The neoteny goldilocks zone: The evolution of neoteny in Ambystoma.

Neoteny is a developmental strategy wherein an organism reaches sexual maturity without associated adult characteristics. In salamanders, neoteny takes the form of individuals retaining aquatic larval characteristics such as external gills upon maturation. Mole salamanders (Ambystoma) occupy a wide range of habitats and areas across the North American continent, and display examples of non-neotenic, facultatively neotenic and obligate neotenic species, providing high variation for investigating the factors influencing the evolution of neoteny. Here, we use phylogenetic comparative methods to test existing hypotheses that neoteny is associated with elevational and latitudinal distribution, cave-associated isolation, and hybridisation-related polyploidy. We also test if neoteny influences the diversity of habitats a species can occupy, since the restriction to an aquatic life should constrain the availability of different niches. We find that neoteny tends to occur in a narrow latitudinal band between 20-30° North, with particularly narrow latitudinal ranges for obligate compared to facultative neotenic species (16-52° North). We also find that facultatively neotenic species occur at elevations more than twice as high as other species on average, and that species with a higher frequency of neoteny typically have lower habitat diversity. Our results suggest that evolutionary transitions between non-neotenic and facultative neoteny states occur at relatively high and approximately equal rates. Moreover, we estimate that obligate neoteny cannot evolve directly from non-neotenic species (and vice versa), such that facultative neoteny acts as an evolutionary 'stepping stone' to and from obligate neoteny. However, our transition rate estimates suggest that obligate neoteny is lost >4-times faster than it evolves, partly explaining the rarity of obligate species. These results support the hypothesis that low latitudes favour the evolution of neoteny, presumably linked to more stable (aquatic) environments due to reduced seasonality, but once evolved it may constrain the diversity of habitats.

Translational eigenstates of He@C60 from four-dimensional ab initio potential energy surfaces interpolated using Gaussian process regression.

We investigate the endofullerene system 3He@C60 with a four-dimensional potential energy surface (PES) to include the three He translational degrees of freedom and C60 cage radius. We compare second order Møller-Plesset perturbation theory (MP2), spin component scaled-MP2, scaled opposite spin-MP2, random phase approximation (RPA)@Perdew, Burke, and Ernzerhof (PBE), and corrected Hartree-Fock-RPA to calibrate and gain confidence in the choice of electronic structure method. Due to the high cost of these calculations, the PES is interpolated using Gaussian Process Regression (GPR), owing to its effectiveness with sparse training data. The PES is split into a two-dimensional radial surface, to which corrections are applied to achieve an overall four-dimensional surface. The nuclear Hamiltonian is diagonalized to generate the in-cage translational/vibrational eigenstates. The degeneracy of the three-dimensional harmonic oscillator energies with principal quantum number n is lifted due to the anharmonicity in the radial potential. The (2l + 1)-fold degeneracy of the angular momentum states is also weakly lifted, due to the angular dependence in the potential. We calculate the fundamental frequency to range between 96 and 110 cm-1 depending on the electronic structure method used. Error bars of the eigenstate energies were calculated from the GPR and are on the order of ∼±1.5 cm-1. Wavefunctions are also compared by considering their overlap and Hellinger distance to the one-dimensional empirical potential. As with the energies, the two ab initio methods MP2 and RPA@PBE show the best agreement. While MP2 has better agreement than RPA@PBE, due to its higher computational efficiency and comparable performance, we recommend RPA as an alternative electronic structure method of choice to MP2 for these systems.

Exploring the parameter space of an endohedral atom in a cylindrical cavity.

