Establishing the accuracy of density functional approaches for the description of noncovalent interactions in biomolecules.

Biomolecules have complex structures, and noncovalent interactions are crucial to determine their conformations and functionalities. It is therefore critical to be able to describe them in an accurate but efficient manner in these systems. In this context density functional theory (DFT) could provide a powerful tool to simulate biological matter either directly for relatively simple systems or coupled with classical simulations like the QM/MM (quantum mechanics/molecular mechanics) approach. Additionally, DFT could play a fundamental role to fit the parameters of classical force fields or to train machine learning potentials to perform large scale molecular dynamics simulations of biological systems. Yet, local or semi-local approximations used in DFT cannot describe van der Waals (vdW) interactions, one of the essential noncovalent interactions in biomolecules, since they lack a proper description of long range correlation effects. However, many efficient and reasonably accurate methods are now available for the description of van der Waals interactions within DFT. In this work, we establish the accuracy of several state-of-the-art vdW-aware functionals by considering 275 biomolecules including interacting DNA and RNA bases, peptides and biological inhibitors and compare our results for the energy with highly accurate wavefunction based calculations. Most methods considered here can achieve close to predictive accuracy. In particular, the non-local vdW-DF2 functional is revealed to be the best performer for biomolecules, while among the vdW-corrected DFT methods, uMBD is also recommended as a less accurate but faster alternative.

Measurement accuracy and uncertainty in plant biomechanics.

All scientific measurements are affected to some degree by both systematic and random errors. The quantification of these errors supports correct interpretation of data, thus supporting scientific progress. Absence of information regarding reliability and accuracy can slow scientific progress, and can lead to a reproducibility crisis. Here we consider both measurement theory and plant biomechanics literature. Drawing from measurement theory literature, we review techniques for assessing both the accuracy and uncertainty of a measurement process. In our survey of plant biomechanics literature, we found that direct assessment of measurement accuracy and uncertainty is not yet common. The advantages and disadvantages of efforts to quantify measurement accuracy and uncertainty are discussed. We conclude with recommended best practices for improving the scientific rigor in plant biomechanics through attention to the issues of measurement accuracy and uncertainty.

Can research align with service? Lessons learned from the Big Experiment and National Biomechanics Day.

Public engagement is an important role for the university academic, but is often neglected due to perceived lack of time and prioritized commitments in research and teaching. Yet, public engagement events offer an untapped opportunity for researchers to collect data from members of the general public who arrive on site at university labs. These engagement events could allow for data collection as part of didactic and demonstrative outreach events to be used in research and science. In this proof of concept study, a collaborative group of international researchers investigated the feasibility of embedding research quality assessment into events surrounding National Biomechanics Day. The Big Experiment collected data on 501 secondary school students (age range: 13 to 18 years) across 9 university sites within a 24-hour period. Data included maximal vertical jump height and self-reported physical activity levels. Vertical jump height was positively correlated to participant height, but not age or body mass. Very physically active students had significantly higher vertical jump heights than individuals who reported being somewhat or not physically active. This feasibility project demonstrates that with substantial preparation and a simple research design, focused research questions can be incorporated into educational outreach initiatives and ultimately provide a rich data source.

Rapporteur Report: ICNIRP international workshop on EMF dosimetry and biophysical aspects relevant to setting exposure guidelines.

The International Commission on Non-Ionizing Radiation Protection has commenced the revision of its EMF guidelines in the frequency range up to 300 GHz. The ICNIRP International EMF Dosimetry Workshop has brought together a range of scientists to discuss the basis of the existing guidelines and to highlight those areas where attention needs to be given. This report is an attempt to extract the key messages from each of the presentations. A tabulation of the important issues discussed in the summary and conclusion session is provided at the end of this report.

Local Field Potentials: Myths and Misunderstandings.

The intracerebral local field potential (LFP) is a measure of brain activity that reflects the highly dynamic flow of information across neural networks. This is a composite signal that receives contributions from multiple neural sources, yet interpreting its nature and significance may be hindered by several confounding factors and technical limitations. By and large, the main factor defining the amplitude of LFPs is the geometry of the current sources, over and above the degree of synchronization or the properties of the media. As such, similar levels of activity may result in potentials that differ in several orders of magnitude in different populations. The geometry of these sources has been experimentally inaccessible until intracerebral high density recordings enabled the co-activating sources to be revealed. Without this information, it has proven difficult to interpret a century's worth of recordings that used temporal cues alone, such as event or spike related potentials and frequency bands. Meanwhile, a collection of biophysically ill-founded concepts have been considered legitimate, which can now be corrected in the light of recent advances. The relationship of LFPs to their sources is often counterintuitive. For instance, most LFP activity is not local but remote, it may be larger further from rather than close to the source, the polarity does not define its excitatory or inhibitory nature, and the amplitude may increase when source's activity is reduced. As technological developments foster the use of LFPs, the time is now ripe to raise awareness of the need to take into account spatial aspects of these signals and of the errors derived from neglecting to do so.

