A finite element method for computational full two-body problem: I. The mutual potential and derivatives over bilinear tetrahedron elements Abstract A finite element method (FEM) for computing the gravitational interactions between two arbitrarily shaped celestial bodies is proposed. Expressions for the gravitational potential, attraction and torques are derived in terms of the finite element mesh division and mass density distribution. This method is implemented to a parallel-simulation package on a local cluster. Benchmarking tests are performed to confirm the convergence properties and to measure the computational costs. For a representative application, we construct the FEM model of the binary Near-Earth asteroid 65803 Didymos and simulate the coupled spin–orbit motion of its two components. The results show our method propagates the binary motion precisely, which is significantly dependent on the primary’s internal structure. In this numeric example, we show the finite element method is capable of modeling complex geometry and dissimilar material properties, which is useful to address questions in predicting the evolution of actual binary asteroids.

On the solution to every Lambert problem Abstract Lambert’s problem is the two-point boundary value problem for Keplerian dynamics. The parameter and solution space is surveyed for both the zero- and multiple-revolution problems, including a detailed look at the stress cases that typically plague Lambert solvers. The problem domain, independent of formulation, is shown to be rectangular for each revolution case, making the elusive initial guess and the solution itself amenable for interpolation. Biquintic splines are implemented to achieve continuous derivatives and quick evaluation. Resulting functions may be used directly as low-fidelity solutions or used with a single update iteration without safeguards. A concise, improved vercosine formulation of the Lambert problem is presented, including new singularity-free and precision-saving equations. The interpolation scheme is applied for up to 100 revolutions. The domain considered includes all practically conceivable flight times, and every possible geometry except a small region near the only physical singularity of the problem: the equal terminal vector case. The solutions are archived and benchmarked for accuracy, memory footprint, and speed. For typical scenarios, users can expect \(\sim 6\) or more digits of velocity vector accuracy using an interpolated solution without iteration. Using a single, unguarded iteration leads to solutions with near machine precision accuracy over the full domain, including the most extreme scenarios. Depending on desired resolution, coefficient files vary in size from \(\sim 3\) to 65 MB for each revolution case. Evaluation runtimes vary from \(\sim 2\) to 5 times faster than the industry benchmark Gooding algorithm. The coefficient files and driver routines are provided online. While the method is currently demonstrated on the vercosine formulation, the 2D interpolation scheme stands to benefit all Lambert problem formulations.

Charged dust close to outer mean-motion resonances in the heliosphere Abstract We investigate the dynamics of charged dust close to outer mean-motion resonances with planet Jupiter. The importance of the interplanetary magnetic field on the orbital evolution of dust is clearly demonstrated. New dynamical phenomena are found that do not exist in the classical problem of uncharged dust. We find changes in the orientation of the orbital planes of dust particles, an increased amount of chaotic orbital motions, sudden ’jumps’ in the resonant argument, and a decrease in time of temporary capture due to the Lorentz force. Variations in the orbital planes of dust grain orbits are found to be related to the angle between the orbital angular momentum and magnetic axes of the heliospheric field and the rotation rate of the Sun. These variations are bound using a simplified model derived from the full dynamical problem using the first-order averaging theory. It is found that the interplanetary magnetic field does not affect the capture process, that is still dominated by the other non-gravitational forces. Our study is based on a dynamical model in the framework of the inclined circular restricted three-body problem. Additional forces include solar radiation pressure, solar wind drag, the Poynting–Robertson effect, and the influence of a Parker spiral-type interplanetary magnetic field model. The analytical estimates are derived on the basis of Gauss’ form of planetary equations of motion. Numerical results are obtained by simulations of dust grain orbits together with the system of variational equations. Chaotic regions in phase space are revealed by means of fast Lyapunov chaos indicators.

A novel analytic continuation power series solution for the perturbed two-body problem Abstract Inspired by the original developments of recursive power series by means of Lagrange invariants for the classical two-body problem, a new analytic continuation algorithm is presented and studied. The method utilizes kinematic transformation scalar variables differentiated to arbitrary order to generate the required power series coefficients. The present formulation is extended to accommodate the spherical harmonics gravity potential model. The scalar variable transformation essentially eliminates any divisions in the analytic continuation and introduces a set of variables that are closed with respect to differentiation, allowing for arbitrary-order time derivatives to be computed recursively. Leibniz product rule is used to produce the needed arbitrary-order expansion variables. With arbitrary-order time derivatives available, Taylor series-based analytic continuation is applied to propagate the position and velocity vectors for the nonlinear two-body problem. This foundational method has been extended to also demonstrate an effective variable step size control for the Taylor series expansion. The analytic power series approach is demonstrated using trajectory calculations for the main problem in satellite orbit mechanics including high-order spherical harmonics gravity perturbation terms. Numerical results are presented to demonstrate the high accuracy and computational efficiency of the produced solutions. It is shown that the present method is highly accurate for all types of studied orbits achieving 12–16 digits of accuracy (the extent of double precision). While this double-precision accuracy exceeds typical engineering accuracy, the results address the precision versus computational cost issue and also implicitly demonstrate the process to optimize efficiency for any desired accuracy. We comment on the shortcomings of existing power series-based general numerical solver to highlight the benefits of the present algorithm, directly tailored for solving astrodynamics problems. Such efficient low-cost algorithms are highly needed in long-term propagation of cataloged RSOs for space situational awareness applications. The present analytic continuation algorithm is very simple to implement and efficiently provides highly accurate results for orbit propagation problems. The methodology is also extendable to consider a wide variety of perturbations, such as third body, atmospheric drag and solar radiation pressure.

The evolution of the Line of Variations at close encounters: an analytic approach Abstract We study the post-encounter evolution of fictitious small bodies belonging to the so-called Line of Variations (LoV) in the framework of the analytic theory of close encounters. We show the consequences of the encounter on the local minimum of the distance between the orbit of the planet and that of the small body and get a global picture of the way in which the planetocentric velocity vector is affected by the encounter. The analytical results are compared with those of numerical integrations of the restricted three-body problem.

Central configurations in planar n -body problem with equal masses for $$n=5,6,7$$ n = 5 , 6 , 7 Abstract We give a computer-assisted proof of the full listing of central configuration for n-body problem for Newtonian potential on the plane for \(n=5,6,7\) with equal masses. We show all these central configurations have a reflective symmetry with respect to some line. For \(n=8,9,10\) , we establish the existence of central configurations without any reflectional symmetry.

