A Quantitative Process for Enhancing End of Phase 2 Drug Development Decisions

The objectives of the phase 2 stage in a drug development programme are to evaluate the safety and tolerability of different doses, select a promising dose range and look for early signs of activity. At the end of phase 2 (EOP2), a decision to initiate phase 3 studies involves the commitment of considerable resources and associated costs. This multi-factorial, critical business decision is made by balancing the current condition of a sponsor organisation’s portfolio, the future cost of development, the competitive landscape, and the expected safety and efficacy benefits of a new therapy. The decision process needs to be efficient, effective and evidentially supported. This PhD presents a practical, formalised and quantitative approach for enhancing the EOP2 decision process. This process ensures that a consistent and explicit evidence-based approach is used to inform decisions for new drug candidates. Broadly following this process will help statisticians increase their strategic influence in drug development programmes. Embedded within the process is a predominantly bayesian approach to predicting the probability of efficacy success (PoS) in a future (frequentist) phase 3 programme at the end of phase 2. Also included are early predictions of the outcomes of indirect treatment comparisons and future treatment ranking between the investigational treatment and alternative treatments either already approved or still in development. Moreover, the incorporation of qualitative factors into the decision making process, and the implementation of a PoS framework when limited or no prior clinical data is available is discussed. The entire process is illustrated using an example from the pancreatic cancer indication, with further supporting examples of predicting the PoS provided for gastric cancer, soft tissue sarcoma, non-small cell lung cancer and ovarian cancer. Additionally, the utility of the PoS framework in practice is highlighted through a review of the PoS for 63 completed phase 3 studies

Multinational perspectives on information technology from academia and industry

As the term \u27information technology\u27 has many meanings for various stakeholders and continues to evolve, this work presents a comprehensive approach for developing curriculum guidelines for rigorous, high quality, bachelor\u27s degree programs in information technology (IT) to prepare successful graduates for a future global technological society. The aim is to address three research questions in the context of IT concerning (1) the educational frameworks relevant for academics and students of IT, (2) the pathways into IT programs, and (3) graduates\u27 preparation for meeting future technologies. The analysis of current trends comes from survey data of IT faculty members and professional IT industry leaders. With these analyses, the IT Model Curricula of CC2005, IT2008, IT2017, extensive literature review, and the multinational insights of the authors into the status of IT, this paper presents a comprehensive overview and discussion of future directions of global IT education toward 2025

Structured transverse orbital angular momentum probed by a levitated optomechanical sensor

The momentum carried by structured light fields exhibits a rich array of surprising features. In this work, we generate transverse orbital angular momentum (TOAM) in the interference field of two parallel and counterpropagating linearly-polarised focused beams, synthesising an array of identical handedness vortices carrying intrinsic TOAM. We explore this structured light field using an optomechanical sensor, consisting of an optically levitated silicon nanorod, whose rotation is a probe of the optical angular momentum, which generates an exceptionally large torque. This simple creation and direct observation of TOAM will have applications in studies of fundamental physics, the optical manipulation of matter and quantum optomechanics

No Evidence for a Cumulative Impact Effect on Concussion Injury Threshold

Recent studies using a helmet-based accelerometer system (Head Impact Telemetry System [HITS]) have demonstrated that concussions result from a wide range of head impact magnitudes. Variability in concussion thresholds has been proposed to result from the cumulative effect of non-concussive head impacts prior to injury. We used the HITS to collect biomechanical data representing >100,000 head impacts in 95 high school football players over 4 years. The cumulative impact histories prior to 20 concussive impacts in 19 athletes were compared to the cumulative impact histories prior to the three largest magnitude non-concussive head impacts in the same athletes. No differences were present in any impact history variable between the concussive and non-concussive high magnitude impacts. These analyses included the number of head impacts, cumulative HIT severity profile value, cumulative linear acceleration, and cumulative rotational acceleration during the same practice or game session, as well as over the 30-min and 1 week preceding these impacts. Our data do not support the proposal that impact volume or intensity influence concussion threshold in high school football athletes.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90490/1/neu-2E2011-2E1910.pd