The European Federation of Organisations for Medical Physics. Policy Statement No. 7.1: The roles, responsibilities and status of the medical physicist including the criteria for the staffing levels in a Medical Physics Department approved by EFOMP Council on 5th February 2016.

This EFOMP Policy Statement is an amalgamation and an update of the EFOMP Policy Statements No. 2, 4 and 7. It presents guidelines for the roles, responsibilities and status of the medical physicist together with recommended minimum staffing levels. These recommendations take into account the ever-increasing demands for competence, patient safety, specialisation and cost effectiveness of modern healthcare services, the requirements of the European Union Council Directive 2013/59/Euratom laying down the basic safety standards for protection against the dangers arising from exposure to ionising radiation, the European Commission's Radiation Protection Report No. 174: "Guidelines on medical physics expert", as well as the relevant publications of the International Atomic Energy Agency. The provided recommendations on minimum staffing levels are in very good agreement with those provided by both the European Commission and the International Atomic Energy Agency.

Ionised concentrations in calcium and magnesium buffers: Standards and precise measurement are mandatory.

In Ca(2+) and Mg(2+) buffer solutions the ionised concentrations ([X(2+)]) are either calculated or measured. Calculated values vary by up to a factor of seven due to the following four problems: 1) There is no agreement amongst the tabulated constants in the literature. These constants have usually to be corrected for ionic strength and temperature. 2) The ionic strength correction entails the calculation of the single ion activity coefficient, which involves non-thermodynamic assumptions; the data for temperature correction is not always available. 3) Measured pH is in terms of activity i.e. pHa. pHa measurements are complicated by the change in the liquid junction potentials at the reference electrode making an accurate conversion from H(+) activity to H(+) concentration uncertain. 4) Ligands such as EGTA bind water and are not 100% pure. Ligand purity has to be measured, even when the [X(2+)] are calculated. The calculated [X(2+)] in buffers are so inconsistent that calculation is not an option. Until standards are available, the [X(2+)] in the buffers must be measured. The Ligand Optimisation Method is an accurate and independently verified method of doing this (McGuigan & Stumpff, Anal. Biochem. 436, 29, 2013). Lack of standards means it is not possible to compare the published [Ca(2+)] in the nmolar range, and the apparent constant (K(/)) values for Ca(2+) and Mg(2+) binding to intracellular ligands amongst different laboratories. Standardisation of Ca(2+)/Mg(2+) buffers is now essential. The parameters to achieve this are proposed.

Instrumented and interactive limb models for biomechanics education: An assessment of efficacy and engagement.

Custom anatomical and instrumented models of the human arm and leg were designed and manufactured to complement the teaching of introductory biomechanics subjects. The models were assessed for engagement and efficacy via questionnaires and unscheduled pop-quizzes, respectively. Questionnaire results demonstrated the ability of the models to provide assistance with understanding and visualising the fundamental principles of biomechanics. Additionally, the majority of students who participated also stated that the models enhanced their motivation to learn and stimulated their interest in biomechanics. Results from the pop-quizzes were ambiguous about the efficacy of the arm and leg models; only one group (out of five) showed significant improvements in pop-quiz scores following exposure to the models. Significance was not reached in the remaining groups. Further assessment is required to expose the true efficacy of the models.

Development of a mechanical testing and loading system for trabecular bone studies for long term culture.

A highly accurate (+/-3%) mechanical loading and measurement system combined with a trabecular bone diffusion culture-loading chamber has been developed, which provides the ability to study trabecular bone (and possibly) cartilage under controlled culture and loading conditions over long periods of time. The loading device has been designed to work in two main modes, either to apply a specific compressive strain to a trabecular bone cylinder or to apply a specific force and measure the resulting deformation. Presently, precisely machined bone cylinders can be loaded at frequencies between 0.1 Hz to 50 Hz and amplitudes over 7,000 microepsilon. The system allows accurate measurement of many mechanical properties of the tissue in real time, including visco-elastic properties. This paper describes the technical components, reproducibility, precision, and the calibration procedures of the loading system. Data on long term culture and mechanical responses to different loading patterns will be published separately.

Code of practice for brachytherapy physics: report of the AAPM Radiation Therapy Committee Task Group No. 56. American Association of Physicists in Medicine.

Recommendations of the American Association of Physicists in Medicine (AAPM) for the practice of brachytherapy physics are presented. These guidelines were prepared by a task group of the AAPM Radiation Therapy Committee and have been reviewed and approved by the AAPM Science Council.

On cochlear impedances and the miscomputation of power gain.

In their article, "Measurement of cochlear power gain in the sensitive gerbil ear," Ren et al. (Nat Commun 2:216, 2011) claim to provide "the first direct experimental evidence of power amplification in the sensitive living cochlea." While we recognize the technical challenges of the experiments and appreciate the beauty of the data, the authors' analysis and interpretation of the measurements are invalid. We review the concept of impedance (i.e., the ratio of pressure to velocity) as it applies to cochlear mechanics and show that Ren et al. mistakenly equate the impedances near the basilar membrane and stapes with the impedance characteristic of an infinite, uniform tube of fluid. As a consequence of this error, Ren et al.'s measurements and analysis provide no evidence for power amplification in the cochlea. Compelling evidence for power amplification has, however, been previously provided by others.

