Microfluidic Tangential Flow Filter and Continuous-Flow Reactor for Bioprocess Development

The development of new biocatalytic processes is hindered by the number of factors that must be investigated and optimised in order to create a robust and reproducible process, particularly where a novel enzyme is involved. It is therefore advantageous to perform process development experiments at micro scale, in order to reduce the material requirement for experimentation and increase experimental throughput by parallelisation. The initial focus of the thesis is on the design of a microfluidic tangential flow filter to test downstream processing conditions. The device was designed for reversible clamp sealing, allowing the simple integration of different filtration membranes, and the seal achieved with the device was shown to be robust up to internal pressures of 100 psi. The filtration device was applied to the recovery of L-erythrulose (ERY) from a synthesis reaction performed using transketolase (TK), where it was demonstrated that the enzyme could be fully retained using a commercially-available membrane, while ERY was able to permeate the membrane freely. The filtration device was joined in-line to the output of a T-junction reactor with a staggered herringbone mixer, used to perform the synthesis reaction. The filter was capable of continuously separating the ERY from the lysate mixture exiting the reactor over the course of several hours, producing 3.6 mg h-1 of pure ERY. A novel multi-input reactor (MIR) is also demonstrated for the purpose of intensifying ERY output, designed to overcome the effect of substrate inhibition on the TK enzyme by mimicking a fed-batch reactor. Feeding strategies were designed for the conversion of various concentrations of the less inhibiting substrate hydroxypyruvate (HPA) and tested in the MIR. A 4.5-fold increase in output concentration and a 5-fold increase in throughput were achieved compared with the single input reactor used in previous experiments. However, conversion in the MIR was reduced at higher concentrations, suggesting that the reaction in the MIR was being inhibited by the evolution of carbon dioxide

Restored saltmarshes have low beta diversity due to limited topographic variation, but this can be countered by management

1. Spatial heterogeneity of species (beta diversity) is an important attribute of ecological communities, but is less frequently considered when assessing restoration success than other aspects of diversity (gamma and alpha). Differences in beta diversity between restored and natural sites may arise due to differences in environmental heterogeneity. 2. We used a nested sampling design to survey plant communities and environmental conditions (elevation, redox potential and metrics of topography) on four pairs of restored and natural saltmarshes. We assessed whether there were differences in both alpha and beta diversity between natural and restored sites and analysed their environmental drivers. 3. Topography was an important driver of plant alpha diversity and beta diversity on saltmarshes. The effects of topography were partly indirect, mediated though changes in redox potential, but topography also influenced plant communities independently of both elevation and redox. 4. Restored saltmarshes were less heterogeneous in topography than natural marshes. This reduced topography was reflected in lower beta diversity; plant communities 1 m apart in natural marshes were as dissimilar as those found 20 m apart in restored marshes. 5. Large-scale topographic manipulation carried out at one site a decade after initial restoration successfully increased topographic heterogeneity and increased beta diversity when surveyed 3 years after manipulation. These changes were still evident when resurveyed after a further 2 years. 6. Synthesis and applications. Increasing environmental heterogeneity can improve restoration outcomes by increasing beta diversity on restored sites. The effect of environmental heterogeneity is likely to be particularly strong within intertidal habitats such as saltmarshes, where small changes in topography can determine whether a species can occur at a given location. Topographic manipulation is a feasible post-restoration technique that can be applied to ensure restored saltmarshes better meet policy targets of biological, physical and functional equivalence with natural marshes

Increased Rate of Hospitalization for Diabetes and Residential Proximity of Hazardous Waste Sites

BACKGROUND: Epidemiologic studies suggest that there may be an association between environmental exposure to persistent organic pollutants (POPs) and diabetes. OBJECTIVE: The aim of this study was to test the hypothesis that residential proximity to POP-contaminated waste sites result in increased rates of hospitalization for diabetes. METHODS: We determined the number of hospitalized patients 25–74 years of age diagnosed with diabetes in New York State exclusive of New York City for the years 1993–2000. Descriptive statistics and negative binomial regression were used to compare diabetes hospitalization rates in individuals who resided in ZIP codes containing or abutting hazardous waste sites containing POPs (“POP” sites); ZIP codes containing hazardous waste sites but with wastes other than POPs (“other” sites); and ZIP codes without any identified hazardous waste sites (“clean” sites). RESULTS: Compared with the hospitalization rates for diabetes in clean sites, the rate ratios for diabetes discharges for people residing in POP sites and “other” sites, after adjustment for potential confounders were 1.23 [95% confidence interval (CI), 1.15–1.32] and 1.25 (95% CI, 1.16–1.34), respectively. In a subset of POP sites along the Hudson River, where there is higher income, less smoking, better diet, and more exercise, the rate ratio was 1.36 (95% CI, 1.26–1.47) compared to clean sites. CONCLUSIONS: After controlling for major confounders, we found a statistically significant increase in the rate of hospitalization for diabetes among the population residing in the ZIP codes containing toxic waste sites