DNA sequence conservation between the Bacillus anthracis pXO2 plasmid and genomic sequence from closely related bacteria

BACKGROUND: Complete sequencing and annotation of the 96.2 kb Bacillus anthracis plasmid, pXO2, predicted 85 open reading frames (ORFs). Bacillus cereus and Bacillus thuringiensis isolates that ranged in genomic similarity to B. anthracis, as determined by amplified fragment length polymorphism (AFLP) analysis, were examined by PCR for the presence of sequences similar to 47 pXO2 ORFs. RESULTS: The two most distantly related isolates examined, B. thuringiensis 33679 and B. thuringiensis AWO6, produced the greatest number of ORF sequences similar to pXO2; 10 detected in 33679 and 16 in AWO6. No more than two of the pXO2 ORFs were detected in any one of the remaining isolates. Dot-blot DNA hybridizations between pXO2 ORF fragments and total genomic DNA from AWO6 were consistent with the PCR assay results for this isolate and also revealed nine additional ORFs shared between these two bacteria. Sequences similar to the B. anthracis cap genes or their regulator, acpA, were not detected among any of the examined isolates. CONCLUSIONS: The presence of pXO2 sequences in the other Bacillus isolates did not correlate with genomic relatedness established by AFLP analysis. The presence of pXO2 ORF sequences in other Bacillus species suggests the possibility that certain pXO2 plasmid gene functions may also be present in other closely related bacteria

Prevalence and risk factors for cervical cancer and pre-cancerous lesions in Rwanda

Introduction: Cervical cancer prevalence in Rwanda has not been well-described. Visual inspection with acetic acid or Lugol solution has been shown to be effective for cervical cancer screening in low resource  settings. The aim of the study is to understand the prevalence and risk factors for cervical cancer and pre- cancerous lesions among Rwandan women between 30 and 50 old undergoing screening.Methods: This  crosssectional analytical study was done in 3 districts of Rwanda from October 2010 to June 2013.  Women aged 30 to 50 years screened for cervical cancer by trained doctors, nurses and  midwives. Prevalence of pre-cancerous and cancerous cervical lesions was determined. Bivariate and multivariate logistic regressions were used to assess risk factors associated with cervical cancer. Results: The prevalence of pre-cancer and invasive cervical cancer was 5.9% (95% CI 4.5, 7.5) and  1.7% (95% CI 0.9, 2.5), respectively. Risk factors associated with cervical cancer in multivariate  analysis included initiation of sexual activity at less than 20 years (OR=1.75; 95% CI=(1.01, 3.03); being unmarried (single, divorced and widowed) (OR=3.29; 95% CI=( 1.26, 8.60)); Older age of participants (OR= 0.52; 95% CI= (0.28, 0.97)), older age at the first pregnancy (OR=2.10; 95% CI=(1.20, 3.67) and higher number of children born (OR=0.42; 95%CI =(0.23, 0.76)) were protective.Conclusion: Cervical cancer continues to be a public health problem in Rwanda, but screening using VIA is practical and feasible even in rural settings.Key words: Rwanda, cervical cancer, screening, VI

Know Your Epidemic, Strengthen Your Response: Developing a New HIV Surveillance Architecture to Guide HIV Resource Allocation and Target Decisions

To guide HIV prevention and treatment activities up to 2020, we need to generate and make better use of high quality HIV surveillance data. To highlight our surveillance needs, a special collection of papers in JMIR Public Health and Surveillance has been released under the title "Improving Global and National Responses to the HIV Epidemic Through High Quality HIV Surveillance Data." We provide a summary of these papers and highlight methods for developing a new HIV surveillance architecture

Opportunities for Enhanced Strategic Use of Surveys, Medical Records, and Program Data for HIV Surveillance of Key Populations: Scoping Review.

