Range uncertainty and dose uniformity in proton therapy in the presence of inhomogeneities in tissue and phantom materials

Proton therapy is an emerging modality for providing radiation treatment to cancer pa-tients. The principal advantages of proton therapy are the reduced total dose deposited into the patient as compared to conventional photon therapy and the finite range of the proton beam. It is considered as a more favorable option for optimum treatment outcomes in terms of maximising tumor control probability and minimising normal tissue complications. The depth dose distribution of the proton beam adds an additional degree of freedom to treat-ment planning. The range in tissue is associated with substantial uncertainties triggered by imaging, patient set-up, beam delivery and dose calculations. Therefore, reduction in uncer-tainties would allow to minimise the treatment volume and thus allow a better usage of the protons. However, the presence of sub-millimeter sized heterogeneities, such is pronounced in trabecular bone and lung parenchyma, in the path of the proton beam can cause the Bragg peak degradation with a widening to the distal fall-o˙. Additionally, the restricted resolution of a classic CT scan used in treatment planning cannot fully resolve such fine structures, potentially leading to inaccuracy in determination of the range.This work aims to investigate the presence of range uncertainties in proton therapy beams when they penetrate through the sub-millimeter sized heterogeneities. The e˙ect of Bragg peak degradation has been demonstrated in bone models with the FLUKA Monte Carlo code and experimental measurements with a 36 MeV proton beam. The bone-substitute material, SAWBONES®, ranging in density from 0.088 to 0.48 g/cc, was used to simulate bone heterogeneities. Micro-CT images were obtained of the SAWBONES® material and used to construct Monte Carlo models of realistic proton radiotherapy treatments and to benchmark experimental studies. Broadening of the Bragg peak and shifts in the range, as defined by the d20% depth-dose parameter were observed both experimentally and in Monte Carlo models, indicating that such e˙ects are in principle, clinically relevant in certain circumstances.Furthermore, a FLUKA Monte Carlo model is benchmarked against the Eclipse treatment planning system (TPS) golden data for proton beam therapy. This project is designed to obtain the proton dose distributions from TPS for a 10 ×10 × 10 cm3 water-filled box. A Monte Carlo analytical model is developed by utilising the information from the TPS to recalculate the dose distribution which are then compared to find any di˙erences (if present) for di˙erent phantom materials. Due to the lack of any experimental information to measure the normalized depth dose as a function of energy, considering the general behaviour of a monitor chamber, it has been assumed that the treatment planning system has a built-in relationship between the monitor units (MU) and dose delivered. A mathematical formula is developed to find the relationship between monitor units (MU) and dose (E). MU α 1/Ea.The value of a is varied from 0 to 1. It has been observed that the beam non-uniformity calculated by using the relationship " MU = E−0.5 " is only 0.15 % for water and 0.43 % for graphite. This non-uniformity in graphite is not severe and it is actually clinically acceptable. This modeling has suggested that the planned dose distributions for water can also be replaced by graphite to a reasonably acceptable standard

Where attention goes, energy flows : enhancing individual sustainability in software engineering

Software engineers are plagued by the same troubles as many others in highly skilled jobs and digitized environments: Ever-expanding to-do lists, time to market pressure from management, deadline- driven development, continuous interruption during working tasks, and the juggle of balancing that with other areas of life (physical, mental and emotional health, family, household, finance, friends, hobbies and community service). These demands of life in combina- tion with a seemingly ever-increasing pace wear or burn out many people in the long run. Specifically, as software engineers, this also leads to decreased creativity and less efficiency in problem-solving. Generally offered solutions are reducing screen time and spending more time outdoors, both of which are hard to do within the work of a software engineer. On a meta level, if the developers of the systems that run most of our world do not develop individual sus- tainability with a balanced pace of life, that imbalance propagates into the systems we develop (similar to Conway’s Law). We argue that mindfulness practices like yoga poses (asanas), breathing prac- tices, and meditation exercises can help individually, and even more effectively in combination. In this exploratory paper, we discuss related work that explores the application of these mitigations in other application domains and propose a research agenda to explore their use within software engineering education and practice.Engaging with mindfulness practices in the context of software engineering promises to enhance creativity and cognitive problem- solving skills, leading to more efficiency and effectiveness during software development and increased individual sustainability. This, in turn, leads to better team spirit as well as increased economic profit, both in terms of maintaining human capital and customer contract deliverables

Study protocol: asymptomatic intracranial atherosclerotic disease in pakistanis.

