This document discusses statistical models for estimating radiation risk. It begins by providing background on radiation epidemiology and examining prevalent risk models like Poisson regression. It notes strengths of these models include large datasets and weaknesses include excess zeros. The document then proposes variations of Poisson regression called Hurdle models to overcome assumptions of Poisson regression for risk estimation. In summary, it analyzes current risk models, discusses their limitations, and proposes an alternative Hurdle model for more accurate radiation risk estimation.
EFFECTS OF X-RAY RADIATION EXPOSURE TOWARD LYMPHOCYTES OF RADIOGRAPHERS IN AB...irjes
X-ray radiation sources in ABCD Hospitalisused as one of the healthfacilities and the role of management, itis not maximized as well in providing protection against the radiographer. The use of personal protective equipmentisstilla rare thingdone right by the radiologist. This studyaimed to analyze the influence of X-ray radiation to the lymphocytes of radiographer in the ABCD Hospital. This studyis a quantitative studyconductedin 4 Hospitals in Mataram, West NusaTenggara (NTB) in June and October 2014. The populations in thisstudywere all radiographerswhoworking in ABCD Hospital as many as 30 people. The sampling technique usedis simple randomsamplingwhere a sample size of 28 people. Data wasanalyzed by usingregressionanalysis. Theseresultsindicatethat the radiologistcharacteristics affect the lymphocytes wereage (p = 0.028), radiation protection training (p = 0.046), use of APD (p = 0.026) and radiation dose (p = 0.046). Radiation protection efforts at A hospital are still not good and B, C and D hospitals are good.
Future of radiation protection regulations presentationMohan Doss
This is the presentation I made at the 2015 Health Physics Society Annual Meeting, in the Special Session called
"Health Risks from Low Doses and Low Dose-Rates of Ionizing Radiation" on July 14, 2015.
Slightly revised version (v1.2) of the Presentation given by Mohan Doss at the CE Session "Radiopharmaceutical Dosimetryand Radiobiology –The Future is Now" at the SNMMI Annual Meeting, Philadelphia, PA on June 25, 2018
Should the alara concept and the image gently campaign be terminated?Mohan Doss
Abstract: Concerns have been raised about the cancer risk from pediatric CT scans based on the linear no-threshold (LNT) model assumption for radiation-induced cancers, and the assumed increased radiosensitivity of children. The pediatric radiology community has responded by initiating the Image Gently campaign and recommendations to keep imaging radiation doses as low as reasonably achievable (ALARA). One of the main evidences quoted for the low-dose radiation cancer concerns are the atomic bomb survivor data. However, with the recent update, these data are not compatible with the LNT model but are more consistent with the concept that low levels of radiation reduce cancers, a phenomenon known as radiation hormesis. In addition, more evidences have validated radiation hormesis hypothesis and major flaws have been identified in the data claimed to support the LNT model. Thus, dose reduction due to the ALARA principle and Image Gently campaigns would not benefit pediatric patients by reducing cancer risk. The false perception that CT scans cause cancer has led to parents refusing indicated scans for children and physicians not ordering the needed scans, potentially jeopardizing patient health. Also, misguided dose reduction efforts have resulted in nondiagnostic images being performed, again potentially harming pediatric patients. Since there are no benefits from the low-dose radiation dose concerns and dose reduction efforts but only potential harm to pediatric patients, the radiological community should firmly disavow the ALARA concept and discontinue the Image Gently campaign.
Is radon remediation causing lung cancers v1.04Mohan Doss
In the first part of the presentation, the two predominant models for the carcinogenic effect of low-dose radiation, the linear no-threshold (LNT) model and radiation hormesis model are discussed. Published evidence for the effect of low-dose radiation on cancer is reviewed. Low-dose radiation in a variety of situations is observed to reduce cancers or resulted in no increase in cancers, contraditcing the LNT model but supporting the Radiation Hormesis model.
In the second part of the presentation, the effect of residential radon on lung cancers is discussed. Residential radon results in low-dose radiation to the lungs. According to the LNT model, increased radon levels would increase lung cancer risk, and according to the radiation hormesis model, increased radon levels would decrease lung cancer risk. To determine which of the models are consistent with data, radon level maps and lung cancer incidence maps are compared for a number of countries/regions. The areas with the highest radon levels are observed to have lower lung cancer rates, and the areas with the highest lung cancer rates are observed to have lower radon levels, barring some exceptions. Considering the universality of this trend in the data in different countries and states, in states with different average levels of radon, in states with different levels of smoking prevalence, etc., these data are more consistent with the radiation hormesis model than with the LNT model. Thus, radon remediation, which would reduce the radiation dose to lungs from low-doses to almost no dose would increase lung cancer risk. This conclusion needs to be verified by a systematic study of measuring the lung cancer risk in residents before and after radon remediation.
Should the radiological community continue the present radiation dose reducti...Mohan Doss
This is a revised version of the presentation given at the 74th Annual Meeting of Japan Radiological Society, Yokohama, Japan on April 17, 2015 in the session entitled "Patient Dose in Radiology: Manage the Invisible". Abstract:
Carcinogenic concerns regarding the radiation dose from diagnostic imaging, based on the linear no-threshold (LNT) model recommended by advisory bodies, have resulted in actions by the radiological community to reduce radiation dose. However, the primary evidence quoted by advisory bodies for the LNT model, the atomic bomb survivor data, no longer support the model with the recent update to the data, and so do not justify low-dose radiation (LDR) cancer concerns. In addition, considerable amount of evidence, which has been ignored by advisory bodies, has accumulated against the LNT model. Though a large number of publications have claimed to provide evidence for the LNT model and/or LDR carcinogenicity, careful scrutiny has shown that they have major flaws in study design, data, analysis, and/or interpretation nullifying their conclusions. Hence, the present dose-reduction efforts would not reduce cancer risk. On the other hand, patient/caregiver/physician concerns have resulted in patients not undergoing recommended diagnostic studies, and dose-reduction efforts have resulted in non-diagnostic images. Considering the hazards to patients from such actions, it is important that the radiological community seek justification for the dose-reduction campaign. The advisory bodies should be asked to provide conclusive evidence for the LNT model and LDR carcinogenicity and reasons to reject the considerable evidence against the LNT model. If these are not provided forthwith, the dose-reduction campaign should be ceased in order to protect patients from harm, since the hazards from dose-reduction efforts are real and the claimed cancers from LDR are illusory in the absence of definitive evidence.
Coping with low dose radiation in fukushima, doss, samrai2014, 3-24-2015Mohan Doss
The disaster-related deaths following the Fukushima Daiichi nuclear power plant accidents in 2011 were not caused by radiation exposures but by the urgent evacuation and its prolongation due to the fear of low-dose radiation, based on the linear no-threshold (LNT) hypothesis recommended by advisory bodies since the 1950s for radiation safety. However, the LNT hypothesis was adopted in an unscientific manner and considerable amount of evidence has accumulated against it over the years. Since the present advisory bodies have not rejected the LNT hypothesis in spite of the evidence against it, and in spite of observing the disastrous consequences from its use, new advisory bodies need to be formed to protect public health. The evacuated population should be educated about the deficiencies in the operation of the current advisory bodies, harm caused by their unjustifiable recommendations, and the evidence for the innocuousness of low-dose radiation exposures to allay their concerns and they should be asked to return to their homes. Nuclear power plants should be re-started after appropriate safety modifications are completed to prevent recurrence of accidents similar to those in Fukushima, since among all the available power sources, nuclear power has proven to be the safest.
EFFECTS OF X-RAY RADIATION EXPOSURE TOWARD LYMPHOCYTES OF RADIOGRAPHERS IN AB...irjes
X-ray radiation sources in ABCD Hospitalisused as one of the healthfacilities and the role of management, itis not maximized as well in providing protection against the radiographer. The use of personal protective equipmentisstilla rare thingdone right by the radiologist. This studyaimed to analyze the influence of X-ray radiation to the lymphocytes of radiographer in the ABCD Hospital. This studyis a quantitative studyconductedin 4 Hospitals in Mataram, West NusaTenggara (NTB) in June and October 2014. The populations in thisstudywere all radiographerswhoworking in ABCD Hospital as many as 30 people. The sampling technique usedis simple randomsamplingwhere a sample size of 28 people. Data wasanalyzed by usingregressionanalysis. Theseresultsindicatethat the radiologistcharacteristics affect the lymphocytes wereage (p = 0.028), radiation protection training (p = 0.046), use of APD (p = 0.026) and radiation dose (p = 0.046). Radiation protection efforts at A hospital are still not good and B, C and D hospitals are good.
Future of radiation protection regulations presentationMohan Doss
This is the presentation I made at the 2015 Health Physics Society Annual Meeting, in the Special Session called
"Health Risks from Low Doses and Low Dose-Rates of Ionizing Radiation" on July 14, 2015.
Slightly revised version (v1.2) of the Presentation given by Mohan Doss at the CE Session "Radiopharmaceutical Dosimetryand Radiobiology –The Future is Now" at the SNMMI Annual Meeting, Philadelphia, PA on June 25, 2018
Should the alara concept and the image gently campaign be terminated?Mohan Doss
Abstract: Concerns have been raised about the cancer risk from pediatric CT scans based on the linear no-threshold (LNT) model assumption for radiation-induced cancers, and the assumed increased radiosensitivity of children. The pediatric radiology community has responded by initiating the Image Gently campaign and recommendations to keep imaging radiation doses as low as reasonably achievable (ALARA). One of the main evidences quoted for the low-dose radiation cancer concerns are the atomic bomb survivor data. However, with the recent update, these data are not compatible with the LNT model but are more consistent with the concept that low levels of radiation reduce cancers, a phenomenon known as radiation hormesis. In addition, more evidences have validated radiation hormesis hypothesis and major flaws have been identified in the data claimed to support the LNT model. Thus, dose reduction due to the ALARA principle and Image Gently campaigns would not benefit pediatric patients by reducing cancer risk. The false perception that CT scans cause cancer has led to parents refusing indicated scans for children and physicians not ordering the needed scans, potentially jeopardizing patient health. Also, misguided dose reduction efforts have resulted in nondiagnostic images being performed, again potentially harming pediatric patients. Since there are no benefits from the low-dose radiation dose concerns and dose reduction efforts but only potential harm to pediatric patients, the radiological community should firmly disavow the ALARA concept and discontinue the Image Gently campaign.