Analytic orbit theory with any arbitrary spherical harmonic as the dominant perturbation Abstract In the gravitational potential of Earth, the oblateness term is the dominant perturbation, with its coefficient at least three orders of magnitude greater than that of any other zonal or tesseral spherical harmonic. Therefore, analytic orbit theories (or satellite theories) are developed using the Keplerian Hamiltonian as the unperturbed solution, oblateness term as the first-order and the remaining spherical harmonics as the second-order perturbations. These orbit theories are generally constructed by applying multiple near-identity canonical transformations to the perturbed Hamiltonian in conjunction with averaging to obtain a secular Hamiltonian, from which the short-period and long-period terms are removed. If the oblateness term is the only first-order perturbation, then the long-period terms appear only in the second- or higher-order terms of the single-averaged Hamiltonian, from which the short-period terms are removed. These second-order long-period terms are separated from the Hamiltonian by the first-order generating function using a second canonical transformation. This results in a secular Hamiltonian dependent only on the momenta. However, in the case of other gravitational bodies with more deformed shapes compared to Earth such as moons and asteroids, the oblateness coefficient may have the same order of magnitude as some of the higher spherical harmonic coefficients. If these higher harmonics are treated as the first-order perturbation along with the oblateness term, then the long-period terms appear in the first-order single-averaged Hamiltonian. These first-order long-period terms cannot be separated using the generating function in the conventional way. This problem occurs because the zeroth-order Hamiltonian, i.e., the Keplerian part, is degenerate in the angular momentum. In this paper, a new approach to the long-period transformation is proposed to resolve this issue and obtain a fully analytic orbit theory when for the perturbing gravitational body, any arbitrary zonal or tesseral harmonic is the dominant perturbation. The proposed theory is closed form in the eccentricity as well. It is applied to predict the motion of artificial satellites for the two test cases: a lunar orbiter and a satellite of 433 Eros asteroid. The prediction accuracy is validated against the numerical propagation using a force model with \(6\times 6\) gravity field.

Structure of the centre manifold of the $$L_1,L_2$$ L 1 , L 2 collinear libration points in the restricted three-body problem Abstract We present a global analysis of the centre manifold of the collinear points in the circular restricted three-body problem. The phase-space structure is provided by a family of resonant 2-DOF Hamiltonian normal forms. The near 1:1 commensurability leads to the construction of a detuned Birkhoff–Gustavson normal form. The bifurcation sequences of the main orbit families are investigated by a geometric theory based on the reduction of the symmetries of the normal form, invariant under spatial mirror symmetries and time reversion. This global picture applies to any values of the mass parameter.

Phase space description of the dynamics due to the coupled effect of the planetary oblateness and the solar radiation pressure perturbations Abstract The aim of this work is to provide an analytical model to characterize the equilibrium points and the phase space associated with the singly averaged dynamics caused by the planetary oblateness coupled with the solar radiation pressure perturbations. A two-dimensional differential system is derived by considering the classical theory, supported by the existence of an integral of motion comprising semi-major axis, eccentricity and inclination. Under the single resonance hypothesis, the analytical expressions for the equilibrium points in the eccentricity-resonant angle space are provided, together with the corresponding linear stability. The Hamiltonian formulation is also given. The model is applied considering, as example, the Earth as major oblate body, and a simple tool to visualize the structure of the phase space is presented. Finally, some considerations on the possible use and development of the proposed model are drawn.

A new radial, natural, higher-order intermediary of the main problem four decades after the elimination of the parallax Abstract Simplifications in dealing with the equation of the center when the short-period effects are removed from a zonal Hamiltonian are commonly attributed to the elimination of parallactic terms. But this interpretation is incorrect, and the simplifications rather stem from the removal of concomitant long-period terms, an outcome that can also be achieved without need of eliminating the parallax. To show that, a Lie transforms simplification is invented that augments the exponents of the inverse of the radius and still achieves analogous simplifications in handling the equation of the center to those provided by the classical elimination of the parallax simplification. The particular case in which the new transformation does not modify the exponents of the parallactic terms of the original problem leads to a new intermediary of the main problem that, while keeping higher-order effects of \(J_2\) , is formally analogous to Cid’s first-order radial intermediary.

The Amaraughaprabodha: New Evidence on the Manuscript Transmission of an Early Work on Haṭha- and Rājayoga Abstract The Amaraughaprabodha is a Sanskrit Śaiva yoga text attributed by its colophons to Gorakṣanātha. It was first published by Kalyani Devi Mallik in 1954 and has been discussed in various secondary sources. Most notably, Christian Bouy (1994, pp. 18–19) identified this work as a source text for the Haṭhapradīpikā of Svātmārāma (mid-fifteenth century). This article presents new manuscript evidence for a shorter recension of the Amaraughaprabodha than the one published by Mallik. Comparing the differences between the short and long recensions reveals that the structure of the shorter one is more cohesive and closer to the original design of the work. The close relationship of the Amaraughaprabodha's short recension with an eleventh-century Vajrayāna work on yoga called the Amṛtasiddhi provides unique insights into how early teachings on Haṭhayoga were formulated. Although the practice of the physical techniques is largely the same in both texts, the author of the Amaraughaprabodha removed or obscured Vajrayāna terminology, added Śaiva metaphysics and framed Haṭhayoga as subordinate to a Śaiva yoga known as Rājayoga. This article proposes that the Amaraughaprabodha's short recension is probably the earliest known work to combine Haṭha- with Rājayoga, on the basis of this recension’s close relationship with the Amṛtasiddhi, its rudimentary nature and the likelihood that Svātmārāma used it, and not the long recension, for composing the Haṭhapradīpikā.

Vidyānandin’s Discussion with the Buddhist on Svasaṃvedana, Pratyakṣa and Pramāṇa Abstract Two of the terms in the title are from Vidyānandin’s Tattvārtha-śloka-vārttika (TAŚV, 1, 6, 11), which is his commentary on Umāsvāti’s Tattvārtha-sūtra (TAS). Sūtra 6 of the TAS states the following: pramāṇa-nayair adhigamaḥ, ‘knowledge—of the seven categories—is obtained through the pramāṇas and the nayas’). Vidyānandin’s commentary on this sūtra 6 entails a total of 56 ślokas, with his own prose vārttika on each of them in varying lengths. TAŚV 1, 6, 1–8 deal with particulars and universals, for which he uses the synonymous pairs aṃśa/aṃśin and avayava/avayavin. That he is attacking the Buddhist position regarding this age old theme in Indian philosophy, is evident also in that he quotes Dharmakīrti’s Pramāṇa-vārttika. By the time he comes to his TAŚV 1, 6, 6, he establishes that an object as a whole is open to perception and that the Buddhist also accepts perception as a valid means of knowledge, but does not accept the perception of an object as a whole. From TAŚV 1, 6, 11 onwards Vidyānandin continues with the same theme, elaborating his attack of the Buddhist view even further, doing so in terms of svasaṃvedana, pratyakṣa and pramāṇa (self-awareness, perception and valid means of knowledge). The presentation will attempt to deal with these concepts in order to see how Vidyānandin vindicates the Jaina position vis-à-vis the Buddhist one. This presentation will continue from my previous study of Vidyānandin’s TAŚV 1, 6, 1–10.

