Delay effects in the response of low-grade gliomas to radiotherapy: a mathematical model and its therapeutical implications

Low-grade gliomas (LGGs) are a group of primary brain tumours usually encountered in young patient populations. These tumours represent a difficult challenge because many patients survive a decade or more and may be at a higher risk for treatment-related complications. Specifically, radiation therapy is known to have a relevant effect on survival but in many cases it can be deferred to avoid side effects while maintaining its beneficial effect. However, a subset of LGGs manifests more aggressive clinical behaviour and requires earlier intervention. Moreover, the effectiveness of radiotherapy depends on the tumour characteristics. Recently Pallud et al. (2012. Neuro-Oncology, 14: , 1-10) studied patients with LGGs treated with radiation therapy as a first-line therapy and obtained the counterintuitive result that tumours with a fast response to the therapy had a worse prognosis than those responding late. In this paper, we construct a mathematical model describing the basic facts of glioma progression and response to radiotherapy. The model provides also an explanation to the observations of Pallud et al. Using the model, we propose radiation fractionation schemes that might be therapeutically useful by helping to evaluate tumour malignancy while at the same time reducing the toxicity associated to the treatment.

Pushing forward in embodied cognition: May we mouse the mathematical mind?

Freely available software has popularized “mousetracking” to study cognitive processing; this involves the on-line recording of cursor positions while participants move a computer mouse to indicate their choice. Movement trajectories of the cursor can then be reconstructed off-line to assess the efficiency of responding in time and across space. Here we focus on the process of selecting among alternative numerical responses. Several studies have recently measured the mathematical mind with cursor movements while people decided about number magnitude or parity, computed sums or differences, or simply located numbers on a number line. After some general methodological considerations about mouse tracking we discuss several conceptual concerns that become particularly evident when “mousing” the mathematical mind.

Sample size considerations using mathematical models: an example with Chlamydia trachomatis infection and its sequelae pelvic inflammatory disease.

BACKGROUND The success of an intervention to prevent the complications of an infection is influenced by the natural history of the infection. Assumptions about the temporal relationship between infection and the development of sequelae can affect the predicted effect size of an intervention and the sample size calculation. This study investigates how a mathematical model can be used to inform sample size calculations for a randomised controlled trial (RCT) using the example of Chlamydia trachomatis infection and pelvic inflammatory disease (PID). METHODS We used a compartmental model to imitate the structure of a published RCT. We considered three different processes for the timing of PID development, in relation to the initial C. trachomatis infection: immediate, constant throughout, or at the end of the infectious period. For each process we assumed that, of all women infected, the same fraction would develop PID in the absence of an intervention. We examined two sets of assumptions used to calculate the sample size in a published RCT that investigated the effect of chlamydia screening on PID incidence. We also investigated the influence of the natural history parameters of chlamydia on the required sample size. RESULTS The assumed event rates and effect sizes used for the sample size calculation implicitly determined the temporal relationship between chlamydia infection and PID in the model. Even small changes in the assumed PID incidence and relative risk (RR) led to considerable differences in the hypothesised mechanism of PID development. The RR and the sample size needed per group also depend on the natural history parameters of chlamydia. CONCLUSIONS Mathematical modelling helps to understand the temporal relationship between an infection and its sequelae and can show how uncertainties about natural history parameters affect sample size calculations when planning a RCT.

Job satisfaction of Swiss general practitioners with and without proficiency certificate in homeopathy

Introduction: Job satisfaction and therefore wellbeing of physicians is an important issue in high quality and safety of health care provision. The role of additional qualification in complementary medicine (CM) for job satisfaction of general practitioners (GPs), however, has not been explored. This study compared job satisfaction of conventional and homeopathic Swiss GPs. Methods: Participants of the Swiss Family Doctors Conference 2013 and members of the Swiss Association of Homeopathic Physicians participated in the survey. They indicated the extent of job satisfaction on 17 questions covering patient care, work-related burden, income-prestige, personal rewards, and professional relations. Results: Data of n = 125 GPs with homeopathic proficiency certificate and data of n = 143 GPs without any proficiency certificate in CM were analyzed. Overall job satisfaction was high and did not differ between the groups. However, due to lower number of patients per day, homeopathic GPs reported higher satisfaction in relations with patients and with workload, and lower satisfaction with income and in relations with peers compared to conventional GPs. Controlling for further confounding variables (e.g. working hours per week, practice setting), homeopathic GPs reported less satisfaction with their income than their conventional colleagues. Conclusions: Longer consultation time and lower number of patients homeopathic GPs see per day, may allowthem to unfold a deeper and more satisfying relationship with their patients and to lessen the workload. However, this comes along with financial discontent compared to conventional GPs. Certification in homeopathy and increased consultation time, respectively, may represent a way to enhance GPs’ job satisfaction.

