High Percentage Of Failures Research Articles

Improving the approach and the stages of new products design in the context of digital development

The relevance of this article lies in digitalization. Digital technologies have become more and more introduced into all spheres of human life. As companies transform, they rethink how they manage new product development. Despite this, a high percentage of failures is associated with problems in management at the initial stage of ego creation. They determine the functionality and characteristics of the new product. Based on this, managing the process of creating a new product becomes crucial. The aim of the study is to consider the approaches and stages of developing new products in the context of digitalization.

Immune checkpoint inhibitors in osteosarcoma: A hopeful and challenging future.

Osteosarcoma (OS), the most common malignant tumor in the musculoskeletal system, mainly occurs in adolescents. OS results in high mortality and disability rates due to a fatal metastatic tendency and subsequent iatrogenic damage caused by surgery, radiotherapy and chemotherapy. Recently, immunotherapies have resulted in promising prognoses with reduced side effects compared with traditional therapies. Immune checkpoint inhibitors (ICIs), which are a representative immunotherapy for OS, enhance the antitumor effects of immune cells. ICIs have shown satisfactory outcomes in other kinds of malignant tumors, especially hemopoietic tumors. However, there is still a high percentage of failures or severe side effects associated with the use of ICIs to treat OS, leading to far worse outcomes. To reveal the underlying mechanisms of drug resistance and side effects, recent studies elucidated several possible reasons, including the activation of other inhibitory immune cells, low immune cell infiltration in the tumor microenvironment, different immune properties of OS subtypes, and the involvement of osteogenesis and osteolysis. According to these mechanisms, researchers have developed new methods to overcome the shortcomings of ICIs. This review summarizes the recent breakthroughs in the use of ICIs to treat OS. Although numerous issues have not been solved yet, ICIs are still the most promising treatment options to cure OS in the long run.

Acute rate control in atrial fibrillation: an urgent need for the clinician.

Rate and rhythm control are still considered equivalent strategies for symptom control using the Atrial Fibrillation Better Care algorithm recommended by the recent atrial fibrillation guideline. In acute situations or critically ill patients, a personalized approach should be used for rapid rhythm or rate control. Even though electrical cardioversion is generally indicated in haemodynamically unstable patients or for rapid effective rhythm control in critically ill patients, this is not always possible due to the high percentage of failure or relapses in such patients. Rate control remains the background therapy for all these patients, and often rapid rate control is mandatory. Short and rapid-onset-acting beta-blockers are the most suitable drugs for acute rate control. Esmolol was the classical example; however, landiolol a newer very selective beta-blocker, recently included in the European atrial fibrillation guideline, has a more favourable pharmacokinetic and pharmacodynamic profile with less haemodynamic interference and is better appropriate for critically ill patients.

Building and Teaching a Statistics Curriculum for Post-Doctoral Biomedical Scientists at a Free-Standing Cancer Center

In the past decade, the cancer research community has made considerable progress in characterizing the genomic features of human tumors. Knowledge of molecular drivers of cancer has therefore increased greatly. Although the oncology community hoped that this would lead to more effective therapies, our ability to translate laboratory cancer research into clinical success has been remarkably low –only 5% of the agents demonstrated to have anticancer activity in laboratory studies went on to achieve success in phase III clinical trials. Many factors are responsible for this high percentage of failures. In addition to the biological difficulties of generalizing lab animal treatments to humans, other factors involved in driving this low rate include misuse or misunderstanding of statistical design and analysis concepts, interpretation and reporting methods. Recognizing the seriousness of these widely prevalent and correctable issues, the National Institutes of Health has called for the full engagement of the entire biomedical research enterprise to implement the resources needed to improve and sustain the statistical rigor and successful translation of preclinical cancer research. To this end, we developed a statistics curriculum for early-career preclinical cancer researchers (i.e., postdoctoral researchers) conducting laboratory research at Memorial Sloan Kettering Cancer Center as well as the broader research community. Our proposed curriculum was delivered over an eight-week period with one 60-90-minute class per week and included hands-on activities with experimental designs, data analysis and participatory dialogues. We developed an evaluation of the curriculum and have plans to make all resources available to the broader statistics and cancer research communities. In this column, we discuss our efforts to build such a statistics curriculum for post-doctoral biomedical scientists at a free-standing cancer center. We share experiences in the development of the curriculum and provide insights from the perspective of students, their laboratory leads, and collaborative biostatisticians.

