The 2P-K Framework: A Personal Knowledge Measurement Framework for the Pharmaceutical Industry

Knowledge is a dynamic human process to justify our personal belief in pursuit of the truth. The intellectual output of any organisation is reliant upon the individual people within that organisation. Despite the eminent role of personal knowledge in organisations, personal knowledge management and measurement have received little attention, particularly in pharmaceutical manufacturing. The pharmaceutical industry is one of the pillars of the global economy and a knowledge-intensive sector where knowledge is described as the second product after medicines. The need of measurement to achieve effective management is not a new concept in management literature. This study offers an explanatory framework for personal knowledge, its underlying constructs and observed measures in the pharmaceutical manufacturing context. Following a sequential mixed method research (MMR) design, the researcher developed a measurement framework based on the thematic analysis of fifteen semi-structured interviews with industry experts and considering the extant academic and regulatory literature. A survey of 190 practitioners from the pharmaceutical manufacturing sector enabled quantitative testing and validation of the proposed models utilising confirmatory factor analysis. The pharmaceutical personal knowledge framework was the fruit of a comprehensive study to explain and measure the manifestations of personal knowledge in pharmaceutical organisations. The proposed framework identifies 41 personal knowledge measures reflecting six latent factors and the underlying personal knowledge. The hypothesised factors include: regulatory awareness, performance, wisdom, organisational understanding, mastership of product and process besides communication and networking skills. In order to enhance the applicability and flexibility of the measurement framework, an abbreviated 15-item form of the original framework was developed. The abbreviated pharmaceutical personal knowledge (2P-K) framework demonstrated superior model fit, better accuracy and reliability. The research results reveal that over 80% of the participant pharmaceutical organisations had a form of structured KM system. However, less than 30% integrated KM with corporate strategies suggesting that KM is still in the early stages of development in the pharmaceutical industry. Also, personal knowledge measurement is still a subjective practice and predominately an informal process. The 2P-K framework offers researchers and scholars a theoretically grounded original model for measuring personal knowledge. Also, it offers a basis for a personal knowledge measurement scale (2P-K-S) in the pharmaceutical manufacturing context. Finally, the study had some limitations. The framework survey relied on self-ratings. This might pose a risk of social desirability bias and Dunning–Kruger effect. Consequently, a 360- degree survey was suggested to achieve accurate assessments. Also, the model was developed and tested in an industry-specific context. A comparative study in similar manufacturing industries (e.g. chemical industries) is recommended to assess the validity of the current model or a modified version of it in other industries

Mechanistic Study on the Antitumor Potential of the Endocannabinoid Reuptake Inhibitor OMDM-2

Introduction: Endocannabinoid signalling has been shown to be enhanced in several cancer tissues. Previous studies propose that this up-regulation contributes to the inhibition of the cancer cell proliferation by affecting different hallmarks of cancer. However, this anti-proliferative activity is suppressed by the rapid uptake and metabolism of endocannabinoids. An inhibition of endocannabinoid metabolism at the site of tumor growth might prolong their selective antitumor activity and avoid the side effects of direct cannabinoid agonists. The present study was undertaken to investigate the anti-tumor activity of OMDM-2, an endocannabinoid reuptake inhibitor, in-vivo and in-vitro. The molecular mechanisms involved in this activity were investigated. In addition we investigated the possible optimization of the treatment by a combination of OMDM-2 with natural or benchmark chemotherapeutics. Methods: Ehrlich ascites carcinoma bearing mice were used for the in-vivo experiments (n= 287). In these experiments we evaluated the effect of a systemic administration of OMDM-2 on tumor volume, mean survival time and increase in the life span. Time course effects of OMDM-2 on tumor weights, serum transforming growth factor beta-1, and the intratumoral expression of the endoglin receptor were observed. Also the effect of OMDM-2 on angiogenesis and hematological parameters were investigated. The in-vitro anti-proliferative activity of OMDM-2 was analyzed against human breast cancer (MCF-7) and glioma cells (U-87). The involvement of the CB-1 and vanilloid (TPRV1) receptors were evaluated by applying adequate pharmacological inhibitors. The type of cell death was investigated by ELISA, DNA electrophoresis, and morphological observations. Signaling pathways were analyzed by western blots for the MAP-kinases ERK 1 and 2 as well as for AKT. The combination of OMDM-2 with curcumin or temozolomide (TMZ) or paclitaxel was evaluated by isobole, combination index, sensitization factor, and dose reduction index methods. Results: OMDM-2 showed in our in-vivo study promising anticancer and antiangiogenic activities. Both activities were not mediated by the CB-1 receptor. The TGF-B1/endoglin system appears to be involved in the mediation of the anti-tumor activity of OMDM-2 at early stages of tumor development. OMDM-2 showed significant anti-proliferative activity against both - MCF-7 and U-87 in-vitro. The receptors, the mechanisms of action, and the signaling pathways involved in this activity differ according to the type of cancer. Co-incubation of curcumin with OMDM-2 showed potent synergistic activity against MCF-7 while this drug combination may be synergistic or antagonistic against U-87 according to the ratio. Combinations of OMDM-2 with TMZ or paclitaxel were able to decrease their individual doses and to increase the sensitivity of cancer cells. Conclusions: We provided for the first time data on the possible use of OMDM-2 as an anti-cancer drug to be an alternative to direct cannabinoid receptor agonists to avoid their psychotropic and immunosuppressive side effects. In particular, combination therapies utilizing both - molecules targeting the endocannabinoid system and natural anticancer agents or benchmark chemotherapeutic agents- are a worthwhile option to be further systematically explored in the treatment of cancer