Is There Anything Like Indian Logic? Anumāna , ‘Inference’ and Inference in the Critique of Jayarāśi Bhaṭṭa Abstract The paper presents an analysis of the anumāna chapter of Jayarāśi’s Tattvôpaplava-siṁha and the nature of his criticism levelled against the anumāna model. The results of the analysis force us to revise our understanding of Jayarāśi Bhaṭṭa as a sceptic. Instead, he emerges as a highly critical (materialist) philosopher. In addition, the nature of Jayarāśi’s criticism of the anumāna model allow us to conclude that anumāna should not be equated with inference, but rather is its limited subset, and may at best be rendered as ‘disputational inference’, ‘debational inference’ or even ‘dialogical inference’. Jayarāśi applies a range of logical laws which clearly represent patterns of what can be classified as a priori reasoning (if we grant that there could be a priori justification for our knowledge at all) and analytical justifications for knowledge, which were traditionally not reckoned sound. Against the backdrop of Jayarāśi’s criticism of anumāna, the paper also attempts to provide an explanation to why Indian philosophy and logic did not develop any concept of proper symbols and variables.

A Buddhist Theory of Persistence: Śāntarakṣita and Kamalaśīla on Rebirth Abstract The so-called Buddhist momentarists (kṣaṇabhaṅgavādin or kṣaṇikavādin), such as Dharmakīrti and his followers, defend the momentariness of all things. However, with equal force they also defend the persistence of all things, not just within a single lifetime but over an indefinite cycle of rebirth. Naturally, they have an interesting theory of persistence, according to which things persist without being self-identical over time. The theory is best presented in the Lokāyatāparīkṣā chapter of Śāntarakṣita’s Tattvasaṃgraha and Kamalaśīla’s Paṅjikā, as they clearly articulate the criteria of persistence without identity. The purpose of this paper is to formulate a Buddhist theory of persistence through the analysis of these texts. Here is the basic formula: Things persist as series (santāna), which is constituted by momentary entities that are causally related as upādāna and upādeya. Upādāna causal relation is demarcated from other causal relations by the principle of changeability with temporal restriction (Ut), and the principle adopts further qualifications to accommodate complex cases and personal persistence. I have addressed a problem that contemporary physicalism might pose a threat to the Buddhist account of personal persistence, and argued that the problem can be evaded by regarding persons as psycho-physical entities rather than strictly non-physical. In its general outlook, the Buddhist theory of persistence is close to Theodore Sider’s stage theory in that persistence is a matter of distinct individuals standing in a special causal relationship. As regards personal persistence, the Buddhist has a stricter condition than Parfit’s IDM thesis, which states that psychological connectedness with any cause is what matters for survival. The Buddhist would say it is moral connectedness (a specific kind of psychological connectedness) with a special cause called upādāna.

Ritual, Self and Yoga: On the Ways and Goals of Salvation in the Kaṭha Upaniṣad Abstract Throughout its history, the renowned Kaṭha Upaniṣad has often been described as being both incoherent and contradictory. The aim of this paper is to show to what purpose the text was created. To this end, it discusses the connection of the three paths to salvation depicted in the text, viz. the Agnicayana (a powerful Vedic fire-ritual), the Upaniṣadic method of self-knowledge, and yoga. The first part retraces how in the Upaniṣads, the Agnicayana was transformed into a non-material or mental ritual and linked with self-knowledge. The second part analyses how the various salvation goals (heaven, the World of Brahman, liberation from rebirth) could be related to each other. First, the authors redefined the Agnicayana’s salvation goal, heaven, to make it identical with liberation. Secondly, they introduced self-knowledge and yoga as alternative and equally powerful means to the same end. In practice, however, the new and world-negating methods were implied to be superior to the costly ritual from which they had drawn their authority. Thus, the authors of the Upaniṣad were more concerned with showing continuity between different religious approaches than upholding consistency of content.

Abhinavagupta on Reflection ( Pratibimba ) in the Tantrāloka Abstract In the celebrated tantric manual, the Tantrāloka, Abhinavagupta (fl.c. 975–1025 CE) and his commentator Jayaratha (fl.c. 1225–1275 CE) establish a non-dual Śaiva theory of reflection (pratibimbavāda) (3.1-65) using the key metaphors of light (prakāśa) and reflective awareness (vimarśa). This paper attempts to explain the philosophical problem of reflection from the standpoint of these non-dual Śaivas. It also evaluates the problem in its hermeneutical context, analysing multiple layers of meaning and interpretation. Is the metaphor of reflection only a way of explaining the particular currents of the Śaiva phenomenology represented by the concepts of prakāśa and vimarśa? What philosophical problem does Abhinavagupta seek to solve by complicating the category of reflection and giving it a quasi-paradoxical status? Why does he use the model of the subtle elements (tanmātras) to explain the theory of reflection? What does the ‘untaintedness (nairmalya) of the mirror of consciousness’ mean for his system? These questions form the focus of this paper.

Ceṭṭiyār Vedānta: Fashioning Hindu Selves in Colonial South India Abstract This article seeks to pluralize current scholarly perceptions of what constitutes Advaita Vedānta in colonial India. It suggests, in particular, that the tendency to concentrate on the so-called “neo-Vedānta” of a handful of cosmopolitan reformers has obscured other kinds of innovative Vedānta-inspired discourses that have significantly shaped the formation of modern Hindu consciousness. These discourses are indebted, in ways that are only beginning to be understood, to religious traditions rooted in particular regions and vernacular languages. The article illustrates this argument with reference to the Kōvilūr Ātīṉam, a Vedānta-affiliated monastic institution in Tamil-speaking South India founded by Mutturāmaliṅka Ñāṉatēcika Cuvāmikaḷ (1791–1847). Examining the significance of this figure’s life story for the wealthy Nāṭṭukkōṭṭai Ceṭṭiyār merchant community that comprises the Ātīṉam’s social base, the article explores how social aspirations, traditions of monastic authority, and vernacular Vedāntic literature contribute toward a colonial project of caste self-fashioning that I refer to as “Ceṭṭiyār Vedānta”.

Studies on Bhartṛhari and the Pratyabhijñā: Language, Knowledge and Consciousness Abstract The article examines the impact the grammarian/philosopher Bhartṛhari (460–510) had on the way the ‘School of Recognition’ (Pratyabhijñā, tenth/eleventh c. CE) elaborated the notion that knowledge and consciousness have a close relationship with language. The paper first lays out Bhartṛhari’s ideas, showing that his theses are rationally defensible and philosophically refined. More specifically, it claims that the grammarian is defending a view which is in many respects similar to ‘higher-order theories’ of consciousness advanced by some contemporary philosophers of mind. In the second part, the paper shows how Utpaladeva and Abhinavagupta adopted Bhartṛhari’s scheme without significant alteration.

