The possible influence of risk management, forecasting, and personnel training in physical asset management

CITATION: Schoeman, J. S. & Vlok, P. J. 2014. The possible influence of risk management, forecasting, and personnel training in physical asset management. South African Journal of Industrial Engineering, 25(2):96-104, doi:10.7166/25-2-740.The original publication is available at http://sajie.journals.ac.zaThe work presented in this paper highlights the possible effects of risk management, forecasting, and personnel training in the physical asset management environment. Each section is taken separately, and an argument is formed as to why it is important and what portion of the physical asset management five-year budget each should receive. This paper considers the long-term and short-term benefits in its conclusion that risk management should receive 60 per cent of the budget, personnel training 25 per cent, and forecasting the final 15 per cent.Hierdie studie beklemtoon die moontlike effekte wat risiko bestuur, voorspelling van voorvalle, en die opleiding van personeel kan hê binne die fisiese bate bestuur omgewing. Die afdelings word elk apart bespreek, en ’n argument word gevorm om te sê waarom die afdeling belangrik is en watter bedrag van ’n maatskappy se vyf- jaar begroting elk moet ontvang. Die finale besluit was dat risiko ’n totaal van 60 persent van die begroting moet ontvang omdat dit so ’n breë afdeling is, die opleiding van personeel vereis 25 persent, en die voorspelling van gebeure die laaste 15 persent.http://sajie.journals.ac.za/pub/article/view/740Publisher's versio

Behavioral response of naïve and non-naïve deer to wolf urine

Large carnivores are recolonizing many regions in Europe, where their ungulate prey have lived without them for >150 years. Whether the returning large carnivores will modify ungulate behavior and indirectly affect lower trophic levels, depends on the ability of ungulates to recognize risk based on past encounters and cues indicating carnivore presence. In two case studies, we tested, by means of camera trapping, the behavioral response of deer to wolf urine. The first case study was in the Netherlands where deer (still) live in absence of wolves, and the second in Poland with long-term wolf presence. As controls we used water (no scent) and all-purpose soap (unfamiliar scent). Deer vigilance level on control plots was 20% in both case studies indicating that wolf occupancy per se does not lead to a consistent difference in behavior. Placing wolf urine did not significantly affect deer behavior in either the wolf-absent or the wolf-present area. More intense cues, or a combination of cues, are likely needed to affect deer behavior. Moreover, we found an unexpected reaction of deer towards all-purpose soap of reduced foraging (and tendency for increased vigilance) in the wolf-present area, whereas it did not affect deer behavior in the wolf-absent area. We hypothesize that deer associate all-purpose soap with human presence, causing no response in human-dominated landscapes (the Netherlands), but triggering a behavioral reaction in more remote areas (Poland). This illustrates attention should be paid to controls used in scent experiments as they may be associated differently than intended

Wolves and tree logs:Landscape-scale and fine-scale risk factors interactively influence tree regeneration

Large carnivores can reduce ungulate numbers by predation and via induced risk effects alter ungulate behavior, indirectly affecting lower trophic levels. However, predator-induced risk effects probably act at different spatial scales, which have often been ignored in trophic cascade studies. We studied how a fine-scale risk factor (distance from tree logs) affects ungulate browsing intensity and how this is modified over a landscape-scale risk gradient (distance from human settlements to wolf core) in the Białowieża forest, Poland. We found that landscape-and fine-scale risk factors strongly interacted in determining the strength and magnitude of carnivore-induced risk effects on lower trophic levels. In low-risk areas, tree logs reduced browsing intensity in small patches (approx. 4–6 m from logs), whereas in high-risk areas browsing intensity was reduced up to at least 16 m from tree logs. Moreover, the magnitude of these effects changed, with the strongest reduction in browsing intensity around tree logs in high-risk areas (up to 37%) and the smallest in low-risk areas (< 20%). Overall, the results of this study indicate that perceived risk factors act at different spatial scales, where impediments (objects blocking view and escape routes) act as a risk factor at a fine scale and carnivore distribution shapes perceived risk at the landscape scale. Moreover, these risk factors strongly interact, thereby determining the functional role of large carnivores in affecting ecosystem processes. These interactive effects should be incorporated in predator-induced trophic cascade studies to understand patterns of tree regeneration in ecosystems where large carnivores and herbivores live together

