Pronged Approach Research Articles

BCStat: A Sustainable Approach to “CollaborationStat”

Baltimore City’s CitiStat, a performance management program designed to increase productivity by requiring key indicators on a regular basis, quickly became a highly lauded model that was replicated by other governments around the world but that has had its own sustainability questioned. Based on lessons learned from the CitiStat experience, Baltimore County’s BCStat program has taken a “three pronged approach” to maximize program benefits and to address the sustainability challenges faced by CitiStat. Specificially, BCStat is focused on collaborative, cross-departmental priorities; the Stat team provides data and consulting support; and data literacy has become infused across all county departments, including programmatic assistance.

Novel Iron Chelator SK4 Drives Cytotoxicity through Inhibiting Mitochondrial Metabolism in Ovarian and Triple Negative Breast Cancer Cell Lines.

Anti-cancer therapy by iron chelation has been shown to inhibit many cellular processes including DNA replication, mitochondrial metabolism and oncogenic signalling pathways (e.g., EGFR). Iron chelator SK4 represents a double pronged approach towards treating cancer. SK4 enters through LAT1, a commonly overexpressed amino acid transporter in tumours, thus targeting iron addiction and LAT1 overexpression. The aim of this study was to characterise the mode of action of SK4 through proteomics, metabolomics, lipidomics and seahorse real-time analysis in ovarian cell line SKOV3 and triple negative breast cancer cell line MDA MB 231. Pathway enrichment of proteomics data showed an overrepresentation of metabolism related pathways. Metabolic change after SK4 exposure have been confirmed in investigations of changes in basal and maximal mitochondrial respiration using seahorse real-time analysis of mitochondrial metabolism. Metabolomics also showed an increase in AMP and glucose-1-phosphate. Interestingly, our lipidomics data show a decrease in phospholipid synthesis in the SKOV3 cells which is in contrast with previous data which showed an upregulation of ceramide driven apoptosis. In summary, our data highlight impairment of energy metabolism as a mechanism of action underlying SK4 apoptosis, but also suggest a potential role of ceramide induction in the phenotypic outcome of the cell model.

A four-prong approach for engaging biomedical engineering students

My involvement in a large medical imaging company for nearly 20 years shaped my approach to teaching biomedical engineering. These experiences are described in Medical Physics International Journal, 6,602–620, May 2021. At Boston University, I taught undergraduates using a four pronged approach. The first part included a “lessons learned” career overview lecture and discussion to incoming freshman. This talk emphasized shifting paradigms in medical device development and changing trends in research and development and how to best prepare for a biomedical engineering career by prudent course selection, practical experience and life-long networking. Second, I designed two ultrasound lab modules which were part of the mandatory physiology lab all juniors took. These laboratories provided condensed theory with hands-on experiments on imaging and Doppler processing/imaging and data analysis. Third, I taught ultrasound and medical imaging courses which included rigorous theory, applications and examples. My book, Diagnostic Ultrasound Imaging: Inside Out, second edition, is being used in ultrasound courses throughout the world. A new book and curriculum, coauthored with Peter Kaczkowski, and sponsored by Verasonics, is underway. Finally, for 15 years, I taught a usually two semester course in entrepreneurship, innovation and engineering design which culminated in a team-based senior project.

Novel iron chelator SK4 demonstrates cytotoxicity in a range of tumour derived cell lines.

