Variational formulation of Eisenhart's unified theory

Eisenhart's classical unified field theory is based on a non-Riemannian affine connection related to the covariant derivative of the electromagnetic field tensor. The sourceless field equations of this theory arise from vanishing of the torsion trace and the symmetrized Ricci tensor. We formulate Eisenhart's theory from the metric-affine variational principle. In this formulation, a Lagrange multiplier constraining the torsion becomes the source for the Maxwell equations.Comment: 7 pages; published versio

Effectiveness of the ADEC as a level 2 screening test for young children with suspected autism spectrum disorders in a clinical setting

Background The Autism Detection in Early Childhood (ADEC) is a clinician-administered, Level 2 screening tool. A retrospective file audit was used to investigate its clinical effectiveness. Method Toddlers referred to an Australian child development service between 2008 and 2010 (N?=?53, M age?=?32.2 months) were screened with the ADEC. Their medical records were reviewed in 2013 when their mean age was 74.5 months, and the original ADEC screening results were compared with later diagnostic outcomes. Results The ADEC had good sensitivity (87.5%) and moderate specificity (62%). Three behaviours predicted autism spectrum disorders (ASDs): response to name, gaze switching, and gaze monitoring (p???.001). Conclusions The ADEC shows promise as a screening tool that can discriminate between young children with ASDs and those who have specific communication disorders or developmental delays that persist into middle childhood but who do not meet the criteria for ASDs

Adherence to prescribing restrictions for HER2-positive metastatic breast cancer in Australia: A national population-based observational study (2001-2016)

Background: Targeted cancer therapy is often complex, involving multiple agents and chemotherapeutic partners. In Australia, prescribing restrictions are put in place to reflect existing evidence of cost-effectiveness of these medicines. As therapeutic options continue to expand, these restrictions may not be perceived to align with best practice and it is not known if their use in the real-world clinic adheres to these restrictions. We examined the treatment of women receiving trastuzumab for HER2-positive metastatic breast cancer (HER2+MBC) to determine the extent to which treatment adhered to national prescribing restrictions. Patients and methods: Our population-based, retrospective cohort study used dispensing records for every Australian woman initiating publicly-subsidised trastuzumab for HER2+MBC between 2001±2013, followed through 2016. We used group-based trajectory models (GBTMs) to cluster patients, first on their patterns of trastuzumab exposure, and then on their patterns of lapatinib and chemotherapy exposure. We described the characteristics of patients within each cluster, and examined their treatments and combinations of treatments to determine restriction adherence. Results: Of 5,052 patients initiating trastuzumab, 1,795 (36%) received at least one non-adherent HER2-targeted treatment. The most common non-adherent treatments were trastuzumab combinations involving vinorelbine (24% of non-adherent treatments); capecitabine (24%); and anthracyclines (10%). Non-adherent lapatinib use was observed in 4% of patients. GBTM identified three trastuzumab exposure clusters, each containing three further subclusters. The largest proportions of non-adherent treatments were in sub-clusters with longer trastuzumab exposure and more non-taxane chemotherapy. Patients in these sub-clusters were younger than those in sub-clusters with less non-adherent treatment. Conclusions: Our study highlights that, even during the relatively simpler treatment era of our study period, a substantial amount of treatment did not adhere to prescribing restrictions. As more trials are conducted exploring pertuzumab and T-DM1 in combination with different chemotherapies and other HER2-targeted therapies, the regulation and funding of HER2-targeted treatment will become more challenging

Spectroscopy of drums and quantum billiards: perturbative and non-perturbative results

We develop powerful numerical and analytical techniques for the solution of the Helmholtz equation on general domains. We prove two theorems: the first theorem provides an exact formula for the ground state of an arbirtrary membrane, while the second theorem generalizes this result to any excited state of the membrane. We also develop a systematic perturbative scheme which can be used to study the small deformations of a membrane of circular or square shapes. We discuss several applications, obtaining numerical and analytical results.Comment: 29 pages, 12 figures, 7 tabl

Age grading \u3cem\u3eAn. gambiae\u3c/em\u3e and \u3cem\u3eAn. arabiensis\u3c/em\u3e using near infrared spectra and artificial neural networks

