Lovastatin biosynthesis depends on the carbon-nitrogen proportion: model development and controller design

Lovastatin biosynthesis depends on the relative concentrations of dissolved oxygen and the carbon and nitrogen resources. An elucidation of the underlying relationship would facilitate the derivation of a controller for the improvement of lovastatin yield in bioprocesses. To achieve this goal, batch submerged cultivation experiments of lovastatin production by Aspergillus flavipus BICC 5174, using both lactose and glucose as carbon sources, were performed in a 7 liter bioreactor and the data used to determine how the relative concentrations of lactose, glucose, glutamine and oxygen affected lovastatin yield. A model was developed based on these results and its prediction was validated using an independent set of batch data obtained from a 15-liter bioreactor using five statistical measures, including the Willmott index of agreement. A nonlinear controller was designed considering that dissolved oxygen and lactose concentrations could be measured online, and using the lactose feed rate and airflow rate as process inputs. Simulation experiments were performed to demonstrate that a practical implementation of the nonlinear controller would result in satisfactory outcomes. This is the first model that correlates lovastatin biosynthesis to carbon-nitrogen proportion and possesses a structure suitable for implementing a strategy for controlling lovastatin production.

Using mixed-methods to examine teachers’ attitudes to educational change:The case of the Skills for Life strategy for improving adult literacy and numeracy skills in England.

This paper reports on a longitudinal study that examines how a national reform introduced in England in the field of adult literacy, language, and numeracy is affecting teachers. The paper focuses on the use of a mixed methodology to explore teachers' attitudes to the reform and how these change over time. The quantitative strand includes the construction and use of a Likert-type instrument for measuring the attitudes of a panel of 1,500 teachers. The qualitative strand builds on the quantitative results and includes focus groups and in-depth interviews with a subsample of teachers in the panel. As the study is still in its initial phase, the purpose is not to present findings, but to discuss how quantitative and qualitative evidence can be combined in evaluation research.

Physical activity assessment in practice: a mixed methods study of GPPAQ use in primary care

Background: Insufficient physical activity (PA) levels which increase the risk of chronic disease are reported by almost two-thirds of the population. More evidence is needed about how PA promotion can be effectively implemented in general practice (GP), particularly in socio-economically disadvantaged communities. One tool recommended for the assessment of PA in GP and supported by NICE (National Institute for Health and Care Excellence) is The General Practice Physical Activity Questionnaire (GPPAQ) but details of how it may be used and of its acceptability to practitioners and patients are limited. This study aims to examine aspects of GPPAQ administration in non-urgent patient contacts using different primary care electronic recording systems and to explore the views of health professionals regarding its use.

Methods: Four general practices, selected because of their location within socio-economically disadvantaged areas, were invited to administer GPPAQs to patients, aged 35-75 years, attending non-urgent consultations, over two-week periods. They used different methods of administration and different electronic medical record systems (EMIS, Premiere, Vision). Participants’ (general practitioners (GPs), nurses and receptionists) views regarding GPPAQ use were explored via questionnaires and focus groups.

Results: Of 2,154 eligible consultations, 192 (8.9%) completed GPPAQs; of these 83 (43%) were categorised as inactive. All practices were located within areas ranked as being in the tertile of greatest socio-economic deprivation in Northern Ireland. GPs/nurses in two practices invited completion of the GPPAQ, receptionists did so in two. One practice used an electronic template; three used paper copies of the questionnaires. End-of-study questionnaires, completed by 11 GPs, 3 nurses and 2 receptionists and two focus groups, with GPs (n = 8) and nurses (n = 4) indicated that practitioners considered the GPPAQ easy to use but not in every consultation. Its use extended consultation time, particularly for patients with complex problems who could potentially benefit from PA promotion.

Conclusions: GPs and nurses reported that the GPPAQ itself was an easy tool with which to assess PA levels in general practice and feasible to use in a range of electronic record systems but integration within routine practice is constrained by time and complex consultations. Further exploration of ways to facilitate PA promotion into practice is needed.