Iron is an essential micronutrient due to its involvement in many cellular processes including DNA replication and OXPHOS. Tumors overexpress iron metabolism linked proteins which allow for iron accumulation driving high levels of proliferation. Our group has designed novel iron chelator SK4 which targets cancer’s “iron addiction.” SK4 comprises of two key moieties: an iron chelation moiety responsible for cytotoxicity and an amino acid moiety which allows entry through amino acid transporter LAT1. We selected LAT1 as a route of entry as it is commonly overexpressed in malignant tumors. SK4 has previously demonstrated promising results in an in vitro model for melanoma. We hypothesized SK4 would be effective against a range of tumor types. We have screened a panel of tumor-derived cell lines from different origins including breast, prostate, ovarian and cervical cancer for SK4 sensitivity and we have found a range of differential sensitivities varying from 111.3 to >500 μM. We validated the iron chelation moiety as responsible for inducing cytotoxicity through control compounds; each lacking a key moiety. Following the screen, we conducted a series of assays to elucidate the mechanism of action behind SK4 cytotoxicity. SK4 was shown to induce apoptosis in triple negative breast cancer cell line MDA MB 231 but not ovarian cancer cell line SKOV3 suggesting SK4 may induce different modes of cell death in each cell line. As MDA MB 231 cells harbor a mutation in p53, we conclude SK4 is capable of inducing apoptosis in a p53-independent manner. SK4 upregulated NDRG1 expression in MDA MB 231 and SKOV3 cells. Interestingly, knockdown of NDRG1 antagonized SK4 in MDA MB 231 cells but not SKOV3 cells suggesting SK4’s mechanism of action may be mediated through NDRG1 in MDA MB 231 cells. In conclusion, we have shown tagging iron chelators with an amino acid moiety to allow entry through the LAT1 transporter represents a double pronged approach to cancer therapy, targeting “iron addiction” and amino acid metabolism dysregulation.

Spectrum of β-Thalassemia and Other Hemoglobinopathies in the Saurashtra Region of Gujarat, India: Analysis of a Large Population Screening Program

Hemoglobinopathies are common genetic disorders of the hemoglobin (Hb) molecule. Globally, 7.0% of the population are carriers of thalassemia with 300,000–400,000 affected births each year. There are >40 million carriers of β-thalassemia (β-thal) in India with 10,000–12,000 affected births every year. This makes control programs crucial in this vast and diverse country. The present study was undertaken to find out the burden of hemoglobinopathies, and in particular, the prevalence of β-thal carriers in the population of Saurashtra region of Gujarat in Western India. A total of 16,780 individuals, including school and college students, were screened. Complete blood counts (CBCs) and high performance liquid chromatography (HPLC) analysis were performed. We detected 1891 (11.26%) individuals with different hemoglobinopathies, of whom 758 (4.52%) were diagnosed to carry β-thal trait, 104 (0.62%) carried Hb D-Punjab (HBB: c.364G>C) trait, 61 (0.36%) carried sickle cell trait, 32 (0.19%) carried δβ-thal trait/HPFH (hereditary persistence of fetal Hb) trait, and other hemoglobinopathies were identified in smaller numbers (0.15%). We encountered 27 individuals with mean corpuscular Hb (MCH) <27.0 pg and mean corpuscular volume (MCV) <80.0 fL levels, who had borderline Hb A2 levels (3.2–3.5%). Twenty castes showed the presence of β-thal or other hemoglobinopathies. A high prevalence of β-thal was found in the Sindhis (11.67%), Lohanas (9.71%), Brahmins (6.31%), Bharvads (6.94%), Harijans (7.57%) and Vankars (7.77%). All the heterozygotes were given appropriate counseling. A multi pronged approach, including screening of high school and college students, needs to be considered for this vast and ethnically diverse country to reduce the burden of hemoglobinopathies.

Occupational multi-level responsiveness: Describing the skills used by occupational therapists working with children seeking asylum in Australia

Background Children seeking asylum face occupational deprivation and human rights violations. No research has investigated how occupational therapists work with child asylum seekers. The World Federation of Occupational Therapists promotes the Canadian Model of Client-Centred Enablement (CMCE) for occupational therapists working to promote human rights. Aims/objectives This research investigates use of CMCE skills to investigate skills occupational therapists use when working with child asylum seekers in Australian immigration detention. Material and methods Interpretive description guided this investigation and purposive sampling was used to recruit 10 occupational therapists. Semi-structured interviews were conducted and thematically analysed. Results Occupational multi-level responsiveness, an overarching practice skill, involved keying into individual, family and socio-political levels to respond to occupational injustices. A wide array of practice skills extending beyond the CMCE framework were used in a nuanced and interwoven manner spanning multiple levels. Conclusions Occupational multi-level responsiveness described occupational therapists working across macro-, meso- and micro-levels. Significance Understanding and enacting occupational multi-level responsiveness may support occupational therapists to plan and implement effective strategies when tackling occupational injustices. The skills identified may be applicable to other complex socio-political fields of practice. More research is needed. Further research should also investigate the occupational experiences of children seeking asylum. KEY POINTS Occupational therapists working with child asylum seekers in Australia take a multi-level approach, responding to individuals, families and socio-political structures. A three pronged approach to implementation of the occupational therapy practice process could support multi-level responsiveness to enhance practice that addresses occupational injustices. CMCE skills are not exhaustive and therapists discussed using other skills beyond those listed in the CMCE. Additional skills reflected humility and efforts towards more equal relationships between therapists and clients.