THE EFFECT OF STRATEGIC PLANNING ON PROFITABILITY OF SMALL MEDIUM ENTERPRISES

Although attention is paid to the effectiveness of business and political relations in emerging economies, there is not much research that explicitly examines business and political relations in the development of small and medium enterprises (SMEs) in emerging economies. The main aim of this study is to investigate importance of strategic planning in attaining competitive advantage in SMEs of Pakistan. The data was collected from different SMEs of Pakistan based on Non probability purposive sampling technique; the data was collected through questionnaires. Descriptive statistics, correlation matrix, and linear regression model were applied for analysis. The independent variables were Vision statement, mission statement, objectives, values and SWOT analysis. According to the results of the study vision statement, mission statement, and objective were found insignificant in achieving competitive advantage whereas, a positive and significant relationship was found for value statement and SWOT analysis with competitive advantage. The results of the study suggested that in Pakistan less attention is paid on development of vison and mission statement which might be the cause of high percentage of failure among many SMEs in Pakistan. As lack of strategic preparation can cause the business to collapse when managers fail to update their goals and objectives regularly therefore strategic it is very important for SMEs to pay significant attention on its strategic planning process, as they have a very significant role in sustainable economic growth of the country.

Cast metal posts versus glass fibre posts: which treatment of choice based on cost-minimisation analysis?

Aim The aim of this randomised clinical trial based on cost-minimisation analysis was to assess and compare four post-retained restorative strategies for endodontically treated teeth.Methods A total of 225 endodontically treated teeth in 141 patients were evaluated annually between 2009 and 2018. In this sense, the teeth were divided into four groups according to the treatment strategy, where three groups were treated with glass fibre posts in combination with composite resin restorations or single metal-ceramic crown with or without ferrules, and one group was treated with cast metal posts with metal-ceramic crowns. According to the outcome of the treatment during follow-up, the teeth received additional treatments, which ranged from restoration repair, re-cementation, endodontic retreatment, apical surgery, post/crown replacement to tooth extraction and replacement through metal-ceramic implant-supported crown. Thus, cost-minimisation analysis was based on November 2018 values from the Brazilian Public Health System, considering the primary costs related to the post, restoration or crown, and incremental costs related to the outcomes during follow-up.Results Primary treatment costs were lower for the group using glass fibre posts in combination with composite resin restorations (US$27.11), while the highest costs were for the group using cast metal post with metal-ceramic crown (US$153,14). In turn, the incremental costs due to tooth removal, implant placement and metal-ceramic crown (US$363.92) were the highest, while the lowest costs were related to procedures for crown re-cementation (US$6.11) followed by repair of the resin restoration (US$16.47). In this regard, the highest percentage of failures was related to restoration fractures in the glass fibre posts in combination with the composite resin restorations group. However, the average annual cost was significantly lower in the group that used glass fibre posts in combination with composite resin restorations (p <0.001) when compared to the other groups, with or without ferrules.Conclusions The treatment of endodontically treated teeth using glass fibre posts in combination with composite resin restorations presented a significantly lower average annual cost when compared to treatments that consider the use of cast metal posts, metal-ceramic crowns, with or without ferrules.

Predictors of failure of two-stage revision in periprosthetic knee infection: a retrospective cohort study with a minimum two-year follow-up.

Despite the standardization of two-stage knee revision protocols, a high percentage of failures still occurs. Identifying the predictors of failure is necessary to determine appropriate management and counsel for patients with a periprosthetic knee infection. This study aimed to identify risk factors predicting the failure, to describe implant survival, and to report the mid-term clinical outcomes of patients undergoing two-stage revision for periprosthetic knee infection. Data of patients who underwent two-stage knee revision from 2012 to 2016 were analyzed, and 108 patients were included. The mean age was 66.6 ± 9.2years. The mean follow-up was 52.9 ± 15.6months. Logistic regression was conducted to identify predictors of treatment failure. Kaplan-Meier curves were generated to assess implant survival. Preoperative functional outcomes were compared to those registered at the final follow-up. Difficult-to-treat infections (OR = 4.2, 95% CI 1.2-14.5, p = 0.025), the number of previous surgeries (OR = 1.8, 95% CI 1.2-2.6, p = 0.005), and the level of tibial bone defect (OR = 2.3, 95% CI 1.1-4.7, p = 0.027) significantly predicted the failure of two-stage knee revision. Survivorship of implants was significantly lower for patients presenting these risk factors (p < 0.05). Mean Knee Society Score improved from 49.0 ± 12.0 to 80.2 ± 13.6 (p < 0.001). Mean Oxford Knee Score improved from 22.2 ± 4.9 to 36.1 ± 6.0 points (p < 0.001). Difficult-to-treat pathogens, the number of previous surgeries, and the level of tibial bone defect were independent risk factors of two-stage knee revision failure. Overall, the two-stage protocol provided a good survival rate and functional outcome.