The need for second-line antiretroviral therapy in adults in sub-Saharan Africa up to 2030: a mathematical modelling study.

BACKGROUND The number of patients in need of second-line antiretroviral drugs is increasing in sub-Saharan Africa. We aimed to project the need of second-line antiretroviral therapy in adults in sub-Saharan Africa up to 2030. METHODS We developed a simulation model for HIV and applied it to each sub-Saharan African country. We used the WHO country intelligence database to estimate the number of adult patients receiving antiretroviral therapy from 2005 to 2014. We fitted the number of adult patients receiving antiretroviral therapy to observed estimates, and predicted first-line and second-line needs between 2015 and 2030. We present results for sub-Saharan Africa, and eight selected countries. We present 18 scenarios, combining the availability of viral load monitoring, speed of antiretroviral scale-up, and rates of retention and switching to second-line. HIV transmission was not included. FINDINGS Depending on the scenario, 8·7-25·6 million people are expected to receive antiretroviral therapy in 2020, of whom 0·5-3·0 million will be receiving second-line antiretroviral therapy. The proportion of patients on treatment receiving second-line therapy was highest (15·6%) in the scenario with perfect retention and immediate switching, no further scale-up, and universal routine viral load monitoring. In 2030, the estimated range of patients receiving antiretroviral therapy will remain constant, but the number of patients receiving second-line antiretroviral therapy will increase to 0·8-4·6 million (6·6-19·6%). The need for second-line antiretroviral therapy was two to three times higher if routine viral load monitoring was implemented throughout the region, compared with a scenario of no further viral load monitoring scale-up. For each monitoring strategy, the future proportion of patients receiving second-line antiretroviral therapy differed only minimally between countries. INTERPRETATION Donors and countries in sub-Saharan Africa should prepare for a substantial increase in the need for second-line drugs during the next few years as access to viral load monitoring improves. An urgent need exists to decrease the costs of second-line drugs. FUNDING World Health Organization, Swiss National Science Foundation, National Institutes of Health.

The Impact of Language Opacity and Proficiency on Reading Strategies in Bilinguals: An Eye Movement Study

Reading strategies vary across languages according to orthographic depth - the complexity of the grapheme in relation to phoneme conversion rules - notably at the level of eye movement patterns. We recently demonstrated that a group of early bilinguals, who learned both languages equally under the age of seven, presented a first fixation location (FFL) closer to the beginning of words when reading in German as compared with French. Since German is known to be orthographically more transparent than French, this suggested that different strategies were being engaged depending on the orthographic depth of the used language. Opaque languages induce a global reading strategy, and transparent languages force a local/serial strategy. Thus, pseudo-words were processed using a local strategy in both languages, suggesting that the link between word forms and their lexical representation may also play a role in selecting a specific strategy. In order to test whether corresponding effects appear in late bilinguals with low proficiency in their second language (L2), we present a new study in which we recorded eye movements while two groups of late German-French and French-German bilinguals read aloud isolated French and German words and pseudo-words. Since, a transparent reading strategy is local and serial, with a high number of fixations per stimuli, and the level of the bilingual participants' L2 is low, the impact of language opacity should be observed in L1. We therefore predicted a global reading strategy if the bilinguals' L1 was French (FFL close to the middle of the stimuli with fewer fixations per stimuli) and a local and serial reading strategy if it was German. Thus, the L2 of each group, as well as pseudo-words, should also require a local and serial reading strategy. Our results confirmed these hypotheses, suggesting that global word processing is only achieved by bilinguals with an opaque L1 when reading in an opaque language; the low level in the L2 gives way to a local and serial reading strategy. These findings stress the fact that reading behavior is influenced not only by the linguistic mode but also by top-down factors, such as readers' proficiency.