Is radon remediation causing lung cancers v1.04Mohan Doss
In the first part of the presentation, the two predominant models for the carcinogenic effect of low-dose radiation, the linear no-threshold (LNT) model and radiation hormesis model are discussed. Published evidence for the effect of low-dose radiation on cancer is reviewed. Low-dose radiation in a variety of situations is observed to reduce cancers or resulted in no increase in cancers, contraditcing the LNT model but supporting the Radiation Hormesis model.
In the second part of the presentation, the effect of residential radon on lung cancers is discussed. Residential radon results in low-dose radiation to the lungs. According to the LNT model, increased radon levels would increase lung cancer risk, and according to the radiation hormesis model, increased radon levels would decrease lung cancer risk. To determine which of the models are consistent with data, radon level maps and lung cancer incidence maps are compared for a number of countries/regions. The areas with the highest radon levels are observed to have lower lung cancer rates, and the areas with the highest lung cancer rates are observed to have lower radon levels, barring some exceptions. Considering the universality of this trend in the data in different countries and states, in states with different average levels of radon, in states with different levels of smoking prevalence, etc., these data are more consistent with the radiation hormesis model than with the LNT model. Thus, radon remediation, which would reduce the radiation dose to lungs from low-doses to almost no dose would increase lung cancer risk. This conclusion needs to be verified by a systematic study of measuring the lung cancer risk in residents before and after radon remediation.
Should the radiological community continue the present radiation dose reducti...Mohan Doss
This is a revised version of the presentation given at the 74th Annual Meeting of Japan Radiological Society, Yokohama, Japan on April 17, 2015 in the session entitled "Patient Dose in Radiology: Manage the Invisible". Abstract:
Carcinogenic concerns regarding the radiation dose from diagnostic imaging, based on the linear no-threshold (LNT) model recommended by advisory bodies, have resulted in actions by the radiological community to reduce radiation dose. However, the primary evidence quoted by advisory bodies for the LNT model, the atomic bomb survivor data, no longer support the model with the recent update to the data, and so do not justify low-dose radiation (LDR) cancer concerns. In addition, considerable amount of evidence, which has been ignored by advisory bodies, has accumulated against the LNT model. Though a large number of publications have claimed to provide evidence for the LNT model and/or LDR carcinogenicity, careful scrutiny has shown that they have major flaws in study design, data, analysis, and/or interpretation nullifying their conclusions. Hence, the present dose-reduction efforts would not reduce cancer risk. On the other hand, patient/caregiver/physician concerns have resulted in patients not undergoing recommended diagnostic studies, and dose-reduction efforts have resulted in non-diagnostic images. Considering the hazards to patients from such actions, it is important that the radiological community seek justification for the dose-reduction campaign. The advisory bodies should be asked to provide conclusive evidence for the LNT model and LDR carcinogenicity and reasons to reject the considerable evidence against the LNT model. If these are not provided forthwith, the dose-reduction campaign should be ceased in order to protect patients from harm, since the hazards from dose-reduction efforts are real and the claimed cancers from LDR are illusory in the absence of definitive evidence.
Coping with low dose radiation in fukushima, doss, samrai2014, 3-24-2015Mohan Doss
The disaster-related deaths following the Fukushima Daiichi nuclear power plant accidents in 2011 were not caused by radiation exposures but by the urgent evacuation and its prolongation due to the fear of low-dose radiation, based on the linear no-threshold (LNT) hypothesis recommended by advisory bodies since the 1950s for radiation safety. However, the LNT hypothesis was adopted in an unscientific manner and considerable amount of evidence has accumulated against it over the years. Since the present advisory bodies have not rejected the LNT hypothesis in spite of the evidence against it, and in spite of observing the disastrous consequences from its use, new advisory bodies need to be formed to protect public health. The evacuated population should be educated about the deficiencies in the operation of the current advisory bodies, harm caused by their unjustifiable recommendations, and the evidence for the innocuousness of low-dose radiation exposures to allay their concerns and they should be asked to return to their homes. Nuclear power plants should be re-started after appropriate safety modifications are completed to prevent recurrence of accidents similar to those in Fukushima, since among all the available power sources, nuclear power has proven to be the safest.
Presentation from Manolis Kogevinas, Head of the Cancer Programme at ISGlobal, on occupational cancer.
Epidemiology in Occupational Health Conference - EPICOH 2017
Potentials of 3D models in anticancer drug screeningAnjali R.
A short presentation about the differences between 2D and 3D culture models, why researchers are moving toward 3D models in anticancer drug screening, the methods used in doing so and a recent case study of 3D tumour model being used for drug screening.
Advancing Innovation and Convergence in Cancer Research: US Federal Cancer Mo...Jerry Lee
Special Seminar at the 8th Taiwan Biosignatures Workshop to share overall work of NCI's Center for Strategic Scientific Initiatives since 2003 as well as CSSI's influence on select projects initiated by the 2016 WH Cancer Moonshot Task Force that include Applied Proteogenomics Organizational Learning and Outcomes (APOLLO) network, International Cancer Proteogenome Consortium, and the Blood Profiling Atlas in Cancer (BloodPAC) commons.
How is machine learning significant to computational pathology in the pharmac...Pubrica
• Plentiful amassing of advanced histopathological pictures has prompted the expanded interest for their examination; for example, PC supported determination utilizing AI procedures.
• In this blog, Pubrica explains the applications of machine learning in digital pathology field using Biostatistics Services.
Continue Reading: https://bit.ly/37Vp6co
Reference: https://pubrica.com/services/research-services/biostatistics-and-statistical-programming-services/
Why Pubrica?
When you order our services, Plagiarism free|onTime|outstanding customer support|Unlimited Revisions support|High-quality Subject Matter Experts.
Contact us :
Web: https://pubrica.com/
Blog: https://pubrica.com/academy/
Email: sales@pubrica.com
WhatsApp : +91 9884350006
United Kingdom: +44- 74248 10299
Mechanical signals inhibit growth of a grafted tumor in vivo proof of conceptRemy BROSSEL
We apply the principles of physical oncology (or mechanobiology) in vivo to show the effect of a “constraint field” on tumor growth.
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0152885
Presentation from Manolis Kogevinas, Head of the Cancer Programme at ISGlobal, on occupational cancer.
Epidemiology in Occupational Health Conference - EPICOH 2017
Potentials of 3D models in anticancer drug screeningAnjali R.
A short presentation about the differences between 2D and 3D culture models, why researchers are moving toward 3D models in anticancer drug screening, the methods used in doing so and a recent case study of 3D tumour model being used for drug screening.
Advancing Innovation and Convergence in Cancer Research: US Federal Cancer Mo...Jerry Lee
Special Seminar at the 8th Taiwan Biosignatures Workshop to share overall work of NCI's Center for Strategic Scientific Initiatives since 2003 as well as CSSI's influence on select projects initiated by the 2016 WH Cancer Moonshot Task Force that include Applied Proteogenomics Organizational Learning and Outcomes (APOLLO) network, International Cancer Proteogenome Consortium, and the Blood Profiling Atlas in Cancer (BloodPAC) commons.
How is machine learning significant to computational pathology in the pharmac...Pubrica
• Plentiful amassing of advanced histopathological pictures has prompted the expanded interest for their examination; for example, PC supported determination utilizing AI procedures.
• In this blog, Pubrica explains the applications of machine learning in digital pathology field using Biostatistics Services.
Continue Reading: https://bit.ly/37Vp6co
Reference: https://pubrica.com/services/research-services/biostatistics-and-statistical-programming-services/
Why Pubrica?
When you order our services, Plagiarism free|onTime|outstanding customer support|Unlimited Revisions support|High-quality Subject Matter Experts.
Contact us :
Web: https://pubrica.com/
Blog: https://pubrica.com/academy/
Email: sales@pubrica.com
WhatsApp : +91 9884350006
United Kingdom: +44- 74248 10299
Mechanical signals inhibit growth of a grafted tumor in vivo proof of conceptRemy BROSSEL
We apply the principles of physical oncology (or mechanobiology) in vivo to show the effect of a “constraint field” on tumor growth.
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0152885
Sheet1Score -54321ScoreAccurately described the leader’s style, t.docxedgar6wallace88877
Sheet1Score ->54321ScoreAccurately described the leader’s style, traits and/or behaviors. Fully described. No additional improvement necessary. Mostly described. Only minimal improvement necessary. Moderately described. Improvement necessary. Minimally described. Room for significant improvement. Did not accurately describe. Applied course material to what you learned about the leader. Fully applied. No further Improvement necessary. Mostly applied. Only minimal improvement necessary. Moderately applied. Improvement necessary. Minimally applied. Room for significant improvement. Did not apply course material. Used citations from the week’s reading materials. Fully cited course materials. No further improvement necessary. Mostly cited course materials. Only minimal improvement necessary. Moderately cited course materials. Improvement necessary. Minimally cited. Room for significant improvement. Did not cite appropriately. Wrote with sufficient detail. Fully detailed. No further improvement necessary. Mostly detailed. Only minimal improvement necessary. Moderately detailed. Improvement necessary. Minimal detail. Room for significant improvement. Did not provide sufficient detail. Used appropriate grammar, punctuation and masters-level writing style Fully used appropriate writing style. No further improvements necessary. Mostly used appropriate writing style. Only minimal improvement necessary. Moderately used appropriate writing style. Improvement necessary. Minimally used appropriate writing style. Room for significant improvement. Did not use appropriate writing style. Final Score0
After reading Chapter 9 of Epidemiology for public health practice, complete Study Questions and Exercises 1–9. This activity is located on pages 431–432. Submit your responses in the form of a Word document.