Posters as a Tool to Improve Hand Hygiene among Health Science Students: Case-Control Study.

(1) Background: Numerous educational interventions have been conducted to improve hand hygiene (HH) compliance and effectiveness among nursing students, with mixed results. The aim is to evaluate the effectiveness of posters as a teaching tool and factors associated with HH quality. (2) Methods: A pre-post experimental intervention study was conducted with a total of 293 nursing students randomly assigned to two groups (experimental and control) who, before and after HH, took cell culture samples from their non-dominant hands. Only the experimental group was exposed to the poster. (3) Results: In the experimental group, significant differences were observed among students older than 22 years (p = 0.017; V = 0.188), with a higher percentage of failures (15.7% vs. 3.6%). Poster displaying was associated with passing, other variables being equal, although without statistical significance (ORa = 2.07; 95% CI = 0.81–5.26). Pre-practice hand contamination was weakly associated with lower HH quality (ORa = 0.99, 95% CI = 0.99–0.99). (4) Conclusions: The use of posters as a teaching method shows indications of efficacy. Prior hand contamination slightly affects the quality of HH. Further evaluation of teaching methods is needed to ensure good technical performance of HH to prevent the spread of infectious diseases during the COVID-19 pandemic.

The Importance of Tumor Stem Cells in Glioblastoma Resistance to Therapy.

Glioblastoma (GBM) is known to be the most common and lethal primary malignant brain tumor. Therapies against this neoplasia have a high percentage of failure, associated with the survival of self-renewing glioblastoma stem cells (GSCs), which repopulate treated tumors. In addition, despite new radical surgery protocols and the introduction of new anticancer drugs, protocols for treatment, and technical advances in radiotherapy, no significant improvement in the survival rate for GBMs has been realized. Thus, novel antitarget therapies could be used in conjunction with standard radiochemotherapy approaches. Targeted therapy, indeed, may address specific targets that play an essential role in the proliferation, survival, and invasiveness of GBM cells, including numerous molecules involved in signal transduction pathways. Significant cellular heterogeneity and the hierarchy with GSCs showing a therapy-resistant phenotype could explain tumor recurrence and local invasiveness and, therefore, may be a target for new therapies. Therefore, the forced differentiation of GSCs may be a promising new approach in GBM treatment. This article provides an updated review of the current standard and experimental therapies for GBM, as well as an overview of the molecular characteristics of GSCs, the mechanisms that activate resistance to current treatments, and a new antitumor strategy for treating GSCs for use as therapy.

Cultural and Philosophical Understanding of Game-based Learning in STEM Subjects

Several reasons have been linked to the high percentage of failure when it comes to Sciences Technolo-gy, Engineering and Mathematics (STEM) subjects for college freshmen. The Higher Learning Commission during its annual conference in 2013 did find out that the leading factor, motivation, seems to play a significant role to inspire students to get involved in the course work. Much research, both in academic journals and mainstream magazines, has been published on how traditional methods of lecturing are neither engaging nor robust enough for STEM learners. In this paper, the author explores the Game-Based Learning method (GBL) as a promising platform to assistance students in their transition from high school to college level STEM courses. Additionally it also looks into the fundamental reasons why biologically, culturally and philosophically, playing has become an essential tool in engaging the real world without having to assume the risk of unwanted consequences.

Perioral Aerosol Sequestration Suction Device Effectively Reduces Biological Cross-Contamination in Dental Procedures.