Microbial communities reveal impacts of unconventional oil and gas development on headwater streams

The demand for natural gas has led to the development of techniques used to access unconventional oil and natural gas (UOG) resources, due to the novelty of UOG, the potential impacts to freshwater ecosystems are not fully understood. We used a dual pronged approach to study the effects of UOG development on microbial biodiversity and function via a laboratory microcosm experiment and a survey study of streams with and without UOG development within their watersheds. The microcosm experiment simulated stream contamination with produced water, a byproduct of UOG operations, using sediment collected from one high water-quality stream and two low water-quality streams. For the survey study, biofilm and sediment samples were collected from streams experiencing varying levels of UOG development. In the microcosm experiment, produced water decreased microbial aerobic and anaerobic CO2 production in the high water-quality stream sediment but had a positive effect on this microbial activity in the lower water-quality stream sediments, suggesting habitat degradation alters the response of microbes to contaminants. Results from the stream survey indicate UOG development alters stream water temperature, chemistry, sediment aerobic and anaerobic CO2 production, and microbial community biodiversity in both sediments and biofilms. Correlations among UOG associated land use, environmental, and microbial variables suggest increases in light availability and sediment delivery to streams, due to deforestation and land disturbance, impact stream microbial communities and their function. Consistent changes in the relative abundance of bacterial taxa suggest microorganisms may be good indicators of the environmental changes associated with UOG development. The observed impacts of UOG development on microbial community composition and carbon cycling could have cascading effects on stream health and broader ecosystem function.

Multi Pronged Approach for Ransomware Analysis

Multi Pronged Approach for Ransomware Analysis

MOMENTOUSNESS OF JOB SATISFACTION FOR THE EMPLOYEE AND THE EMPLOYER

This study is a blend of an approach that witness job satisfaction is equally important at the end of employer as it is at the end of employee. The paper encompasses the dual pronged approach that not only show importance of Job Satisfaction for the workers but also for the owners and their business. This study summarizes all the reasons that why job satisfaction is important in a working environment and also that job satisfaction of employers and employee is equally important as the top management and the people executing the commands of top management, all should be satisfied with their job and eager to work. To increase the cumulative job satisfaction employers should address factors like remuneration, supervision and work environment to increase the job satisfaction of the employees while what employees should do is to show interest and engagement in their work.

Have we forgotten about the Person with Disabilities for COVID 19 Vaccination – A need of the hour!!!

Persons with disabilities (PwDs) are less likely to access health care facilities, education, and employment in their day-to-day life. They are more likely to experience higher rates of neglect and abuse. The present COVID-19 pandemic situation has further affected the PwDs in terms of physical and social neglect. Moreover, the concept of social distancing, using a face mask, and following cough hygiene, which is fundamental in controlling the spread of COVID 19, is likely to be followed by the person with an intellectual impairment since they are highly dependent on their caretakers for their day to day activities. This scenario is even worse with PwDs who are living in congregate settings like residential camps, nursing facilities, and psychiatric institutions where infectivity is very higher. Thus a pronged approach is needed to assure that PwDs are not left behind during the times of pandemic. This paper argues that PwDs, because of their increased risk for exposure to COVID-19 and its consequences of developing morbidity and even possible deaths, should be prioritized in vaccination strategies. Otherwise, they will be left behind, experiencing disproportionate loss of lives and livelihoods, inaccessible health care services, and disconnection from society.