Endohedral fullerenes, or endofullerenes, are chemical systems of fullerene cages encapsulating single atoms or small molecules. These species provide an interesting challenge of Potential Energy Surface determination as examples of non-covalently bonded, bound systems. While the majority of studies focus on C60 as the encapsulating cage, introducing some anisotropy by using a different fullerene, e.g., C70 can unveil a double well potential along the unique axis. By approximating the potential as a pairwise Lennard-Jones (LJ) summation over the fixed C cage atoms, the parameter space of the Hamiltonian includes three tunable variables: (M, ɛ, σ) representing the mass of the trapped species, the LJ energy, and length scales respectively. Fixing the mass and allowing the others to vary can imitate the potentials of endohedral species trapped in more elongated fullerenes. We choose to explore the LJ parameter space of an endohedral atom in C70 with ɛ ∈ [20, 150 cm-1], and σ ∈ [2.85, 3.05 Å]. As the barrier height and positions of these wells vary between [1, 264 cm-1] and [0.35, 0.85 Å] respectively, using a 3D direct product basis of 1D harmonic oscillator (HO) wavefunctions centred at the origin where there is a local maximum is unphysical. Instead we propose the use of a non-orthogonal basis set, using 1D HO wavefunctions centred in each minimum and compare this to other choices. The ground state energy of the X@C70 is tracked across the LJ parameter space, along with its corresponding nuclear translational wavefunctions. A classification of the wavefunction characteristics, namely the prolateness and "peanut-likeness" based on its statistical moments is also proposed. Excited states of longer fullerenes are assigned quantum numbers, and the fundamental transitions of Ne@C70 are tracked across the parameter space.

Transport characteristics of DNA-tagged silica colloids as a colloidal tracer in saturated sand columns; role of solution chemistry, flow velocity, and sand grain size.

In recent years, DNA-tagged silica colloids have been used as an environmental tracer. A major advantage of this technique is that the DNA-coding provides an unlimited number of unique tracers without a background concentration. However, little is known about the effects of physio-chemical subsurface properties on the transport behavior of DNA-tagged silica tracers. We are the first to explore the deposition kinetics of this new DNA-tagged silica tracer for different pore water chemistries, flow rates, and sand grain size distributions in a series of saturated sand column experiments in order to predict environmental conditions for which the DNA-tagged silica tracer can best be employed. Our results indicated that the transport of DNA-tagged silica tracer can be well described by first order kinetic attachment and detachment. Because of massive re-entrainment under transient chemistry conditions, we inferred that attachment was primarily in the secondary energy minimum. Based on calculated sticking efficiencies of the DNA-tagged silica tracer to the sand grains, we concluded that a large fraction of the DNA-tagged silica tracer colliding with the sand grain surface did also stick to that surface, when the ionic strength of the system was higher. The experimental results revealed the sensitivity of DNA-tagged silica tracer to both physical and chemical factors. This reduces its applicability as a conservative hydrological tracer for studying subsurface flow paths. Based on our experiments, the DNA-tagged silica tracer is best applicable for studying flow routes and travel times in coarse grained aquifers, with a relatively high flow rate. DNA-tagged silica tracers may also be applied for simulating the transport of engineered or biological colloidal pollution, such as microplastics and pathogens.

Music and low-frequency vibrations for the treatment of chronic musculoskeletal pain in elderly: A pilot study.

BACKGROUND: Transcutaneous vagal nerve stimulation has analgesic potential and might be elicited by abdominally administered low-frequency vibrations. The objective was to study the safety and effect of a combination of music and abdominally administered low-frequency vibrations on pain intensity in elderly patients with chronic musculoskeletal pain. METHODS: This trial was an international multicenter, randomized controlled pilot study. Patients at age ≥ 65 years with musculoskeletal pain for ≥ 3 months and a daily pain score ≥ 4 out of 10 were recruited at three centers. They were randomized to receive either a combination of music and low-frequency (20-100 Hz) vibrations administered to the abdomen, or a combination with the same music but with higher frequency (200-300 Hz) vibrations administered to the abdomen. Low-frequency vibrations were expected to result in pain reduction measured with a numeric pain rating scale (NRS). Patients in both groups received eight treatments of the music combined with the vibrations in three weeks. Primary outcomes were safety (Serious Adverse Events) and pain intensity measured at baseline, after the last treatment and at six weeks follow-up. Multilevel linear model analyses were performed to study group and time effects. RESULTS: A total of 45 patients were analyzed according to intention-to-treat principle. After 344 treatments, 1 Adverse Event was found related to the intervention, while 13 Adverse Events were possibly related. A multilevel linear model showed that the interaction effect of group by time did not predict pain intensity (F[1, 45.93] = 0.002, p = 0.97) when comparing pain intensity at baseline, after the last treatment and at follow-up. CONCLUSIONS: The combination of music and abdominally administered vibrations was found to be safe and well tolerated by the elderly patients. However, over time, neither the low-frequency treatment group nor the high-frequency treatment group provided clinically meaningful pain relief. There is no evidence that the low-frequency treatment elicited vagal nerve stimulation. TRIAL REGISTRATION: The trial was prospectively registered in the Netherlands Trial Register (NTR: NL7606) on 21-03-2019.