A framework for the definition of standardized protocols for measuring upper-extremity kinematics.

BACKGROUND: Increasing interest in upper extremity biomechanics has led to closer investigations of both segment movements and detailed joint motion. Unfortunately, conceptual and practical differences in the motion analysis protocols used up to date reduce compatibility for post data and cross validation analysis and so weaken the body of knowledge. This difficulty highlights a need for standardised protocols, each addressing a set of questions of comparable content. The aim of this work is therefore to open a discussion and propose a flexible framework to support: (1) the definition of standardised protocols, (2) a standardised description of these protocols, and (3) the formulation of general recommendations. METHODS: Proposal of a framework for the definition of standardized protocols. FINDINGS: The framework is composed by two nested flowcharts. The first defines what a motion analysis protocol is by pointing out its role in a motion analysis study. The second flowchart describes the steps to build a protocol, which requires decisions on the joints or segments to be investigated and the description of their mechanical equivalent model, the definition of the anatomical or functional coordinate frames, the choice of marker or sensor configuration and the validity of their use, the definition of the activities to be measured and the refinements that can be applied to the final measurements. Finally, general recommendations are proposed for each of the steps based on the current literature, and open issues are highlighted for future investigation and standardisation. INTERPRETATION: Standardisation of motion analysis protocols is urgent. The proposed framework can guide this process through the rationalisation of the approach.

Doppler and biophysical assessment in growth restricted fetuses: distribution of test results.

OBJECTIVE: Multi-vessel Doppler ultrasonography and biophysical profile scoring (BPS) are used in the surveillance of growth restricted fetuses (IUGR). The interpretation of both tests performed concurrently may be complex. This study examines the relationship between Doppler ultrasonography and biophysical test results in IUGR fetuses. METHODS: Three hundred and twenty-eight IUGR fetuses (abdominal circumference < 5th percentile, elevated umbilical artery (UA) pulsatility index (PI)) had concurrent surveillance with UA, middle cerebral artery (MCA) and ductus venosus (DV) Doppler ultrasonography and BPS (fetal tone, movement, breathing, maximal amniotic fluid pocket and fetal heart rate). Patients were stratified into three groups according to their Doppler examination: (1) abnormal UA alone; (2) brain sparing (MCA-PI > 2 SD below mean for gestational age); and (3) abnormal DV (PI > 2 SD above the mean for gestational age) and BPS groups: (1) normal (> 6/10); (2) equivocal (6/10); and (3) abnormal (< 6/10). Predictions of short-term perinatal outcomes by both modalities were compared for stratification. The distribution and concordance of Doppler and BPS test results were examined for the whole patient group and based on delivery prior to 32 weeks' gestation. RESULTS: Abnormal UA Doppler results alone were observed in 109 fetuses (33.2%), brain sparing in 87 (26.5%) and an abnormal DV in 132 (40.2%). The BPS was normal in 158 (48.2%), equivocal in 68 (20.7%) and abnormal in 102 (31.1%). Both testing modalities stratified patients into groups with comparable acid-base disturbance and perinatal outcome. Of the nine possible test combinations the largest subgroups were: abnormal UA alone/normal BPS (n = 69; 21%) and abnormal DV Doppler/abnormal BPS (n = 62; 18.9%). Assessment of compromise by both testing modalities was concordant in 146 (44.5%) cases. In 182 fetuses with discordant results the BPS grade was better in 115 (63.2%, P < 0.0001). Marked disagreement of test abnormality was present in 57 (17.4%) fetuses. Of these, abnormal venous Doppler in the presence of a normal BPS constituted the largest group (Chi-square P < 0.002). Stratification was not significantly different in patients delivered prior to 32 weeks' gestation. CONCLUSION: Doppler ultrasonography and BPS effectively stratify IUGR fetuses into risk categories, but Doppler and BPS results do not show a consistent relationship with each other. Since fetal deterioration appears to be independently reflected in these two testing modalities further research is warranted to investigate how they are best combined.

Science and standards. RF-hazards and standards: an historical perspective.

The following topics are discussed: Standard of safety considerations. Early efforts in bioengineering and biophysics before and after World War II, Work after World War II (1950s), Early interest in hazards, Soviet work and The Tri-Service area and ANSI. The author concludes that the historical development of biophysics and bioengineering, both as a whole and in the specialty area of nonionizing radiation, proceeded in a fairly rational fashion. Formulation of exposure standards in the West was based on the biophysical approach, which prevails in the interdisciplinary sciences involving biomedical and engineering disciplines. No pressure by an "industrial-military establishment" was evident in the quest for standards, and the Soviet approach and work were under surveillance from the late 1950's. A continuous interest in athermal effects has persisted since the 1930's. Historical accounts are based on personal experience and study of the literature. They are therefore limited to the extent that such experience and study is incomplete. The author had the good fortune to participate over a professional lifetime in the development of biophysical and biomedical engineering sciences, including those that address nonionizing radiation and Western standards of safety.