Pushing the Limits using Business Model Innovation a Three Pronged Approach and Lessons Learned

In a constantly changing business environment, with increasing digitisation and fourth industrial revolution blurring the traditional value creation boundaries, companies need to explore ways to push the limits to remain competitive. Business model innovation offers companies the dynamic capability to differentiate business models and find innovative revenue streams while reducing costs. As such, the question arises as to how company may use business model innovation to remain competitive as the world digitises. Based on a literature review and empirical research involving six case studies, a three pronged approach in support of business model innovation is proposed. Business model innovation has the potential to push the limits when company executives and academia focus on the interrelation between drivers, process and components. Moreover, both effective and ineffective practices based on the research are presented. In conclusion, for companies to use business model innovation in pushing the limits, there is need to respond to the business model innovation drivers, adopt a systematic process and change at least one or more business model components and taking into account the interactions between these three concepts. This article may contribute to existing theory in the field of business model innovation and lessons learned from executives that have pushed the limits using business model innovation. Doi: 10.28991/HEF-2021-02-01-03 Full Text: PDF

Demistifying the Alliance between the Law and Politics

This article examines integral characteristics of the relationship between national law and politics. The law functions in relation to politics in a three pronged typology approach namely a goal, a means or an obstacle.

Strategies for Successful Research to Application Projects: A Case Study of the National Sea Grant College Program

As coastal landscapes change, management professionals are working hard to transition research results into actions that support scientifically informed decisions impacting coastal communities. This type of research faces many challenges due to competing priorities, but boundary spanning organizations can help mediate these conflicts by forming transdisciplinary collaborations. The National Sea Grant College Program (Sea Grant), a National Oceanic and Atmospheric Administration based agency, is a networked organization of 34 university-based state programs that uses a three pronged approach of research, extension, and education to move academic research into the hands of stakeholders and decision makers. The objective of this study is to better understand strategies for successful research to application (R2A) projects that address complex environmental problems occurring in a socio-economic context. Specifically, this work examines R2A projects from the Sea Grant network to better understand the drivers for project development and common deliverables produced through the R2A process. We identify five common facilitating factors that enabled ‘successful’ R2A across all projects: platforms for partnerships, iterative communication, transparent planning, clear examples of R2A, and graduate student involvement. By providing examples of successful frameworks, we hope to encourage more organizations to engage in the R2A process.

Two pronged approach for prevention and therapy of COVID-19 (Sars-CoV-2) by a multi-targeted herbal drug, a component of ayurvedic decoction

IntroductionSARS-CoV-2 a new virus of the zoonotic coronavirus family causes the disease COVID-19, which has become a global pandemic. One of the ways for prevention of COVID-19 is by disabling its spike protein which results in inhibiting its binding with angiotensin-converting enzyme 2 (ACE-2). The other alternative is to inhibit its replication once inside the body. The aim of this study was to explore the literature to identify whether there were any Ayurvedic remedies which contained ingredients which demonstrated this dual effect. MethodsIn silico studies were carried out to find the structures of the targets i.e. spike protein of the virus and its main protease (Mpro). Databases were searched to identify the composition of Ayurvedic decoctions used for respiratory ailments. ResultsWe have found that two components out of 26 active ingredients of Ayurvedic decoctions are strong binders for spike protein as well as corresponding Mpro (3CL protease) which plays an essential role in mediating viral replication and transcription, making it an attractive antiviral drug target. Out of 26 components of Ayurvedic herbal decoction used for influenza, one compound was found to be most active. It is a well-known antioxidant, antinflammatory and hepatoprotective molecule. ConclusionThe resultant compound could act as a repurposed drug or like other methoxyphenols, could be a good lead molecule for a potent drug for COVID-19.

To study the attitude on marital adjustment of selected respondents from Mehsana and Ahmadabad city

The present study was conducted in Mehsana (urban and rural area) and Ahmadabad (urban and rural area) city. The sample size was 720 women and they were selected from both the cities. The women who were educated upto 12th standard, graduate and post graduate were randomly selected for the study. Purposive random sampling technique was used for selection of the sample. The research design for the present paper was two pronged approach. A descriptive survey with pre-tested, validated interview schedule was used to acquire the information needed to study the attitude on marital adjustment.