How well do the public understand palliative care? A mixed methods study

Background: International research suggests that the general public appear to be confused about what palliative care is and who provides it.1 2 An understanding of public views is needed in order to target education and policy campaigns and to manage future needs, expectations and resourcing of care.

Aim: The aim of this study was to establish the current levels of awareness and perceptions of palliative care among the general public in Northern Ireland.

Methods: A mixed methods study comprising two phases was undertaken. A community-based cross-sectional survey with a population of 3,557 individuals aged over 17 years was performed. Information was collected using a structured questionnaire consisting of 17 items. Open questions were subject to content analysis; closed questions were subject to descriptive statistics with inferential testing as appropriate. This was followed by semi structured telephone interviews (n=50).

Results: Responses indicated limited knowledge about palliative care. Respondents who worked in healthcare themselves or who had a close relative or friend who had used a palliative care service were more aware of palliative care and the availability of different palliative care services. The main barriers to raising awareness were fear, lack of interaction with health services and perception of lack of resources. A key aspect identified for promoting palliative care was the development of understanding and use of the term itself and targeted educational strategies.

Conclusions: Public awareness of the concept of palliative care and of service availability remains insufficient. An increased awareness of palliative care is needed, in order to improve knowledge of and access to services when required, empower individuals, involve communities and ultimately to improve the delivery of palliative and end-of-life care.

Self-assembly of hybrid organic–inorganic polyoxovanadates: functionalised mixed-valent clusters and molecular cages’

Herein we report the intra- and inter-molecular assembly of a {V5O9} subunit. This mixed-valent structural motif can be stabilised as [V5O9(L1–3)4]5−/9− (1–3) by a range of organoarsonate ligands (L1–L3) whose secondary functionalities influence its packing arrangement within the crystal structures. Variation of the reaction conditions results in the dodecanuclear cage structure [V12O14(OH)4(L1)10]4− (4) where two modified convex building units are linked via two dimeric {O4VIV(OH)2VIVO4} moieties. Bi-functional phosphonate ligands, L4–L6 allow the intramolecular connectivity of the {V5O9} subunit to give hybrid capsules [V10O18(L4–6)4]10− (5–7). The dimensions of the electrophilic cavities of the capsular entities are determined by the incorporated ligand type. Mass spectrometry experiments confirm the stability of the complexes in solution. We investigate and model the temperature-dependent magnetic properties of representative complexes 1, 4, 6 and 7 and provide preliminary cell-viability studies of three different cancer cell lines with respect to Na8H2[6]·36H2O and Na8H2[7]·2DMF·29H2O.

Natural variation of rice strigolactone biosynthesis is associated with the deletion of two MAX1 orthologs

Rice (Oryza sativa) cultivar Azucena--belonging to the Japonica subspecies--exudes high strigolactone (SL) levels and induces high germination of the root parasitic plant Striga hermonthica. Consistent with the fact that SLs also inhibit shoot branching, Azucena is a low-tillering variety. In contrast, Bala, an Indica cultivar, is a low-SL producer, stimulates less Striga germination, and is highly tillered. Using a Bala × Azucena F6 population, a major quantitative trait loci--qSLB1.1--for the exudation of SL, tillering, and induction of Striga germination was detected on chromosome 1. Sequence analysis of the corresponding locus revealed a rearrangement of a 51- to 59-kbp stretch between 28.9 and 29 Mbp in the Bala genome, resulting in the deletion of two cytochrome P450 genes--SLB1 and SLB2--with high homology to the Arabidopsis SL biosynthesis gene, MAX1. Both rice genes rescue the Arabidopsis max1-1 highly branched mutant phenotype and increase the production of the SL, ent-2'-epi-5-deoxystrigol, when overexpressed in Bala. Furthermore, analysis of this region in 367 cultivars of the publicly available Rice Diversity Panel population shows that the rearrangement at this locus is a recurrent natural trait associated with the Indica/Japonica divide in rice.

