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PDF file - 22K, Supplemental Fig. S3. Effect of cytoplasmic MET immunohistochemistry (IHC) staining on objective response rate in patients treated with panitumumab (pmab) plus rilotumumab (AMG 102) versus pmab plus placebo.

PDF file - 37K, Supplemental Fig. S4. The effect of baseline IGF and IGF-related protein expression on overall survival.

PDF file - 76K, Supplemental Fig. S1. (A) Randomized phase Ib/II trial of panitumumab plus rilotumumab (AMG 102) or ganitumab (AMG 479). (B) CONSORT diagram for part 2. *Panitumumab 6 mg/kg; rilotumumab 10 mg/kg with dose de-escalation to 5 mg/kg as necessary. �Panitumumab 6 mg/kg; rilotumumab 10 mg/kg; ganitumab 12 mg/kg. �Rilotumumab 10 mg/kg; ganitumab 12 mg/kg.

PDF file - 38K, Supplemental Fig. S5. The effect of baseline IGF and IGF-related protein expression on objective response rate.

PDF file - 38K, Supplemental Fig. S2. Best percent change of the sum of longest diameters of target lesions from baseline to post-baseline. (A) Panitumumab plus rilotumumab.(B) Panitumumab plus ganitumab. (C) Panitumumab alone.

Purpose: Panitumumab, a fully human anti-epidermal growth factor receptor monoclonal antibody (mAb), has demonstrated efficacy in patients with wild-type KRAS metastatic colorectal cancer (mCRC). Rilotumumab and ganitumab are investigational, fully human mAbs against hepatocyte growth factor (HGF)/scatter factor and IGF1R, respectively. Here we evaluate combining rilotumumab or ganitumab with panitumumab in previously treated patients with wild-type KRAS mCRC.Experimental Design: Part 1 was a phase Ib dose-finding study of panitumumab plus rilotumumab. The primary endpoint was the incidence of dose-limiting toxicities (DLT). Part 2 was a randomized phase II trial of panitumumab in combination with rilotumumab, ganitumab, or placebo. The primary endpoint was objective response rate (ORR); safety, progression-free survival (PFS), and overall survival (OS) were secondary endpoints. Archival tissue specimens were collected for exploratory correlative work.Results: In part 1, no DLTs were reported. A recommended phase II dose of 10 mg/kg rilotumumab was selected. In part 2, for the panitumumab plus rilotumumab (n = 48), panitumumab plus ganitumab (n = 46), and panitumumab plus placebo arms (n = 48), the ORRs were 31%, 22%, and 21%, respectively. The median PFS was 5.2, 5.3, and 3.7 months and median OS 13.8, 10.6, and 11.6 months, respectively. Adverse events were tolerable. Exploratory biomarker analyses, including MET and IGF-related protein expression, failed to indicate conclusive predictive evidence on efficacy endpoints.Conclusions: Panitumumab plus rilotumumab met the prespecified criterion for improvement in ORR whereas ganitumab did not. This is the first study to suggest a benefit for combining an HGF inhibitor (rilotumumab) with panitumumab in previously treated patients with wild-type KRAS mCRC. Clin Cancer Res; 20(16); 4240–50. ©2014 AACR.

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We report the synthesis of conjugated polymer nanoparticles carrying stable luminescent radical units. These monodisperse conjugated radical nanoparticles can be tuned in their diameter over several hundred nanometers. They are stable in aqueous medium and highly luminescent in the red and near infrared spectrum, representing a powerful future tool for bioimaging. Moreover, the polymer nanoparticles exhibit paramagnetic properties, making them highly suitable for dual-mode optical and magnetic resonance imaging. In this study, we investigate their synthesis, optical and magnetic properties, and use quantum mechanical calculations to elucidate the effect of the conjugated polymer backbone and electron-withdrawing substituents on the electronic properties of the open-shell molecule in the polymer network of the particles.

During the COVID-19 pandemic, the Virtual Training Academy (VTA) was established to rapidly develop a contact-tracing workforce for California. Through June 2021, more than 10 000 trainees enrolled in a contact-tracing or case investigation course at the VTA. To evaluate program effectiveness, we analyzed trainee pre- and postassessment results using the Wilcoxon signed-rank test. There was a statistically significant (P

Public and Patient involvement and engagement in research design: Co-create a toolkit that enables quality time together for Dementia. There is a growing consensus in the U.K. that public and patient involvement and engagement (PPIE) - e.g. people living with dementia (PLWD), their families, carers, professionals and community - in dementia research is instrumental in improving the quality of research projects and strengthening its relevance and impact. However, publications on PPIE during dementia design research is lacking knowledge and learning exchange within research communities. This project fills in this knowledge gap by involving and engaging 12 family caregivers, care workers and professionals who care for PLWD aged 65 and above at any stage (mild, moderate, and severe) as well as relevant stakeholders. The participants contributed in the research design to co-create an easy access, supportive toolkit that could be used by both PLWD as well as their in/formal carers to promote person centredness care in dementia. This was achieved through participatory approaches with dementia carer focus group workshops and a stakeholder engagement workshop to: (a) generate the ideas and research questions by spending meaningful/quality time together face-to-face and digitally across the dementia journey, (b) using an experience-based co-design approach to design the research methodology for co-creation workshops, (c) co-produce a research funding proposal which has strong PPIE in all stages. d) feedback on the experience with the design research. We argued a participatory approach to PPIE during design research can be time consuming and costly though critical. Firstly, the primary strength of participatory approach was the target population trying our initial research design, then design the research collaboratively. Secondly, it developed a sense of ownership and ongoing commitment among the PPIE groups. Thirdly, it helped us to ensure culturally and logistically appropriate design research. Fourthly, it helped participants to be more meaningfully engaged in research, which in turn concluded with a co-created research design that could have greater potential to produce relevant, meaningful research findings translated to care practice and policy.

