The world needs young people who are skillful in and enthusiastic about science and who view science as their future career field. Ensuring that we will have such young people requires initiatives ...that engage students in interesting and motivating science experiences. Today, students can investigate scientific phenomena using the tools, data collection techniques, models, and theories of science in physical laboratories that support interactions with the material world or in virtual laboratories that take advantage of simulations. Here, we review a selection of the literature to contrast the value of physical and virtual investigations and to offer recommendations for combining the two to strengthen science learning.
Assessing the value of undergraduate research
Undergraduate research experiences often engender enthusiasm in the students involved, but how useful are they in terms of enhancing student learning? ...Linn
et al.
review studies that focus on the effectiveness of undergraduate research programs. Undergraduate research experiences in a class were distinguished from those involving individualized participation in a research program. Mentoring emerges as both an important component of a successful experience and a target for improvement.
Science
, this issue
10.1126/science.1261757
For any undergraduate contemplating a career in scientific research, participating in authentic research seems like a good opportunity. But what are authentic research experiences? How do they benefit undergraduates? What forms of mentoring are successful? What needs improvement? And how can these experiences meet the needs of interested students while at the same time be cost-effective in large research universities?
We review the research tackling these questions and find few answers. While most undergraduates give high ratings to research experiences, specific benefits have not been documented. Of the 60 empirical studies published in the last 5 years, only 4 directly measured gains in research capabilities or conceptual understanding. Most studies draw conclusions from self-report surveys or interviews, notoriously poor methods for documenting impacts. These studies leave us with few insights into what works and little idea about how to make the experiences more effective.
BACKGROUND
Most colleges and universities offer Undergraduate Research Experiences (UREs) and/or Course-based Undergraduate Research Experiences (CUREs) (Fig. 1). Two large surveys, the 2004 Freshman Survey and the 2008 College Senior Survey, administered at over 200 institutions, generated data about the impact of undergraduate research experiences on persistence in science and intention to pursue graduate school. These studies document that students appreciate undergraduate research experiences. The surveys are unable, however, to distinguish between UREs and CUREs. In addition, the value that undergraduate research adds cannot be disentangled from precollege preparation, especially for students from groups that are underrepresented in science.
ADVANCES
Designers of UREs expect students to benefit from participating in a scientific laboratory but have not determined optimal ways to orient and guide participants. Students often expect the URE to mimic their college laboratory experiences with procedural guidance and planned outcomes. During the first year of a URE, students often report spending most of their effort on setting up and conducting experiments and limited effort on understanding the investigation or interpreting the results. Students would benefit from an orientation that integrates their beliefs and expectations with the realities of the research experience. The few studies that measure changes in understanding of scientific practices or relevant science concepts report little or no gains after 1 year in a URE. Students who spend over a year in a URE often learn new methodological techniques, collect their own data, interpret findings, and formulate new research questions. The slow enculturation into lab activities may make sense, especially when students join labs investigating questions that do not arise in undergraduate education. The time and resources needed, however, limit the scalability of UREs. Students encounter new ideas during their research experiences but often need guidance to integrate these ideas with their expectations. We discuss ways that designers of UREs can speed up enculturation and strengthen guidance.
Individual mentoring emerges as an effective way to guide students and improve learning from research experiences. Activities that could help students benefit from research experiences include discussion with mentors, participation in group meetings where current research is discussed, guided opportunities to explore relevant research literature, reflection on observations in weekly journals, and synthesis of their insights by creating research proposals, reports, or posters. We discuss ways to prepare mentors so that they can efficiently guide students.
OUTLOOK
Undergraduate research experiences absorb a lot of time, money, and effort. The costs and benefits of research experiences for building human capital, benefitting undergraduates, improving workforce diversity, and strengthening educational outcomes need better understanding. Making the best use of extramural funds and the (often voluntary) contributions of faculty to improve undergraduate research experiences requires a strong research base.
More rigorous research is needed, and the field could benefit by building on insights from the learning sciences. We use the knowledge integration framework to interpret the available findings and to identify gaps in the research base.
We discuss ways to develop validated, generalizable assessments such as methods for measuring ability to locate and interpret primary literature. We suggest techniques for developing criteria for evaluating mentoring interactions. We identify ways to strengthen mentoring and to ensure that research experiences meet the needs of diverse students.
