 2 × 2 factorial randomised controlled trial delivered in a postal questionnaire survey. Two outcome measures will be assessed: behavioural intention and behavioural simulation.This study is funded by the European Commission Research Directorate as part of a multi-partner program: Research Based Education and Quality Improvement (ReBEQI): A Framework and tools to develop effective quality improvement programs in European healthcare. (Proposal No: QLRT-2001-00657)

Cytokinesis in bloodstream stage Trypanosoma brucei requires a family of katanins and spastin

Microtubule severing enzymes regulate microtubule dynamics in a wide range of organisms and are implicated in important cell cycle processes such as mitotic spindle assembly and disassembly, chromosome movement and cytokinesis. Here we explore the function of several microtubule severing enzyme homologues, the katanins (KAT80, KAT60a, KAT60b and KAT60c), spastin (SPA) and fidgetin (FID) in the bloodstream stage of the African trypanosome parasite, Trypanosoma brucei. The trypanosome cytoskeleton is microtubule based and remains assembled throughout the cell cycle, necessitating its remodelling during cytokinesis. Using RNA interference to deplete individual proteins, we show that the trypanosome katanin and spastin homologues are non-redundant and essential for bloodstream form proliferation. Further, cell cycle analysis revealed that these proteins play essential but discrete roles in cytokinesis. The KAT60 proteins each appear to be important during the early stages of cytokinesis, while downregulation of KAT80 specifically inhibited furrow ingression and SPA depletion prevented completion of abscission. In contrast, RNA interference of FID did not result in any discernible effects. We propose that the stable microtubule cytoskeleton of T. brucei necessitates the coordinated action of a family of katanins and spastin to bring about the cytoskeletal remodelling necessary to complete cell divisio

SUPPORT Tools for evidence-informed health Policymaking (STP) 7: Finding systematic reviews

This article is part of a series written for people responsible for making decisions about health policies and programmes and for those who support these decision makers

A Comparison of Radiographic Alignment between Bilateral and Unilateral Interbody Cages in Patients Undergoing Transforaminal Lumbar Interbody Fusion

Study Design Retrospective cohort study. Purpose: To compare radiographic outcomes between unilateral and bilateral cage placement in transforaminal lumbar interbody fusions (TLIF) and to determine if the rate of fusion at the 1-year postoperative point was different in patients who received bilateral versus unilateral cages. Overview of Literature There is no clear evidence to dictate whether bilateral or unilateral cages promote superior radiographic or surgical outcomes in TLIF. Methods: Patients \u3e18 years old who underwent primary one- or two-level TLIFs at our institution were identified and propensity-matched in a 3:1 fashion (unilateral:bilateral). Patient demographics, surgical characteristics, and radiographic outcomes, including vertebral endplate obliquity, segmental lordosis, subsidence, and fusion status, were compared between groups. Results: Of the 184 patients included, 46 received bilateral cages. Bilateral cage placement was associated with greater subsidence (1.06±1.25 mm vs. 0.59±1.16 mm, p=0.028) and enhanced restoration of segmental lordosis (5.74°±14.1° vs. −1.57°±10.9°, p=0.002) at the 1-year postoperative point, while unilateral cage placement was associated with an increased correction of endplate obliquity (−2.02°±4.42° vs. 0.24°±2.81°, p\u3c0.001). Bilateral cage placement was significantly associated with radiographic fusion on bivariate analysis (89.1% vs. 70.3%, p=0.018) and significantly predicted radiographic fusion on multivariable regression analysis (estimate, 1.35; odds ratio, 3.87; 95% confidence interval, 1.51–12.05; p=0.010). Conclusions: Bilateral interbody cage placement in TLIF procedures was associated with restoration of lumbar lordosis and increased fusion rates. However, endplate obliquity correction was significantly greater for patients who received a unilateral cage

Does Physical Therapy Impact Clinical Outcomes After Lumbar Decompression Surgery?

OBJECTIVES: The objectives of our study were to (1) determine if physical therapy (PT) impacts patient-reported outcomes (PROMs) after lumbar decompression surgery and (2) determine if PT impacts postsurgical readmissions or reoperations after lumbar decompression surgery. METHODS: Patients \u3e18 years of age who underwent primary one‑ or two‑level lumbar decompression at our institution were identified. Patient demographics, surgical characteristics, surgical outcomes (all‑cause 90 days readmissions and 90 days surgical readmissions), and patient‑reported outcomes (PROMs) were compared between the groups. Multivariate linear regression was utilized to determine the individual predictors of 90 days readmissions and PROMs at the 1‑year postoperative point. Alpha was set at P \u3c 0.05. RESULTS: Of the 1003 patients included, 421 attended PT postoperatively. On univariate analysis, PT attendance did not significantly impact 90‑day surgical reoperations (P = 0.225). Although bivariate analysis suggests that attendance of PT is associated with worse improvement in physical function (P = 0.041), increased preoperative Visual Analogue Scale leg pain (0 = 0.004), and disability (P = 0.006), as measured by the Oswestry Disability Index, our multivariate analysis, which accounts for confounding variables found there was no difference in PROM improvement and PT was not an independent predictor of 90‑day all‑cause readmissions (P = 0.06). Instead, Charlson Comorbidity Index (P = 0.025) and discharge to a skilled nursing facility (P = 0.013) independently predicted greater 90‑day all‑cause readmissions. CONCLUSIONS: Postoperative lumbar decompression PT attendance does not significantly affect clinical improvement, as measured by PROMs or surgical outcomes including all-cause 90 days readmissions and 90-day surgical readmissions

The Function and Organization of Lateral Prefrontal Cortex: A Test of Competing Hypotheses

The present experiment tested three hypotheses regarding the function and organization of lateral prefrontal cortex (PFC). The first account (the information cascade hypothesis) suggests that the anterior-posterior organization of lateral PFC is based on the timing with which cue stimuli reduce uncertainty in the action selection process. The second account (the levels-of-abstraction hypothesis) suggests that the anterior-posterior organization of lateral PFC is based on the degree of abstraction of the task goals. The current study began by investigating these two hypotheses, and identified several areas of lateral PFC that were predicted to be active by both the information cascade and levels-of-abstraction accounts. However, the pattern of activation across experimental conditions was inconsistent with both theoretical accounts. Specifically, an anterior area of mid-dorsolateral PFC exhibited sensitivity to experimental conditions that, according to both accounts, should have selectively engaged only posterior areas of PFC. We therefore investigated a third possible account (the adaptive context maintenance hypothesis) that postulates that both posterior and anterior regions of PFC are reliably engaged in task conditions requiring active maintenance of contextual information, with the temporal dynamics of activity in these regions flexibly tracking the duration of maintenance demands. Activity patterns in lateral PFC were consistent with this third hypothesis: regions across lateral PFC exhibited transient activation when contextual information had to be updated and maintained in a trial-by-trial manner, but sustained activation when contextual information had to be maintained over a series of trials. These findings prompt a reconceptualization of current views regarding the anterior-posterior organization of lateral PFC, but do support other findings regarding the active maintenance role of lateral PFC in sequential working memory paradigms