Opportunities for Process Control and Quality Assurance Using Online NIR Analysis to a Continuous Wet Granulation Tableting Line

This paper investigates the application of online near-infrared measurements as a means to measure blend uniformity in a continuous tableting line. Underlying all the monitoring and control methods is the ability to measure key tablet properties online at a rate suitable for control purposes. The use of NIR to determine any deviations in blend uniformity is demonstrated by interpreting the relevant spectral signature allowing quantitative information to be acquired for process monitoring and quality assurance. In addition to demonstrating the functionality of the NIR probe, the practical issues arising in the application are discussed. The composition of the blend was measured using an NIR probe over a range of concentrations and the results were calculated comparing sub unit dose scale of scrutiny of small populations. This was compared with predicted product quality for whole tablets over the whole production period. This technique has demonstrated how data collected online can be used to successfully predict the quality of the whole production run for the purposes of real-time product quality assurance

Utilisation of key descriptors from protein sequence data to aid bioprocess route selection

The large-scale manufacture of biological products results in the generation of significant quantities of process information that can be used to inform future design decisions. Currently this information is not exploited to its full potential. The challenge is thus to identify and/or develop tools that allow the utilisation of this valuable resource. The main objective of the research reported in this paper was to investigate whether it was possible to utilise information, in particular that extracted from protein sequence data, from previous processes, with the goal of informing process route selection early in development. The approach adopted draws on tools in the areas of data mining and pattern recognition including the techniques of Fisher correlation score and self-organising maps. The methodology developed was applied to two case studies utilising data from the amino acid sequences of 41 proteins previously developed at Avecia Biologics, along with associated information relating to the downstream processing steps used during their large scale manufacture. The results demonstrate that information from previous processes can be used to inform process route selection

Habitat structure: a fundamental concept and framework for urban soil ecology

Habitat structure is defined as the composition and arrangement of physical matter at a location. Although habitat structure is the physical template underlying ecological patterns and processes, the concept is relatively unappreciated and underdeveloped in ecology. However, it provides a fundamental concept for urban ecology because human activities in urban ecosystems are often targeted toward management of habitat structure. In addition, the concept emphasizes the fine-scale, on-the-ground perspective needed in the study of urban soil ecology. To illustrate this, urban soil ecology research is summarized from the perspective of habitat structure effects. Among the key conclusions emerging from the literature review are: (1) habitat structure provides a unifying theme for multivariate research about urban soil ecology; (2) heterogeneous urban habitat structures influence soil ecological variables in different ways; (3) more research is needed to understand relationships among sociological variables, habitat structure patterns and urban soil ecology. To stimulate urban soil ecology research, a conceptual framework is presented to show the direct and indirect relationships among habitat structure and ecological variables. Because habitat structure serves as a physical link between sociocultural and ecological systems, it can be used as a focus for interdisciplinary and applied research (e.g., pest management) about the multiple, interactive effects of urbanization on the ecology of soils

Consistent phenological shifts in the making of a biodiversity hotspot: the Cape flora

Background The best documented survival responses of organisms to past climate change on short (glacial-interglacial) timescales are distributional shifts. Despite ample evidence on such timescales for local adaptations of populations at specific sites, the long-term impacts of such changes on evolutionary significant units in response to past climatic change have been little documented. Here we use phylogenies to reconstruct changes in distribution and flowering ecology of the Cape flora - South Africa's biodiversity hotspot - through a period of past (Neogene and Quaternary) changes in the seasonality of rainfall over a timescale of several million years. Results Forty-three distributional and phenological shifts consistent with past climatic change occur across the flora, and a comparable number of clades underwent adaptive changes in their flowering phenology (9 clades; half of the clades investigated) as underwent distributional shifts (12 clades; two thirds of the clades investigated). Of extant Cape angiosperm species, 14-41% have been contributed by lineages that show distributional shifts consistent with past climate change, yet a similar proportion (14-55%) arose from lineages that shifted flowering phenology. Conclusions Adaptive changes in ecology at the scale we uncover in the Cape and consistent with past climatic change have not been documented for other floras. Shifts in climate tolerance appear to have been more important in this flora than is currently appreciated, and lineages that underwent such shifts went on to contribute a high proportion of the flora's extant species diversity. That shifts in phenology, on an evolutionary timescale and on such a scale, have not yet been detected for other floras is likely a result of the method used; shifts in flowering phenology cannot be detected in the fossil record

At What Stage of Neural Processing Does Cocaine Act to Boost Pursuit of Rewards?

