The application of ‘just in time’ to reverse logistics: a feasibility study from the UK multiple retail sector

Purpose: The purpose of the research is to assess the operational feasibility of applying just in time (JIT) practices to a UK multiple retailers’ reverse logistics (RL) function for waste packaging materials, whilst also assessing possible benefits which may be derived from such an application. Research Approach: The research adopts an embedded case study approach, which included multiple analyses at different nodes of the retail and distribution operational units within the organisation. Interviews were undertaken which allowed for the creation of a narrative outlining the organisation’s operating environments and RL function dynamics, this was then compared to key JIT success factors. Findings: At the functional level there are a number of attributes within the case organisation which would positively influence the adoption of JIT processes, given their relationship with critical success factors outlined within the literature. It is also observed that where negative relationships do exist, they are mainly attitudinal in nature and thus through process reengineering and appropriate training could be averted. On balance the findings indicate that with minimal restructuring and investment the case organisation would be capable of supporting JIT processes. Possible implications of a successful JIT implementation are also discussed. These suggest that although duplicate movement within the network may occur, there would also be efficiency increases in both forward and reverse operations allowing for significant savings. Practical Impact: A new process model is proposed for the case organisations forward and reverse operations which incorporates JITP elements into the RL function. This creates a new just in time reverse logistics (JITRL) environment where collection activities are removed from forward operations, resulting in possible cost savings for the overall distribution network derived from increased efficiencies and capital expenditure. Originality: The research presented provides a unique and novel approach to the application of JIT systems, not only showing that it is possible in operational contexts, but also that JITRL systems may offer significant benefits beyond this organisation, to distribution networks in operations within a similar environment to that of the case organisation

Patient reported burden of asthma on resource use and productivity across 11 countries in europe

ACKNOWLEDGMENTS Sponsorship for this study and article processing charges were funded by Mundipharma International Limited (Cambridge, UK). All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship of this manuscript, take responsibility for the integrity of the work as a whole, and have given final approval to the version to be published. We thank Emily Taylor, Incite Marketing Planning Limited (London, UK) for assistance in data analysis and Caoimhe McKerr (Adelphi Values, Bollington, UK) for editorial assistance. Support for this assistance was funded by Mundipharma International Limited. Open Access. This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.Peer reviewedPublisher PD

Challenging the view that lack of fibre causes childhood constipation

Objectives: To assess evidence supporting the view that ‘low fibre causes childhood constipation’. Design: Triangulation integrated three approaches: a systematic review NICE guideline CG99 examining effectiveness of increasing fibre; a cohort study, Avon Longitudinal Study of Parents and Children (ALSPAC), to assess if constipation (or hard stools) can precede fibre intake at weaning; and a literature search for twin studies to calculate heredity. Setting: CG99 examined the literature regarding the effectiveness of increasing fibre. ALSPAC asked parents about: hard stools at 4 weeks, 6 months and 2.5 years and constipation at age 4–10 years, as well as fibre intake at 2 years. Twin studies and data from ALSPAC were pooled to calculate concordance of constipation comparing monozygotic and dizygous twin pairs. Participants: CG99 reported six randomised controlled trials (RCTs). ALSPAC hard stool data from 6796 children at 4 weeks, 9828 at 6 months and 9452 at 2.5 years plus constipation data on 8401 at 4–10 years were compared with fibre intake at 2 years. Twin studies had 338 and 93 twin pairs and ALSPAC added a further 45. Results: Increasing fibre did not effectively treat constipation. Hard stools at 4 weeks predated fibre and at 6 months predicted lower fibre intake at 2 years (p=0.003). Heredity explained 59% of constipation. Conclusions: RCTs indicate that increasing fibre is not an effective treatment for constipation in children. Hard stools can precede and predict later fibre intake. Genetic inheritance explains most childhood constipation. Extended treatment with stool softeners may improve fibre intake and limit long-term damaging sequelae of constipation

Prevalence and patterns of antidepressant switching amongst Primary Care patients in the UK

Objective: Non-response to antidepressant treatment is a substantial problem in primary care, and many patients with depression require additional second-line treatments. This study aimed to examine the prevalence and patterns of antidepressant switching in the UK, and identify associated demographic and clinical factors. Method: Cohort analysis of antidepressant prescribing data from the Clinical Practice Research Datalink, a large, anonymised UK primary care database. The sample included 262,844 patients who initiated antidepressant therapy between 1 January 2005 and 31 June 2011. Results: 9.3% of patients switched to a different antidepressant product, with most switches (60%) occurring within 8 weeks of the index date. The proportion switching was similar for selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants and other antidepressants (9.3%, 9.8% and 9.2%, respectively). Most switches were to an SSRI (64.5%), and this was the preferred option regardless of initial antidepressant class. Factors predictive of switching included male gender, age, and history of self-harm and psychiatric illness. Conclusion: Over one in every 11 patients who initiates antidepressant therapy will switch medication, suggesting that initial antidepressant treatment has been unsatisfactory. Evidence to guide choice of second-line treatment for individual patients is currently limited. Additional research comparing different pharmacological and psychological second-line treatment strategies is required in order to inform guidelines and improve patient outcomes. </jats:sec