Mādhyamikas Playing Bad Hands: The Case of Customary Truth Abstract This article looks at the Indian canonical sources for Mādhyamika Buddhist refusals to personally endorse truth claims, even about customary matters. These sources, on a natural reading, seem to suggest that customary truth (saṃvṛtisatya) is only widespread error and that the Buddhist should do little more than duplicate, or acquiesce in, what the common man (or “the world”) recognizes (lokaprasiddha) about it. The combination of those Indian canonical themes probably contributed to frequent Indo-Tibetan Madhyamaka positions on truth, i.e., that the customary is no more than surface level truth, mere consensus amongst the mistaken, or, similarly, that there can be no right answers or truth claims to endorse about customary matters, as there are no sources of knowledge (tshad ma = pramāṇa) that have them as objects. Tsong kha pa and the dGe lugs pa, by contrast, adopted what I consider to be a philosophically more promising stance, one that recognized the need for a robust normativity: things customary are not just reduced to accepted errors; there are right answers about them that should be endorsed and may well defy current consensus of opinion. Not surprisingly, however, they needed a quite different and even strained exegesis of that same Indian textual legacy.

Non-existent Things as Subject of Inference in Bhāviveka’s Dacheng Zhangzhen Lun Abstract This paper is a preliminary study of Bhāviveka’s Svātantrika-Mādhyamika justifications for taking non-existent things as the subject (pakṣa) of an inference, based on his Dacheng Zhangzhen Lun (*Karatalaratna). Bhāviveka’s treatment of inference is similar to that of Dignāga in that the subject is required to be existent. Bhāviveka also holds that, in a conventional sense, words refer to universals and to the existent entities that possess them, while the two are cognised together. However, in his inference for the unreality of unconditioned things, he likens these things (the subject) to a sky-flower (the example, dṛṣṭānta) that never arises and is unreal even conventionally. This paper first demonstrates how taking unconditioned things (being non-existent) as the subject of an inference can be problematic for Bhāviveka. Then, it discusses Bhāviveka’s attempts to address the problems by subsuming the unconditioned things under the domain of conventional reality. The paper concludes that these attempts show his flexibility in terms of what is taken as conventionally real.

Ouabain Accelerates Collective Cell Migration Through a cSrc and ERK1/2 Sensitive Metalloproteinase Activity The original version of the article unfortunately contained an error in the author group. Dr. Isabel Larré was not submitted and published in the original version.

Prevailing Effects of Ibutilide on Fast Delayed Rectifier K + Channel Abstract Effects of ibutilide, a class III antiarrhythmic drug, on delayed rectifier potassium currents (IK) in freshly isolated guinea pig ventricular myocytes were studied. Experiments were performed using the whole-cell configuration of patch-clamp technique under blockade of L-type calcium currents (Cav1). Ibutilide at concentrations ranging between 10 nM and 100 µM inhibited IKr in dose-dependent manner with a half maximal effective concentration of 2.03 ± 0.74 µM (n = 5–10). The amplitude of tail currents activated by prepulse to + 20 mV was decreased from 253 ± 52 to 130 ± 25 pA (n = 8, p < 0.01) in the presence of 1 µM ibutilide. The envelope test revealed time-dependent changes in ratio of IK-tail/ΔIK during 0.2–2 s pulse durations in the absence of drug. With ibutilide, regardless of pulse duration, a relatively constant ratio was estimated, indicative of predominant involvement of IKr component. The slow IKs persisted to greater extent even at 100 μM ibutilide revealing a distinguishable selectivity toward the IKr component.

Role of Lipid Composition in the Interaction and Activity of the Antimicrobial Compound Fengycin with Complex Membrane Models Abstract Fengycins are compounds produced by bacteria of the Bacillus genus with strong antifungal activity. In this work, lipids extracted from fungal and oomycetal molds were used to assess the ability of fengycin to bind and insert into complex membrane models prepared as Langmuir lipid monolayers. In addition, fengycin-induced leakage in liposomes prepared from these complex lipid extracts was also evaluated. Fengycin’s ability to bind and incorporate into these membranes seemed to be mainly related to ergosterol content. Other membrane characteristics such as phospholipid fatty acyl chain length played a more peripheral role. A high ergosterol concentration appeared to allow other membrane characteristics generally associated with fengycin binding and/or insertion, such as higher proportion of phosphatidylcholine head groups or increased fatty acyl unsaturation, to be present without adversely affecting membrane integrity. Increased membrane leakage was also generally associated with the presence of low or no ergosterol. Leakage was also correlated with the previously reported biological activity of fengycin on these molds.

Comparative Proteomics Analysis of Four Commonly Used Methods for Identification of Novel Plasma Membrane Proteins Abstract Plasma membrane proteins perform a variety of important tasks in the cells. These tasks can be diverse as carrying nutrients across the plasma membrane, receiving chemical signals from outside the cell, translating them into intracellular action, and anchoring the cell in a particular location. When these crucial roles of plasma membrane proteins are considered, the need for their characterization becomes inevitable. Certain characteristics of plasma membrane proteins such as hydrophobicity, low solubility, and low abundance limit their detection by proteomic analyses. Here, we presented a comparative proteomics study in which the most commonly used plasma membrane protein enrichment methods were evaluated. The methods that were utilized include biotinylation, selective CyDye labeling, temperature-dependent phase partition, and density-gradient ultracentrifugation. Western blot analysis was performed to assess the level of plasma membrane protein enrichment using plasma membrane and cytoplasmic protein markers. Quantitative evaluation of the level of enrichment was performed by two-dimensional electrophoresis (2-DE) and benzyldimethyl-n-hexadecylammonium chloride/sodium dodecyl sulfate polyacrylamide gel electrophoresis (16-BAC/SDS-PAGE) from which the protein spots were cut and identified. Results from this study demonstrated that density-gradient ultracentrifugation method was superior when coupled with 16-BAC/SDS-PAGE. This work presents a valuable contribution and provides a future direction to the membrane sub-proteome research by evaluating commonly used methods for plasma membrane protein enrichment.

Direct Drug Targeting into Intracellular Compartments: Issues, Limitations, and Future Outlook Abstract Intracellular compartment drug delivery is a promising strategy for the treatment of diseases. By this way, medicines can delivered to particular intracellular compartments. This maximizes the therapeutic efficacy and safety of medicines, particularly of anticancer and antiviral drugs. Intracellular compartment drug delivery is either indirectly by targeting of cell nucleus as central compartment of the cell or directly through the targeting of compartments itself. Drugs or nanoshuttles labeled with compartment’s localization signal represent a smart tactic for subcellular compartment targeting. There are several boundaries prevent the arrival of shuttles to the specified intracellular compartments. These boundaries include selective permeability of biomembranes, efflux transporters, and lysosomes. The utilization of specific ligands during design of drug delivery nanoshuttles permits the targeting of specified intracellular compartment. Therefore drugs targeting could correct the diseases associated organelles. This review highlights the direct targeting of the medicines into subcellular compartment as a promising therapeutic strategy.