Objective The infection risk during dental procedures is a common concern for dental professionals which has increased due to coronavirus (severe acute respiratory syndrome coronavirus 2) pandemic. The development of devices to specifically mitigate cross-contamination by droplet/splatter is crucial to stop infection transmission. The objective of this study is to assess the effectiveness of a perioral suction device (Oral BioFilter, OBF) to reduce biological contamination spread during dental procedures. Materials and Methods Forty patients were randomized 1:1 to a standard professional dental hygiene treatment with OBF and without. Adenosine triphosphate (ATP) bioluminescence assay was used to evaluate the spread of potential contaminants. The total number of relative light units (RLU) from key dental operatory locations: operator’s face-shield, back of the surgical operator’s-gloves, patient’s safety-goggles, and instrumental table were measured. Percentage contamination reductions between control and OBF were compared. Statistical Analysis Primary outcome, total RLU, was analyzed by comparing the means of logged data, using a two-sided two-sample t -test. Secondary outcomes as RLU of logged data for the different locations were analyzed in the same way. Proportion of patients from whom different locations reported events (clean, acceptable, and failure) were analyzed by using Fisher’s exact test. Results For the whole dental environment, RLUs reduction (<150 units) achieved with OBF was 98.4% (97.4–99%). By dental operatory location the reduction in RLUs was from 99.6%, on the operator face-shield, to 83% on instrumental table. The control group reported a very high percentage of failures, (>300) being 100% on the surfaces closer to the patient’s mouth and decreasing to 70% on instrumental table. In contrast, the higher failure percentage in the OBF group was found on the patient’s goggles (40%), while the operator face-shield showed an absence of contamination. Conclusion OBF device has shown efficient reduction of biological aerosol cross-contamination during dental procedures as proved by ATP-bioluminescence assay. Nevertheless, for maximum safety, its use must be combined with standard protective gear such as goggles, face shield, and surgical gloves.

Cultural and Philosophical Understanding of Game-based Learning in STEM Subjects

Several reasons have been linked to the high percentage of failure when it comes to Sciences Technology, Engineering and Mathematics (STEM) subjects for college freshmen. The Higher Learning Commission during its annual conference in 2013 did find out that the leading factor, motivation, seems to play a significant role to inspire students to get involved in the course work. Much research, both in academic journals and mainstream magazines, has been published on how traditional methods of lecturing are neither engaging nor robust enough for STEM learners. In this paper, the author explores the Game-Based Learning method (GBL) as a promising platform to assistance students in their transition from high school to college level STEM courses. Additionally it also looks into the fundamental reasons why biologically, culturally and philosophically, playing has become an essential tool in engaging the real world without having to assume the risk of unwanted consequences

Long-term results of total joint arthroplasty and phalangeal hemiarthroplasty of the first metatarsophalangeal joint using the ToeFit Plus™ system

BackgroundThis paper compares long term success rate of MTP joint replacement for hallux rigidus. We provide long term results of MTP joint replacement with the use of the ToeFit Plus™ System. Materials and methodsOur group consisted of 19 total joint replacements and 12 hemiarthroplasties in 18 and 11 patients respectively, performed between 2005−2009. The average follow-up period was 12.2 years (range 9.8–13.7, SD 1.1) for total arthroplasty group and 11.1 years (range 9.5–13.9, SD 1.7) for hemiarthroplasty group. In all followed patients AOFAS score was calculated along with the range of motion assessment. ResultsAverage AOFAS score improved from 37 preoperatively to 79 at the time of last follow-up in total arthroplasty group and from 45 to 86 in the hemiarthroplasty group, with consideration to the statistically considerable difference of both groups. The total range of motion improved on average from 14° to the current 32° in patients with total arthroplasty and from 15° to 32° with hemiarthroplasty. The total number of cases that required surgical revision was 7 (37%) in total arthroplasty group and 2 (17%) in hemiarthroplasty group. ConclusionDue to the high percentage of failure that was shown in our long term results, we no longer utilise the ToeFit Plus™ System.

Therapeutic Opportunities for Repair GPCRs during Intestinal Mucosal Wound Healing

G protein-coupled receptors (GPCRs) are crucial for establishing the resolution phase following an intestinal inflammatory episode. Because current treatments for intestinal inflammation have a high percentage of failure and lead to immunosuppression, repair GPCRs have promising therapeutic potential because they trigger resolution pathways without compromising the immune response.