Pharmacological aspects of neonatal antidepressant withdrawal

Depression is common in reproductive age women, and continued pharmacologic treatment of depression during pregnancy may be necessary to prevent relapse, which could be harmful for both the fetus and the mother. Although data on drug safety are imperfect and incomplete, the benefits of antidepressant therapy during pregnancy generally outweigh the risks. Neonates who are exposed to antidepressant medications during gestation are at increased risk to have neonatal withdrawal syndrome, although the exact incidence of this complication is unknown because the definition of the syndrome is not clear and withdrawal reactions are probably underreported. Tricyclic antidepressant withdrawal syndrome is most likely related to muscarinergic activity and individual drug half-lives, and selective serotonin reuptake inhibitor withdrawal may be due to a decrease in available synaptic serotonin in the face of down-regulated serotonin receptors, the secondary effects of other neurotransmitters, and biological or cognitive sensitivity. Other factors that influence neonatal toxicity or withdrawal include the normal physiologic changes of pregnancy, the altered activity of CYP450 enzymes during pregnancy, drug-drug transporter (PgP and OCT3) interaction, and the presence of genetic polymorphisms in genes influencing drug metabolism. Further research is necessary

Fluorescence-guided imaging for resection margin evaluation in head and neck cancer patients using cetuximab-800CW:A quantitative dose-escalation study

Tumor-positive resection margins are present in up to 23% of head and neck cancer (HNC) surgeries, as intraoperative techniques for real-time evaluation of the resection margins are lacking. In this study, we investigated the safety and potential clinical value of fluorescence-guided imaging (FGI) for resection margin evaluation in HNC patients. We determined the optimal cetuximab-800CW dose by quantification of intrinsic fluorescence values using multi-diameter single-fiber reflectance, single-fiber fluorescence (MDSFR/SFF) spectroscopy. Methods: Five cohorts of three HNC patients received cetuximab-800CW systemically: three single dose cohorts (10, 25, 50 mg) and two cohorts pre-dosed with 75 mg unlabeled cetuximab (15 or 25 mg). Fluorescence visualization and MDSFR/SFF spectroscopy quantification was performed and were correlated to histopathology. Results: There were no study-related adverse events higher than Common Terminology Criteria for Adverse Events grade-II. Quantification of intrinsic fluorescence values showed a dose-dependent increase in background fluorescence in the single dose cohorts (p<0.001, p<0.001), which remained consistently low in the pre-dosed cohorts (p=0.6808). Resection margin status was evaluated with a sensitivity of 100% (4/4 tumor-positive margins) and specificity of 91% (10/11 tumor-negative margins). Conclusion: A pre-dose of 75 mg unlabeled cetuximab followed by 15 mg cetuximab-800CW was considered the optimal dose based on safety, fluorescence visualization and quantification of intrinsic fluorescence values. We were able to use a lower dose cetuximab-800CW than previously described, while remaining a high sensitivity for tumor detection due to application of equipment optimized for IRDye800CW detection, which was validated by quantification of intrinsic fluorescence values

Feasibility of ex vivo fluorescence imaging of angiogenesis in (non-) culprit human carotid atherosclerotic plaques using bevacizumab-800CW

Vascular endothelial growth factor-A (VEGF-A) is assumed to play a crucial role in the development and rupture of vulnerable plaques in the atherosclerotic process. We used a VEGF-A targeted fluorescent antibody (bevacizumab-IRDye800CW [bevacizumab-800CW]) to image and visualize the distribution of VEGF-A in (non-)culprit carotid plaques ex vivo. Freshly endarterectomized human plaques (n = 15) were incubated in bevacizumab-800CW ex vivo. Subsequent NIRF imaging showed a more intense fluorescent signal in the culprit plaques (n = 11) than in the non-culprit plaques (n = 3). A plaque received from an asymptomatic patient showed pathologic features similar to the culprit plaques. Cross-correlation with VEGF-A immunohistochemistry showed co-localization of VEGF-A over-expression in 91% of the fluorescent culprit plaques, while no VEGF-A expression was found in the non-culprit plaques (p < 0.0001). VEGF-A expression was co-localized with CD34, a marker for angiogenesis (p < 0.001). Ex vivo near-infrared fluorescence (NIRF) imaging by incubation with bevacizumab-800CW shows promise for visualizing VEGF-A overexpression in culprit atherosclerotic plaques in vivo