Transport of silica encapsulated DNA microparticles in controlled instantaneous injection open channel experiments.

Surface water tracing is a widely used technique to investigate in-stream mass transport including contaminant migration. Recently, a microparticle tracer was developed with unique synthetic DNA encapsulated in an environmentally-friendly silica coating (Si-DNA microparticle). Previous tracing applications of such tracers reported detection and quantification, but a massive loss of tracer mass. However, the transport behavior of these DNA-tagged microparticle tracers has not been rigorously quantified and compared with that of solute tracers. Therefore, we compared the transport behavior of Si-DNA microparticles to the behavior of solute NaCl in 6 different, environmentally representative water types using breakthrough curves (BTCs), obtained from laboratory open channel injection experiments, whereby no Si-DNA microparticle tracer mass was lost. Hereafter, we modelled the BTCs using a 1-D advection-dispersion model with one transient storage zone (OTIS) by calibrating the hydrodynamic dispersion coefficient D and a storage zone exchange rate coefficient. We concluded that the transport behavior of Si-DNA microparticles resembled that of NaCl in surface-water relevant conditions, evidenced by BTCs with a similar range of D; however, the Si-DNA microparticle had a more erratic BTC than its solute counterpart, whereby the scatter increased as a function of water quality complexity. The overall larger confidence interval of DSi-DNA was attributed to the discrete nature of colloidal particles with a certain particle size distribution and possibly minor shear-induced aggregations. This research established a solid methodological foundation for field application of Si-DNA microparticles in surface water tracing, providing insight in transport behavior of equivalent sized and mass particles in rivers.

Machine Learning: New Potential for Local and Regional Deep-Seated Landslide Nowcasting.

Nowcasting and early warning systems for landslide hazards have been implemented mostly at the slope or catchment scale. These systems are often difficult to implement at regional scale or in remote areas. Machine Learning and satellite remote sensing products offer new opportunities for both local and regional monitoring of deep-seated landslide deformation and associated processes. Here, we list the key variables of the landslide process and the associated satellite remote sensing products, as well as the available machine learning algorithms and their current use in the field. Furthermore, we discuss both the challenges for the integration in an early warning system, and the risks and opportunities arising from the limited physical constraints in machine learning. This review shows that data products and algorithms are available, and that the technology is ready to be tested for regional applications.

Unbiased atomistic insight in the competing nucleation mechanisms of methane hydrates.

Methane hydrates have important industrial and climate implications, yet their formation via homogeneous nucleation under natural, moderate conditions is poorly understood. Obtaining such understanding could lead to improved control of crystallization, as well as insight into polymorph selection in general, but is hampered by limited experimental resolution. Direct molecular dynamics simulations using atomistic force fields could provide such insight, but are not feasible for moderate undercooling, due to the rare event nature of nucleation. Instead, we harvest ensembles of the rare unbiased nucleation trajectories by employing transition path sampling. We find that with decreasing undercooling the mechanism shifts from amorphous to crystalline polymorph formation. At intermediate temperature the 2 mechanisms compete. Reaction coordinate analysis reveals the amount of a specific methane cage type is crucial for crystallization, while irrelevant for amorphous solids. Polymorph selection is thus governed by kinetic accessibility of the correct cage type and, moreover, occurs at precritical nucleus sizes, apparently against Ostwald's step rule. We argue that these results are still in line with classical nucleation theory. Our findings illuminate how selection between competing methane hydrate polymorphs occurs and might generalize to other hydrates and molecular crystal formation.

Large scale parallelization in stochastic coupled cluster.