Dopamine-containing neurons have been implicated in reward and decision making. One element of the supporting evidence is that cocaine, like other drugs that increase dopaminergic neurotransmission, powerfully potentiates reward seeking. We analyze this phenomenon from a novel perspective, introducing a new conceptual framework and new methodology for determining the stage(s) of neural processing at which drugs, lesions and physiological manipulations act to influence reward-seeking behavior. Cocaine strongly boosts the proclivity of rats to work for rewarding electrical brain stimulation. We show that the conventional conceptual framework and methods do not distinguish between three conflicting accounts of how the drug produces this effect: increased sensitivity of brain reward circuitry, increased gain, or decreased subjective reward costs. Sensitivity determines the stimulation strength required to produce a reward of a given intensity (a measure analogous to the KM of an enzyme) whereas gain determines the maximum intensity attainable (a measure analogous to the vmax of an enzyme-catalyzed reaction). To distinguish sensitivity changes from the other determinants, we measured and modeled reward seeking as a function of both stimulation strength and opportunity cost. The principal effect of cocaine was a two-fourfold increase in willingness to pay for the electrical reward, an effect consistent with increased gain or decreased subjective cost. This finding challenges the long-standing view that cocaine increases the sensitivity of brain reward circuitry. We discuss the implications of the results and the analytic approach for theories of how dopaminergic neurons and other diffuse modulatory brain systems contribute to reward pursuit, and we explore the implications of the conceptual framework for the study of natural rewards, drug reward, and mood

Perivascular Fat and the Microcirculation: Relevance to Insulin Resistance, Diabetes, and Cardiovascular Disease

Type 2 diabetes and its major risk factor, obesity, are a growing burden for public health. The mechanisms that connect obesity and its related disorders, such as insulin resistance, type 2 diabetes, and hypertension, are still undefined. Microvascular dysfunction may be a pathophysiologic link between insulin resistance and hypertension in obesity. Many studies have shown that adipose tissue-derived substances (adipokines) interact with (micro)vascular function and influence insulin sensitivity. In the past, research focused on adipokines from perivascular adipose tissue (PVAT). In this review, we focus on the interactions between adipokines, predominantly from PVAT, and microvascular function in relation to the development of insulin resistance, diabetes, and cardiovascular disease

A narrative review on the similarities and dissimilarities between myalgic encephalomyelitis/chronic fatigue syndrome (me/cfs) and sickness behavior

It is of importance whether myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a variant of sickness behavior. The latter is induced by acute infections/injury being principally mediated through proinflammatory cytokines. Sickness is a beneficial behavioral response that serves to enhance recovery, conserves energy and plays a role in the resolution of inflammation. There are behavioral/symptomatic similarities (for example, fatigue, malaise, hyperalgesia) and dissimilarities (gastrointestinal symptoms, anorexia and weight loss) between sickness and ME/CFS. While sickness is an adaptive response induced by proinflammatory cytokines, ME/CFS is a chronic, disabling disorder, where the pathophysiology is related to activation of immunoinflammatory and oxidative pathways and autoimmune responses. While sickness behavior is a state of energy conservation, which plays a role in combating pathogens, ME/CFS is a chronic disease underpinned by a state of energy depletion. While sickness is an acute response to infection/injury, the trigger factors in ME/CFS are less well defined and encompass acute and chronic infections, as well as inflammatory or autoimmune diseases. It is concluded that sickness behavior and ME/CFS are two different conditions

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700