1- Calculate the etiologic fraction when the RR for disease associated with a given exposure is 1.2, 1.8, 3, and 15.
2- The impact of an exposure on a population does not depend upon:
· a.the strength of the association between exposure and disease.
· b.the prevalence of the exposure.
· c.the case fatality rate.
· d.the overall incidence rate of disease in the population.
· The next seven questions (3–9) are based on the following data: The death rate per 100,000 for lung cancer is 7 among nonsmokers and 71 among smokers. The death rate per 100,000 for coronary thrombosis is 422 among nonsmokers and 599 among smokers. The prevalence of smoking in the population is 55%. (If necessary, refer to the chapter on cohort studies for formulas for RR.)
3- What is the RR of dying of lung cancer for smokers versus nonsmokers?
4-What is the RR of dying of coronary thrombosis for smokers versus nonsmokers?
5-What is the etiologic fraction of disease due to smoking among individuals with lung cancer?
6-What is the etiologic fraction of disease due to smoking among individuals with coronary thrombosis?
7-What is the population etiologic fraction of lung c.
Risk factors in Multiple Sclerosis: Detection and Treatment in Daily Life
Caroline Pot and Patrice Lalive
Unit of Neuroimmunology and Multi Sclerosis Geneva University Hospital
Study on Physicians Request for Computed Tomography Examinations for Patients...IRJESJOURNAL
Background and objectives: There is a lot controversy about the use of Computed tomography (CT) for patients with minor head injury. We aimed to determine the practice of guiding rules for the safety of radiation and increasing awareness of physicians about risks of ionizing radiation and find out the reasons of emergency doctors for sending head injury patients to CT scan exams. Materials and Methods: A descriptive questionnaire in the Emergency Department (ED) based study was performed to assess physicians' knowledge of radiation doses received from radiological treatments and knowledge about Clinic Decision Support rules (CDS). The questionnaire consisted of 26 questions distributed to physicians working in the emergency department in six hospitals in East Java. Finally, the data collected have been analyzed by some tests using SPSS version 15 and Smart PLS. Results: In this study 44 participants had taken part. The percentage of general knowledge and awareness that shows the response of people who work in the emergency departments was total 44 respondents, by percent 6.8% of the respondents had passably knowledge, awareness and 84.1% they were having a good knowledge and awareness and 9.1% the respondents had very good knowledge and awareness. That means almost of respondents have good knowledge and awareness. To find out if an indicator is forming a construct (latent variables) testing the convergent validity of the measurement model with a reflexive indicator assessed based on the correlation between the item score to construct scores were calculated with the help of software Smart PLS. Size reflexive considered valid if the individual has a correlation (loading) to construct (latent variables) to be measured ≥ 0.5 or the value of t-statistics should ≥1.96 (test two tailed) at a significance level of α = 0.05. If one of the indicators has a leading value <0.5,><1.96, then the indicator should be discarded (dropped) because it indicates that the indicators are not good enough to measure the construct in right. The positive influence between general knowledge and awareness against to knowledge about radiation doses can be interpreted that the better general knowledge and awareness, then it will be followed by an increase in their knowledge about radiation doses. And vice versa, the worse general knowledge and awareness, then this will decrease their knowledge about radiation doses too. Conclusion: The present study has illustrated that the level of awareness and knowledge physicians who deal with ionizing radiation in CT scan units are adequate overall. There is a good influence between the diligence in applying the principles of guidance and rules stipulated by the nuclear energy in Indonesia by physicians to adjust the use of CT in the emergency department, the majority of participants who have a good awareness & knowledge, there are some of them do not have enough knowledge.
1- Why was the Tomasetti et al article so misinterpreted by thAgripinaBeaulieuyw
1- Why was the Tomasetti et al article so misinterpreted by the media? Draw from
your own personal experiences to discuss other scientific phenomenon that has
been similarly misinterpreted.
2- What might be the consequences of scientific misreporting of this article?
3- What is the overall value of the Tomasetti et al paper? Cite two and be specific in
your rational for selecting these reasons.
4- Cite three criticisms of this paper. Be specific in the rationale for your criticism.
5- Design an experiment which might distinguish between environmental effects
and replicative errors in canter etiology.
You may assume you have access to all resources currently available to scientists
today,
Be specific in elucidating the application of the scientific method to your
experiment:
1) Observation
2) Hypothesis
3) Predictions
4) Experiment: Independent and dependent variables, controls, uncontrolled
variables, sample size
5) Results (predicted): How would you analyze your data
6)Conclusions: predict conclusions for the various outcomes of your experiment
REPORT
◥
CANCER ETIOLOGY
Stem cell divisions, somatic
mutations, cancer etiology, and
cancer prevention
Cristian Tomasetti,1,2* Lu Li,2 Bert Vogelstein3*
Cancers are caused by mutations that may be inherited, induced by environmental
factors, or result from DNA replication errors (R). We studied the relationship between
the number of normal stem cell divisions and the risk of 17 cancer types in 69 countries
throughout the world. The data revealed a strong correlation (median = 0.80) between
cancer incidence and normal stem cell divisions in all countries, regardless of their
environment. The major role of R mutations in cancer etiology was supported by an
independent approach, based solely on cancer genome sequencing and epidemiological
data, which suggested that R mutations are responsible for two-thirds of the mutations
in human cancers. All of these results are consistent with epidemiological estimates of the
fraction of cancers that can be prevented by changes in the environment. Moreover, they
accentuate the importance of early detection and intervention to reduce deaths from the
many cancers arising from unavoidable R mutations.
I
t is now widely accepted that cancer is the
result of the gradual accumulation of driver
gene mutations that successively increase cell
proliferation (1–3). But what causes these muta-
tions? The role of environmental factors (E)
in cancer development has long been evident
from epidemiological studies, and this has fun-
damental implications for primary prevention.
The role of heredity (H) has been conclusively
demonstrated from both twin studies (4) and the
identification of the genes responsible for cancer
predisposition syndromes (3, 5). We recently hy-
pothesized that a third source—mutations due to
the random mistakes made during normal DNA
replication (R)—can explain why cancers occur
much more commonly in som ...
1- Why was the Tomasetti et al article so misinterpreted by thsachazerbelq9l
1- Why was the Tomasetti et al article so misinterpreted by the media? Draw from
your own personal experiences to discuss other scientific phenomenon that has
been similarly misinterpreted.
2- What might be the consequences of scientific misreporting of this article?
3- What is the overall value of the Tomasetti et al paper? Cite two and be specific in
your rational for selecting these reasons.
4- Cite three criticisms of this paper. Be specific in the rationale for your criticism.
5- Design an experiment which might distinguish between environmental effects
and replicative errors in canter etiology.
You may assume you have access to all resources currently available to scientists
today,
Be specific in elucidating the application of the scientific method to your
experiment:
1) Observation
2) Hypothesis
3) Predictions
4) Experiment: Independent and dependent variables, controls, uncontrolled
variables, sample size
5) Results (predicted): How would you analyze your data
6)Conclusions: predict conclusions for the various outcomes of your experiment
REPORT
◥
CANCER ETIOLOGY
Stem cell divisions, somatic
mutations, cancer etiology, and
cancer prevention
Cristian Tomasetti,1,2* Lu Li,2 Bert Vogelstein3*
Cancers are caused by mutations that may be inherited, induced by environmental
factors, or result from DNA replication errors (R). We studied the relationship between
the number of normal stem cell divisions and the risk of 17 cancer types in 69 countries
throughout the world. The data revealed a strong correlation (median = 0.80) between
cancer incidence and normal stem cell divisions in all countries, regardless of their
environment. The major role of R mutations in cancer etiology was supported by an
independent approach, based solely on cancer genome sequencing and epidemiological
data, which suggested that R mutations are responsible for two-thirds of the mutations
in human cancers. All of these results are consistent with epidemiological estimates of the
fraction of cancers that can be prevented by changes in the environment. Moreover, they
accentuate the importance of early detection and intervention to reduce deaths from the
many cancers arising from unavoidable R mutations.
I
t is now widely accepted that cancer is the
result of the gradual accumulation of driver
gene mutations that successively increase cell
proliferation (1–3). But what causes these muta-
tions? The role of environmental factors (E)
in cancer development has long been evident
from epidemiological studies, and this has fun-
damental implications for primary prevention.
The role of heredity (H) has been conclusively
demonstrated from both twin studies (4) and the
identification of the genes responsible for cancer
predisposition syndromes (3, 5). We recently hy-
pothesized that a third source—mutations due to
the random mistakes made during normal DNA
replication (R)—can explain why cancers occur
much more commonly in som ...
1- Why was the Tomasetti et al article so misinterpreted by th.docxjeremylockett77
1- Why was the Tomasetti et al article so misinterpreted by the media? Draw from
your own personal experiences to discuss other scientific phenomenon that has
been similarly misinterpreted.
2- What might be the consequences of scientific misreporting of this article?
3- What is the overall value of the Tomasetti et al paper? Cite two and be specific in
your rational for selecting these reasons.