Ouabain Accelerates Collective Cell Migration Through a cSrc and ERK1/2 Sensitive Metalloproteinase Activity Abstract Studies made in the Madin-Darby canine kidney (MDCK) epithelial cell line showed that ouabain regulates cell adhesion and cell-adhesion-related biological processes, such as migration. Here, we demonstrated that 10 nM ouabain accelerates collective cell migration and heals wounds in cultured MDCK cell monolayers. Ouabain-induced acceleration of cell migration depends on activation of the cSrc-ERK1/2 signaling cascade, as it was inhibited by the kinase inhibitors PP2 and PD98059. Activation of the cSrc-ERK1/2 signaling cascade increased expression and activation of the extracellular matrix metalloproteinase-2 (MMP-2). Inhibition of MMP activity using the generic inhibitor GM6001 or the potent iMMP-2 inhibitor prevented the accelerative effect of ouabain. Likewise, Focal Adhesion Kinase (FAK) inhibition with the transfection of dominant negative peptide FRNK impaired the effect of ouabain. These results suggest that ouabain binding to the Na+,K+-ATPase accelerates collective migration of MDCK cells through activation of the cSrc-ERK1/2-FAK signaling cascade and promoting secretion and MMP activity.

Transport of Docosahexaenoic Acid via the Human Placenta: A Theoretical Study Abstract The high demand of the fetus for Docosahexaenoic acid, DHA, is satisfied by a concert of several mechanisms that take place in the placental terminal villi. Scarcity of laboratory data makes the detailed description of these mechanisms elusive. Here, the DHA transport across the placenta is modeled as a boundary value problem that accounts for diffusion, reactions with fatty acids binding proteins, FABPs, and metabolic consumption within the Syncytiotrophoblast, ST. For any given DHA fluxes at the bordering membranes, analytical and numerical solutions yield the DHA concentration profile within the ST. We find that in order to comply with adequate DHA delivery to the fetus and with physiological DHA concentrations in the maternal and fetal circulations, it is essential to have a significant rise of DHA concentration at the microvillus membrane, MVM and a rapid dissociation of the DHA from the FABP. The model establishes the relations between the concentrations of the FABPs in the ST, their equilibrium dissociation constant from the DHA, and the placental DHA metabolic degradation rate, hitherto unknown. We conclude that the bound (to the protein) DHA molecule is degraded at a rate of 0.3–0.45 s−1.

Synchronization Modulation of Na/K Pumps Induced Membrane Potential Hyperpolarization in Both Physiological and Hyperkalemic Conditions Abstract The capability of the synchronization modulation (SM) technique in enhancing the function of Na/K pumps has been demonstrated in various cells and tissues, including cardiomyocytes, a monolayer of cultured MDCK kidney cells, peripheral blood vessels, and frog skeletal muscles. This study characterized the membrane potential hyperpolarization induced by SM in both physiological and high [K+]o conditions on single skeletal muscle fibers. The results showed that SM could consistently induce membrane potential hyperpolarization by a few millivolts, and this hyperpolarization was not possible in the presence of ouabain. In contrast, the same electrical pulses but with random frequencies, constant frequencies, or synchronization with backward-modulation could not hyperpolarize the membrane potential. Prolonged field application and higher field intensity enhanced the effects of SM-induced hyperpolarization. Finally, the effect of SM was tested on skeletal muscle fibers incubated in a solution with high external potassium. Results showed that the SM electric field could hyperpolarize the membrane potential even if the external K+ concentration was higher than the normal, which implied the therapeutic effects of the SM electric field on the hyperkalemic situation.

Evidence to Suggest Bacterial Lipoprotein Diacylglyceryl Transferase (Lgt) is a Weakly Associated Inner Membrane Protein Abstract The unique and ubiquitous bacterial lipoprotein biosynthesis pathway is an attractive new antibiotic target. Crystal structures of its three biosynthetic enzymes have been solved recently. The first enzyme, Phosphatidylglycerol:proLipoprotein diacylglyceryl Transferase (Lgt), which initiates the post-translational modification at the metabolic interface of protein biosynthesis, phospholipid biosynthesis, protein secretion and lipid modification was reported to be a seven-transmembrane helical structure with a catalytic periplasmic head. Its complete solubilization in water or mild detergent in a fully active state, its chromatographic behaviour as an active monomer in the absence of detergent and recovery of active whole-length protein after proteolytic treatment of spheroplasts cast serious doubts about its proposed membrane association and orientation. Rather, it could be a seven-helical bundle partially embedded in the inner membrane’s inner leaflet aided by hydrophobic interaction. In fact, there are examples where originally reported seven-transmembrane proteins were later shown to be seven-helical peripheral membrane proteins based on solubilization criterion and re-analysis. Validated computational tool, Membrane Optimal Docking Area (MODA), also predicted a weaker association of Lgt’s helices with the membrane compared to typical transmembrane proteins. This insight is crucial to Lgt-based antibiotic design.

Life During Wartime: A Personal Recollection of the Circa 1990 Prestegard Lab and Its Contributions to Membrane Biophysics Abstract A subjective account is presented of challenges and excitement of being a postdoctoral trainee in the lab of James H. Prestegard at Yale University in New Haven, Connecticut from 1989 to 1991. This includes accounts of the early development of bicelles and of oriented sample NMR results that contributed to our modern understanding of the properties of the water–lipid interface of disordered phase biological membranes.

Time trends in oral bisphosphonate initiation in Ontario, Canada over 20 years reflect drug policy and healthcare delivery changes

Abstract

Summary

Characteristics of patients starting oral bisphosphonate therapy changed over time, reflecting trends in osteoporosis management (e.g., new drugs to market), and general healthcare delivery (e.g., benzodiazepine use declined, statin use increased). When designing studies that examine osteoporosis drug effects, potential time-related biases must be considered.

Introduction

To describe the type of oral bisphosphonate initiated and characteristics of patients starting oral bisphosphonate therapy over time.

Methods

We identified community-dwelling older adults (ages ≥ 66 years) initiating oral bisphosphonate therapy from April 1996 to March 2016 (1996 to 2015 fiscal years) using healthcare administrative data in Ontario. Patients with conditions other than osteoporosis that may impact bisphosphonate prescribing were excluded. The bisphosphonate initiated and patient characteristics were summarized by fiscal year and stratified by sex.

Results

We identified 560,817 eligible patients (81% women). Most patients initiated cyclical etidronate from 1996 until 2005, and then weekly regimens became dominant. In 2008, risedronate became the main oral bisphosphonate (46% risedronate, 43% alendronate, 11% etidronate); with its use increasing after availability of monthly and delayed-release risedronate formulations. In 2015, 71% of patients started risedronate, 28% started alendronate, and less than 2% started etidronate. Characteristics of patients changed over time, reflecting changes in osteoporosis management and general healthcare delivery. Over time, a larger proportion of men (9% to 28%) and patients with diabetes (women 10% to 17%, men 14% to 22%) initiated therapy; benzodiazepine (women 22% to 13%, men 20% to 10%) and estrogen-based hormone replacement therapy (12% to 15% of women 1996–2002 to 3% since 2008) decreased, while statin use increased (women 15% to 39%, men 14% to 52%).