Tumor mutational load, CD8+ T cells, expression of PD-L1 and HLA class I to guide immunotherapy decisions in NSCLC patients

Objectives: A minority of NSCLC patients benefit from anti-PD1 immune checkpoint inhibitors. A rational combination of biomarkers is needed. The objective was to determine the predictive value of tumor mutational load (TML), CD8+ T cell infiltration, HLA class-I and PD-L1 expression in the tumor. Materials and methods: Metastatic NSCLC patients were prospectively included in an immune-monitoring trial (NTR7015) between April 2016-August 2017, retrospectively analyzed in FFPE tissue for TML (NGS: 409 cancer-related-genes) and by IHC staining to score PD-L1, CD8+ T cell infiltration, HLA class-I. PFS (RECISTv1.1) and OS were analyzed by Kaplan–Meier methodology. Results: 30 patients with adenocarcinoma (67%) or squamous cell carcinoma (33%) were included. High TML was associated with better PFS (p = 0.004) and OS (p = 0.025). Interaction analyses revealed that patients with both high TML and high total CD8+ T cell infiltrate (p = 0.023) or no loss of HLA class-I (p = 0.026), patients with high total CD8+ T cell infiltrate and no loss of HLA class-I (p = 0.041) or patients with both high PD-L1 and high TML (p = 0.003) or no loss of HLA class-I (p = 0.032) were significantly associated with better PFS. Unsupervised cluster analysis based on these markers revealed three sub-clusters, of which cluster-1A was overrepresented by patients with progressive disease (15 out of 16), with significant effect on PFS (p = 0.007). Conclusion: This proof-of-concept study suggests that a combination of PD-L1 expression, TML, CD8+ T cell infiltration and HLA class-I functions as a better predictive biomarker for response to anti-PD-1 immunotherapy. Consequently, refinement of this set of biomarkers and validation in a larger set of patients is warranted

When Limb Surgery Has Become the Only Life-Saving Therapy in FOP: A Case Report and Systematic Review of the Literature

Fibrodysplasia ossificans progressiva (FOP) is a rare disease in which heterotopic ossification (HO) is formed in muscles, tendons and ligaments. Traumatic events, including surgery, are discouraged as this is known to trigger a flare-up with risk of subsequent HO. Anesthetic management for patients with FOP is challenging. Cervical spine fusion, ankylosis of the temporomandibular joints, thoracic insufficiency syndrome, restrictive chest wall disease, and sensitivity to oral trauma complicate airway management and anesthesia and pose life-threatening risks. We report a patient with FOP suffering from life-threatening antibiotic resistant bacterial infected ulcers of the right lower leg and foot. The anesthetic, surgical and postoperative challenges and considerations are discussed. In addition, the literature on limb surgeries of FOP patients is systemically reviewed. The 44 year-old female patient was scheduled for a through-knee amputation. Airway and pulmonary evaluation elicited severe abnormalities, rendering standard general anesthesia a rather complication-prone approach in this patient. Thus, regional anesthesia, supplemented with intravenous analgosedation and N2O-inhalation were performed in this case. The surgery itself was securely planned to avoid any unnecessary tissue damage. Postoperatively the patient was closely monitored for FOP activity by ultrasound and [18F]PET/CT-scan. One year after surgery, a non-significant amount of HO had formed at the operated site. The systematic review revealed seventeen articles in which thirty-two limb surgeries in FOP patients were described. HO reoccurrence was described in 90% of the cases. Clinical improvement due to improved mobility of the operated joint was noted in 16% of the cases. It should be noted, though, that follow-up time was limited and no or inadequate imaging modalities were used to follow-up in the majority of these cases. To conclude, if medically urgent, limb surgery in FOP is possible even when general anesthesia is not preferred. The procedure should be well-planned, alternative techniques or procedures should be tested prior to surgery and special attention should be paid to the correct positioning of the patient. According to the literature recurrent HO should be expected after surgery of a limb, even though it was limited in the case described