BACKGROUND: Normative guidelines from the World Health Organization recommend tracking strategic information indicators among key populations. Monitoring progress in the global response to the HIV epidemic uses indicators put forward by the Joint United Nations Programme on HIV/AIDS. These include the 90-90-90 targets that require a realignment of surveillance data, routinely collected program data, and medical record data, which historically have developed separately. OBJECTIVE: The aim of this study was to describe current challenges for monitoring HIV-related strategic information indicators among key populations ((men who have sex with men [MSM], people in prisons and other closed settings, people who inject drugs, sex workers, and transgender people) and identify future opportunities to enhance the use of surveillance data, programmatic data, and medical record data to describe the HIV epidemic among key populations and measure the coverage of HIV prevention, care, and treatment programs. METHODS: To provide a historical perspective, we completed a scoping review of the expansion of HIV surveillance among key populations over the past three decades. To describe current efforts, we conducted a review of the literature to identify published examples of SI indicator estimates among key populations. To describe anticipated challenges and future opportunities to improve measurement of strategic information indicators, particularly from routine program and health data, we consulted participants of the Third Global HIV Surveillance Meeting in Bangkok, where the 2015 World Health Organization strategic information guidelines were launched. RESULTS: There remains suboptimal alignment of surveillance and programmatic data, as well as routinely collected medical records to facilitate the reporting of the 90-90-90 indicators for HIV among key populations. Studies (n=3) with estimates of all three 90-90-90 indicators rely on cross-sectional survey data. Programmatic data and medical record data continue to be insufficiently robust to provide estimates of the 90-90-90 targets for key populations. CONCLUSIONS: Current reliance on more active data collection processes, including key population-specific surveys, remains warranted until the quality and validity of passively collected routine program and medical record data for key populations is optimized

Report from the STEM 2026 Workshop on Assessment, Evaluation, and Accreditation

A gathering of science, technology, engineering, and math (STEM) higher education stakeholders met in November 2018 to consider the relationship between innovation in education and assessment. When we talk about assessment in higher education, it is inextricably linked to both evaluation and accreditation, so all three were considered. The first question we asked was can we build a nation of learners? This starts with considering the student, first and foremost. As educators, this is a foundation of our exploration and makes our values transparent. As educators, how do we know we are having an impact? As members and implementers of institutions, programs and professional societies, how do we know students are learning and that what they are learning has value? The focus of this conversation was on undergraduate learning, although we acknowledge that the topic is closely tied to successful primary and secondary learning as well as graduate education. Within the realm of undergraduate education, students can experience four-year institutions and two-year institutions, with many students learning at both at different times. Thirty-seven participants spent two days considering cases of innovation in STEM education, learning about the best practices in assessment, and then discussing the relationship of innovation and assessment at multiple levels within the context of higher education. Six working groups looked at course-level, program-level, and institution-level assessment, as well as cross-disciplinary programs, large-scale policy issues, and the difficult-to-name “non-content/cross-content” group that looked at assessment of transferable skills and attributes like professional skills, scientific thinking, mindset, and identity, all of which are related to post-baccalaureate success. These conversations addressed issues that cut across multiple levels, disciplines, and course topics, or are otherwise seen as tangential or perpendicular to perhaps “required” assessment at institutional, programmatic, or course levels. This report presents the context, recommendations, and “wicked” challenges from the meeting participants and their working groups. Along with the recommendations of workshop participants, these intricate challenges weave a complex web of issues that collectively need to be addressed by our community. They generated a great deal of interest and engagement from workshop participants, and act as a call to continue these conversations and seek answers that will improve STEM education through innovation and improved assessment. This material is based upon work supported by the National Science Foundation under Grant No. DUE-1843775. Any opinions, findings, and conclusions or recommendations expressed in this material are those of the author(s) and do not necessarily reflect the views of the National Science Foundation