Conclusions

The characteristics of patients starting oral bisphosphonate therapy have changed over time. Consideration must be given to these time trends when designing studies that examine osteoporosis drug effects.

Correction to: CD4 T cell count is positively associated with lumbar spine bone mass in HIV-infected men under the age of 50 years Two sentences in the Discussion section were incorrect.

Letter to the Editor about the article “A systematic review and meta-analysis of the effect of bisphosphonate drug holidays on bone mineral density and osteoporotic fracture risk”

FGF 23 and trabecular microarchitecture

FGF23 and bone microarchitecture

Revisit three “I” model: a novel five “I” model of fracture liaison service

Influence of fall environment and fall direction on risk of injury among pre-frail and frail adults Abstract Summary In this prospective study, half of all falls resulted in injury. Pre-frail adults sustained more injuries, while more frail adults had injuries requiring hospitalization or fractures. Pre-frail adults fell more often when in movement compared with frail adults who fell more often when standing and in indoor public spaces. Purpose To assess prospectively how fall environment and direction are related to injury among pre-frail and frail adults. Methods We included 200 community-dwelling adults with a prior fall (pre-frail, mean age 77 years) and 173 adults with acute hip fracture (frail, mean age 84 years; 77% community-dwelling). Falls were prospectively recorded using standardized protocols in monthly intervals, including date, time, fall direction and environment, and injury. We used logistic regression to assess the odds of injury adjusting for age, body mass index (BMI), and gender. Results We recorded 513 falls and 331 fall-related injuries (64.5%) among the 373 participants. While the fall rate was similar between groups, pre-frail adults had more injuries (71% among pre-frail vs. 56% among frail, p = 0.0004) but a lower incidence of major injuries (9% among pre-frail vs. 27% among frail, p = 0.003). Pre-frail adults fell more often while in movement (84% among pre-frail vs. 55% among frail, p < 0.0001), and frail adults fell more often while standing (26% vs. 15% respectively, p = 0.01). The odds of injury among frail adults was increased 3.3-fold when falling sideways (OR = 3.29, 95% CI = 1.68–6.45) and 2.4-fold when falling in an indoor public space (OR = 2.35, 95% CI = 1.00–5.53), and was reduced when falling at home (OR = 0.55, 95% CI = 0.31–0.98). The odds of injury among pre-frail adults was not influenced by environment and was 53% lower when falling backwards (OR = 0.47, 95% CI = 0.26–0.82). Conclusion While pre-frail adults sustain more fall-related injuries, frail adults were more likely to sustain major injuries, especially when falling sideways or outside their home.

Fracture prediction from self-reported falls in routine clinical practice: a registry-based cohort study Abstract Summary A simple question construct regarding number of falls in the previous year, ascertained by a single question, was strongly associated with incident fractures in routine clinical practice using a population-based dual-energy X-ray absorptiometry (DXA) registry. Introduction There is conflicting evidence from research cohorts that falls independently increase fracture risk. We examined the independent effects of falls on subsequent fractures in a large clinical registry of bone mineral density (BMD) results for the Province of Manitoba, Canada that has been systematically collecting self-reported falls information since September 1, 2012. Methods The study population consisted of 24,943 women and men aged 40 years and older (mean age 65.5 ± 10.2 years) with fracture probability assessment (FRAX), self-reported falls for the previous year (categorized as none, 1, 2, or > 3) and fracture outcomes. Adjusted hazard ratios (HR) with 95 confidence intervals (CI) for time to fracture were estimated using Cox proportional hazards models. Results During mean observation time of 2.7 ± 1.0 years, 863 (3.5%) sustained one or more major osteoporotic fractures (MOF), 212 (0.8%) sustained a hip fracture, and 1210 (4.9%) sustained any incident fracture. Compared with no falls in the previous year (referent), there was a gradient of increasing risk for fracture with increasing number of falls (all P < 0.001). Results showed minimal attenuation with covariate adjustment. When adjusted for baseline fracture probability (FRAX score with BMD) the HR for MOF increased from 1.49 (95% CI 1.25–1.78) for one fall to 1.74 (1.33–2.27) for two falls to 2.62 (2.06–3.34) for ≥ 3 falls. HRs were similar for any incident fracture and slightly greater for prediction of hip fracture, reaching 3.41 (95% CI 2.19–5.31) for ≥ 3 previous falls. Conclusions Self-report number of falls in the previous year is strongly associated with incident fracture risk in the routine clinical practice setting, and this risk is independent of age, sex, BMD, and baseline fracture probability. Moreover, there is dose–response with multiple falls (up to a maximum of 3) conferring greater risk than a single fall.

Effects of anti-osteoporosis medications on radiological and clinical results after acute osteoporotic spinal fractures: a retrospective analysis of prospectively designed study Abstract Summary Effects of anti-osteoporosis medications such as anti-resorptive and anabolic agents on healing of osteoporotic spinal fracture were retrospectively investigated. The use of anabolic agent significantly enhanced fracture healing, reduced progressive collapse, and presented good pain relief. These findings suggest that proper selection of medication could improve initial management of acute osteoporotic spinal fractures (OSFs). Introduction Although anti-osteoporosis medications have beneficial effects on prevention of osteoporotic spinal fractures (OSFs), few studies have compared effects of medications on fracture healing following OSFs. Therefore, the purpose of this study was to elucidate the effects of different anti-osteoporosis medications on radiological and clinical outcomes after acute OSFs. Methods A total of 132 patients diagnosed with acute OSFs were enrolled and allocated into three groups [group I (n = 39, no anti-osteoporosis medication), group II (n = 66, bisphosphonate), and group III (n = 27, parathyroid hormone (PTH)]. Radiological parameters including magnetic resonance (MR) classification, occurrence of intravertebral cleft (IVC), and clinical outcomes such as numerical rating scale (NRS) and Oswestry disability index were assessed. Risk analyses for IVC and progressive collapse were done along the related factors and medication type. Results IVC sign was observed in 30 patients. The rate of IVC sign was lower in group III (7.4%) than that in group I (20.5%) or group II (30.3%), although the difference was not statistically significant. Moreover, the degree of NRS improvement was better in group III than that in group I or group II (5.7 vs. 3.1 vs. 3.5, p < 0.001). On multiple regression analysis, mid-portion type fracture in MR classification was a significant risk factor for progressive OSFs. The use of PTH showed significant lower incidences of occurrence of IVC (odds ratio (OR) = 0.160) and increase in height loss (OR = 0.325). Conclusions Different anti-osteoporosis medications presented different clinical and radiological results after acute OSFs. The use of anabolic agent significantly enhanced fracture healing, reduced progressive collapse, and presented better clinical outcomes. Proper selection of medication might improve initial management of acute OSFs.