The Stability of Monoclonal Antibodies

The Stability of Monoclonal Antibodies Monoclonal antibodies (mAbs) are antibodies which are homogeneous and are of constant specificity and affinity. These properties make them ideal targets for rational drug design as molecular biology techniques allows the therapy to be genetically designed to fit the disease or condition, but, the inherent instability and aggregation propensity of such protein drugs poses serious problems for the pharmaceutical industry. With these problems in mind, the stability of mAbs in solution has been extensively studied using a range of biophysical techniques. With a view to correlating thermal unfolding data with protein drug shelf-life, differential scanning calorimetry (DSC) was used to study the thermal unfolding of three mAbs (Campath-IH, 4162W94 and 1209W95). It was found that each of the antibodies unfolds irreversibly and, by complementing DSC results with results from circular dichroism (CD) and intrinsic tryptophan fluorescence spectroscopy, we show all three mAbs unfold by firstly undergoing a small change in tertiary structure which is then followed by, at a higher temperature, major changes in both tertiary and secondary structure after which all structure is lost. Kinetic analysis of these irreversible processes over a range of pH and DSC scan rates resulted in the calculation of the activation energy (EA) and rate constants of unfolding. Extrapolation of these rate constants to physiological conditions afforded an estimate of drug shelf-life which we have shown is relevant only when thermal unfolding is the only reaction resulting in protein denaturation. The effect of various additives on the thermal unfolding of the antibodies has also been studied using both DSC and fluorescence spectroscopy, in particular fluorescence quenching techniques and the use of the extrinsic fluorescent probe ANS (8-anilino-1-naphthalene sulfonic acid). These studies revealed that mannitol exerts a strong stabilising influence i.e. increases the mean unfolding temperature (Tm) whereas cyclodextrins decrease the Tm and are therefore considered destabilising additives. Cyclodextrins also prevent gross thermal aggregation of the mAbs possibly as a result of binding to exposed hydrophobic amino acid residues and masking hydrophobic patches which are indicated in aggregate formation

Effect before cause: supramodal recalibration of sensorimotor timing.

YesBackground: Our motor actions normally generate sensory events, but how do we know which events were self generated and which have external causes? Here we use temporal adaptation to investigate the processing stage and generality of our sensorimotor timing estimates. Methodology/Principal Findings: Adaptation to artificially-induced delays between action and event can produce a startling percept¿upon removal of the delay it feels as if the sensory event precedes its causative action. This temporal recalibration of action and event occurs in a quantitatively similar manner across the sensory modalities. Critically, it is robust to the replacement of one sense during the adaptation phase with another sense during the test judgment. Conclusions/Significance: Our findings suggest a high-level, supramodal recalibration mechanism. The effects are well described by a simple model which attempts to preserve the expected synchrony between action and event, but only when causality indicates it is reasonable to do so. We further demonstrate that this model successfully characterises related adaptation data from outside the sensorimotor domain

Asynchrony adaptation reveals neural population code for audio-visual timing

The relative timing of auditory and visual stimuli is a critical cue for determining whether sensory signals relate to a common source and for making inferences about causality. However, the way in which the brain represents temporal relationships remains poorly understood. Recent studies indicate that our perception of multisensory timing is flexible—adaptation to a regular inter-modal delay alters the point at which subsequent stimuli are judged to be simultaneous. Here, we measure the effect of audio-visual asynchrony adaptation on the perception of a wide range of sub-second temporal relationships. We find distinctive patterns of induced biases that are inconsistent with the previous explanations based on changes in perceptual latency. Instead, our results can be well accounted for by a neural population coding model in which: (i) relative audio-visual timing is represented by the distributed activity across a relatively small number of neurons tuned to different delays; (ii) the algorithm for reading out this population code is efficient, but subject to biases owing to under-sampling; and (iii) the effect of adaptation is to modify neuronal response gain. These results suggest that multisensory timing information is represented by a dedicated population code and that shifts in perceived simultaneity following asynchrony adaptation arise from analogous neural processes to well-known perceptual after-effects