4- Cite three criticisms of this paper. Be specific in the rationale for your criticism.
5- Design an experiment which might distinguish between environmental effects
and replicative errors in canter etiology.
You may assume you have access to all resources currently available to scientists
today,
Be specific in elucidating the application of the scientific method to your
experiment:
1) Observation
2) Hypothesis
3) Predictions
4) Experiment: Independent and dependent variables, controls, uncontrolled
variables, sample size
5) Results (predicted): How would you analyze your data
6)Conclusions: predict conclusions for the various outcomes of your experiment
REPORT
◥
CANCER ETIOLOGY
Stem cell divisions, somatic
mutations, cancer etiology, and
cancer prevention
Cristian Tomasetti,1,2* Lu Li,2 Bert Vogelstein3*
Cancers are caused by mutations that may be inherited, induced by environmental
factors, or result from DNA replication errors (R). We studied the relationship between
the number of normal stem cell divisions and the risk of 17 cancer types in 69 countries
throughout the world. The data revealed a strong correlation (median = 0.80) between
cancer incidence and normal stem cell divisions in all countries, regardless of their
environment. The major role of R mutations in cancer etiology was supported by an
independent approach, based solely on cancer genome sequencing and epidemiological
data, which suggested that R mutations are responsible for two-thirds of the mutations
in human cancers. All of these results are consistent with epidemiological estimates of the
fraction of cancers that can be prevented by changes in the environment. Moreover, they
accentuate the importance of early detection and intervention to reduce deaths from the
many cancers arising from unavoidable R mutations.
I
t is now widely accepted that cancer is the
result of the gradual accumulation of driver
gene mutations that successively increase cell
proliferation (1–3). But what causes these muta-
tions? The role of environmental factors (E)
in cancer development has long been evident
from epidemiological studies, and this has fun-
damental implications for primary prevention.
The role of heredity (H) has been conclusively
demonstrated from both twin studies (4) and the
identification of the genes responsible for cancer
predisposition syndromes (3, 5). We recently hy-
pothesized that a third source—mutations due to
the random mistakes made during normal DNA
replication (R)—can explain why cancers occur
much more commonly in som ...
A Novel Method for Prevention of Bandwidth Distributed Denial of Service AttacksIJERD Editor
Distributed Denial of Service (DDoS) Attacks became a massive threat to the Internet. Traditional
Architecture of internet is vulnerable to the attacks like DDoS. Attacker primarily acquire his army of Zombies,
then that army will be instructed by the Attacker that when to start an attack and on whom the attack should be
done. In this paper, different techniques which are used to perform DDoS Attacks, Tools that were used to
perform Attacks and Countermeasures in order to detect the attackers and eliminate the Bandwidth Distributed
Denial of Service attacks (B-DDoS) are reviewed. DDoS Attacks were done by using various Flooding
techniques which are used in DDoS attack.
The main purpose of this paper is to design an architecture which can reduce the Bandwidth
Distributed Denial of service Attack and make the victim site or server available for the normal users by
eliminating the zombie machines. Our Primary focus of this paper is to dispute how normal machines are
turning into zombies (Bots), how attack is been initiated, DDoS attack procedure and how an organization can
save their server from being a DDoS victim. In order to present this we implemented a simulated environment
with Cisco switches, Routers, Firewall, some virtual machines and some Attack tools to display a real DDoS
attack. By using Time scheduling, Resource Limiting, System log, Access Control List and some Modular
policy Framework we stopped the attack and identified the Attacker (Bot) machines
Hearing loss is one of the most common human impairments. It is estimated that by year 2015 more
than 700 million people will suffer mild deafness. Most can be helped by hearing aid devices depending on the
severity of their hearing loss. This paper describes the implementation and characterization details of a dual
channel transmitter front end (TFE) for digital hearing aid (DHA) applications that use novel micro
electromechanical- systems (MEMS) audio transducers and ultra-low power-scalable analog-to-digital
converters (ADCs), which enable a very-low form factor, energy-efficient implementation for next-generation
DHA. The contribution of the design is the implementation of the dual channel MEMS microphones and powerscalable
ADC system.
Influence of tensile behaviour of slab on the structural Behaviour of shear c...IJERD Editor
-A composite beam is composed of a steel beam and a slab connected by means of shear connectors
like studs installed on the top flange of the steel beam to form a structure behaving monolithically. This study
analyzes the effects of the tensile behavior of the slab on the structural behavior of the shear connection like slip
stiffness and maximum shear force in composite beams subjected to hogging moment. The results show that the
shear studs located in the crack-concentration zones due to large hogging moments sustain significantly smaller
shear force and slip stiffness than the other zones. Moreover, the reduction of the slip stiffness in the shear
connection appears also to be closely related to the change in the tensile strain of rebar according to the increase
of the load. Further experimental and analytical studies shall be conducted considering variables such as the
reinforcement ratio and the arrangement of shear connectors to achieve efficient design of the shear connection
in composite beams subjected to hogging moment.
Gold prospecting using Remote Sensing ‘A case study of Sudan’IJERD Editor
Gold has been extracted from northeast Africa for more than 5000 years, and this may be the first
place where the metal was extracted. The Arabian-Nubian Shield (ANS) is an exposure of Precambrian
crystalline rocks on the flanks of the Red Sea. The crystalline rocks are mostly Neoproterozoic in age. ANS
includes the nations of Israel, Jordan. Egypt, Saudi Arabia, Sudan, Eritrea, Ethiopia, Yemen, and Somalia.
Arabian Nubian Shield Consists of juvenile continental crest that formed between 900 550 Ma, when intra
oceanic arc welded together along ophiolite decorated arc. Primary Au mineralization probably developed in
association with the growth of intra oceanic arc and evolution of back arc. Multiple episodes of deformation
have obscured the primary metallogenic setting, but at least some of the deposits preserve evidence that they
originate as sea floor massive sulphide deposits.
The Red Sea Hills Region is a vast span of rugged, harsh and inhospitable sector of the Earth with
inimical moon-like terrain, nevertheless since ancient times it is famed to be an abode of gold and was a major
source of wealth for the Pharaohs of ancient Egypt. The Pharaohs old workings have been periodically
rediscovered through time. Recent endeavours by the Geological Research Authority of Sudan led to the
discovery of a score of occurrences with gold and massive sulphide mineralizations. In the nineties of the
previous century the Geological Research Authority of Sudan (GRAS) in cooperation with BRGM utilized
satellite data of Landsat TM using spectral ratio technique to map possible mineralized zones in the Red Sea
Hills of Sudan. The outcome of the study mapped a gossan type gold mineralization. Band ratio technique was
applied to Arbaat area and a signature of alteration zone was detected. The alteration zones are commonly
associated with mineralization. The alteration zones are commonly associated with mineralization. A filed check
confirmed the existence of stock work of gold bearing quartz in the alteration zone. Another type of gold
mineralization that was discovered using remote sensing is the gold associated with metachert in the Atmur
Desert.
Reducing Corrosion Rate by Welding DesignIJERD Editor
The paper addresses the importance of welding design to prevent corrosion at steel. Welding is
used to join pipe, profiles at bridges, spindle, and a lot more part of engineering construction. The
problems happened associated with welding are common issues in these fields, especially corrosion.
Corrosion can be reduced with many methods, they are painting, controlling humidity, and also good
welding design. In the research, it can be found that reducing residual stress on the welding can be
solved in corrosion rate reduction problem.
Preheating on 500oC and 600oC give better condition to reduce corosion rate than condition after
preheating 400oC. For all welding groove type, material with 500oC and 600oC preheating after 14 days
corrosion test is 0,5%-0,69% lost. Material with 400oC preheating after 14 days corrosion test is 0,57%-0,76%
lost.
Welding groove also influence corrosion rate. X and V type welding groove give better condition to reduce
corrosion rate than use 1/2V and 1/2 X welding groove. After 14 days corrosion test, the samples with
X welding groove type is 0,5%-0,57% lost. The samples with V welding groove after 14 days corrosion test is
0,51%-0,59% lost. The samples with 1/2V and 1/2X welding groove after 14 days corrosion test is 0,58%-
0,71% lost.
Router 1X3 – RTL Design and VerificationIJERD Editor
Routing is the process of moving a packet of data from source to destination and enables messages
to pass from one computer to another and eventually reach the target machine. A router is a networking device
that forwards data packets between computer networks. It is connected to two or more data lines from different
networks (as opposed to a network switch, which connects data lines from one single network). This paper,
mainly emphasizes upon the study of router device, it‟s top level architecture, and how various sub-modules of
router i.e. Register, FIFO, FSM and Synchronizer are synthesized, and simulated and finally connected to its top
module.
Active Power Exchange in Distributed Power-Flow Controller (DPFC) At Third Ha...IJERD Editor
This paper presents a component within the flexible ac-transmission system (FACTS) family, called
distributed power-flow controller (DPFC). The DPFC is derived from the unified power-flow controller (UPFC)
with an eliminated common dc link. The DPFC has the same control capabilities as the UPFC, which comprise
the adjustment of the line impedance, the transmission angle, and the bus voltage. The active power exchange
between the shunt and series converters, which is through the common dc link in the UPFC, is now through the
transmission lines at the third-harmonic frequency. DPFC multiple small-size single-phase converters which
reduces the cost of equipment, no voltage isolation between phases, increases redundancy and there by
reliability increases. The principle and analysis of the DPFC are presented in this paper and the corresponding
simulation results that are carried out on a scaled prototype are also shown.