FRAX-based intervention and assessment thresholds for osteoporosis in Iran Abstract Summary We compared the utility of the current Iranian guidelines that recommend treatment in women with a T-score ≤ − 2.5 SD with a FRAX-based intervention threshold equivalent to women of average BMI with a prior fragility fracture. Whereas the FRAX-based intervention threshold identified women at high fracture probability, the T-score threshold was less sensitive, and the associated fracture risk decreased markedly with age. Introduction The fracture risk assessment algorithm FRAX® has been recently calibrated for Iran, but guidance is needed on how to apply fracture probabilities to clinical practice. Methods The age-specific ten-year probabilities of a major osteoporotic fracture were calculated in women with average BMI to determine fracture probabilities at two potential intervention thresholds. The first comprised the age-specific fracture probabilities associated with a femoral neck T-score of − 2.5 SD, in line with current guidelines in Iran. The second approach determined age-specific fracture probabilities that were equivalent to a woman with a prior fragility fracture, without BMD. The parsimonious use of BMD was additionally explored by the computation of upper and lower assessment thresholds for BMD testing. Results When a BMD T-score ≤ − 2.5 SD was used as an intervention threshold, FRAX probabilities in women aged 50 years was approximately two-fold higher than in women of the same age but with an average BMD and no risk factors. The relative increase in risk associated with the BMD threshold decreased progressively with age such that, at the age of 80 years or more, a T-score of − 2.5 SD was actually protective. The 10-year probability of a major osteoporotic fracture by age, equivalent to women with a previous fracture rose with age from 4.9% at the age of 50 years to 17%, at the age of 80 years, and identified women at increased risk at all ages. Conclusion Intervention thresholds based on BMD alone do not effectively target women at high fracture risk, particularly in the elderly. In contrast, intervention thresholds based on fracture probabilities equivalent to a “fracture threshold” target women at high fracture risk.

Multiple Group IRT Measurement Invariance Analysis of the Forms of Self-Criticising/Attacking and Self-Reassuring Scale in Thirteen International Samples Abstract The purpose of this study was to examine the measurement invariance of the Forms of Self-Criticising/Attacking & Self-Reassuring Scale (FSCRS) in terms of Item Response Theory differential test functioning in thirteen distinct samples (N = 7714) from twelve different countries. We assessed differential test functioning for the three FSCRS subscales, Inadequate-Self, Hated-Self and Reassured-Self separately. 32 of the 78 pairwise comparisons between samples for Inadequate-Self, 42 of the 78 pairwise comparisons for Reassured-Self and 54 of the 78 pairwise comparisons for Hated-Self demonstrated no differential test functioning, i.e. measurement invariance. Hated-Self was the most invariant of the three subscales, suggesting that self-hatred is similarly perceived across different cultures. Nonetheless, all three subscales of FSCRS are sensitive to cross-cultural differences. Considering the possible cultural and linguistic differences in the expression of self-criticism and self-reassurance, future analyses of the meanings and connotations of these constructs across the world are necessary in order to develop or tailor a scale which allows cross-cultural comparisons of various treatment outcomes related to self-criticism.

The Effect of Cognitive Behavioral Group Therapy on Infertility Stress, General Health, and Negative Cognitions: A Randomized Controlled Trial Abstract This study determined the effect of a cognitive behavioral group therapy (CBGT) program administered to infertile women on infertility-related stress, depressive and anxious thoughts, and general health state. A randomized controlled design was used for this study. The study was conducted with 107 infertile women: 55 in the experimental group and 52 in the control group. The CBGT was administered to the experimental group for 11 weeks. The pretest, posttest, and trimester follow-up results of this group were compared with those of the control group. The experimental group’s Fertility Problem Inventory pretest mean score was 188.47 ± 30.699, posttest mean score was 135.84 ± 22.571, and follow-up mean score was 140.61 ± 20.16. A statistically significant difference was found between the experimental and control groups’ pretest, posttest, and follow-up mean scores on depressive and anxious cognitions (CCL), FPI and its subscales, and the General Health Questionnaire-28 and its subscales (p < 0.05). The CBGT intervention reduced the infertility-related psychosocial problems experienced by infertile women and promoted improvement in their depressive and anxious cognitions, and their mental health.

Dysfunctional Beliefs and Personality Traits Abstract This study examined the pattern of associations between dimensions of personality dysfunction, dysfunctional beliefs, and adverse emotional outcomes. We recruited two samples of undergraduates (n = 167; n = 104). Dysfunctional beliefs showed positive correlations with pathological personality dimensions Negative Emotionality, Introversion, and Psychoticism, and negative correlations with Big Five dimensions of Emotional Stability, Conscientiousness, Openness, and Conscientiousness. Hierarchical regression analyses showed that dysfunctional beliefs are predictive of adverse emotional outcomes above and beyond dimensions of personality dysfunction. Dysfunctional beliefs also mediated the relationship between personality traits (Negative Emotionality, Emotional Stability) and important emotional outcomes like depression, anxiety, anger, demoralization and cynicism. The implication of the mediation analyses is that dimensions of personality (i.e., Negative Emotionality, Emotional Stability) have their effect on a variety of affective outcomes by operating through the mechanism of dysfunctional beliefs.

Self-Reported Dysfunctional Anger in Men and Women at a Psychiatric Outpatient Clinic Abstract Gender differences in anger and aggression are disputed in the literature. This study examined self-reported gender differences in a clinical sample of individuals referred for concerns about dysfunctional anger on measures of anger and aggression. The sample consisted of adults aged 18 years or over (N = 543; 90 [17%] women and 453 [83%] men) who presented at an outpatient anger clinic for treatment of their dysfunctional anger between 2003 and 2014. We found that women in the psychiatric outpatient sample significantly outscored men on many of the anger variables and reported similar levels of aggression, which contradicts previous reports in nonclinical populations. These results are of clinical importance because women’s dysfunctional anger may be under-reported. Dysfunctional anger screening and treatment may need to be adjusted accordingly based on gender.

Conceptual Confusion in Psychological Therapy: Towards a Taxonomy of Therapies Abstract This paper addresses confusion apparent in the discussion of psychological therapies. Such confusion relates to the differentiation, or lack of, of therapy constructs across categorical levels. Conceptual confusion is identified in terms of an apparent failure to differentiate theoretical frameworks of human functioning, specific therapy packages, and individual techniques from one another. Confusing to which level various concepts belong results in misunderstandings in psychological research, practice and education. The paper further sets out to provide a framework to help delineate these conceptual levels and to highlight the problems arising from confusing them.