Vitamin D Receptor Activation and Photodynamic Priming Enables Durable Low-dose Chemotherapy.

Patients with cancer often confront the decision of whether to continue high-dose chemotherapy at the expense of cumulative toxicities. Reducing the dose of chemotherapy regimens while preserving efficacy is sorely needed to preserve the performance status of these vulnerable patients, yet has not been prioritized. Here, we introduce a dual pronged approach to modulate the microenvironment of desmoplastic pancreatic tumors and enable significant dose deescalation of the FDA-approved chemotherapeutic nanoliposomal irinotecan (nal-IRI) without compromising tumor control. We demonstrate that light-based photodynamic priming (PDP) coupled with vitamin D3 receptor (VDR) activation within fibroblasts increases intratumoral nal-IRI accumulation and suppresses protumorigenic CXCL12/CXCR7 crosstalk. Combined photodynamic and biochemical modulation of the tumor microenvironment enables a 75% dose reduction of nal-IRI while maintaining treatment efficacy, resulting in improved tolerability. Modifying the disease landscape to increase the susceptibility of cancer, via preferentially modulating fibroblasts, represents a promising and relatively underexplored strategy to enable dose deescalation. The approach presented here, using a combination of three clinically available therapies with nonoverlapping toxicities, can be rapidly translated with minimal modification to treatment workflow, and challenges the notion that significant improvements in chemotherapy efficacy can only be achieved at the expense of increased toxicity.

847-P: Effect of Simple Multipronged Strategies in a Real-World Situation in Prevention of Diabetes in a Developing Country: Interim Report from South India

Aim: Implementation of newer intervention strategies in Prediabetes (PDM) may delay the onset of DM. Aim was to see the effect of simple multi pronged approach in a real world situation to prevent progression to DM. Methods: PDM subjects (n=220) were assigned into 2 groups(Gp) from Aug 2017 in a diabetes centre in Chennai, India. OGTT was done and diagnosis was by WHO criteria. PDM subjects; IFG, IGT, Elevated 1h PG, were assigned to control and intervention groups; (n=110 in each). Gp1 received standard care, Gp2 intensive counseling on physical activity (PA) and diet (reducing calories, carbohydrates, fat, increasing fibre). PA included walking for 150min/week and customized advice based on profession. Working subjects to avoid prolonged sitting at work place, using stairs in work areas, walking instead of hiring vehicles for short distances; Business professionals advised to walk in corridors during stay in hotels for business purpose; Housewives to do simple walks in balconies and terrace, to avoid electronic appliances. Subjects were followed up(FU) once in 6 months and repeated OGTT. Calls, mails and SMS used for FU. Those came for FU(n=91;47vs41) till Sep 2019 were included for interim analysis. Results: Mean age of subjects was 44 years and duration of FU was 12.1 (range 4-28) months. There was a significant difference in conversion rate to DM. (Gp1 vs. 2;34 vs. 9.1%,p=0.004). The subjects who reverted back to normal was significantly higher in Gp 2 compared to Gp1 (31.8 vs. 10.6%;p =0.012). The survival curve showed mean survival time for Gp1 was 19.6 (95% CI 16.6-22.8) and Gp2 was 22.2 months (CI 19.9-24.4;p=0.014). In Gp2, there was a significant reduction in Wt, body fat (p=0.022), WHR(P=0.003), elevated 1 hr glucose (p=0.004) whereas in Gp1 reduction was observed only in glucose levels (p&amp;lt;0.001). Conclusion: It was possible to prevent diabetes in subjects with prediabetes using multi-pronged intervention strategies in real world scenario. Disclosure V. Viswanathan: None. R. Parveen: None. P. Murugan: None. S. Kumpatla: None.

COVID-19 Pandemic: A Comparative Study of Oscillococcinum versus Arsenic Album

The cases of COVID-19 are rising in an explosive manner, with no treatment options. A multi pronged approach is needed to combat the pandemic by adopting both preventive as well as treatment regimen. Keeping this in view, an attempt is made to compare between the suggested preventive medicine, ‘Arsenic album’ and one of the most suitable medicine for influenza, ‘Oscillococcinum’.