We report the synthesis of conjugated polymer nanoparticles carrying stable luminescent radical units. These monodisperse conjugated radical nanoparticles can be tuned in their diameter over several hundred nanometers. They are stable in aqueous medium and highly luminescent in the red and near infrared spectrum, representing a powerful future tool for bioimaging. Moreover, the polymer nanoparticles exhibit paramagnetic properties, making them highly suitable for dual-mode optical and magnetic resonance imaging. In this study, we investigate their synthesis, optical and magnetic properties, and use quantum mechanical calculations to elucidate the effect of the conjugated polymer backbone and electron-withdrawing substituents on the electronic properties of the open-shell molecule in the polymer network of the particles.

There are two broad views of children's theory of mind. The mentalist view is that it emerges in infancy and is possibly innate. The minimalist view is that it emerges more gradually in childhood and is heavily dependent on learning. According to minimalism, children initially understand behaviors rather than mental states, and they are assisted in doing so by recognizing repeating patterns in behavior. The regularities in behavior allow them to predict future behaviors, succeed on theory-of-mind tasks, acquire mental state words, and eventually, understand the mental states underlying behavior. The present study provided the first clear evidence for the plausibility of this view by fitting head cameras to 54 infants aged 6 to 25 months, and recording their view of the world in their daily lives. At 6 and 12 months, infants viewed an average of 146.5 repeated behaviors per hour, a rate consistent with approximately 560,000 repetitions in their first year, and with repetitions correlating with children's acquisition of mental state words, even after controlling for their general vocabulary and a range of variables indexing social interaction. We also recorded infants' view of people searching or searching for and retrieving objects. These were 92 times less common and did not correlate with mental state vocabulary. Overall, the findings indicate that repeated behaviors provide a rich source of information for children that would readily allow them to recognize patterns in behavior and help them acquire mental state words, providing the first clear evidence for this claim of minimalism. RESEARCH HIGHLIGHTS: Six- to 25-month-olds wore head cameras to record home life from infants' point-of-view and help adjudicate between nativist and minimalist views of theory-of-mind (ToM). Nativists say ToM is too early developing to enable learning, whereas minimalists say infants learn to predict behaviors from behavior patterns in environment. Consistent with minimalism, infants had an incredibly rich exposure (146.5/h,560,000 in first year) to repeated behaviors (e.g., drinking from a cup repeatedly). Consistent with minimalism, more repeated behaviors correlated with infants' mental state vocabulary, even after controlling for gender, age, searches witnessed and non-mental state vocabulary.

In this case study, the researchers examine how Mrs. Flora was purposeful in her use of technology to make her asynchronous and synchronous lessons digestible, clear, and connected to prior knowledge. In her choice of technology tools, she was mindful of ensuring that learning could occur anyplace, anytime, even if students had little to no internet in their homes. Takeaways from this chapter demonstrate how Mrs. Flora used technology not for technology's sake, rather as a means to deepen her fifth graders' knowledge base on fractions. Mrs. Flora used technology first to establish authentic relationships with students and families, and then she focused on planning. Mrs. Flora was laser-focused in her planning and delivery of online instruction, as well as clear in her explanation, examples and guided practice, and feedback. Readers will learn how one teacher used low-tech options to successfully teach her students fractions during COVID-19 and will be presented with a model of best practices to consider whether developing an online unit or teaching virtually.

The aqueous self-assembly of amphiphiles into aggregates such as micelles and vesicles has been widely investigated over the past decades with applications ranging from materials science to drug delivery. The combination of characteristic properties of nucleic acids and amphiphiles is of substantial interest to mimic biological self-organization and compartmentalization. Herein, we present ribose- and ribonucleotide-based amphiphiles and investigate their self-assembly as well as their fundamental reactivity. We found that various types of aggregates are formed, ranging in size from nanometers to micrometers and all amphiphiles exhibit aggregation-induced emission (AIE) in solution as well as in the solid state. We also observed that the addition of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) leads to rapid and selective dimerization of the amphiphiles into pyrophosphates, which decreases the critical aggregation concentration (CAC) by a factor of 25 when compared to the monomers. Since the propensity for amphiphile dimerization is correlated with their tendency to self-assemble, our results may be relevant for the formation of rudimentary compartments under prebiotic conditions.

Microfluidic capture chips are useful for preparing or analyzing a wide range of different chemical, biological, and medical samples. A typical microfluidic capture chip contains features that capture certain targets (i.e. molecules, particles, cells) as they flow through the chip. However, creating optimal capture chip designs is difficult because of the inherent relationship between capture efficiency and flow resistance: as more capture features are added to the chip, the capture efficiency increases, but the additional features slow the flow of fluid through the chip. This paper introduces the use of multi-objective optimization to generate capture chip designs that balance the trade-off between maximizing target capture efficiency and minimizing resistance to fluid flow. Design automation for this important class of microfluidic chips has not been attempted previously. Our approach automatically produces a Pareto front of non-dominated chip designs in a reasonable amount of time, and most of these designs have comparable capture efficiency to hand-designed chips with far lower flow resistance. By choosing from the chip designs on the Pareto front, a user can obtain high capture efficiency without exceeding the flow resistance constraints of their application.