Background Near infrared spectroscopy (NIRS) is currently complementing techniques to age-grade mosquitoes. NIRS classifies lab-reared and semi-field raised mosquitoes into \u3c or ≥ 7 days old with an average accuracy of 80%, achieved by training a regression model using partial least squares (PLS) and interpreted as a binary classifier. Methods and findings We explore whether using an artificial neural network (ANN) analysis instead of PLS regression improves the current accuracy of NIRS models for age-grading malaria transmitting mosquitoes. We also explore if directly training a binary classifier instead of training a regression model and interpreting it as a binary classifier improves the accuracy. A total of 786 and 870 NIR spectra collected from laboratory reared An. gambiae and An. arabiensis, respectively, were used and pre-processed according to previously published protocols. The ANN regression model scored root mean squared error (RMSE) of 1.6 ± 0.2 for An. gambiae and 2.8 ± 0.2 for An. arabiensis; whereas the PLS regression model scored RMSE of 3.7 ± 0.2 for An. gambiae, and 4.5 ± 0.1 for An. arabiensis. When we interpreted regression models as binary classifiers, the accuracy of the ANN regression model was 93.7 ± 1.0% for An. gambiae, and 90.2 ± 1.7% for An. arabiensis; while PLS regression model scored the accuracy of 83.9 ± 2.3% for An. gambiae, and 80.3 ± 2.1% for An. arabiensis. We also find that a directly trained binary classifier yields higher age estimation accuracy than a regression model interpreted as a binary classifier. A directly trained ANN binary classifier scored an accuracy of 99.4 ± 1.0 for An. gambiae and 99.0 ± 0.6% for An. arabiensis; while a directly trained PLS binary classifier scored 93.6 ± 1.2% for An. gambiae and 88.7 ± 1.1% for An. arabiensis. We further tested the reproducibility of these results on different independent mosquito datasets. ANNs scored higher estimation accuracies than when the same age models are trained using PLS. Regardless of the model architecture, directly trained binary classifiers scored higher accuracies on classifying age of mosquitoes than regression models translated as binary classifiers. Conclusion We recommend training models to estimate age of An. arabiensis and An. gambiae using ANN model architectures (especially for datasets with at least 70 mosquitoes per age group) and direct training of binary classifier instead of training a regression model and interpreting it as a binary classifier

Kelvin Wave Cascade and Decay of Superfluid Turbulence

Kelvin waves (kelvons)--the distortion waves on vortex lines--play a key part in the relaxation of superfluid turbulence at low temperatures. We present a weak-turbulence theory of kelvons. We show that non-trivial kinetics arises only beyond the local-induction approximation and is governed by three-kelvon collisions; corresponding kinetic equation is derived. On the basis of the kinetic equation, we prove the existence of Kolmogorov cascade and find its spectrum. The qualitative analysis is corroborated by numeric study of the kinetic equation. The application of the results to the theory of superfluid turbulence is discussed.Comment: 4 pages, RevTe

Rationality as the Rule of Reason

The demands of rationality are linked both to our subjective normative perspective (given that rationality is a person-level concept) and to objective reasons or favoring relations (given that rationality is non-contingently authoritative for us). In this paper, I propose a new way of reconciling the tension between these two aspects: roughly, what rationality requires of us is having the attitudes that correspond to our take on reasons in the light of our evidence, but only if it is competent. I show how this view can account for structural rationality on the assumption that intentions and beliefs as such involve competent perceptions of downstream reasons, and explore various implications of the account

Use and outcomes of targeted therapies in early and metastatic HER2-positive breast cancer in Australia: Protocol detailing observations in a whole of population cohort

Background: The management of human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC) has changed dramatically with the introduction and widespread use of HER2-targeted therapies. However, there is relatively limited real-world information on patterns of use, effectiveness and safety in whole of population cohorts. The research programme detailed in this protocol will generate evidence on the prescribing patterns, safety monitoring and outcomes of patients with BC treated with HER2- targeted therapies in Australia. Methods/design: Our ongoing research programme will involve a series of retrospective cohort studies that include every patient accessing Commonwealth-funded HER2-targeted therapies for the treatment of early BC and advanced BC in Australia. At the time of writing, our cohorts consist of 11 406 patients with early BC and 5631 with advanced BC who accessed trastuzumab and lapatinib between 2001 and 2014. Pertuzumab and trastuzumab emtansine were publicly funded for metastatic BC in 2015, and future data updates will include patients accessing these medicines. We will use dispensing claims for cancer and other medicines, medical service claims and demographics data for each patient accessing HER2- targeted therapies to undertake this research. Ethics and dissemination: Ethics approval has been granted by the Population Health Service Research Ethics Committee and data access approval has been granted by the Australian Department of Human Services (DHS) External Review Evaluation Committee. Our findings will be reported in peer-reviewed publications, conference presentations and policy forums. By providing detailed information on the use and outcomes associated with HER2-targeted therapies in a national cohort treated in routine clinical care, our research programme will better inform clinicians and patients about the real-world use of these treatments and will assist third-party payers to better understand the use and economic costs of these treatments