Background : Intracranial atherosclerotic disease (ICAD) is the most frequent subtype of ischemic stroke globally. It is important to describe the determinants of early ICAD as a strategy to prevent strokes from clinically evident and progressive ICAD. Our objective is to report the determinants of asymptomatic ICAD by linking the presence or absence of ICAD on magnetic resonance angiogram (MRA) with detailed risk assessment in asymptomatic adults. Methods : This is an observational cross-sectional analytical study. We plan to recruit 200 adult participants from the radiology departments of two tertiary care centers of Karachi, Pakistan. The participants will first be screened for the absence of stroke symptoms via the Questionnaire for Verifying Stroke Free Status (QVSFS). QVSFS negative will be participants will be eligible. After written informed consent, participants will undergo detailed medical, sociodemographic, lifestyle, and anthropometric evaluation by a detailed interview. They will, in addition, undergo MRA to study the presence, degree, and distribution of asymptomatic ICAD. All MRA scans will be reviewed centrally by vascular neurologists blinded to clinical information. These images would be reviewed on DICOM Viewer 3.0 used for calculating the degree of stenosis using Warfarin–Aspirin Symptomatic Intracranial Disease (WASID) study defined criteria employing electronic calipers. A sample size of 200 will achieve 80% power for detecting a minimum difference of 20% in the prevalence of exposure factors (medical and lifestyle) between asymptomatic ICAD positive and ICAD negative persons. This study will generate regional data on risks for ICAD development and prevention in a high-risk susceptible population

Clinical, lifestyle, socioeconomic determinants and rate of asymptomatic intracranial atherosclerosis in stroke free Pakistanis.

Background: Intracranial Atherosclerotic Disease (ICAD) is the most frequent etiology of stroke with high prevalence among Asians. Despite this, early determinants of ICAD have not been described from this region. Methods: The study is an analytical prospective cross-sectional study of 200 adults from Radiology Departments of two diagnostic centers in Karachi. Eligible participants confirmed the absence of stroke symptoms via the Questionnaire for Verifying Stroke Free Status (QVSFS) and underwent an interview covering medical, socio demographic, lifestyle and anthropometric evaluation using locally validated and standardized definitions. Magnetic Resonance Images (MRI) were centrally reviewed to detect ICAD using the criterion used in the Warfarin–Aspirin Symptomatic Intracranial Disease study. The risk factors associated with asymptomatic ICAD are reported along with prevalence ratios. Results: Of the 200 participants, ICAD was found in 34.5% (n = 69) of the participants. Mean age was 37.1 (S.D 15.1) years with 62% younger than 45 years. Self-reported hypertension was found in 26.5% subjects, diabetes in 9%, dyslipidemia in 5% and depression in 60%. Smokeless tobacco (Adjusted PR 3.27 (1.07-6.05)), Western diet, high socioeconomic status (Adjusted PR 2.26 (1.99-5.62)) and dyslipidemia (Adjusted PR 1.88 (1.25-2.21)) had significant associations with ICAD after multivariable analysis. Age, gender, diabetes, hypertension, depression and physical activity did not have a significant association. Conclusion: ICAD was found on MRI in one in three asymptomatic Pakistanis and was associated with modifiable risks. Initiatives targeting primary prevention may be able to decrease the burden of disease caused by stroke due to ICAD

A randomized controlled behavioral intervention trial to improve medication adherence in adult stroke patients with prescription tailored Short Messaging Service (SMS)-SMS4Stroke study.

Background: The effectiveness of mobile technology to improve medication adherence via customized Short Messaging Service (SMS) reminders for stroke has not been tested in resource poor areas. We designed a randomized controlled trial to test the effectiveness of SMS on improving medication adherence in stroke survivors in Pakistan. Methods: This was a parallel group, assessor-blinded, randomized, controlled, superiority trial. Participants were centrally randomized in fixed block sizes. Adult participants on multiple medications with access to a cell phone and stroke at least 4 weeks from onset (Onset as defined by last seen normal) were eligible. The intervention group, in addition to usual care, received reminder SMS for 2 months that contained a) Personalized, prescription tailored daily medication reminder(s) b) Twice weekly health information SMS. The Health Belief Model and Social Cognitive theory were used to design the language and content of messages. Frontline SMS software was used for SMS delivery. Medication adherence was self-reported and measured on the validated Urdu version of Morisky Medication Adherence Questionnaire. Multiple linear regression was used to model the outcome against intervention and other covariates. Analysis was conducted by intention-to-treat principle. Results: Two hundred participants were enrolled. 38 participants were lost to follow-up. After 2 months, the mean medication score was 7.4 (95 % CI: 7.2–7.6) in the intervention group while 6.7 (95 % CI: 6.4–7.02) in the control group. The adjusted mean difference (Δ) was 0.54 (95 % CI: 0.22–0.85). The mean diastolic blood pressure in the intervention group was 2.6 mmHg (95 % CI; −5.5 to 0.15) lower compared to the usual care group. Conclusion: A short intervention of customized SMS can improve medication adherence and effect stroke risk factors like diastolic blood pressure in stroke survivors with complex medication regimens living in resource poor areas

Mapping age- and sex-specific HIV prevalence in adults in sub-Saharan Africa, 2000-2018