Mitigation of Voltage Sag/Swell with Fuzzy Control Reduced Rating DVRIJERD Editor
Power quality has been an issue that is becoming increasingly pivotal in industrial electricity
consumers point of view in recent times. Modern industries employ Sensitive power electronic equipments,
control devices and non-linear loads as part of automated processes to increase energy efficiency and
productivity. Voltage disturbances are the most common power quality problem due to this the use of a large
numbers of sophisticated and sensitive electronic equipment in industrial systems is increased. This paper
discusses the design and simulation of dynamic voltage restorer for improvement of power quality and
reduce the harmonics distortion of sensitive loads. Power quality problem is occurring at non-standard
voltage, current and frequency. Electronic devices are very sensitive loads. In power system voltage sag,
swell, flicker and harmonics are some of the problem to the sensitive load. The compensation capability
of a DVR depends primarily on the maximum voltage injection ability and the amount of stored
energy available within the restorer. This device is connected in series with the distribution feeder at
medium voltage. A fuzzy logic control is used to produce the gate pulses for control circuit of DVR and the
circuit is simulated by using MATLAB/SIMULINK software.
Study on the Fused Deposition Modelling In Additive ManufacturingIJERD Editor
Additive manufacturing process, also popularly known as 3-D printing, is a process where a product
is created in a succession of layers. It is based on a novel materials incremental manufacturing philosophy.
Unlike conventional manufacturing processes where material is removed from a given work price to derive the
final shape of a product, 3-D printing develops the product from scratch thus obviating the necessity to cut away
materials. This prevents wastage of raw materials. Commonly used raw materials for the process are ABS
plastic, PLA and nylon. Recently the use of gold, bronze and wood has also been implemented. The complexity
factor of this process is 0% as in any object of any shape and size can be manufactured.
Spyware triggering system by particular string valueIJERD Editor
This computer programme can be used for good and bad purpose in hacking or in any general
purpose. We can say it is next step for hacking techniques such as keylogger and spyware. Once in this system if
user or hacker store particular string as a input after that software continually compare typing activity of user
with that stored string and if it is match then launch spyware programme.
A Blind Steganalysis on JPEG Gray Level Image Based on Statistical Features a...IJERD Editor
This paper presents a blind steganalysis technique to effectively attack the JPEG steganographic
schemes i.e. Jsteg, F5, Outguess and DWT Based. The proposed method exploits the correlations between
block-DCTcoefficients from intra-block and inter-block relation and the statistical moments of characteristic
functions of the test image is selected as features. The features are extracted from the BDCT JPEG 2-array.
Support Vector Machine with cross-validation is implemented for the classification.The proposed scheme gives
improved outcome in attacking.
Secure Image Transmission for Cloud Storage System Using Hybrid SchemeIJERD Editor
- Data over the cloud is transferred or transmitted between servers and users. Privacy of that
data is very important as it belongs to personal information. If data get hacked by the hacker, can be
used to defame a person’s social data. Sometimes delay are held during data transmission. i.e. Mobile
communication, bandwidth is low. Hence compression algorithms are proposed for fast and efficient
transmission, encryption is used for security purposes and blurring is used by providing additional
layers of security. These algorithms are hybridized for having a robust and efficient security and
transmission over cloud storage system.
Application of Buckley-Leverett Equation in Modeling the Radius of Invasion i...IJERD Editor
A thorough review of existing literature indicates that the Buckley-Leverett equation only analyzes
waterflood practices directly without any adjustments on real reservoir scenarios. By doing so, quite a number
of errors are introduced into these analyses. Also, for most waterflood scenarios, a radial investigation is more
appropriate than a simplified linear system. This study investigates the adoption of the Buckley-Leverett
equation to estimate the radius invasion of the displacing fluid during waterflooding. The model is also adopted
for a Microbial flood and a comparative analysis is conducted for both waterflooding and microbial flooding.
Results shown from the analysis doesn’t only records a success in determining the radial distance of the leading
edge of water during the flooding process, but also gives a clearer understanding of the applicability of
microbes to enhance oil production through in-situ production of bio-products like bio surfactans, biogenic
gases, bio acids etc.
Gesture Gaming on the World Wide Web Using an Ordinary Web CameraIJERD Editor
- Gesture gaming is a method by which users having a laptop/pc/x-box play games using natural or
bodily gestures. This paper presents a way of playing free flash games on the internet using an ordinary webcam
with the help of open source technologies. Emphasis in human activity recognition is given on the pose
estimation and the consistency in the pose of the player. These are estimated with the help of an ordinary web
camera having different resolutions from VGA to 20mps. Our work involved giving a 10 second documentary to
the user on how to play a particular game using gestures and what are the various kinds of gestures that can be
performed in front of the system. The initial inputs of the RGB values for the gesture component is obtained by
instructing the user to place his component in a red box in about 10 seconds after the short documentary before
the game is finished. Later the system opens the concerned game on the internet on popular flash game sites like
miniclip, games arcade, GameStop etc and loads the game clicking at various places and brings the state to a
place where the user is to perform only gestures to start playing the game. At any point of time the user can call
off the game by hitting the esc key and the program will release all of the controls and return to the desktop. It
was noted that the results obtained using an ordinary webcam matched that of the Kinect and the users could
relive the gaming experience of the free flash games on the net. Therefore effective in game advertising could
also be achieved thus resulting in a disruptive growth to the advertising firms.
Hardware Analysis of Resonant Frequency Converter Using Isolated Circuits And...IJERD Editor
-LLC resonant frequency converter is basically a combo of series as well as parallel resonant ckt. For
LCC resonant converter it is associated with a disadvantage that, though it has two resonant frequencies, the
lower resonant frequency is in ZCS region[5]. For this application, we are not able to design the converter
working at this resonant frequency. LLC resonant converter existed for a very long time but because of
unknown characteristic of this converter it was used as a series resonant converter with basically a passive
(resistive) load. . Here, it was designed to operate in switching frequency higher than resonant frequency of the
series resonant tank of Lr and Cr converter acts very similar to Series Resonant Converter. The benefit of LLC
resonant converter is narrow switching frequency range with light load[6] . Basically, the control ckt plays a
very imp. role and hence 555 Timer used here provides a perfect square wave as the control ckt provides no
slew rate which makes the square wave really strong and impenetrable. The dead band circuit provides the
exclusive dead band in micro seconds so as to avoid the simultaneous firing of two pairs of IGBT’s where one
pair switches off and the other on for a slightest period of time. Hence, the isolator ckt here is associated with
each and every ckt used because it acts as a driver and an isolation to each of the IGBT is provided with one
exclusive transformer supply[3]. The IGBT’s are fired using the appropriate signal using the previous boards
and hence at last a high frequency rectifier ckt with a filtering capacitor is used to get an exact dc
waveform .The basic goal of this particular analysis is to observe the wave forms and characteristics of
converters with differently positioned passive elements in the form of tank circuits.
Simulated Analysis of Resonant Frequency Converter Using Different Tank Circu...IJERD Editor
LLC resonant frequency converter is basically a combo of series as well as parallel resonant ckt. For
LCC resonant converter it is associated with a disadvantage that, though it has two resonant frequencies, the
lower resonant frequency is in ZCS region [5]. For this application, we are not able to design the converter
working at this resonant frequency. LLC resonant converter existed for a very long time but because of
unknown characteristic of this converter it was used as a series resonant converter with basically a passive
(resistive) load. . Here, it was designed to operate in switching frequency higher than resonant frequency of the
series resonant tank of Lr and Cr converter acts very similar to Series Resonant Converter. The benefit of LLC
resonant converter is narrow switching frequency range with light load[6] . Basically, the control ckt plays a
very imp. role and hence 555 Timer used here provides a perfect square wave as the control ckt provides no
slew rate which makes the square wave really strong and impenetrable. The dead band circuit provides the
exclusive dead band in micro seconds so as to avoid the simultaneous firing of two pairs of IGBT’s where one
pair switches off and the other on for a slightest period of time. Hence, the isolator ckt here is associated with
each and every ckt used because it acts as a driver and an isolation to each of the IGBT is provided with one
exclusive transformer supply[3]. The IGBT’s are fired using the appropriate signal using the previous boards
and hence at last a high frequency rectifier ckt with a filtering capacitor is used to get an exact dc
waveform .The basic goal of this particular analysis is to observe the wave forms and characteristics of
converters with differently positioned passive elements in the form of tank circuits. The supported simulation
is done through PSIM 6.0 software tool
Amateurs Radio operator, also known as HAM communicates with other HAMs through Radio
waves. Wireless communication in which Moon is used as natural satellite is called Moon-bounce or EME
(Earth -Moon-Earth) technique. Long distance communication (DXing) using Very High Frequency (VHF)
operated amateur HAM radio was difficult. Even with the modest setup having good transceiver, power
amplifier and high gain antenna with high directivity, VHF DXing is possible. Generally 2X11 YAGI antenna
along with rotor to set horizontal and vertical angle is used. Moon tracking software gives exact location,
visibility of Moon at both the stations and other vital data to acquire real time position of moon.
“MS-Extractor: An Innovative Approach to Extract Microsatellites on „Y‟ Chrom...IJERD Editor
Simple Sequence Repeats (SSR), also known as Microsatellites, have been extensively used as
molecular markers due to their abundance and high degree of polymorphism. The nucleotide sequences of
polymorphic forms of the same gene should be 99.9% identical. So, Microsatellites extraction from the Gene is
crucial. However, Microsatellites repeat count is compared, if they differ largely, he has some disorder. The Y
chromosome likely contains 50 to 60 genes that provide instructions for making proteins. Because only males
have the Y chromosome, the genes on this chromosome tend to be involved in male sex determination and
development. Several Microsatellite Extractors exist and they fail to extract microsatellites on large data sets of
giga bytes and tera bytes in size. The proposed tool “MS-Extractor: An Innovative Approach to extract
Microsatellites on „Y‟ Chromosome” can extract both Perfect as well as Imperfect Microsatellites from large
data sets of human genome „Y‟. The proposed system uses string matching with sliding window approach to
locate Microsatellites and extracts them.