Coupled cluster theory is a vital cornerstone of electronic structure theory and is being applied to ever-larger systems. Stochastic approaches to quantum chemistry have grown in importance and offer compelling advantages over traditional deterministic algorithms in terms of computational demands, theoretical flexibility, or lower scaling with system size. We present a highly parallelizable algorithm of the coupled cluster Monte Carlo method involving sampling of clusters of excitors over multiple time steps. The behavior of the algorithm is investigated on the uniform electron gas and the water dimer at coupled-cluster levels including up to quadruple excitations. We also describe two improvements to the original sampling algorithm, full non-composite, and multi-spawn sampling. A stochastic approach to coupled cluster results in an efficient and scalable implementation at arbitrary truncation levels in the coupled cluster expansion.

Auditing local methods for quality assurance in radiotherapy using the same set of predefined treatment plans.

BACKGROUND AND PURPOSE: Local implementation of plan-specific quality assurance (QA) methods for intensity-modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT) treatment plans may vary because of dissimilarities in procedures, equipment and software. The purpose of this work is detecting possible differences between local QA findings and those of an audit, using the same set of treatment plans. METHODS: A pre-defined set of clinical plans was devised and imported in the participating institute's treatment planning system for dose computation. The dose distribution was measured using an ionisation chamber, radiochromic film and an ionisation chamber array. The centres performed their own QA, which was compared to the audit findings. The agreement/disagreement between the audit and the institute QA results were assessed along with the differences between the dose distributions measured by the audit team and computed by the institute. RESULTS: For the majority of the cases the results of the audit were in agreement with the institute QA findings: ionisation chamber: 92%, array: 88%, film: 76% of the total measurements. In only a few of these cases the evaluated measurements failed for both: ionisation chamber: 2%, array: 4%, film: 0% of the total measurements. CONCLUSION: Using predefined treatment plans, we found that in approximately 80% of the evaluated measurements the results of local QA of IMRT and VMAT plans were in line with the findings of the audit. However, the percentage of agreement/disagreement depended on the characteristics of the measurement equipment used and on the analysis metric.

Radiographic Evaluation of Intermetatarsal Angle Correction Following First MTP Joint Arthrodesis for Severe Hallux Valgus.

BACKGROUND: Arthrodesis is a standard operative treatment for symptomatic arthritis of the first metatarsophalangeal (MTP) joint. Patients with degenerative joint disease (DJD), severe hallux valgus, and metatarsus primus varus may also require fusion of the first MTP joint. An important question in the latter group of patients is whether a proximal first metatarsal osteotomy is required, in addition to the first MTP joint fusion. Our hypothesis was that patients with severe hallux valgus and metatarsus primus varus, treated with first MTP joint arthrodesis alone, would have correction of the first-to-second intermetatarsal angle (1-2 IMA) and hallux valgus angle (HVA) to near population norms, without the addition of a proximal first metatarsal osteotomy. METHODS: Preoperative and postoperative radiographs of 19 feet, in 17 patients, with preoperative IMA greater than 15 were analyzed. Weight-bearing radiographs were divided into pre- and postoperative cohorts. Three independent reviewers measured these radiographs and mean 1-2 IMA and HVA were calculated. Mean follow-up was 10 months. RESULTS: The mean preoperative 1-2 IMA was 19.2 degrees (15.6-24.3). The mean preoperative HVA was 48.5 (36-56.6). The mean postoperative values for 1-2 IMA and HVA were 10.8 and 12.3 degrees, respectively. The mean change in IMA was 8.3 degrees and in the hallux valgus angle was 36.4 degrees. The differences between pre- and postoperative measurement for both angles were statistically significant (P < .001). Seven of 19 (37%) feet were corrected to an IMA of less than 9 degrees (normal), whereas in 15/19 feet the postoperative IMA was 12.3 degrees or less. The postoperative HVA was less than 15 degrees in 15/19 (79%) feet. CONCLUSION: This pre- and postoperative radiographic analysis of patients with severe bunion deformity demonstrated that HVA and 1-2 IMA were acceptably corrected without the addition of a proximal first metatarsal osteotomy. LEVEL OF EVIDENCE: Level III, retrospective comparative series.

Understanding and improving the efficiency of full configuration interaction quantum Monte Carlo.

