Pemetrexed, Carboplatin, and Concomitant Radiation followed by Surgery for Locally Advanced Esophageal Cancer: Results of a Planned Interim Toxicity Analysis of North Central Cancer Treatment Group Study N044E

Purpose This brief report describes a planned, interim, 6-patient toxicity analysis that confirms the safety of pemetrexed, carboplatin, radiation with subsequent surgery, as prescribed in the North Central Cancer Treatment Group trial N044E, in patients with locally advanced esophageal cancer. Methods Six patients with locally advanced, potentially resectable esophageal cancer received pemetrexed 500 mg/m 2 and carboplatin AUC = 6 on days 1 and 22 with 5040 centigray of concomitant radiation in 28 fractions over 5.5 weeks followed by esophagectomy as a prelude to a phase II multi-institutional trial. Results Only 1 of the 6 patients experienced a grade 4 adverse event (neutropenia). This patient also experienced a grade 3 depression. Of the remaining 5 patients, three experienced at least one grade 3 adverse event (neutropenia, nausea/vomiting, and esophagitis). There were no deaths. Incidentally, one patient manifested a complete pathologic response, three a partial pathologic response, and one stable disease. Conclusion These preliminary observations on safety suggest that this regimen can be further studied in this clinical setting

Interaction Between the Broad-Lined Type Ic Supernova 2012ap and Carriers of Diffuse Interstellar Bands

The diffuse interstellar bands (DIBs) are absorption features observed in optical and near-infrared spectra that are thought to be associated with carbon-rich polyatomic molecules in interstellar gas. However, because the central wavelengths of these bands do not correspond with electronic transitions of any known atomic or molecular species, their nature has remained uncertain since their discovery almost a century ago. Here we report on unusually strong DIBs in optical spectra of the broad- lined Type Ic supernova SN2012ap that exhibit changes in equivalent width over short (. 30 days) timescales. The 4428 A and 6283 A DIB features get weaker with time, whereas the 5780 A feature shows a marginal increase. These nonuniform changes suggest that the supernova is interacting with a nearby source of the DIBs and that the DIB carriers possess high ionization potentials, such as small cations or charged fullerenes. We conclude that moderate-resolution spectra of supernovae with DIB absorptions obtained within weeks of outburst could reveal unique information about the mass-loss environment of their progenitor systems and provide new constraints on the properties of DIB carriers

Using a coproduced educational workshop to change the focus of verbal instructions delivered by professional youth soccer coaches: a case study

Background The predominant instructional method utilised by soccer coaches are verbal instructions that occur whilst (during) players are executing soccer-skill. However, little is known on the specificity of the information contained within. These verbal instructions can guide the learner to either the performance characteristics of a movement (internal focus) or the intended movement effects (external), with the latter known to facilitate superior motor performance, retention, and transfer. Purpose The aims in the present study were to quantify the focus of concurrent verbal instructions utilised by professional youth soccer coaches during drill-based (i.e. isolated) practice activities, and to modulate how these instructions are delivered in coaching sessions following the engagement in a coproduced evidence-based educational workshop. Method Systematic observation was used pre and post the workshop to quantify the nature of verbal instructions delivered by 5 male coaches (31–47 years of age with 4–24 years of coaching experience) across 34 sessions with players from 8 to 13 years of age. For instructions provided during (concurrent) action-execution, we further quantified whether these instructions were focused on motor performance characteristics (internal) or the intended movement outcome effects (external) using criteria outlined in the revised Arizona State University Observation Instrument. To facilitate behaviour change, all coaches engaged in an educational workshop led by skill acquisition specialists (SAS). The workshop was designed so that educational material related to the principles of skill acquisition, and motor control and learning, were presented using a pedagogical delivery method containing verbal information, data presented in illustrations, and videos. In addition, the results that quantified coaching behaviour during the pre-workshop systematic observation period were presented to coaches as quantitative feedback. To guide the coaches to appraise the quantitative feedback in relation to the delivered educational material, the SAS built an educational environment that encouraged discussion opportunities for coaches to compare and appraise feedback with other coaches and process the feedback in relation to data and concepts regarding skill acquisition. Results and findings The pre-workshop systematic observation data indicated that coaches delivered significantly more (64%) verbal instructions whilst (concurrently) players were executing motor skills, compared to before (15%) or after (21%). Within concurrent feedback, coaches used instructions that had a more internal, compared to external focus of attention. Post-workshop data indicated the coaches significantly changed the utilisation of instructions using a greater proportion of external focus. The data confirms coaches deliver a greater proportion of concurrent verbal instructions during coaching sessions focused training drill-based activities, but engaging in an educational workshop coaches modulated the focus of these instructions from internal to external, indicating behaviour change and an opportunity to facilitate skill acquisition in soccer academy players