Trident : An Automated System Tool for Collecting and Analyzing Performance Counters

Trident, a qualitative analysis tool that can look at various low level metrics with respect to the Core, Memory and I/O to highlight performance bottlenecks during the execution of an application. Trident uses a three pronged approach in analysing a node's utilisation of hardware resources and to help a non system expert understand the stress on different parts of the system by a given job. Currently metrics such as memory bandwidth, core utilization, active processor cyles, etc., are being collected. Interpretation of the data in raw form is often non intuitive. Therefore, the tool converts these data into derived metrics that are then represented as a system wide extended Top-Down analysis that helps developers and site managers likewise understand the application behavior without the need for in-depth expertise of architecture details.

Tackling Cancer Associated Thrombosis: A Multi-Professional Approach

Abstract Introduction Thromboembolism is a leading cause of death in people with cancer; second only to the cancer itself. There is an urgent need to raise the profile of cancer associated thrombosis amongst not only patients but staff treating people with cancer. Aims This project aimed to educate cancer patients about their thrombotic risk and to improve both the prevention and treatment of cancer associated thrombosis. Methods A review of attitudes and use of thromboprophylaxis was performed in a large, UK-based, teaching hospital; prior to and following the introduction of a new strategy to improve knowledge of cancer associated thrombosis. The study was performed between March and July 2018, with the strategy fully implemented by May 2018. This strategy included a three pronged approach: the introduction of a regular teaching programme for nurses, pharmacists and doctors; the implementation of new guidelines relating to cancer associated thrombosis; and the use of educational videos and posters within patient areas. The knowledge of clots/thrombosis of people with cancer, discussions with staff concerning thrombotic risk and use of tinzaparin thromboprophylaxis at a high risk dose (4500 units) were all investigated. Cancer patients admitted to the hospital were eligible for the study only if they had been admitted for at least 24 hours, this allowed staff the opportunity to discuss the risk of thrombosis with them. A typical one week period was chosen to complete each part of the study, the second week occurred two months after the introduction of the new strategy. A p value of &lt;0.05 was considered significant and was calculated using a Chi-square test. Results A total of 91 patients were included in the study (42 prior to the intervention and 49 following). They included a mix of both out-patients (32/42, 74% prior to intervention and 25/49, 51% following) and in-patients (10/42, 26% prior to and 24/49, 49% following). Median age was 65 years (range 21 - 87 years) prior to intervention and 67 years (range 21 - 86 years) following. For those admitted to hospital, the median length of admission was 3 days (range 1-84 days) prior to intervention and 4 days (range 2-33 days) following. Overall there was a slight male preponderance (55% both prior to intervention and following). People with a range of cancer types were interviewed. In the cohort prior to intervention the most common cancer sites were: lung (8/42), bowel (8/42) and skin (7/42). Following the intervention the most common were: breast (6/49), skin (5/49) and lung (4/49). A higher proportion of people questioned before the intervention had known metastases (29/42, 69% prior to and 22/49, 45% following; p&lt;0.05). Generally people with cancer had a good knowledge of venous thromboembolism and this remained high following the intervention (39/42, 93% to 41/49, 84%; p=0.18). There was a significant increase in the number of people who had discussed thrombotic risk with a healthcare professional during their hospital admission or out-patient treatment (12/42, 24% to 24/49, 51%; p&lt;0.05). The use of tinzaparin thromboprophylaxis in those eligible to receive it, remained high following the intervention (13/16, 81% to 16/17, 91%, p=0.26) and the appropriate use of a higher risk dose (4500 units) rose significantly (1/13, 8% to 12/16, 75%, p&lt;0.001). Conclusion The use of a multi-professional approach to preventing and treating cancer associated thrombosis increased discussion between staff and patients regarding thrombosis and improved accuracy of thromboprophylaxis dosing. Our results strongly support the use of a strategy based on regular training and patient education. Disclosures Gabriel: Leo Pharma: Other: Travel and accommodation sponsorship. Musgrave:Leo Pharma: Other: Travel and accomodation sponsorship.