Within full configuration interaction quantum Monte Carlo, we investigate how the statistical error behaves as a function of the parameters which control the stochastic sampling. We define the inefficiency as a measure of the statistical error per particle sampling the space and per time step and show there is a sizeable parameter regime where this is minimised. We find that this inefficiency increases sublinearly with Hilbert space size and can be reduced by localising the canonical Hartree-Fock molecular orbitals, suggesting that the choice of basis impacts the method beyond that of the sign problem.

Linked coupled cluster Monte Carlo.

We consider a new formulation of the stochastic coupled cluster method in terms of the similarity transformed Hamiltonian. We show that improvement in the granularity with which the wavefunction is represented results in a reduction in the critical population required to correctly sample the wavefunction for a range of systems and excitation levels and hence leads to a substantial reduction in the computational cost. This development has the potential to substantially extend the range of the method, enabling it to be used to treat larger systems with excitation levels not easily accessible with conventional deterministic methods.

Minimising biases in full configuration interaction quantum Monte Carlo.

We show that Full Configuration Interaction Quantum Monte Carlo (FCIQMC) is a Markov chain in its present form. We construct the Markov matrix of FCIQMC for a two determinant system and hence compute the stationary distribution. These solutions are used to quantify the dependence of the population dynamics on the parameters defining the Markov chain. Despite the simplicity of a system with only two determinants, it still reveals a population control bias inherent to the FCIQMC algorithm. We investigate the effect of simulation parameters on the population control bias for the neon atom and suggest simulation setups to, in general, minimise the bias. We show a reweight ing scheme to remove the bias caused by population control commonly used in diffusion Monte Carlo [Umrigar et al., J. Chem. Phys. 99, 2865 (1993)] is effective and recommend its use as a post processing step.

A short-term rural placement can change metropolitan medical students' knowledge of, and attitudes to, rural practice.

OBJECTIVE: To determine whether a short-term placement of metropolitan medical students in a rural environment can improve their knowledge of, and change their attitudes to, rural health issues. DESIGN AND PARTICIPANTS: Medical students taking part in the March and May 2013 3-week Rural Health Modules (RHMs) were invited to participate in focus groups and complete questionnaires before undertaking the RHM, after a 2-day rural orientation and at the end of the RHM. Students were asked to comment on a range of issues affecting rural health care including their attitude to pursuing a rural career. Focus group transcripts were thematically analysed and questionnaire data were statistically analysed. SETTING: The RHM is a 3-week program designed and run by the University of Melbourne's Rural Health Academic Centre. MAIN OUTCOME MEASURES: Responses to questionnaire items from before and after completing the RHM, scored on a seven-point Likert scale. RESULTS: 69 of the 101 RHM students took part in this study. The focus groups identified five main themes in rural health care: access; teamwork, models of care and generalist practice; overlapping relationships; indigenous health; and working in a rural career. In all five areas, a change was seen in the depth of knowledge students had about these issues and in the students' attitudes towards rural health care. The questionnaires also showed a significant shift in the students' appreciation of, and positivity towards, rural health issues. CONCLUSION: Undertaking a 3-week RHM changed students' perceptions of rural health and significantly improved their knowledge of issues facing rural health practitioners and patients.

The caudate: a key node in the neuronal network imbalance of insomnia?

Insomnia is prevalent, severe and partially heritable. Unfortunately, its neuronal correlates remain enigmatic, hampering the development of mechanistic models and rational treatments. Consistently reported impairments concern fragmented sleep, hyper-arousal and executive dysfunction. Because fronto-striatal networks could well play a role in sleep, arousal regulation and executive functioning, the present series of studies used an executive task to evaluate fronto-striatal functioning in disturbed sleep. Patients with insomnia showed reduced recruitment of the head of the left caudate nucleus during executive functioning, which was not secondary to altered performance or baseline perfusion. Individual differences in caudate recruitment were associated with hyper-arousal severity. Seed-based functional connectivity analysis suggested that attenuated input from a projecting orbitofrontal area with reduced grey matter density contributes to altered caudate recruitment in patients with insomnia. Attenuated caudate recruitment persisted after successful treatment of insomnia, warranting evaluation as a potential vulnerability trait. A similar selective reduction in caudate recruitment could be elicited in participants without sleep complaints by slow-wave sleep fragmentation, providing a model to facilitate investigation of the causes and consequences of insomnia.