URE in action.
Biofuel research engages a Berkeley undergraduate researcher during a summer internship with the Synthetic Biology Engineering Research Center (funded by NSF grant 1132670).
Most undergraduates give high ratings to research experiences. Studies report that these experiences improve participation and persistence, often by strengthening students’ views of themselves as scientists. Yet, the evidence for these claims is weak. More than half the 60 studies reviewed rely on self-report surveys or interviews. Rather than introducing new images of science, research experiences may reinforce flawed images especially of research practices and conceptual understanding. The most convincing studies show benefits for mentoring and for communicating the nature of science, but the ideas that students learn are often isolated or fragmented rather than integrated and coherent. Rigorous research is needed to identify ways to design research experiences so that they promote integrated understanding. These studies need powerful and generalizable assessments that can document student progress, help distinguish effective and ineffective aspects of the experiences, and illustrate how students interpret the research experiences they encounter. To create research experiences that meet the needs of interested students and make effective use of scarce resources, we encourage systematic, iterative studies with multiple indicators of success.
Highlights ► Activation of α7 nAChR induces neuroprotection. ► PNU 282987 protects RGCs from glutamate-induced excitotoxicity. ► Rat RGCs contain α7 nAChR subunits. ► Implications for diseases of the ...CNS associated with excitotoxicity.
A gender gap in mathematics achievement persists in some nations but not in others. In light of the underrepresentation of women in careers in science, technology, mathematics, and engineering, ...increasing research attention is being devoted to understanding gender differences in mathematics achievement, attitudes, and affect. The gender stratification hypothesis maintains that such gender differences are closely related to cultural variations in opportunity structures for girls and women. We meta-analyzed 2 major international data sets, the 2003 Trends in International Mathematics and Science Study and the Programme for International Student Assessment, representing 493,495 students 14-16 years of age, to estimate the magnitude of gender differences in mathematics achievement, attitudes, and affect across 69 nations throughout the world. Consistent with the gender similarities hypothesis, all of the mean effect sizes in mathematics achievement were very small (
d
< 0.15); however, national effect sizes showed considerable variability (
d
s = −0.42 to 0.40). Despite gender similarities in achievement, boys reported more positive math attitudes and affect (
d
s = 0.10 to 0.33); national effect sizes ranged from
d
= −0.61 to 0.89. In contrast to those of previous tests of the gender stratification hypothesis, our results point to specific domains of gender equity responsible for gender gaps in math. Gender equity in school enrollment, women's share of research jobs, and women's parliamentary representation were the most powerful predictors of cross-national variability in gender gaps in math. Results are situated within the context of existing research demonstrating apparently paradoxical effects of societal gender equity and highlight the significance of increasing girls' and women's agency cross-nationally.
"Science Learning and Instruction" describes advances in understanding the nature of science learning and their implications for the design of science instruction. The authors show how design ...patterns, design principles, and professional development opportunities coalesce to create and sustain effective instruction in each primary scientific domain: earth science, life science, and physical science. Calling for more in depth and less fleeting coverage of science topics in order to accomplish knowledge integration, the book highlights the importance of designing the instructional materials, the examples that are introduced in each scientific domain, and the professional development that accompanies these materials. It argues that unless all these efforts are made simultaneously, educators cannot hope to improve science learning outcomes. The book also addresses how many policies, including curriculum, standards, guidelines, and standardized tests, work against the goal of integrative understanding, and discusses opportunities to rethink science education policies based on research findings from instruction that emphasizes such understanding. This book contains the following chapters: (1) Introduction and Overview; (2) Typical Instructional Patterns; (3) Transforming Science Instruction with Technology: A Thermodynamics Case Study; (4) Particulate Structure of Matter: A Case Study; (5) Knowledge Integration Principals and Patterns; (6) Lectures and Technology; (7) Experimentation and Knowledge Integration; (8) Making Visualizations Valuable; (9) Collaboration for Knowledge Integration; (10) Professional Development for Knowledge Integration; (11) The Case for Knowledge Integration. Also included are an index and references.