BACKGROUND: Human immunodeficiency virus and acquired immune deficiency syndrome (HIV/AIDS) is still among the leading causes of disease burden and mortality in sub-Saharan Africa (SSA), and the world is not on track to meet targets set for ending the epidemic by the Joint United Nations Programme on HIV/AIDS (UNAIDS) and the United Nations Sustainable Development Goals (SDGs). Precise HIV burden information is critical for effective geographic and epidemiological targeting of prevention and treatment interventions. Age- and sex-specific HIV prevalence estimates are widely available at the national level, and region-wide local estimates were recently published for adults overall. We add further dimensionality to previous analyses by estimating HIV prevalence at local scales, stratified into sex-specific 5-year age groups for adults ages 15-59 years across SSA. METHODS: We analyzed data from 91 seroprevalence surveys and sentinel surveillance among antenatal care clinic (ANC) attendees using model-based geostatistical methods to produce estimates of HIV prevalence across 43 countries in SSA, from years 2000 to 2018, at a 5 × 5-km resolution and presented among second administrative level (typically districts or counties) units. RESULTS: We found substantial variation in HIV prevalence across localities, ages, and sexes that have been masked in earlier analyses. Within-country variation in prevalence in 2018 was a median 3.5 times greater across ages and sexes, compared to for all adults combined. We note large within-district prevalence differences between age groups: for men, 50% of districts displayed at least a 14-fold difference between age groups with the highest and lowest prevalence, and at least a 9-fold difference for women. Prevalence trends also varied over time; between 2000 and 2018, 70% of all districts saw a reduction in prevalence greater than five percentage points in at least one sex and age group. Meanwhile, over 30% of all districts saw at least a five percentage point prevalence increase in one or more sex and age group. CONCLUSIONS: As the HIV epidemic persists and evolves in SSA, geographic and demographic shifts in prevention and treatment efforts are necessary. These estimates offer epidemiologically informative detail to better guide more targeted interventions, vital for combating HIV in SSA

Mapping age- and sex-specific HIV prevalence in adults in sub-Saharan Africa, 2000–2018

Background: Human immunodeficiency virus and acquired immune deficiency syndrome (HIV/AIDS) is still among the leading causes of disease burden and mortality in sub-Saharan Africa (SSA), and the world is not on track to meet targets set for ending the epidemic by the Joint United Nations Programme on HIV/AIDS (UNAIDS) and the United Nations Sustainable Development Goals (SDGs). Precise HIV burden information is critical for effective geographic and epidemiological targeting of prevention and treatment interventions. Age- and sex-specific HIV prevalence estimates are widely available at the national level, and region-wide local estimates were recently published for adults overall. We add further dimensionality to previous analyses by estimating HIV prevalence at local scales, stratified into sex-specific 5-year age groups for adults ages 15–59 years across SSA. Methods: We analyzed data from 91 seroprevalence surveys and sentinel surveillance among antenatal care clinic (ANC) attendees using model-based geostatistical methods to produce estimates of HIV prevalence across 43 countries in SSA, from years 2000 to 2018, at a 5 × 5-km resolution and presented among second administrative level (typically districts or counties) units. Results: We found substantial variation in HIV prevalence across localities, ages, and sexes that have been masked in earlier analyses. Within-country variation in prevalence in 2018 was a median 3.5 times greater across ages and sexes, compared to for all adults combined. We note large within-district prevalence differences between age groups: for men, 50% of districts displayed at least a 14-fold difference between age groups with the highest and lowest prevalence, and at least a 9-fold difference for women. Prevalence trends also varied over time; between 2000 and 2018, 70% of all districts saw a reduction in prevalence greater than five percentage points in at least one sex and age group. Meanwhile, over 30% of all districts saw at least a five percentage point prevalence increase in one or more sex and age group. Conclusions: As the HIV epidemic persists and evolves in SSA, geographic and demographic shifts in prevention and treatment efforts are necessary. These estimates offer epidemiologically informative detail to better guide more targeted interventions, vital for combating HIV in SSA

Software engineering wastes - a perspective of modern code review

Identification and eradication of waste are the principal emphases of lean thinking. Waste is defined as any activity that consumes resources but does not deliver any value to the stakeholder and it can also be demarcated as an impediment to process flow. Lean thinking has been applied in the software engineering domain concerning overall software development, however, still, there is a need to take action regarding waste identification and elimination concerning specific software engineering activities. This paper describes the wastes generated during Modern Code Review (MCR). MCR is a socio-technical software engineering activity and acknowledged as a lightweight process for defect identification, code improvement and software quality enhancement. It involves coordination and communication among multiple software engineers having different personalities, preferences, and technical skills, thus it can generate multiple types of wastes. Therefore, the study has two objectives that are to recognize and report various wastes generated during MCR and to map the identified MCR wastes on the existing software engineering wastes. Systematic Literature Review and grounded theory has been utilized to recognize and produce a unique list of the waste generated during MCR. The identified unique list of MCR wastes and their mapping on existing software engineering wastes are validated through software engineering experts. The study findings report 28 unique wastes out of which 25 wastes map to the existing software engineering wastes. However, 3 wastes such as negative emotions, inequality/biasness and insignificant feedback are not reported in the existing software engineering literature. The study will be useful for researchers to identify the wastes in same context or for other software engineering activities and to provide the strategies to minimize the generation of identified wastes