Radiographic correction of stage III posterior tibial tendon dysfunction with a modified triple arthrodesis.

BACKGROUND: The literature supports fusion as the surgical treatment of choice for stage III posterior tibial tendon dysfunction (PTTD). The present study reports the radiographic correction following a modified triple arthrodesis (fusions of the subtalar, talonavicular, and first tarsometatarsal joints) in patients with stage III PTTD. METHODS: An institutional review board-approved retrospective study was performed to assess the radiographic outcome of a modified triple arthrodesis in 21 patients (22 feet). Pre- and postoperative weight-bearing radiographs were reviewed in a blinded fashion by clinicians of varying levels of training. The talo-first metatarsal, talocalcaneal, and talonavicular coverage angles were measured on anteroposterior views. On lateral views, the talo-first metatarsal (Meary's), talocalcaneal, calcaneal pitch, and talar declination angles and the medial cuneiform to floor distance were measured. Statistical analysis was performed to compare pre- and postoperative measurements, assess the degree of correction, and determine interobserver reliability of the radiographic measurements. RESULTS: All measurements improved significantly after treatment with a modified triple arthrodesis (P ≤ .001). The medial cuneiform to floor distance (0.910), talonavicular coverage angle (0.896), and lateral talo-first metatarsal angle (0.873) were the most reproducible between observers. Postoperatively, 100% of feet were corrected to normal medial cuneiform to floor distance and talonavicular coverage angle, and 90.9% were corrected to a normal lateral talo-first metatarsal angle. CONCLUSION: The modified triple arthrodesis resulted in a reliable and reproducible correction of the deformity seen in rigid stage III PTTD. LEVEL OF EVIDENCE: Level IV, case series.

Lateral ankle radiographs: do we really understand what we are seeing?

OBJECTIVES: To evaluate the validity of using lateral intraoperative fluoroscopic imaging to assess the reduction of the tibial plafond articular surface, two hypotheses were tested: 1) the distal tibial subchondral shadow on the lateral ankle radiograph is created equally by the medial, central, and lateral portions of the distal tibia; and (2) displacement of a 5-mm width osteochondral fragment is consistently recognizable on lateral fluoroscopic imaging. METHODS: Six human fresh-frozen tibial plafond cadaveric specimens were sagitally sectioned in 5-mm increments after removal of the anterior soft tissue and stabilization of the position of the ankle through external fixation. To test the first hypothesis, a perfect lateral radiograph was taken after sectioning the specimens. The sagittal sections were then removed sequentially from medial to lateral. A perfect lateral radiograph was taken after each change. The sagittal sections were then removed beginning laterally and moving medially. A perfect lateral radiograph was taken after each change. The images were then compared with specific evaluation of the change in the subchondral shadow density. To test the second hypothesis, three malreductions were created by displacing a 5-mm osteochondral segment. After each malreduction, a perfect lateral radiograph was saved. These saved fluoroscopic images were placed in random order with lateral images of normal specimens. Four experienced ankle surgeons were then asked to determine whether the radiographs revealed displacement. Inter- and intraobserver reliability was then evaluated. RESULTS: First, the subchondral shadow of the distal tibia appears to be created by an equal confluence of the subchondral bone of the medial, central, and lateral aspects of the tibial plafond. Second, fellowship-trained observers experienced in pilon fracture treatment correctly identified malreduction only 45% of the time. Intraclass correlation coefficient revealed very poor interobserver reliability with an alpha reliability statistic of 0.183. Intraobserver reliability across all four observers yielded an alpha statistic of 0.474, indicating inconsistencies in observers' evaluation of identical images at separate viewings. CONCLUSIONS: It is difficult to discern rotational or translational displacement of a 5-mm osteochondral fragment on a perfect lateral fluoroscopic view of the ankle. Even with what appears to be a perfect lateral fluoroscopic view intraoperatively, displacement may still be present. When small osteochondral fragments are present, direct visualization of the articular surface is necessary to confidently establish that an anatomic reduction has been achieved.