Importance of Measurements in Smart GridIJERD Editor
- The need to get reliable supply, independence from fossil fuels, and capability to provide clean
energy at a fixed and lower cost, the existing power grid structure is transforming into Smart Grid. The
development of a smart energy distribution grid is a current goal of many nations. A Smart Grid should have
new capabilities such as self-healing, high reliability, energy management, and real-time pricing. This new era
of smart future grid will lead to major changes in existing technologies at generation, transmission and
distribution levels. The incorporation of renewable energy resources and distribution generators in the existing
grid will increase the complexity, optimization problems and instability of the system. This will lead to a
paradigm shift in the instrumentation and control requirements for Smart Grids for high quality, stable and
reliable electricity supply of power. The monitoring of the grid system state and stability relies on the
availability of reliable measurement of data. In this paper the measurement areas that highlight new
measurement challenges, development of the Smart Meters and the critical parameters of electric energy to be
monitored for improving the reliability of power systems has been discussed.
Study of Macro level Properties of SCC using GGBS and Lime stone powderIJERD Editor
One of the major environmental concerns is the disposal of the waste materials and utilization of
industrial by products. Lime stone quarries will produce millions of tons waste dust powder every year. Having
considerable high degree of fineness in comparision to cement this material may be utilized as a partial
replacement to cement. For this purpose an experiment is conducted to investigate the possibility of using lime
stone powder in the production of SCC with combined use GGBS and how it affects the fresh and mechanical
properties of SCC. First SCC is made by replacing cement with GGBS in percentages like 10, 20, 30, 40, 50 and
by taking the optimum mix with GGBS lime stone powder is blended to mix in percentages like 5, 10, 15, 20 as
a partial replacement to cement. Test results shows that the SCC mix with combination of 30% GGBS and 15%
limestone powder gives maximum compressive strength and fresh properties are also in the limits prescribed by
the EFNARC.
DISSERTATION on NEW DRUG DISCOVERY AND DEVELOPMENT STAGES OF DRUG DISCOVERYNEHA GUPTA
The process of drug discovery and development is a complex and multi-step endeavor aimed at bringing new pharmaceutical drugs to market. It begins with identifying and validating a biological target, such as a protein, gene, or RNA, that is associated with a disease. This step involves understanding the target's role in the disease and confirming that modulating it can have therapeutic effects. The next stage, hit identification, employs high-throughput screening (HTS) and other methods to find compounds that interact with the target. Computational techniques may also be used to identify potential hits from large compound libraries.
Following hit identification, the hits are optimized to improve their efficacy, selectivity, and pharmacokinetic properties, resulting in lead compounds. These leads undergo further refinement to enhance their potency, reduce toxicity, and improve drug-like characteristics, creating drug candidates suitable for preclinical testing. In the preclinical development phase, drug candidates are tested in vitro (in cell cultures) and in vivo (in animal models) to evaluate their safety, efficacy, pharmacokinetics, and pharmacodynamics. Toxicology studies are conducted to assess potential risks.
Before clinical trials can begin, an Investigational New Drug (IND) application must be submitted to regulatory authorities. This application includes data from preclinical studies and plans for clinical trials. Clinical development involves human trials in three phases: Phase I tests the drug's safety and dosage in a small group of healthy volunteers, Phase II assesses the drug's efficacy and side effects in a larger group of patients with the target disease, and Phase III confirms the drug's efficacy and monitors adverse reactions in a large population, often compared to existing treatments.
After successful clinical trials, a New Drug Application (NDA) is submitted to regulatory authorities for approval, including all data from preclinical and clinical studies, as well as proposed labeling and manufacturing information. Regulatory authorities then review the NDA to ensure the drug is safe, effective, and of high quality, potentially requiring additional studies. Finally, after a drug is approved and marketed, it undergoes post-marketing surveillance, which includes continuous monitoring for long-term safety and effectiveness, pharmacovigilance, and reporting of any adverse effects.
These lecture slides, by Dr Sidra Arshad, offer a quick overview of the physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar lead (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
6. Describe the flow of current around the heart during the cardiac cycle
7. Discuss the placement and polarity of the leads of electrocardiograph
8. Describe the normal electrocardiograms recorded from the limb leads and explain the physiological basis of the different records that are obtained
9. Define mean electrical vector (axis) of the heart and give the normal range
10. Define the mean QRS vector
11. Describe the axes of leads (hexagonal reference system)
12. Comprehend the vectorial analysis of the normal ECG
13. Determine the mean electrical axis of the ventricular QRS and appreciate the mean axis deviation
14. Explain the concepts of current of injury, J point, and their significance
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. Chapter 3, Cardiology Explained, https://www.ncbi.nlm.nih.gov/books/NBK2214/
7. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
Antimicrobial stewardship to prevent antimicrobial resistanceGovindRankawat1
India is among the nations with the highest burden of bacterial infections.
India is one of the largest consumers of antibiotics worldwide.
India carries one of the largest burdens of drug‑resistant pathogens worldwide.
Highest burden of multidrug‑resistant tuberculosis,
Alarmingly high resistance among Gram‑negative and Gram‑positive bacteria even to newer antimicrobials such as carbapenems.
NDM‑1 ( New Delhi Metallo Beta lactamase 1, an enzyme which inactivates majority of Beta lactam antibiotics including carbapenems) was reported in 2008
Integrating Ayurveda into Parkinson’s Management: A Holistic ApproachAyurveda ForAll
Explore the benefits of combining Ayurveda with conventional Parkinson's treatments. Learn how a holistic approach can manage symptoms, enhance well-being, and balance body energies. Discover the steps to safely integrate Ayurvedic practices into your Parkinson’s care plan, including expert guidance on diet, herbal remedies, and lifestyle modifications.
Recomendações da OMS sobre cuidados maternos e neonatais para uma experiência pós-natal positiva.
Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
Estas diretrizes visam melhorar a qualidade dos cuidados pós-natais essenciais e de rotina prestados às mulheres e aos recém-nascidos, com o objetivo final de melhorar a saúde e o bem-estar materno e neonatal.
Uma “experiência pós-natal positiva” é um resultado importante para todas as mulheres que dão à luz e para os seus recém-nascidos, estabelecendo as bases para a melhoria da saúde e do bem-estar a curto e longo prazo. Uma experiência pós-natal positiva é definida como aquela em que as mulheres, pessoas que gestam, os recém-nascidos, os casais, os pais, os cuidadores e as famílias recebem informação consistente, garantia e apoio de profissionais de saúde motivados; e onde um sistema de saúde flexível e com recursos reconheça as necessidades das mulheres e dos bebês e respeite o seu contexto cultural.
Estas diretrizes consolidadas apresentam algumas recomendações novas e já bem fundamentadas sobre cuidados pós-natais de rotina para mulheres e neonatos que recebem cuidados no pós-parto em unidades de saúde ou na comunidade, independentemente dos recursos disponíveis.
É fornecido um conjunto abrangente de recomendações para cuidados durante o período puerperal, com ênfase nos cuidados essenciais que todas as mulheres e recém-nascidos devem receber, e com a devida atenção à qualidade dos cuidados; isto é, a entrega e a experiência do cuidado recebido. Estas diretrizes atualizam e ampliam as recomendações da OMS de 2014 sobre cuidados pós-natais da mãe e do recém-nascido e complementam as atuais diretrizes da OMS sobre a gestão de complicações pós-natais.
O estabelecimento da amamentação e o manejo das principais intercorrências é contemplada.
Recomendamos muito.
Vamos discutir essas recomendações no nosso curso de pós-graduação em Aleitamento no Instituto Ciclos.
Esta publicação só está disponível em inglês até o momento.
Prof. Marcus Renato de Carvalho
www.agostodourado.com
Local Advanced Lung Cancer: Artificial Intelligence, Synergetics, Complex Sys...Oleg Kshivets
Overall life span (LS) was 1671.7±1721.6 days and cumulative 5YS reached 62.4%, 10 years – 50.4%, 20 years – 44.6%. 94 LCP lived more than 5 years without cancer (LS=2958.6±1723.6 days), 22 – more than 10 years (LS=5571±1841.8 days). 67 LCP died because of LC (LS=471.9±344 days). AT significantly improved 5YS (68% vs. 53.7%) (P=0.028 by log-rank test). Cox modeling displayed that 5YS of LCP significantly depended on: N0-N12, T3-4, blood cell circuit, cell ratio factors (ratio between cancer cells-CC and blood cells subpopulations), LC cell dynamics, recalcification time, heparin tolerance, prothrombin index, protein, AT, procedure type (P=0.000-0.031). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and N0-12 (rank=1), thrombocytes/CC (rank=2), segmented neutrophils/CC (3), eosinophils/CC (4), erythrocytes/CC (5), healthy cells/CC (6), lymphocytes/CC (7), stick neutrophils/CC (8), leucocytes/CC (9), monocytes/CC (10). Correct prediction of 5YS was 100% by neural networks computing (error=0.000; area under ROC curve=1.0).