Summary Background Investigators of registry-based studies report improved survival for breast-conserving surgery plus radiotherapy compared with mastectomy in early breast cancer. As these studies ...did not present long-term overall and breast cancer-specific survival, the effect of breast-conserving surgery plus radiotherapy might be overestimated. In this study, we aimed to evaluate 10 year overall and breast cancer-specific survival after breast-conserving surgery plus radiotherapy compared with mastectomy in Dutch women with early breast cancer. Methods In this population-based study, we selected all women from the Netherlands Cancer Registry diagnosed with primary, invasive, stage T1–2, N0–1, M0 breast cancer between Jan 1, 2000, and Dec 31, 2004, given either breast-conserving surgery plus radiotherapy or mastectomy, irrespective of axillary staging or dissection or use of adjuvant systemic therapy. Primary outcomes were 10 year overall survival in the entire cohort and breast cancer-specific survival in a representative subcohort of patients diagnosed in 2003 with characteristics similar to the entire cohort. We estimated breast cancer-specific survival by calculating distant metastasis-free and relative survival for every tumour and nodal category. We did multivariable Cox proportional hazard analysis to estimate hazard ratios (HRs) for overall and distant metastasis-free survival. We estimated relative survival by calculating excess mortality ratios using life tables of the general population. We did multiple imputation to account for missing data. Findings Of the 37 207 patients included in this study, 21 734 (58%) received breast-conserving surgery plus radiotherapy and 15 473 (42%) received mastectomy. The 2003 representative subcohort consisted of 7552 (20%) patients, of whom 4647 (62%) received breast-conserving surgery plus radiotherapy and 2905 (38%) received mastectomy. For both unadjusted and adjusted analysis accounting for various confounding factors, breast-conserving surgery plus radiotherapy was significantly associated with improved 10 year overall survival in the whole cohort overall compared with mastectomy (HR 0·51 95% CI 0·49–0·53; p<0·0001; adjusted HR 0·81 0·78–0·85; p<0·0001), and this improvement remained significant for all subgroups of different T and N stages of breast cancer. After adjustment for confounding variables, breast-conserving surgery plus radiotherapy did not significantly improve 10 year distant metastasis-free survival in the 2003 cohort overall compared with mastectomy (adjusted HR 0·88 0·77–1·01; p=0·07), but did in the T1N0 subgroup (adjusted 0·74 0·58–0·94; p=0·014). Breast-conserving surgery plus radiotherapy did significantly improve 10 year relative survival in the 2003 cohort overall (adjusted 0·76 0·64–0·91; p=0·003) and in the T1N0 subgroup (adjusted 0·60 0·42–0·85; p=0·004) compared with mastectomy. Interpretation Adjusting for confounding variables, breast-conserving surgery plus radiotherapy showed improved 10 year overall and relative survival compared with mastectomy in early breast cancer, but 10 year distant metastasis-free survival was improved with breast-conserving surgery plus radiotherapy compared with mastectomy in the T1N0 subgroup only, indicating a possible role of confounding by severity. These results suggest that breast-conserving surgery plus radiotherapy is at least equivalent to mastectomy with respect to overall survival and may influence treatment decision making for patients with early breast cancer. Funding None.
Organophosphoate (OP) chemicals are known to inhibit the enzyme acetylcholinesterase (AChE). Studying OP poisoning is difficult because common small animal research models have serum ...carboxylesterase, which contributes to animals’ resistance to OP poisoning. Historically, guinea pigs have been used for this research; however, a novel genetically modified mouse strain (KIKO) was developed with nonfunctional serum carboxylase (Es1 KO) and an altered acetylcholinesterase (AChE) gene, which expresses the amino acid sequence of the human form of the same protein (AChE KI). KIKO mice were injected with 1xLD50 of an OP nerve agent or vehicle control with or without atropine. After one to three minutes, animals were injected with 35 mg/kg of the currently fielded Reactivator countermeasure for OP poisoning. Postmortem brains were imaged on a Bruker RapifleX ToF/ToF instrument. Data confirmed the presence of increased acetylcholine in OP-exposed animals, regardless of treatment or atropine status. More interestingly, we detected a small amount of Reactivator within the brain of both exposed and unexposed animals; it is currently debated if reactivators can cross the blood–brain barrier. Further, we were able to simultaneously image acetylcholine, the primary affected neurotransmitter, as well as determine the location of both Reactivator and acetylcholine in the brain. This study, which utilized sensitive MALDI-MSI methods, characterized KIKO mice as a functional model for OP countermeasure development.