P1475Impact of automatic screening and parasternal rights positions in the eligibility of patients with hypertrophic cardiomyopathy for subcutaneous automatic cardioverter defibrillator implant

Abstract Background A high percentage of failures in the detection of QRS and T wave in patients (pts) with hypertrophic cardiomyopathy (HCM) have been reported. This finding would prevent them from being eligible for an implantable subcutaneous automatic defibrillator (S-ICD). However, recently 2 changes in the detection have been proposed, automatic screening and the use of right parasternal position of the lead. The aim of our work was to study if the elegibility proportion of patients was increased with both 2 advacements. Methods We included 31 patients (18 male)with a diagnosis of HCM and at least 1 risk factor for sudden death, in follow-up at the outdoor clinic of of 2 cardiology centers. We performed elegibility screening test in supine position and standing using both the automatic screening (AS) obtained by Boston Scientific Zoom Latitude programmer) and the manual (MS), to simulate the detection of the 3 vectors utilized in S-ICD detection. And both screens were registered with the surface electrodes in parasternal left and right position. A pte was considered eligible if at least one vector was correct in supine position and in standing position, well in parasternal left or right position. Results Using MS with left parasternal position, 22 patients (71%) were eligible. Adding the right parasternal lead, the eligibility increased by 10%, reaching 81%. In addition, in automatic screening, eligibility in right shifts (81%) it is 7% more than in the left and, with the addition of the rights to the left, the eligibility reaches up to 84%. Figure shows the three-lead ECG factors influencing screening pass vs failure. Conclusion AS, right parasternal lead position and the combination of right and left parasternal lead position, increase the eligibility of sICD candidates with HCM. Abstract Figure. ECG factors influencing screening pass

The use of readiness assessment for big data projects

Big data projects, including smart-city-related big data projects, are facing an alarmingly high percentage of failure. The reasons behind this phenomenon and the lessons learned from it are well researched. However, big data projects are still failing, as there is a lack of effective models to leverage the lessons learned from previous projects to evaluate an organization’s readiness for a big data project.In this paper, the authors introduce a novel readiness assessment model. This model leverages the lessons learned from previous projects and the experience of experts to be better prepared for an upcoming smart-city-related big data project. Cities can use the model to evaluate their readiness for this type of project in a structured and comprehensive way that will allow for higher chances of conducting a successful big data project.To develop the model, hierarchical decision modeling (HDM) and expert judgment quantification were used to provide the categorization and relative ranking of factors that influence smart-city-related big data projects. HDM is an effective way to understand the relationship between multiple factors and allows for expert panels to prioritize those factors. Moreover, desirability functions were used to extend the understanding of the factors’ dynamics and what needs to be done to better prepare for the challenges associated with each factor. Finally, the model was tested by applying it to several smart-city-related big data projects to show its value.This research highlights the importance of readiness assessment for conducting big data projects and provides a readiness assessment model that cities can use to prepare for an upcoming big data project.

Using ‘The Write Stuff’ Module to Enhance the Writing Skills of ESL Primary School Students

Malaysian Ministry of Education (MOE) puts a significant emphasis on improving the proficiency level of English language among students by developing numerous English programs. However, the outcomes are undesirable with the amount of investment put in. It is evident in the Primary School Evaluation Report 2018 where 25.45% of National School students failed the English language writing paper. The high percentage of failure indicates their ineptitude in writing skills. The exam-oriented learning culture has caused teachers to resort to traditional rote-learning and memorization methods which lead to meaningless teaching and no output. Hence, this study introduced a writing module, ‘The Write Stuff’ based on Project-based Learning techniques to enhance students’ writing skill. This mixed method study collected data from sixty students of two different schools. Survey questionnaires, content analysis and pre-test and post-test were used in the data collection. The results of the evaluation show an increment in students’ mean scores in the post-test which indicates that student writing skills were improving. The results also show potential use of ‘The Write Stuff’ to promote fun and active learning, as well as enhancing learners’ collaborative participation and dedication in completing the tasks in hand.

Mesenchymal stem cells for the treatment of complex perianal fistulas in patients with Crohn disease.