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
share - Lions, tigers, AI and health misinformation, oh my!.pptxTina Purnat
• Pitfalls and pivots needed to use AI effectively in public health
• Evidence-based strategies to address health misinformation effectively
• Building trust with communities online and offline
• Equipping health professionals to address questions, concerns and health misinformation
• Assessing risk and mitigating harm from adverse health narratives in communities, health workforce and health system
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
Tests for analysis of different pharmaceutical.pptx
J1036471
1. International Journal of Engineering Research and Development
e-ISSN: 2278-067X, p-ISSN: 2278-800X, www.ijerd.com
Volume 10, Issue 3 (March 2014), PP.64-71
64
Statistical Model For Risk Estimation
1
Dr. Vahida Attar, 2
Dr. D. Datta
1
Department of computer and IT, College of Engineering Pune ,Shivaji Nagar, Pune India.
2
Department of atomic energy, BRNS Mumbai, India.
Abstract:- The study of the distribution and determinants of disease prevalence in man is done primarily in
Radiation Epidemiology. Epidemiologists seek to relate risk of disease to different levels and patterns of
radiation exposure. In this paper we examine statistical model of Poisson regression previously employed for
the estimation of radiation risk. We examine different regression techniques, which overcome the underlying
assumptions of Poisson Regression for risk estimation and propose Hurdle's Model for the same. The models
need application of logarithmic transform to yield the additive model instead of multiplicative model, which is
usually used in Risk Assessment and thus obtain the Linear Dose-Response Model.
I. INTRODUCTION
Epidemiology is concerned with study of distribution of disease and determinants of health-related
states or events in specified human populations and application of this study for control of human health
problems. It is observed that, people exposed to radiation usually suffer from cancer and other fatal diseases. For
instance, there are two ways in which nuclear workers are exposed to radiation according to the Canadian
Nuclear Safety Commission, either while working with sources of man-made radiation (nuclear industry, health
care, research institutions or manufacturing) or they are exposed to elevated levels of natural radiation (mining,
air crews construction).
Radiation is categorized as ionizig and non-ionizing.[8] Ionizing radiation is radiation with enough
energy so that during an interaction with an atom it can remove bound electrons, i.e., it can ionize atoms.
Examples are X-Rays and electrons.Non-ionizing radiation is radiation without enough energy to remove bound
electrons from their orbits around atoms. Examples are microwaves and visible light.The ionizing radiation
interacts with the cells and damages them, which in turn results in malignant growth in the body. Thus studying
the levels of radiation and its corresponding effects can prove beneficial in setting the safety levels of exposure.
In our study we intend to develop a generalized model for risk evaluation or odds ratio for death due to
cardiovascular disease and other cancer due to ionizing radiation. Radiation Effects Research Foundation has
played an important role of carrying out cohort study on the Japanese Atomic Bomb survivors with a follow-up
of 50 years. This report makes use of data obtained from the Radiation Effects Research Foundation (RERF),
Hiroshima and Nagasaki, Japan. RERF is a private, non-profit foundation funded by the Japanese Ministry of
Health, Labour and Welfare (MHLW) and the U.S. Department of Energy, the latter through the National
Academy of Sciences. The objective is to apply suitable methods to gain further insight in the model developed
by RERF on Cardiovascular diseases. Main outcome is to measure Mortality from stroke or heart disease as the
underlying cause of death and dose response relations with atomic bomb radiation. This finding would
significantly benefit the humanity as with growing technology, there are associated hazards. This is an
interdisciplinary problem as it encompasses Epidemiology, Statistics and Data Analysis Methods. The paper
starts discussion of prevalent risk models for low-ionized radiation. Aanalyse the strengths and limitations of the
models used. This is followed by provision of theoretical background of Poisson Model, used for count data and
estimation of relative risk. It comprises of multiplicative and additive models of relative risk. Finally it proposes
the use of variations of Poisson Regression called Hurdle model.
II. RISK OF RADIATION EXPOSURE
Comparing the acute exposure experienced by atomic bomb survivors with the low dose rate exposures
experienced gradually over time due to occupational, environmental or natural background circumstances is
now frequently done. Wide ranges of risk estimates have been reported with some significantly lower than the
2. Statistical Model For Risk Estimation
65
estimate of cancer incidence among atomic bomb survivors and some higher but not significantly so. The
differences are in large part related to chance, different dose ranges, different lengths of follow-up, differences
in ethnicity and background cancer rates, and biases and confounding that play a much more important role
when studying populations exposed to low doses.
Manmade verses Natural Resources radiation exposure: Whether it is taken from external exposure or
from intakes of radioactive material . Depending on dose: The lower the dose, the lower the risk but the lower
the dose, the greater the difficulty in detecting any increase in the number of cancers possibly attributable to
radiation. In higher doses the risk is also higher but the chases of detecting the cancer are also more. At doses
below 100 millisieverts (mSv), it is not possible to distinguish cancer due to radiation from that of the natural
variation of the disease among the general population.
Radiation epidemiology has revealed that ' a single exposure can increase the lifetime risk of cancer;
the young are more susceptible than the old (although not markedly so); females are more susceptible than
males; the foetus is not more susceptible than the child; genetic (heritable) effects have not been found in
humans to date; risks differ by organ or tissue and some cancers have not been convincingly increased after
exposure. Many small exposures over years can significantly decrease lifetime.'
Epidemiologists use the term “risk” in two different ways to describe the associations that are noted in
data. Relative risk is the ratio of the rate of disease among groups having some risk factor, such as radiation,
divided by the rate among a group not having that factor. Absolute risk is the simple rate of disease among a
population and Excess absolute risk (EAR) is the difference between two absolute risks.[2]
Figure 1. Modelling of data
III. RISK MODELS
Poisson regression methods for grouped survival data were used to describe the dependence of risk on
radiation dose and to evaluate the variation of the dose response with respect to city, sex, age at exposure, and
attained age. Significance tests and confidence intervals (CI) were based on likelihood ratio statistics. The
results were considered statistically significant when the two-sided P < 0.05. The models used here are as
follows.
3. Statistical Model For Risk Estimation
66
Excess Relative Risk (ERR) model:
λ0 (c, s, a, b) [1+ERR (d, e, s, a)] (1)
Excess Absolute Risk (EAR) model:
λ0 (c, s, a, b) [1+EAR (d, e, s, a)] (2)
Where λ0 is the baseline or background mortality rate at zero dose, depending on city (c), sex (s), birth
year (b), and attained age (a). λ0 was modelled by stratification for the ERR model and by parametric function
involving relevant factors for the EAR model. ERR or EAR depends on radiation dose (d) and, if necessary,
effect modification by sex, age at exposure (e), and attained age.
Effect modification was described using multiplicative-function models as follows:
(e,s,a) = exp(.e+.ln(a))(1+.s) (3)
where , and were the coefficients for effect modification by age at exposure, attained age, and sex,
respectively. The term that includes sex (s = 1 for men and s = -1 for women) as a modifier allows the 1
parameter to represent sex-averaged risk estimates.[1] Therefore, ERR and EAR models were, respectively,
0(c,s,b,a)[1+1d.exp(e+.ln(a)) (1+s)] (4)
0(c,s,b,a)[1d.exp(e+ln(a)) (1+s)] (5)
3.1 Strengths
This study has several strengths, including a large population not pre-selected for existing disease or
occupational fitness, a wide but relatively low dose range (0->3 Gy) and well characterized doses, a 53 year
follow-up with virtually complete mortality ascertainment, and corroborative evidence from more detailed
clinical and biomarker studies of risk of circulatory disease on a random subsample of the cohort. The analyses
of radiation dose with stroke and heart disease mortality showed that the association is reasonably robust with
respect to confounding by lifestyle, sociodemographic, or other health factors or misdiagnosis.
3.2 Limitations
The model also has several limitations and uncertainties. Ascertainment of circulatory disease from
death certificates is of limited diagnostic accuracy and represents only a fraction of cases of incident disease.
Some selection effects due to dose related early mortality from the bombs may have occurred, although the
impact of these is likely to be small. Other limitations include unclear dose-response effects below about 0.5 Gy,
inadequate information about possible biological mechanisms, and uncertainty about the generalisability of
these results to Western populations because of differences in genetic factors, dietary and lifestyle risk factors,
and baseline levels of risk for stroke and heart disease.
Another problem is excess zeros. In this situation, the distribution has more zeros than would be
expected from a Poisson distribution. Often this is caused by two processes creating the data set, one of the
processes having an expected count of zero. Thus model is always overly restrictive when it comes to estimating
features of the population other than the mean, such as the variance or the probability of single outcomes.[1]
3.3 Model for Group Data
The data layout consists of a table with J rows (j = 1. . . J) And K columns (k = 1. . . K). Within the cell
formed by the intersection of the jth
row and kth
column, one records the number of incident cases or deaths djk
and the person-years denominators njk where j is used for indexing J age intervals and k for representing one of
K exposure categories.
Observed rate jk=djk/njk (6)
4. Statistical Model For Risk Estimation
67
djk =No of deaths, njk = person years
This is considered as an estimate of a true rate λjk that could be known exactly only if an infinite
amount of observation time were available. The goal of the statistical analysis is to uncover the basic structure in
the underlying rates λjk, and in particular, to disentangle the separate effects of age and exposure.[3]
Various possible structures for the rates satisfy the requirement of consistency. In particular, it holds if
the effect of exposure at level k is to add a constant amount βk to the age-specific rates λj1 , for individuals in
the baseline or non-exposed category (k = 1).The model equation is :
jk = αj + βk (7)
Where αj = λj1 and βk (β1 = 0) are parameters to be estimated from the data. If additivity does not hold on the
original scale of measurement, it may hold for some transformation of the rates. The log transform
log λjk = αj+ βk (8)
yields the multiplicative model where
λjk = Ѳj * ᴪk (9)
here, αj = log(Ѳj) , βk = log(ᴪk) , ᴪk = Relative risk of decease at exposure level k.