Our study aimed to provide a comprehensive overview of trends in incidence, survival, mortality and treatment of first primary invasive breast cancer (BC), according to age, stage and receptor ...subtype in the Netherlands between 1989 and 2017. Data from all women diagnosed with first primary stage I to IV BC (N = 320 249) were obtained from the Netherlands Cancer Registry. BC mortality and general population data were retrieved from Statistics Netherlands. Age‐standardised incidence and mortality rates were calculated with annual percentage change (APC) and average annual percentage change (AAPC) statistics. The relative survival (RS) was used as estimator for disease‐specific survival. The BC incidence for all BC patients combined significantly increased until 2013 from 126 to 158 per 100 000 person‐years, after which a declining trend was observed. Surgery became less extensive, but (neo‐)adjuvant systemic treatments and their combinations were given more frequently. The RS improved for all age groups and for most stages and receptor subtypes, but remained stable for all subtypes since 2012 to 2013 and since 2000 to 2009 for Stage IV BC at 15 years of follow‐up. Overall, the 5‐ and 10‐year RS increased from 76.8% (95% confidence interval CI: 76.1, 77.4) and 55.9% (95% CI: 54.7, 57.1) in 1989 to 1999 to 91.0% (95% CI: 90.5, 91.5) and 82.9% (95% CI: 82.2, 83.5), respectively, in 2010 to 2016. BC mortality improved regardless of age and overall decreased from 57 to 35 per 100 000 person‐years between 1989 and 2017. In conclusion, the BC incidence in the Netherlands has steadily increased since 1989, but the latest trends show promising declines. Survival improved markedly for most patients and the mortality decreased regardless of age.
What's new?
Studies that simultaneously capture incidence, survival, and mortality trends in breast cancer are scarce, and receptor subtype‐specific trends have remained largely unexplored. This study provides an up‐to‐date and comprehensive overview of first primary invasive breast cancer trends in the Netherlands in 1989 to 2017. Breast cancer incidence increased for all breast cancer patients combined until 2013, but the latest trends show a promising decline. Treatment strategies became more complex. Relative survival improved for all age groups and for most stages and receptor subtypes, and mortality decreased overall. The results may be useful in supporting healthcare management and informing current clinical practice.
A large-scale RNA interference screen to discover genes involved in trastuzumab resistance in breast cancer identified only PTEN as a modulator of drug sensitivity. Oncogenic mutants of PIK3CA ...(activator of the same pathway and frequently mutated in breast cancer) also conferred resistance to trastuzumab in cell culture. In a cohort of 55 breast cancer patients, activation of the PI3K pathway, as judged by the presence of oncogenic PIK3CA mutations or low PTEN expression, was associated with poor prognosis after trastuzumab therapy, and the combined analysis of PTEN and PIK3CA identified twice as many patients at increased risk for progression compared to PTEN alone. Thus, assessment of PI3K pathway activation may provide a biomarker to identify patients unlikely to respond to trastuzumab-based therapy.
Abstract Predictive biomarkers are essential for personalized medicine since they select the best treatment for a specific patient. However, of all biomarkers that are evaluated, only few are ...eventually used in clinical practice. Many promising biomarkers may be erroneously abandoned because they are investigated in small studies using standard statistical techniques which can cause small sample bias or lack of power. The standard technique for failure time endpoints is Cox proportional hazards regression with a multiplicative interaction term between binary variables of biomarker and treatment. Properties of this model in small studies have not been evaluated so far, therefore we performed a simulation study to understand its small sample behavior. As a remedy, we applied a Firth correction to the score function of the Cox model and obtained confidence intervals (CI) using a profile likelihood (PL) approach. These methods are generally recommended for small studies of different design. Our results show that a Cox model estimates the biomarker-treatment interaction term and the treatment effect in one of the biomarker subgroups with bias, and overestimates their standard errors. Bias is however reduced and power is increased with Firth correction and PL CIs. Hence, the modified Cox model and PL CI should be used instead of a standard Cox model with Wald based CI in small studies of predictive biomarkers.
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