The Impact of Foundation Medicine Testing on Cancer Patients: A Single Academic Centre Experience

BackgroundThe use of Next-Generation Sequencing (NGS) has recently allowed significant improvements in cancer treatment. Foundation Medicine® (FM) provides a genomic profiling test based on NGS for a variety of cancers. However, it is unclear if the Foundation Medicine test would result in a better outcome than the standard on-site molecular testing. In this retrospective chart review, we identified the FM cases from an academic Canadian hospital and determined whether these test results improved treatment options for those patients.Materials and MethodsA retrospective analysis was performed on patients with solid tumors who had FM testing between May 1, 2014 and May 1, 2018. Clinical factors and outcomes were measured using descriptive statistics using Microsoft Excel® Software.ResultsOut of 66 FM tests, eight patients (= 12%) had a direct change in therapy based on the FM tests. Identified were 285 oncogenic mutations (median 1, range 0–31); where TP53 (n = 31, 10.9%), CDKN2A (n = 19, 6.7%), KRAS (n = 16, 5.6%) and APC (n = 9, 3.2%) were the most common FM mutations identified.ConclusionA small proportion of FM reports identified actionable mutations and led to direct treatment change. FM testing is expensive and a few of the identified mutations are now part of routine on-site testing. NGS testing is likely to become more widespread, but this research suggests that its true clinical impact may be restricted to a minority of patients.

Increased anxiety of public situations during the COVID-19 pandemic: Evidence from a community and a patient sample

Background Increases in emotional distress in response to the global outbreak of the SARS-CoV-2 (COVID-19) pandemic have been reported. So far, little is known about how anxiety responses in specific everyday public life situations have been affected. Method Self-reported anxiety in selected public situations, which are relevant in the COVID-19 pandemic, was investigated in non-representative samples from the community (n = 352) and patients undergoing psychotherapy (n = 228). Situational anxiety in each situation was rated on a 5-point Likert scale (0 = no anxiety at all to 4 = very strong anxiety). Situational anxiety during the pandemic was compared with retrospectively reported situational anxiety before the pandemic (direct change) and with anxiety levels in a matched sample assessed before the pandemic (n = 100; indirect change). Results In the community and patient sample, indirect and direct change analyses demonstrated an increase in anxiety in relevant public situations but not in control situations. Average anxiety levels during the pandemic were moderate, but 5-28% of participants reported high to very high levels of anxiety in specific situations. Interestingly, the direct increase in anxiety levels was higher in the community sample: patients reported higher anxiety levels than the community sample before, but not during the pandemic. Finally, a higher increase in situational anxiety was associated with a higher perceived danger of COVID-19, a higher perceived likelihood of contracting COVID-19, and stronger symptoms of general anxiety and stress. Conclusions Preliminary findings demonstrate an increase in anxiety in public situations during the COVID-19 pandemic in a community and a patient sample. Moderate anxiety may facilitate compliance with public safety measures. However, high anxiety levels may result in persistent impairments and should be monitored during the pandemic.

The Differential Effects of the Amount of Training on Sensitivity of Distinct Actions to Reward Devaluation

Shifting between goal-directed and habitual behaviors is essential for daily functioning. An inability to do so is associated with various clinical conditions, such as obsessive–compulsive disorder (OCD). Here we developed a new behavioral model in mice allowing us to produce and examine the development of different behaviors under goal-directed or habitual control. By using overtraining of instrumental associations between two levers and two rewards, and later devaluating one of the rewards, we differentiate and explore the motivational control of behaviors within the task which consequentially promotes what seems like excessive irrational behavior. Using our model, we found that the ability of instrumental behavior, to adapt to a change in the value of a known reward, is a function of practice. Once an instrumental action was practiced extensively it becomes habitual and, thus, under S–R control and could not be amended, not even when resulting in a noxious outcome. However, direct consummatory or Pavlovian actions, such as licking or checking, responds immediately to the change in value. This imbalance could render an instrumental behavior excessive and unresponsive to changes in outcome while the direct change in consumption implies that the change was in fact registered. This could suggest a system that, when out of balance, can create excessive behaviors, not adapting to an acknowledged change.

ACUTE AND CHRONICAL BIOLOGICAL EFFECTS OF W BAND MILLIMETRIC WAVES EXPOSURE IN RATS

The biological effects of millimetric waves systems, MMW (e.g. 5G communications, automotive radars, or crowd control systems, ADS) systems are still scarcely investigated. Hairless rats were exposed to 2 94GHz continuous wave (MMW, CW), under acute high power conditions (3sec at10kW/m ) and under 2 environmental/professional lower power exposure (4 hours a day, for 5 days a week, for 6 months at 10mW/cm ). It was found that the 94 GHz acute exposure provoked the disappearance of the epidermis upper corneal layers and the increase of the inammatory gene expression SOCS-3 after 3Hrs. Besides, neither histological nor genetic modication could be observed after chronic 94 GHz exposure and after an acute and a chronic capsaicin exposure. Conclusions :After a powerful acute exposition a thermal effect is observable, associated with a localized inammatory response. After chronic, low power exposition, an hypoalgesia effect was found, possibly related with an increase in brain plasticity. Mechanistically, the hypothesis is based on low noise stimulation of thermal pain receptors at subthreshold level. Conversely, neither inammation nor no direct change in was found.

MEASURING PROTEST FOR COMPARISONS: MULTIDIMENSIONAL SCALING OF ACTION, MESSAGE, AND COMMUNITY*

We introduce a fine-grained method of categorizing protests by their strategies and tactics that places protests in a multidimensional space based on motivations—direct change towards a policy or goal; changing public discourse narratives; and building movement identities or communities. This technique recognizes that multiple motivations may exist and allows protests to be compared based on where they are in multiple dimensions. To test our method and the theoretical dimensions we hypothesize, we surveyed protesters at the 2016 Republican and Democratic National Conventions. Using questions about participant goals and targets, and confirmatory factor analysis, we corroborate the existence of three dimensions. We show these dimensions provide real information about the differences between protests outside the two conventions. We conclude by discussing how our multidimensional measure can be extended to other events, social movement organizations, or whole movements to facilitate comparisons of events, organizations, or movements across time and space.

