When designers set out to create a mathematics learning activity, they have a fair sense of its objectives: students will understand a concept and master relevant procedural skills. In reform-oriented activities, students first engage in concrete situations, wherein they achieve situated, intermediary learning objectives (SILOs), and only then they rearticulate their solutions formally. We define SILOs as heuristics learners devise to accommodate contingencies in an evolving problem space, e.g., monitoring and repairing manipulable structures so that they model with fidelity a source situation. Students achieve SILOs through problem-solving with media, instructors orient toward SILOs via discursive solicitation, and designers articulate SILOs via analyzing implementation data. We describe the emergence of three SILOs in developing the activity Giant Steps for Algebra. Whereas the notion of SILOs emerged spontaneously as a framework to organize a system of practice, i.e. our collaborative design, it aligns with phenomenological theory of knowledge as instrumented action.

Introduction Injury is a major cause of morbidity and mortality in low- and middle-income countries. Effective trauma surveillance is imperative to guide research and quality improvement interventions, so an accurate metric for quantifying injury severity is crucial. The objectives of this study are (1) to assess the feasibility of calculating five injury scoring systems - ISS (injury severity score), RTS (revised trauma score), KTS (Kampala trauma score), MGAP (mechanism, GCS (Glasgow coma score), age, pressure) and GAP (GCS, age, pressure) - with data from a trauma registry in a lower middle-income country and (2) to determine which of these scoring systems most accurately predicts in-hospital mortality in this setting. Patients and methods This is a retrospective analysis of data from an institutional trauma registry in Mumbai, India. Values for each score were calculated when sufficient data were available. Logistic regression was used to compare the correlation between each score and in-hospital mortality. Results There were sufficient data recorded to calculate ISS in 73% of patients, RTS in 35%, KTS in 35%, MGAP in 88% and GAP in 92%. ISS was the weakest predictor of in-hospital mortality, while RTS, KTS, MGAP and GAP scores all correlated well with in-hospital mortality (area under ROC (receiver operating characteristic) curve 0.69 for ISS, 0.85 for RTS, 0.86 for KTS, 0.84 for MGAP, 0.85 for GAP). Respiratory rate measurements, missing in 63% of patients, were a major barrier to calculating RTS and KTS. Conclusions Given the realities of medical practice in low- and middle-income countries, it is reasonable to modify the approach to characterising injury severity to favour simplified injury scoring systems that accurately predict in-hospital mortality despite limitations in trauma registry datasets.

This is a summary of the activities of the working group on cosmology at WHEPP-X. The three main problems that were discussed at some length by the group during the course of the workshop were (i) canceling a 'large' cosmological constant, (ii) non-Gaussianities in inflationary models and (iii) stability of interacting models of dark energy and dark matter. We have briefly outlined these problems and have indicated the progress made.

Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), infects an estimated two billion people worldwide and is the leading cause of mortality due to infectious disease. The development of new anti-TB therapeutics is required, because of the

Background

Treatment options are limited for patients with recurrent or metastatic squamous cell carcinoma of the head and neck (HNSCC) following progression after first-line platinum-based therapy, particularly in Asian countries.

Patients and methods

In this randomised, open-label, phase III trial, we enrolled Asian patients aged ≥18 years, with histologically or cytologically confirmed recurrent/metastatic HNSCC following first-line platinum-based therapy who were not amenable for salvage surgery or radiotherapy, and had an Eastern Cooperative Oncology Group (ECOG) performance status of 0/1. Patients were randomised (2 : 1) to receive oral afatinib (40 mg/day) or intravenous methotrexate (40 mg/m2/week), stratified by ECOG performance status and prior EGFR-targeted antibody therapy. The primary end point was progression-free survival (PFS) assessed by an independent central review committee blinded to treatment allocation.

Results

A total of 340 patients were randomised (228 afatinib; 112 methotrexate). After a median follow-up of 6.4 months, afatinib significantly decreased the risk of progression/death by 37% versus methotrexate (hazard ratio 0.63; 95% confidence interval 0.48-0.82; P = 0.0005; median 2.9 versus 2.6 months; landmark analysis at 12 and 24 weeks, 58% versus 41%, 21% versus 9%). Improved PFS was complemented by quality of life benefits. Objective response rate was 28% with afatinib and 13% with methotrexate. There was no significant difference in overall survival. The most common grade ≥3 drug-related adverse events were rash/acne (4% with afatinib versus 0% with methotrexate), diarrhoea (4% versus 0%), fatigue (1% versus 5%), anaemia (<1% versus 5%) and leukopenia (0% versus 5%).

Conclusions

Consistent with the phase III LUX-Head & Neck 1 trial, afatinib significantly improved PFS versus methotrexate, with a manageable safety profile. These results demonstrate the efficacy and feasibility of afatinib as a second-line treatment option for certain patients with recurrent or metastatic HNSCC.

Clinical trial registration

ClinicalTrials.gov identifier: NCT01856478.