Superior Mesenteric Artery Syndrome Managed with Laparoscopic Duodenojejunostomy

BACKGROUND: Superior mesenteric artery (SMA) syndrome is a rare disorder that may be managed surgically if conservative management fails. Different surgical techniques have been described, division of the ligament of Treitz, gastrojejunostomy, and duodenojejunostomy. The aim of this case series is to show that laparoscopic duodenojejunostomy is a safe and technically feasible management for superior mesenteric artery syndrome. METHODS: In this case series, we retrospectively identified all patients who underwent laparoscopic duodenojejunostomy for SMA syndrome in our tertiary university center between December 2016 and July 2019. Data collected included demographics, presenting symptoms, comorbidities, pre and postoperative body mass index (BMI), operative approach, operative blood loss, operative duration, clinical and radiological results, in hospital/30-day complications, mortality, and postoperative follow-up outcomes. RESULTS: We identified eleven patients, 10 females and 1 male, with a median age 23 years (range 17–43 years). All patients had refractory symptoms after a minimum of two months of conservative management and subsequently underwent laparoscopic duodenojejunostomy. There were no intraoperative complications and no in-hospital or 30-day postoperative mortality or complications were identified. Follow-up data showed complete resolution in 73% of patients (n = 8) and only one patient with no improvement postoperatively. Results also showed a median BMI increase of 2 kg/m(2) (range 1–9 kg/m(2)) at a median follow-up of 16 months (range 4–48 months). CONCLUSION: Laparoscopic duodenojejunostomy is a safe treatment option for SMA syndrome and should be considered when patients do not respond to conservative management

Antifungal activity of rice straw extract on some phytopathogenic fungi

The antifungal activity of allelochemicals extracted from rice straw on the radial growth rate and the activity of some hydrolyzing enzymes of Aspergillus flavus, Alternaria alternata and Botrytis cinerea were studied in vitro. Five different concentrations (2, 4, 6, 8 and 10%, w/v) of water, methanol and acetone extracts of rice straw were tested. All extracts significantly (P<0.05) inhibited the radial growth rate and protease, carboxymethyl cellulase (CMCase) and amylase activities of the tested fungal species. The most potent solvent was methanol. The present study suggests that rice straw extract had antifungal properties, thus it can be used as a natural alternative approach to synthetic fungicide.Key words: Rice straw, allelochemicals, antifungal, Aspergillus flavus, Alternaria alternata, Botrytis cinerea, amylase, protease, carboxymethyl cellulase

A hybrid process-mining approach for simulation modeling

This paper presents a hybrid Modeling and Simulation framework to address business process challenges. The framework has integrated process mining techniques in the conceptual modeling phase to support developing simulation models that are unbiased and close reflection of reality in a timely manner. The hybrid approach overcomes the pitfalls of traditional conceptual modeling by using process mining techniques to discover valuable process knowledge from the analysis of event logs. The proposed hybrid framework has been applied to an Emergency Department (ED) in order to identify performance bottlenecks and explore improvement strategies in an attempt to meet national performance targets. A large number of unique process flows (i.e. patient pathways) within the ED were uncovered and deviations from process guidelines were accurately identified. Results show that unblocking of ED outflows have a significant impact on patients length of stay (over 80% improvement) rather than increasing the ED physical capacity

Knowledge Management in the Pharmaceutical Industry: Between Academic Research and Industry Regulations