Mindfulness-based stress reduction in Parkinson’s disease: a systematic review

Background: Mindfulness based stress reduction (MBSR) is increasingly being used to improve outcomes such as stress and depression in a range of long-term conditions (LTCs). While systematic reviews on MBSR have taken place for a number of conditions there remains limited information on its impact on individuals with Parkinson’s disease (PD). Methods: Medline, Central, Embase, Amed, CINAHAL were searched in March 2016. These databases were searched using a combination of MeSH subject headings where available and keywords in the title and abstracts. We also searched the reference lists of related reviews. Study quality was assessed based on questions from the Cochrane Collaboration risk of bias tool. Results: Two interventions and three papers with a total of 66 participants were included. The interventions were undertaken in Belgium (n = 27) and the USA (n = 39). One study reported significantly increased grey matter density (GMD) in the brains of the MBSR group compared to the usual care group. Significant improvements were reported in one study for a number of outcomes including PD outcomes, depression, mindfulness, and quality of life indicators. Only one intervention was of reasonable quality and both interventions failed to control for potential confounders in the analysis. Adverse events and reasons for drop-outs were not reported. There was also no reporting on the costs/benefits of the intervention or how they affected health service utilisation. Conclusion: This systematic review found limited and inconclusive evidence of the effectiveness of MBSR for PD patients. Both of the included interventions claimed positive effects for PD patients but significant outcomes were often contradicted by other results. Further trials with larger sample sizes, control groups and longer follow-ups are needed before the evidence for MBSR in PD can be conclusively judged

Champions, converts, doubters, and defectors: the impact of shifting perceptions on momentum for change

Maintaining momentum is a key influence on the ultimate success of large-scale change. In this paper, we develop theory to explain how stable vs. shifting change-supportive perceptions over time differentially influence the perceived momentum associated with goal-directed change (i.e., change-based momentum). We use cross-level polynomial regression and data obtained early and one year later within an organization implementing a lean manufacturing transformation to model changes in individual perceptions. Results suggest that momentum perceptions are higher for “Champions” (stable and high perceptions over time) as compared to “Converts” (increasing perceptions over time), but momentum perceptions are lower for “Defectors” (decreasing perceptions over time) as compared to “Doubters” (stable and low perceptions over time). We find that even if participants converge upon change-supportive perceptions later in the change process, early divergent perceptions influence subsequent momentum for the change. These findings highlight the important role of temporal shifts in perceptions for organizational change processes

Mindfulness based interventions in multiple sclerosis: a systematic review

<b>Background</b> Multiple sclerosis (MS) is a stressful condition; depression, anxiety, pain and fatigue are all common problems. Mindfulness based interventions (MBIs) mitigate stress and prevent relapse in depression and are increasingly being used in healthcare. However, there are currently no systematic reviews of MBIs in people with MS. This review aims to evaluate the effectiveness of MBIs in people with MS.<p></p> <b>Methods</b> Systematic searches were carried out in seven major databases, using both subject headings and key words. Papers were screened, data extracted, quality appraised, and analysed by two reviewers independently, using predefined criteria. Study quality was assessed using the Cochrane Collaboration risk of bias tool. Perceived stress was the primary outcome. Secondary outcomes include mental health, physical health, quality of life, and health service utilisation. Statistical meta-analysis was not possible. Disagreements were adjudicated by a third party reviewer.<p></p> <b>Results</b> Three studies (n = 183 participants) were included in the final analysis. The studies were undertaken in Wales (n = 16, randomised controlled trial - (RCT)), Switzerland (n = 150, RCT), and the United States (n = 17, controlled trial). 146 (80%) participants were female; mean age (SD) was 48.6 (9.4) years. Relapsing remitting MS was the main diagnostic category (n = 123, 67%); 43 (26%) had secondary progressive disease; and the remainder were unspecified. MBIs lasted 6–8 weeks; attrition rates were variable (5-43%); all employed pre- post- measures; two had longer follow up; one at 3, and one at 6 months. Socio-economic status of participants was not made explicit; health service utilisation and costs were not reported. No study reported on perceived stress. All studies reported quality of life (QOL), mental health (anxiety and depression), physical (fatigue, standing balance, pain), and psychosocial measures. Statistically significant beneficial effects relating to QOL, mental health, and selected physical health measures were sustained at 3- and 6- month follow up.<p></p> <b>Conclusion</b> From the limited data available, MBIs may benefit some MS patients in terms of QOL, mental health, and some physical health measures. Further studies are needed to clarify how MBIs might best serve the MS population.<p></p&gt

Negative emotions in informal feedback: The benefits of disappointment and drawbacks of anger

Using the emotions as social information (EASI) model, this study investigated the emotional, attitudinal and behavioral reactions to failure feedback by manipulating negative emotional displays (angry, disappointed or none) and the position level and relational distance of the feedback source. Undergraduate students (N = 260) responded to an organizational failure feedback vignette and completed a subsequent performance task. Results demonstrated that guilt was the complementary emotional experience following displays of disappointment, while reciprocal anger followed displays of anger. These emotional reactions served as important mediators between the emotional displays paired with the feedback message and participant responses of social behaviors, creative task performance and perceptions of the feedback source. In addition, our findings indicated that negative emotions can have positive organizational and interpersonal outcomes. Guilt in response to disappointed displays resulted in beneficial behaviors and attitudes, while anger in response to angry displays was socially detrimental. The emotion displayed during feedback provision also served as a consistent contextual factor that did not interact with the position level or relational distance of the feedback source to impact behavioral and attitudinal reactions. Overall, this study indicates that discrete negative emotions have unique social-functional properties that require further investigation.Yeshttps://us.sagepub.com/en-us/nam/manuscript-submission-guideline