Filling the gap: A 60 ky record of mixed carbonate-siliciclastic turbidite deposition from the Great Barrier Reef

Late Pleistocene to Holocene margin sedimentation on the Great Barrier Reef, a mixed carbonatesiliciclastic margin, has been explained by a transgressive shedding model. This model has challenged widely accepted sequence stratigraphic models in terms of the timing and type of sediment (i.e. carbonate vs. siliciclastic) deposited during sea-level oscillations. However, this model documents only hemipelagic sedimentation and the contribution of coarse-grained turbidite deposition, and the role of submarine canyons in this process, remain elusive on this archetypal margin. Here we present a new model of turbidite deposition for the last 60 ky in the north-eastern Australia margin. Using highresolution bathymetry, 58 new and existing radiometric ages, and the composition of 81 turbidites from 15 piston cores, we found that the spatial and temporal variation of turbidites is controlled by the relationship between sea-level change and the variable physiography along the margin. Siliciclastic and mixed carbonate-siliciclastic turbidites were linked to canyons indenting the shelf-break and the welldeveloped shelf-edge reef barriers that stored sediment behind them. Turbidite deposition was sustained while the sea-level position allowed the connection and sediment bypassing through the interreef passages and canyons. Carbonate turbidites dominated in regions with more open conditions at the outer-shelf and where slope-confined canyons dominated or where canyons are generally less abundant. The turn-on and maintenance of carbonate production during sea-level fluctuations also influenced the timing of carbonate turbidite deposition. We show that a fundamental understanding of the variable physiography inherent to mixed carbonate-siliciclastic margins is essential to accurately interpret deep-water, coarse-grained deposition within a sequence stratigraphic context. 

Preliminary investigation of mixed adsorbents for the removal of copper and methylene blue from aqueous solutions

With most recent studies being focused on the development of
advanced chemical adsorbents, this paper investigates the possibility of
using two natural low-cost materials for selective adsorption. Multiadsorbent
systems containing tea waste and dolomite have been tested for
their effectiveness in the removal of copper and methylene blue from
aqueous solutions. The effects of contact time, solution pH and
adsorption isotherms on the sorption behaviour were investigated. The
Langmuir and Freundlich isotherms adequately described the adsorption of
copper ions and methylene blue by both materials in different systems.
The highest adsorption capacities for Cu and MB were calculated as 237.7
at pH 4.5 and 150.44 mg.g‒1 at pH 7 for DO and TW+DO respectively. Tea
waste (TW) and dolomite (DO) were characterized by Fourier transform
infrared spectroscopy, scanning electron microscopy and Energy dispersive
X-ray analysis. The removal of Cu and MB by dolomite was mainly via
surface complexation while physisorption was responsible for most of the
Cu and MB adsorption onto tea waste. Identifying the fundamental mechanisms and behaviour is key to the development of practical multi-adsorbent packed columns.

Elucidation of the Burkholderia cenocepacia hopanoid biosynthesis pathway uncovers functions for conserved proteins in hopanoid-producing bacteria