The pharmaceutical sector is one of the pillars of the world’s economy. A significant proportion of its value lies in intellectual assets generated through continuous innovation and lengthy development cycles within a strictly regulated environment. The purpose of this paper is to address the gap between knowledge management (KM) as an expanding academic discipline in the pharmaceutical industry and at the same time a growing regulatory expectation. A systematic review of 137 refereed KM articles revealed six empirical research themes in the pharmaceutical industry. In a subsequent step, the discovered themes and subthemes were compared with the extant regulatory expectations as explained in 128 regulatory guidelines. Findings shed the light on the gap between academic KM research and the current thinking of regulatory bodies. Some regulated knowledge processes were underrepresented in academic literature. The paper offers also novel insights and recommendations for future developments in academic research, regulations and/or industry

Jitter-Tolerance and Blocker-Tolerance of Delta-Sigma Analog-to-Digital Converters for Saw-Less Multi-Standard Receivers

The quest for multi-standard and software-defined radio (SDR) receivers calls for high flexibility in the receiver building-blocks so that to accommodate several wireless services using a single receiver chain in mobile handsets. A potential approach to achieve flexibility in the receiver is to move the analog-to-digital converter (ADC) closer to the antenna so that to exploit the enormous advances in digital signal processing, in terms of technology scaling, speed, and programmability. In this context, continuous-time (CT) delta-sigma (ΔƩ) ADCs show up as an attractive option. CT ΔƩ ADCs have gained significant attention in wideband receivers, owing to their amenability to operate at a higher-speed with lower power consumption compared to discrete-time (DT) implementations, inherent anti-aliasing, and robustness to sampling errors in the loop quantizer. However, as the ADC moves closer to the antenna, several blockers and interferers are present at the ADC input. Thus, it is important to investigate the sensitivities of CT ΔƩ ADCs to out-of-band (OOB) blockers and find the design considerations and solutions needed to maintain the performance of CT ΔƩ modulators in presence of OOB blockers. Also, CT ΔƩ modulators suffer from a critical limitation due to their high sensitivity to the clock-jitter in the feedback digital-to-analog converter (DAC) sampling-clock. In this context, the research work presented in this thesis is divided into two main parts. First, the effects of OOB blockers on the performance of CT ΔƩ modulators are investigated and analyzed through a detailed study. A potential solution is proposed to alleviate the effect of noise folding caused by intermodulation between OOB blockers and shaped quantization noise at the modulator input stage through current-mode integration. Second, a novel DAC solution that achieves tolerance to pulse-width jitter by spectrally shaping the jitter induced errors is presented. This jitter-tolerant DAC doesn’t add extra requirements on the slew-rate or the gain-bandwidth product of the loop filter amplifiers. The proposed DAC was implemented in a 90nm CMOS prototype chip and provided a measured attenuation for in-band jitter induced noise by 26.7dB and in-band DAC noise by 5dB, compared to conventional current-steering DAC, and consumes 719µwatts from 1.3V supply

Palate of turkey (Meleagris gallopavo): Gross Anatomical, Light and Scanning Electron Microscopical Study

This investigation aimed to determine the morphological characteristics of the palate of bronze black turkey by gross anatomy, light and scanning electron microscopy. The oral roof (palate) constitutes 87.73% of the oropharyngeal roof length, comprising two parts; rostral and caudal. The rostral part of is characterized by the presence of median palatine ridge, rostral and caudal lateral palatine ridges, narrow part of the choanal slit and three rows of palatine papillae. The median palatine ridge shows rostral continued and caudal interrupted parts. This ridge as shown by scanning electron microscopy (SEM) bears 4-5 transverse furrows at the level of the beginning of the caudal lateral palatine ridges. Numerous Periodic Acid-Schiff (PAS)-positive compound tubular mucous maxillary, palatine and sphenopterygoid salivary glands are distributed in the mucosa of the palate. From all above mentioned, it's clear that the palate in turkey reveals some different anatomical features in compared with that of the other birds

Morphological Studies on the Upper Beak of Turkey (Meleagris gallopavo)

This study was carried out to provide a detailed description about the upper beak of turkey, regarding its gross anatomical, light and scanning electron microscopic morphology. The upper beak extends in a hook like infront of the lower beak. It measures 53.80 mm long. The height and width of the upper beak increase caudalwards. SEM shows that the tip and the lateral sides of the upper beak are covered with numerous flakes of keratin. At the free tip of the beak, these keratinized flakes have an irregular appearance which may be due to desquamation of the epithelium during manipulation of foods. Immediately in front of the angle of the mouth, the lateral edge of the upper beak is characterized by the presence of transverse furrows which giving it a serrated appearance. The upper beak of the turkey consists of a bony support covered by dermal and epidermal layers