The secreted triose phosphate isomerase of Brugia malayi is required to sustain microfilaria production in vivo

Human lymphatic filariasis is a major tropical disease transmitted through mosquito vectors which take up microfilarial larvae from the blood of infected subjects. Microfilariae are produced by long-lived adult parasites, which also release a suite of excretory-secretory products that have recently been subject to in-depth proteomic analysis. Surprisingly, the most abundant secreted protein of adult Brugia malayi is triose phosphate isomerase (TPI), a glycolytic enzyme usually associated with the cytosol. We now show that while TPI is a prominent target of the antibody response to infection, there is little antibody-mediated inhibition of catalytic activity by polyclonal sera. We generated a panel of twenty-three anti-TPI monoclonal antibodies and found only two were able to block TPI enzymatic activity. Immunisation of jirds with B. malayi TPI, or mice with the homologous protein from the rodent filaria Litomosoides sigmodontis, failed to induce neutralising antibodies or protective immunity. In contrast, passive transfer of neutralising monoclonal antibody to mice prior to implantation with adult B. malayi resulted in 60–70% reductions in microfilarial levels in vivo and both oocyte and microfilarial production by individual adult females. The loss of fecundity was accompanied by reduced IFNγ expression by CD4+ T cells and a higher proportion of macrophages at the site of infection. Thus, enzymatically active TPI plays an important role in the transmission cycle of B. malayi filarial parasites and is identified as a potential target for immunological and pharmacological intervention against filarial infections

Impaired decisional impulsivity in pathological videogamers

Abstract Background Pathological gaming is an emerging and poorly understood problem. Impulsivity is commonly impaired in disorders of behavioural and substance addiction, hence we sought to systematically investigate the different subtypes of decisional and motor impulsivity in a well-defined pathological gaming cohort. Methods Fifty-two pathological gaming subjects and age-, gender- and IQ-matched healthy volunteers were tested on decisional impulsivity (Information Sampling Task testing reflection impulsivity and delay discounting questionnaire testing impulsive choice), and motor impulsivity (Stop Signal Task testing motor response inhibition, and the premature responding task). We used stringent diagnostic criteria highlighting functional impairment. Results In the Information Sampling Task, pathological gaming participants sampled less evidence prior to making a decision and scored fewer points compared with healthy volunteers. Gaming severity was also negatively correlated with evidence gathered and positively correlated with sampling error and points acquired. In the delay discounting task, pathological gamers made more impulsive choices, preferring smaller immediate over larger delayed rewards. Pathological gamers made more premature responses related to comorbid nicotine use. Greater number of hours played also correlated with a Motivational Index. Greater frequency of role playing games was associated with impaired motor response inhibition and strategy games with faster Go reaction time. Conclusions We show that pathological gaming is associated with impaired decisional impulsivity with negative consequences in task performance. Decisional impulsivity may be a potential target in therapeutic management

Childhood socioeconomic position and objectively measured physical capability levels in adulthood: a systematic review and meta-analysis

<p><b>Background:</b> Grip strength, walking speed, chair rising and standing balance time are objective measures of physical capability that characterise current health and predict survival in older populations. Socioeconomic position (SEP) in childhood may influence the peak level of physical capability achieved in early adulthood, thereby affecting levels in later adulthood. We have undertaken a systematic review with meta-analyses to test the hypothesis that adverse childhood SEP is associated with lower levels of objectively measured physical capability in adulthood.</p> <p><b>Methods and Findings:</b> Relevant studies published by May 2010 were identified through literature searches using EMBASE and MEDLINE. Unpublished results were obtained from study investigators. Results were provided by all study investigators in a standard format and pooled using random-effects meta-analyses. 19 studies were included in the review. Total sample sizes in meta-analyses ranged from N = 17,215 for chair rise time to N = 1,061,855 for grip strength. Although heterogeneity was detected, there was consistent evidence in age adjusted models that lower childhood SEP was associated with modest reductions in physical capability levels in adulthood: comparing the lowest with the highest childhood SEP there was a reduction in grip strength of 0.13 standard deviations (95% CI: 0.06, 0.21), a reduction in mean walking speed of 0.07 m/s (0.05, 0.10), an increase in mean chair rise time of 6% (4%, 8%) and an odds ratio of an inability to balance for 5s of 1.26 (1.02, 1.55). Adjustment for the potential mediating factors, adult SEP and body size attenuated associations greatly. However, despite this attenuation, for walking speed and chair rise time, there was still evidence of moderate associations.</p> <p><b>Conclusions:</b> Policies targeting socioeconomic inequalities in childhood may have additional benefits in promoting the maintenance of independence in later life.</p&gt