Hopanoids are bacterial surrogates of eukaryotic membrane sterols and among earth's most abundant natural products. Their molecular fossils remain in sediments spanning more than a billion years. However, hopanoid metabolism and function are not fully understood. Burkholderia species are environmental opportunistic pathogens that produce hopanoids and also occupy diverse ecological niches. We investigated hopanoids biosynthesis in Burkholderia cenocepacia by deletion mutagenesis and structural characterization of the hopanoids produced by the mutants. The enzymes encoded by hpnH and hpnG were essential for production of all C35 extended hopanoids, including bacteriohopanetetrol (BHT), BHT glucosamine and BHT cyclitol ether. Deletion of hpnI resulted in BHT production, while ΔhpnJ produced only BHT glucosamine. Thus, HpnI is required for BHT glucosamine production while HpnJ is responsible for its conversion to the cyclitol ether. The ΔhpnH and ΔhpnG mutants could not grow under any stress condition tested, whereas ΔhpnI, ΔhpnJ and ΔhpnK displayed wild-type growth rates when exposed to detergent, but varying levels of sensitivity to low pH and polymyxin B. This study not only elucidates the biosynthetic pathway of hopanoids in B. cenocepacia, but also uncovers a biosynthetic role for the conserved proteins HpnI, HpnJ and HpnK in other hopanoid-producing bacteria.whereas ΔhpnI, ΔhpnJ and ΔhpnK displayed wild-type growth rates when exposed to detergent, but varying levels of sensitivity to low pH and polymyxin B. This study not only elucidates the biosynthetic pathway of hopanoids in B. cenocepacia, but also uncovers a biosynthetic role for the conserved proteins HpnI, HpnJ and HpnK in other hopanoid-producing bacteria.

Developing a best practice model for partnership practice between specialist palliative care and intellectual disability services: a mixed methods study

Background: The lack of access to good quality palliative care for people with intellectual disabilities is highlighted in the international literature. In response, more partnership practice in end-of-life care is proposed. 
Aim: This study aimed to develop a best practice model to guide and promote partnership practice between specialist palliative care and intellectual disability services. 
Design: A mixed methods research design involving two phases was used, underpinned by a conceptual model for partnership practice. 
Setting/participants: Phase 1 involved scoping end-of-life care to people with intellectual disability, based on self-completed questionnaires. In all, 47 of 66 (71.2%) services responded. In Phase 2, semi-structured interviews were undertaken with a purposive sample recruited of 30 health and social care professionals working in intellectual disability and palliative care services, who had provided palliative care to someone with intellectual disability. For both phases, data were collected from primary and secondary care in one region of the United Kingdom. 
Results: In Phase 1, examples of good practice were apparent. However, partnership practice was infrequent and unmet educational needs were identified. Four themes emerged from the interviews in Phase 2: challenges and issues in end-of-life care, sharing and learning, supporting and empowering and partnership in practice. 
Conclusion: Joint working and learning between intellectual disability and specialist palliative care were seen as key and fundamental. A framework for partnership practice between both services has been developed which could have international applicability and should be explored with other services in end-of-life care.

The Management of Long-Term Sickness Absence in Large Public Sector Healthcare Organisations: A Realist Evaluation Using Mixed Methods

Purpose The success of measures to reduce long-term sickness absence (LTSA) in public sector organisations is contingent on organisational context. This realist evaluation investigates how interventions interact with context to influence successful management of LTSA. Methods Multi-method case study in three Health and Social Care Trusts in Northern Ireland comprising realist literature review, semi-structured interviews (61 participants), Process-Mapping and feedback meetings (59 participants), observation of training, analysis of documents. Results Important activities included early intervention; workplace-based occupational rehabilitation; robust sickness absence policies with clear trigger points for action. Used appropriately, in a context of good interpersonal and interdepartmental communication and shared goals, these are able to increase the motivation of staff to return to work. Line managers are encouraged to take a proactive approach when senior managers provide support and accountability. Hindering factors: delayed intervention; inconsistent implementation of policy and procedure; lack of resources; organisational complexity; stakeholders misunderstanding each other’s goals and motives. Conclusions Different mechanisms have the potential to encourage common motivations for earlier return from LTSA, such as employees feeling that they have the support of their line manager to return to work and having the confidence to do so. Line managers’ proactively engage when they have confidence in the support of seniors and in their own ability to address LTSA. Fostering these motivations calls for a thoughtful, diagnostic process, taking into account the contextual factors (and whether they can be modified) and considering how a given intervention can be used to trigger the appropriate mechanisms.