354 research outputs found
An Empirical Analysis of the Financial Impact of Supply Chain Management on Small Firms
In this article we test the value proposition hypothesis of supply chain management (SCM) by examining survey results of 570 US managers. First, we find that large firms use SCM initiatives significantly more than small firms. Second, in univariate and multivariate tests, we find that SCM leads to significant improvements in asset utilization, revenue generation, and competitive performance, regardless of firm size. These two major findings suggest that managers at small firms that are not actively engaged in SCM should reevaluate their opportunity to capture the competitive benefits of SCM that many large firms currently enjoy
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Chronic thoracic hemisection spinal cord injury in adult rats induces a progressive decline in transmission from uninjured fibers to lumbar motoneurons
Although most spinal cord injuries are anatomically incomplete, only limited functional recovery has been observed in people and rats with partial lesions. To address why surviving fibers cannot mediate more complete recovery, we evaluated the physiological and anatomical status of spared fibers after unilateral hemisection (HX) of thoracic spinal cord in adult rats. We made intracellular and extracellular recordings at L5 (below HX) in response to electrical stimulation of contralateral white matter above (T6) and below (L1) HX. Responses from T6 displayed reduced amplitude, increased latency and elevated stimulus threshold in the fibers across from HX, beginning 1-2 weeks after HX. Ultrastructural analysis revealed demyelination of intact axons contralateral to the HX, with a time course similar to the conduction changes. Behavioral studies indicated partial recovery which arrested when conduction deficits began. These findings suggest a chronic pathological state in intact fibers and necessity for prompt treatment to minimize it
Astrocyte response to motor neuron injury promotes structural synaptic plasticity via STAT3-regulated TSP-1 expression.
The role of remote astrocyte (AC) reaction to central or peripheral axonal insult is not clearly understood. Here we use a transgenic approach to compare the direct influence of normal with diminished AC reactivity on neuronal integrity and synapse recovery following extracranial facial nerve transection in mice. Our model allows straightforward interpretations of AC-neuron signalling by reducing confounding effects imposed by inflammatory cells. We show direct evidence that perineuronal reactive ACs play a major role in maintaining neuronal circuitry following distant axotomy. We reveal a novel function of astrocytic signal transducer and activator of transcription-3 (STAT3). STAT3 regulates perineuronal astrocytic process formation and re-expression of a synaptogenic molecule, thrombospondin-1 (TSP-1), apart from supporting neuronal integrity. We demonstrate that, through this new pathway, TSP-1 is responsible for the remote AC-mediated recovery of excitatory synapses onto axotomized motor neurons in adult mice. These data provide new targets for neuroprotective therapies via optimizing AC-driven plasticity.This is the final version. It was first published in Nature Communications here: http://www.nature.com/ncomms/2014/140711/ncomms5294/abs/ncomms5294.html
Novel Trial Design: CHIEF-HF
BACKGROUND: The expense of clinical trials mandates new strategies to efficiently generate evidence and test novel therapies. In this context, we designed a decentralized, patient-centered randomized clinical trial leveraging mobile technologies, rather than in-person site visits, to test the efficacy of 12 weeks of canagliflozin for the treatment of heart failure, regardless of ejection fraction or diabetes status, on the reduction of heart failure symptoms.
METHODS: One thousand nine hundred patients will be enrolled with a medical record-confirmed diagnosis of heart failure, stratified by reduced (≤40%) or preserved (\u3e40%) ejection fraction and randomized 1:1 to 100 mg daily of canagliflozin or matching placebo. The primary outcome will be the 12-week change in the total symptom score of the Kansas City Cardiomyopathy Questionnaire. Secondary outcomes will be daily step count and other scales of the Kansas City Cardiomyopathy Questionnaire.
RESULTS: The trial is currently enrolling, even in the era of the coronavirus disease 2019 (COVID-19) pandemic.
CONCLUSIONS: CHIEF-HF (Canagliflozin: Impact on Health Status, Quality of Life and Functional Status in Heart Failure) is deploying a novel model of conducting a decentralized, patient-centered, randomized clinical trial for a new indication for canagliflozin to improve the symptoms of patients with heart failure. It can model a new method for more cost-effectively testing the efficacy of treatments using mobile technologies with patient-reported outcomes as the primary clinical end point of the trial
Do agri-environment schemes result in improved water quality?
Welsh Government. Grant Number: 183/2007/0
A call to arms: setting the framework for a code of practice for mosquito management in European wetlands
1. Wetlands provide multiple services to human societies. Despite policies dedicated to their protection, current European policies do not address the need to balance mosquito management approaches to mitigate dis‐services to human health and well‐being while ensuring that wetland conservation goals are met.
2. Herein, we outline criteria for consideration when developing mosquito control programmes in European wetlands that will allow managers and public health authorities to adopt effective and ecologically sound approaches.
3. Synthesis and applications . The proposed code of practice provides practical advice to local authorities and those involved in mosquito control in order to design an integrated mosquito management strategy that aligns with current environmental legislation. Although this code of practice was developed by European experts, it is transferable to other geographical contexts, integrating the expertise and knowledge of local stakeholders and researchers from the fields of medical entomology, human and animal health and ecology
Case Report: Highlighting Male Genital Schistosomiasis (MGS) in Fishermen from the Southwestern Shoreline of Lake Malawi, Mangochi District
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Hypomorphic PCNA mutation underlies a novel human DNA repair disorder
A number of human disorders, including Cockayne syndrome, UV-sensitive syndrome, xeroderma pigmentosum and trichothiodystrophy, result from the mutation of genes encoding molecules important for nucleotide excision repair. Here, we describe a novel syndrome in which the cardinal clinical features include postnatal growth retardation, hearing loss, premature aging, telangiectasia, neurological signs and photosensitivity, resulting from a homozygous missense (p.Ser228Ile) sequence alteration of the proliferating cell nuclear antigen (PCNA). PCNA is a highly conserved sliding clamp protein essential for DNA replication and repair. Due to this fundamental role, mutations in PCNA that profoundly impair protein function would be incompatible with life. Interestingly, while the p.Ser228Ile alteration appears to have no effect on protein levels or DNA replication, patient cells exhibit significant abnormalities in response to UV irradiation displaying substantial reductions in both UV survival and RNA synthesis recovery. The p.Ser228Ile change also profoundly alters PCNA’s interaction with Flap endonuclease 1 and DNA Ligase 1, DNA metabolism enzymes. Taken together our findings detail the first mutation of PCNA in humans, associated with a unique neurodegenerative disease displaying clinical and molecular features common to other DNA repair disorders, which we show to be attributable to a hypomorphic amino acid alteration
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