Design strategies for exploring and bridging: Intersections of everyday life and decision-making for sustainability

Transitions of unsustainable everyday practices into more sustainable ones require new approaches to explore possible futures and encourage change. Trying new practices and experiencing alternative configurations of socio-material assemblages can increase reflexivity as well as assist in exploring potential futures. Design can assist in co-creating possible futures and bridging discussions about the preferred strategies to reach them. If sustainability is defined as an on-going process calling for dialogue, there could be potentials for using practice-based design research, and in particular co-design approaches, at the intersections of these dialogues. By analysing methods for reflexivity and collaboration in two design research projects within sustainable mobility, we here suggest design strategies for prototyping change at an individual level and communicating the experiences of such change to people with power to trigger and direct change. This may be particularly useful for addressing sustainability which both requires dealing with complex problems and extensive collaboration.

From B-Boys to Broadway: Activism and Directed Change in Hip-hop

In this article, I examine how the dominant paradigm of development led to the Bronx being in a state of ruin, the development of hip-hop culture as a self-empowerment tool, and how that tool is used to direct change in blighted urban areas around the US through rap at all levels—from street corners to the Broadway stage. I use a combination of theories from development communication, ethnomusicology and popular culture to perform my analysis and conclude that hip-hop culture empowers individuals and communities to make change in their neighbourhoods. I also conclude that Lin-Manuel Miranda, coming from that culture, has gone on to bring this empowerment and directed change to Broadway to make fundamental changes there that have an impact that reach far from the hallowed halls of the Great White Way.

Assessing Drug Interaction and Pharmacokinetics of Loxoprofen in Mice Treated with CYP3A Modulators

Loxoprofen (LOX) is a non-selective cyclooxygenase inhibitor that is widely used for the treatment of pain and inflammation caused by chronic and transitory conditions. Its alcoholic metabolites are formed by carbonyl reductase (CR) and they consist of trans-LOX, which is active, and cis-LOX, which is inactive. In addition, LOX can also be converted into an inactive hydroxylated metabolite (OH-LOXs) by cytochrome P450 (CYP). In a previous study, we reported that CYP3A4 is primarily responsible for the formation of OH-LOX in human liver microsomes. Although metabolism by CYP3A4 does not produce active metabolites, it can affect the conversion of LOX into trans-/cis-LOX, since CYP3A4 activity modulates the substrate LOX concentration. Although the pharmacokinetics (PK) and metabolism of LOX have been well defined, its CYP-related interactions have not been fully characterized. Therefore, we investigated the metabolism of LOX after pretreatment with dexamethasone (DEX) and ketoconazole (KTC), which induce and inhibit the activities of CYP3A, respectively. We monitored their effects on the PK parameters of LOX, cis-LOX, and trans-LOX in mice, and demonstrated that their PK parameters significantly changed in the presence of DEX or KTC pretreatment. Specifically, DEX significantly decreased the concentration of the LOX active metabolite formed by CR, which corresponded to an increased concentration of OH-LOX formed by CYP3A4. The opposite result occurred with KTC (a CYP3A inhibitor) pretreatment. Thus, we conclude that concomitant use of LOX with CYP3A modulators may lead to drug–drug interactions and result in minor to severe toxicity even though there is no direct change in the metabolic pathway that forms the LOX active metabolite.

Southeast Asia

This chapter examines the development experiences of six countries, Malaysia, Philippines, Thailand, Cambodia, Lao People’s Democratic Republic, and Myanmar—collectively ‘the Six’—fifty years after Gunnar Myrdal’s Asian Drama. Myrdal took an unambiguously pessimistic view of Asian prospects for development on the basis of obstacles to raising agricultural productivity, and the low perceived level of capability of governments to intervene effectively in favour of industrial development—the latter being a handicap that included extensive corruption at all levels of government. The record of the Six mostly defied Myrdal’s prognosis, raising agricultural productivity faster than population growth and displaying sufficient state capability to direct change towards a respectable level of industrial development. By using a more socially grounded analytical approach à la Myrdal, it is possible to understand how unorthodox economic policies have been effective in overcoming developmental disadvantages. However, shortfalls in social development could make future progress difficult.

Impact of Multiple Sclerosis Project ECHO (Extension for Community Healthcare Outcomes) on Provider Confidence and Clinical Practice

Background: Project ECHO (Extension for Community Healthcare Outcomes) represents a novel approach to addressing disparities in multiple sclerosis (MS) care. A primary mechanism of the program is the use of case consultations to rapidly transfer knowledge from content experts to community providers who care for individuals with MS. Methods: MS Project ECHO was pilot tested as a weekly 60-minute videoconference delivered to 24 clinicians across 13 practice sites over 41 weeks. Participants completed a variety of measures related to their experience in the program and answered qualitative questions via exit interview. We report on the responses to exit interview questions related to the case consultation component of MS Project ECHO. Results: Participant responses regarding case consultations generated four themes: 1) improved confidence among participants in the existing treatment decision, 2) direct change in the care of the patient provided by the participant, 3) changed practice habits for all of the participant's patients with MS, and 4) increased perception that patients had confidence in the participant as an MS care provider. Conclusions: Participant responses support MS Project ECHO as a program that may directly and indirectly affect the way providers deliver MS care in underserved areas. Further research is needed to examine the resulting effect on patient outcomes.