Bridging the gap between science and application: the use of cocreation educational workshops in professional youth soccer

We examined whether practice activities adopted by professional youth soccer coaches are modulated through the implementation of and engagement with cocreative evidence-based programs. Across two experiments, we used systematic observation to identify the practice activities of seven coaches across 134 sessions. In Experiment A, drill-based and games-based activities were recorded and quantified. To encourage behaviour change across the study, the systematic observation data were compared with skill acquisition literature to provide coaches with quantitative feedback and recommendations during workshops. Postworkshop systematic observation data indicated that practice activities used by coaches changed in accordance with the evidenced-based information (increase in games-based activities) delivered within the workshop. Interview data indicated that coaches typically stated that the workshop was a key reason for behaviour change. In a follow-up Experiment B, feedback and recommendations were delivered using an interactive video-based workshop. The systematic observation data indicated that coaches increased the use of soccer activities that contained active decision making with coaches citing the workshop as a key reason for behaviour change. These findings indicate that coaching practice activities can be supported and shaped through the implementation of cocreated workshops wherein coaches collaborate with sport scientists and researchers to bridge the gap between science and application

Infrastructural Speculations: Tactics for Designing and Interrogating Lifeworlds

This paper introduces “infrastructural speculations,” an orientation toward speculative design that considers the complex and long-lived relationships of technologies with broader systems, beyond moments of immediate invention and design. As modes of speculation are increasingly used to interrogate questions of broad societal concern, it is pertinent to develop an orientation that foregrounds the “lifeworld” of artifacts—the social, perceptual, and political environment in which they exist. While speculative designs often imply a lifeworld, infrastructural speculations place lifeworlds at the center of design concern, calling attention to the cultural, regulatory, environmental, and repair conditions that enable and surround particular future visions. By articulating connections and affinities between speculative design and infrastructure studies research, we contribute a set of design tactics for producing infrastructural speculations. These tactics help design researchers interrogate the complex and ongoing entanglements among technologies, institutions, practices, and systems of power when gauging the stakes of alternate lifeworlds

Loss of the nutrient sensor TAS1R3 leads to reduced bone resorption

The taste receptor type 1 (TAS1R) family of heterotrimeric G protein-coupled receptors participates in monitoring energy and nutrient status. TAS1R member 3 (TAS1R3) is a bi-functional protein that recognizes amino acids such as L-glycine and L-glutamate or sweet molecules such as sucrose and fructose when dimerized with TAS1R member 1 (TAS1R1) or TAS1R member 2 (TAS1R2), respectively. It was recently reported that deletion of TAS1R3 expression in Tas1R3 mutant mice leads to increased cortical bone mass but the underlying cellular mechanism leading to this phenotype remains unclear. Here, we independently corroborate the increased thickness of cortical bone in femurs of 20-week-old male Tas1R3 mutant mice and confirm that Tas1R3 is expressed in the bone environment. Tas1R3 is expressed in undifferentiated bone marrow stromal cells (BMSCs) in vitro and its expression is maintained during BMP2-induced osteogenic differentiation. However, levels of the bone formation marker procollagen type I N-terminal propeptide (PINP) are unchanged in the serum of 20-week-old Tas1R3 mutant mice as compared to controls. In contrast, levels of the bone resorption marker collagen type I C-telopeptide are reduced greater than 60% in Tas1R3 mutant mice. Consistent with this, Tas1R3 and its putative signaling partner Tas1R2 are expressed in primary osteoclasts and their expression levels positively correlate with differentiation status. Collectively, these findings suggest that high bone mass in Tas1R3 mutant mice is due to uncoupled bone remodeling with reduced osteoclast function and provide rationale for future experiments examining the cell-type-dependent role for TAS1R family members in nutrient sensing in postnatal bone remodeling

Prognostic Significance of Defective Mismatch Repair and BRAF V600E in Patients with Colon Cancer

Colon tumors with defective DNA mismatch repair (dMMR) have a well characterized phenotype and accounts for ~15–20% of sporadic colon cancer (CC) as well as those colon cancer patients with Lynch Syndrome. Although the presence of dMMR appears to be a favorable prognostic marker, data suggests that these patients do not respond as well to adjuvant chemotherapy

Announcing The Lancet Global Health Commission on Global Eye Health

Description to be added.Cannot be left empt