Treatment of perianal fistulizing Crohn's disease is demanding and burdened with a high percentage of failures, which forces clinicians to search for new, more effective therapeutic options. One of these options is the use of adipose-derived mesenchymal stem cells in local administration. Due to their multipotentiality and complex mechanism of action, stem cells are the promising new therapeutic approach for the treatment-refractory complex perianal fistulas - demonstrating both high efficacy and a favorable safety profile. The paper presents current knowledge on the mechanisms of action and manner of administration of mesenchymal stem cells, as well as the effectiveness and safety of their use in the treatment of perianal Crohn's disease based on available literature.

The Small Molecule Ephrin Receptor Inhibitor, GLPG1790, Reduces Renewal Capabilities of Cancer Stem Cells, Showing Anti-Tumour Efficacy on Preclinical Glioblastoma Models.

Therapies against glioblastoma (GBM) show a high percentage of failure associated with the survival of glioma stem cells (GSCs) that repopulate treated tumours. Forced differentiation of GSCs is a promising new approach in cancer treatment. Erythropoietin-producing hepatocellular (Eph) receptors drive tumourigenicity and stemness in GBM. We tested GLPG1790, a first small molecule with inhibition activity versus inhibitor of various Eph receptor kinases, in preclinical GBM models using in vitro and in vivo assays. GLPG1790 rapidly and persistently inhibited Ephrin-A1-mediated phosphorylation of Tyr588 and Ser897, completely blocking EphA2 receptor signalling. Similarly, this compound blocks the ephrin B2-mediated EphA3 and EphB4 tyrosine phosphorylation. This resulted in anti-glioma effects. GLPG1790 down-modulated the expression of mesenchymal markers CD44, Sox2, nestin, octamer-binding transcription factor 3/4 (Oct3/4), Nanog, CD90, and CD105, and up-regulated that of glial fibrillary acidic protein (GFAP) and pro-neural/neuronal markers, βIII tubulin, and neurofilaments. GLPG1790 reduced tumour growth in vivo. These effects were larger compared to radiation therapy (RT; U251 and T98G xenografts) and smaller than those of temozolomide (TMZ; U251 and U87MG cell models). By contrast, GLPG1790 showed effects that were higher than Radiotherapy (RT) and similar to Temozolomide (TMZ) in orthotopic U87MG and CSCs-5 models in terms of disease-free survival (DFS) and overall survival (OS). Further experiments were necessary to study possible interactions with radio- and chemotherapy. GLPG1790 demonstrated anti-tumor effects regulating both the differentiative status of Glioma Initiating Cells (GICs) and the quality of tumor microenvironment, translating into efficacy in aggressive GBM mouse models. Significant common molecular targets to radio and chemo therapy supported the combination use of GLPG1790 in ameliorative antiglioma therapy.

Acetabular Retroversion Is a Risk Factor for Less Optimal Outcome After Femoroacetabular Impingement Surgery

BackgroundPatients with acetabular retroversion are at risk of labral tear and hip pain. It is unknown whether femoroacetabular osteoplasty (FAO) without reverse periacetabular osteotomy can be used in these patients. This study evaluated the outcome of mini-open FAO in patients with acetabular retroversion and compared that to patients without acetabular retroversion. MethodsFifty-one patients (29 male, 22 female) with acetabular retroversion who had undergone FAO between 2007 and 2015 were identified. The minimum 2-year clinical and radiological outcome was compared with 550 patients without dysplasia or retroversion who underwent FAO by the same surgeon. The preoperative and postoperative alpha angle, center-edge angle, Tonnis grade, joint space, and presence of labral tear and chondral lesion were determined. ResultsThe mean age in the retroversion cohort was 27.4 ± 9.5 years compared to 34.5 ± 11.2 years in the control. The mean follow-up was 4.8 ± 1.5 years for retroversion and 4.1 ± 1.2 years for the control. The mean preoperative Short-Form 36 Health Survey and modified Harris hip score were not different between the cohorts. At the latest follow-up, the mean modified Harris hip score and Short-Form 36 Health Survey were significantly lower in the retroversion group (75.4 and 76.5) compared to the control (83.4 and 85.6). There was a higher percentage of failure among retroversion patients (13.7%) compared to the control (2.5%). ConclusionAcetabular retroversion resulting in femoroacetabular impingent may be treated by FAO, but the outcome appears to be less optimal compared to patients with femoroacetabular impingent and no evidence of dysplasia and acetabular retroversion. Hip preservation surgeons should be aware of this anatomic variation and possible inferior treatment results after FAO in these patients.