The excess (additive) and relative (multiplicative) risk models are ubiquitous models to describe the
relationship between the effects of exposure and the effects of age and other factors that may account for
background or spontaneous cases. These have been used to describe different aspects of radiation carcinogenesis
in human populations (Committee on the Biological Effects of Ionizing Radiation, 1980).[2]. Due to the sharp
rise in background incidence with age, relative risk estimates derived from current data generally predict a
greater lifetime radiation risk than do the estimates of additive effect.[3]
3.4 Multiplicative Model for Rate
The basic data consist of the counts of deaths djk and the person-years denominators nik in each cell,
together with p-dimensional row vectors xjk = (xjk1
, . . . , xjkp
)) of regression variables . These latter may
represent either qualitative or quantitative effects of the exposures on the stratum-specific rates, interactions
among the exposures and interactions between exposure variables and stratification (nuisance) variables.
A general form of the multiplicative model is:
log λjk = j+ xjk *β (10)
where the λjk are the unknown true disease rates, the j are nuisance parameters specifying the effects of
age and other stratification variables, and β= (β1,β2,...,βp)T
is a p-dimensional column vector of regression
coefficients that describe the effects of primary interest. An important feature of this model is that the disease
rates depend on the exposures only through the quantity αj+ xjk *β, which is known as the linear predictor. If the
regression variables xjk depend only on the exposure category k and not on j, above equation specifies a purely
multiplicative relationship such that the ratio of disease rates λjk/λjk', for two exposure levels k and k', namely
exp {(xk - xk')β), is constant over the strata.
3.5 Additive Model for Risk
The limitation of multiplicative model is that when applied with quantitative exposure variables, it
leads to relative risk functions that increase exponentially with increasing exposure: RR(x) = exp(xβ). This need
not be applicable to different diseases and thus one needs to apply suitable transform. Many of the quantitative
dose-response relations actually observed in cancer epidemiology approximate a power relationship of the form
5. Statistical Model For Risk Estimation
68
𝑅𝑅(𝑥) = (𝑥 + 𝑥0)^𝛽 (11)
This relative risk function may be approximated by first transforming the dose to z = log (x + x0) and
then fitting the multiplicative model in the form
log( λjk) = αj+ zk*β =αj+ log(xk+x0)*β (12)
The choice xo= 1 is not uncommon as a 'starter' dose since it yields the usual RR(x) = 1 at the baseline
level x = 0. xo may also be treated as an unknown parameter and the best fitting value, found by trial and error
or some other more systematic technique. Certain formulations of multistage theory and other more general
considerations lead to relative risk functions that are linear or quadratic in measured exposures, for example
RR(x) = 1+βx or RR(x) = 1 + βk + 𝑥2
(13)
These are special cases of a general class of models of the form
λjk = exp (αj){l + xjk}β (14)
One drawback of these is that the range of the β parameters is necessarily restricted by the requirement
that xjk*β > -1 for all values of xjk, since negative relative risks would otherwise result. This suggests that,
wherever possible, the regression variables xjk be coded so that they have positive coefficients.
As usually happens for models in which there is a range restriction on the parameters, the log-
likelihood function is skewed and not at all like the quadratic, symmetric log-likelihood of the approximating
normal distribution. Estimates of the parameters may be unstable, and standard errors that are determined from
the usual likelihood calculations may be unhelpful in assessing the degree of uncertainty. With suitable
transformation, we fit the additive relative risk model to Poisson rates and thus obtain a family of general
relative risk modes which is given by
λjk = exp (αj) r( xjk , β) (15)
where the relative risk function is specified by the power relation
log r (xjk*β) = (1+ xjk*β)^/ !=0
log r (xjk*β) =log(1+ xjk*β) =0 (16)
This yields the additive relative risk model at = 0 and the standard multiplicative model at = 1.[3]
IV. PROPOSED MODEL
4. 1 Poisson Regression Model
The typical Poisson regression model expresses the natural logarithm of the event or outcome of
interest as a linear function of a set of predictors. The dependent variable is a count of the occurrences of interest
e.g. the number of cases of a disease that occur over a period of follow-up. Typically, one can estimate a rate
ratio associated with a given predictor or exposure. A measure of the goodness of fit of the Poisson regression
model is obtained by using the deviance statistic of a base-line model against a fuller model.
When the response variable is in the form of a count and for rare events the Poisson distribution
(rather than the Normal) is more appropriate since the Poisson mean > 0. So the logarithm of the response
variable is linked to a linear function of explanatory variables such that
ln(Y)= β0 + β1 Χ1 + β2Χ2 … (17)
6. Statistical Model For Risk Estimation
69
The basic Poisson regression model relates the probability function of a dependent variable yi (also referred
to as regress and, endogenous, or dependent variable) to a vector of independent variables xi (also referred to as
repressors, exogenous, or independent variable).[9] The standard uni-variates Poisson regression model makes
the following assumptions:
Logarithm of the disease rate changes linearly with equal increment increases in the exposure variable.
Changes in the rate from combined effects of different exposures or risk factors are multiplicative.
At each level of the covariates the number of cases has variance equal to the mean.
Observations are independent.
This paper uses the Poisson Model with variation to obtain the risk coefficients. This section describes
the statistical models used in estimation of risk. These risk estimates are of prime interest for the epidemiologist.
Moreover, the coefficients obtained for risk, depend on the statistical model used for fitting the data. Therefore
the type of model used for fitting the data determines the risk estimates and their accuracy.
Poisson regression is appropriate when the conditional distributions of Y are expected to be Poisson
distributions. This often happens when you are trying to regress on count data. In fact, its applicability extends
well beyond the traditional domain of count data. The Poisson regression model can be used for any constant
elasticity mean function, whether the dependent variable is a count or continuous, and there are good reasons
why it should be preferred over the more common log transformation of the dependent variable.
The simplicity of the Poisson regression model, an asset when modelling the mean, turns them into a liability,
and more elaborate models are needed. There are two common difficulties in Poisson regression and they are
both caused by heterogeneity in the data.
1. Over dispersion- This occurs when the variance of the fitted model is larger than what is expected by the
assumptions (the mean and the variance are equal) of the Poisson model. Over dispersion is typically caused by
a Poisson regression that is missing an important independent variable or by data being collected in clusters (like
collecting data inside family units).
2. The second problem, also caused by heterogeneity, is excess zeros. In this situation, the distribution has more
zeros than would be expected from a Poisson distribution. Often this is caused by two processes creating the
data set, one of the processes having an expected count of zero. Poisson model is always overly restrictive when
it comes to estimating features of the population other than the mean, such as the variance or the probability of
single outcomes.
4.2 Hurdle Model
To overcome the limitations of Poisson Hurdles Model is used
Figure 2. Risk estimation Model
7. Statistical Model For Risk Estimation
70
Hurdles model (each assuming either the Poisson or negative binomial distribution of the outcome) has
been developed to cope with zero-inflated outcome data with over-dispersion (negative binomial) or without
(Poisson distribution). Hurdle model deals with the high occurrence of zeros in the observed data,
A hurdle model is a modified count model in which there are two processes, one generating the zeros
and one generating the positive values. The two models are not constrained to be the same. The concept
underlying the hurdle model is that a binomial probability model governs the binary outcome of whether a count
variable has a zero or a positive value. If the value is positive, the "hurdle is crossed," and the conditional
distribution of the positive values is governed by a zero-truncated count model.
More formally, the hurdle model combines a count data model count
(y; x, ) (that is left-truncated at y = 1) and
a zero hurdle model zero
(y; x, ) (right censored at y = 1).
(18)
The model parameters , and potentially one or two dispersion parameters (if or both are
negative binomial densities) are estimated by Maximum Likelihood, where specification of the likelihood has
the advantage that the count and the hurdle component can be maximized separately . Since the risk estimates
are exponential for doses groups, we would apply log transform on dose variables for obtaining the linear
relationship.[9]
4.3 Comparison of hurdle with Poisson regression
The models are compared by applying Vuong test. The Vuong test shows that the hurdles model
provides a better fit than Poisson regression model. From the comparison of AIC values it is observed that
hurdles model provides better fit.
Table 1. Odds ratios of hurdle model
Age
Categories
Odds Ratio
Agexcat8 4.2799616
Agexcat9 5.5625905
Agexcat10 7.4448636
Agexcat11 10.1254675
Agexcat12 10.2122343
Agexcat13 10.6221722
Agexcat14 10.1927220
Agexcat15 6.8081283
s2 0.6887824
8. Statistical Model For Risk Estimation
71
Table 2. Comparison of Models
Model AIC
Multiplicative Poisson
Additive Poisson
Additive hurdle
20687.0
20686.6
20686.2
V. CONCLUSION AND FUTURE WORK
Poisson regression has various limitations. There are several alternative models like Negative Binomial
Regression and Zero-inflated Poisson Regression to fit the data to the model. We developed Hurdles model as
an alternative to Poisson model for risk estimation and observed that it provides a better fit as compared to
Poisson model. There are other models like Negative Binomial and ZIP to cope up with the problem of excess
zeros and over dispersion. Future work includes fitting data to these models and comparing the model
parameters for obtaining the best fit of data.
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[3]. N.E. Breslow and N.E. Day, Methods in Cancer Research Volume II - The Analysis of Cohort Studies
W.N. Venables, D.M.Smith and the R CORE Team, An Introduction to R www.rerf.or.jp Radiation
Effects Research Foundation
[4]. Analysis of epidemiological data using R and Epicalc -Virasakdi Chongsuvivatwong Probability and
Statistics- Walpole Steven L. Simon, Ph.D. Radiation Epidemiology Branch, Division of Cancer
Epidemiology and Genetics, National Cancer Institute,
[5]. Introduction to Radiation Physics and Dosimetry Regression Models for count data in R.