Rational Emotive Digital Storytelling Therapy for Improving HIV/AIDS Knowledge and Risk Perception Among Schoolchildren: A Group Randomized Trial Abstract HIV/AIDS has remained a public health issue affecting both children and adults. Children including those in school settings are known to be at risk of contracting HIV/AIDS from numerous avenues which they may not have the knowledge. This study examined the effectiveness of rational emotive digital storytelling therapy (REDStory) on HIV/AIDS knowledge and risk perception among Nigerian schoolchildren. The design of the study was a group randomized trial design. A total of eighty schoolchildren participated in the study. For the collection of data, we utilized the HIV Knowledge Questionnaire (Carey and Schroder in AIDS Educ Prev 14:174–184, 2002) and the Perceived Risk of HIV Scale (Napper et al. in AIDS Behav 16(40):1075–1083, 2012). To analyze the collected data, we employed ANOVA with repeated-measures and t test statistics. The study post-treatment results showed that the REDStory intervention significantly improved the degree of knowledge and perception of risk of HIV/AIDS among the schoolchildren in the treatment group in comparison to those in the waitlisted control group. In addition, follow-up results showed that the schoolchildren in the treatment group maintained the significant effect which the REDStory intervention had on them with regard to improved knowledge and risk perception of HIV/AIDS. The study outcomes implies that the application of REDStory for improving knowledge and perception of risk of HIV/AIDS among Nigerian schoolchildren is beneficial and therefore warrants further clinical utility and adaptation.

Interconnections Among Perceived Stress, Social Problem Solving, and Gastrointestinal Symptom Severity Abstract Maladaptive social problem-solving (SPS) plays a significant mediating role in the negative impact of stressful life events on wellbeing. With a basis in D’Zurilla and Nezu’s (Problem-solving therapies, 2nd ed., The Guilford Press, New York, pp. 211–245, 2001) relational/problem-solving model of stress and wellbeing, we examined interrelations amongst stress, SPS, and gastrointestinal (GI) symptoms and tested several mediational models: maladaptive forms of SPS as mediators of the relationship between stress and GI symptoms, and stress as a mediator of maladaptive forms of SPS and GI symptoms. Undergraduates (N = 345) completed the Perceived Stress Scale, the Social Problem-Solving Inventory-Revised, and the Birmingham IBS Symptom Questionnaire. Pearson correlation coefficients revealed that all measures were significantly related in the expected directions. Stress was a significant mediator in the models with maladaptive SPS dimensions as independent variables, but SPS did not mediate the stress/GI symptom relationship. Results demonstrate links amongst stress, SPS, and GI symptoms, and suggest that poorer SPS leads to higher levels of stress, which, in turn, increases GI symptom severity.

How Can Stoic Philosophy Inspire Psychosocial Genetic Counseling Practice? An Introduction and Exploration Abstract Stoicism is an ancient philosophical tradition with the goal of teaching individuals how to live virtuously and attain tranquility. Stoicism was built upon the concept of fate and the limits of an individual’s power to change their fate (i.e. external circumstances). Many Stoic practices aim to remind oneself of the limits of their power and to shift one’s attention and concern to phenomena in which they have control. The goal is to cultivate a rational, healthy internal locus of control. There is minimal exploration of philosophical traditions in the genetic counseling literature, and Stoic practices may lend themselves to psychosocial genetic counseling work. Themes and applications of Stoic philosophy are explored here, and these practices may aid patients in developing an internal locus of control. The theme of reorienting one’s perception of control over their diagnosis, health, or situation may have benefit in patient psychosocial adaptation. This work serves to introduce genetic counselors to therapeutic applications of Stoic philosophy which may aid advanced counseling practice. We hope to stimulate future exploration and discussion regarding this and similar approaches in clinical genetic counseling.

Our Memories of Maxie C. Maultsby Jr. 1932–2016 Abstract In this article, the authors present the life and work of Dr. Maxie C. Maultsby, Jr, the most distinguished and influential black psychiatrist, as well as the founder of Rational Behavior Therapy (RBT), a comprehensive cognitive-behavioral therapeutic model. We document the pioneering ideas and concepts formulated by Dr. Maultsby and present RBT as a distinct form of theory-driven cognitive-behavior therapy, grounded in neurophysiology, its singular learning theory, unique concepts, and specific therapeutic techniques. His exceptional idealism of making mass mental health prevention and therapeutic interventions accessible to the underserved populations produced the unparalleled self-help features of RBT, allowing for its effectiveness and lasting results to be attainable to the average person. Dr. Maultsby was innovative in identifying clear criteria for healthy thinking that were empowering, patient-centered, and applicable to all forms of beliefs including spiritual, religious, existential, and deeply philosophical. His thorough knowledge of cognitive neuroscience and its underlying mechanisms of learning and re-learning of emotional habits gave rise to a radical reformulation of existing concepts like the traditional ABC model of emotions. This article is the first in a series about RBT and its founder.

Procrastination and Rational/Irrational Beliefs: A Moderated Mediation Model Abstract The present study focuses on the integrated effect of self-doubt, rational and irrational beliefs, and fear of failure on procrastination in a sample of Turkish undergraduate students (N = 293). The results confirm prior evidence indicating that self-doubt, fear of failure, and rational/irrational beliefs were important predictors of procrastination. The results show that (a) both self-doubt and irrational beliefs have direct and interactive effects on fear of failure, (b) fear of failure mediates the relationship between self-doubt and procrastination, (c) rational beliefs moderated the predictive effect of fear of failure on procrastination, and (d) the indirect effect of self-doubt on procrastination via fear of failure may vary depending on the level of rational and irrational beliefs. These findings suggest that future intervention attempts should focus on modifying irrational beliefs and enhancing rational beliefs to cope with procrastination.

Change in MRI findings of medial collateral ligament injury in adolescent baseball players with no clinical symptoms over time Abstract Objective Elbow screening of adolescent baseball players began in 2014 using ultrasound, palpation, and dedicated magnetic resonance imaging (MRI). We frequently encountered subjects showing MCL injury on MRI but no clinical symptoms. We assessed variations in asymptomatic MCL injury findings at follow-up MRI, and clarified the pathogenesis of these findings. Materials and methods Using a 0.2-T-dedicated MRI, 30 subjects with asymptomatic MCL injury at initial MRI who agreed to follow-up MRI were included. We classified the findings at repeat MRI as follows: (a) disappeared, (b) better, and (c) worse. Results There were 6, 16, and 8 subjects in groups a, b, and c, respectively. The average age at follow-up was 14.0, 12.1, and 12.4 years in groups a, b, and c, respectively. There were significant differences between groups a and b and between groups a and c. Average height at follow-up of groups a, b, and c was 1.64, 1.52, and 1.57 cm, respectively, with a statistically significant difference between groups a and b. The average size of the short axis of the MCL of subjects in group a was 2.0 cm on the dominant side and 1.5 cm on the contradominant side (P < 0.04). Conclusion Players with asymptomatic MCL injury can continue to play baseball with no limitations, as these findings usually disappear around the age of 14.0 years, when the growth spurt occurs. This finding may be a precursor of ‘adaptation’, which is generally observed in high school baseball players, suggesting that the MCL adapts as growth occurs.

Correction to: Ultrasound localization of lacerated flexor tendon ends in the hand: a cadaveric study In the results section of the abstract, it states “99.0% (n = 05/96 tendons)” when it should state “99.0% (n = 95/96 tendons)”.

Camptodactyly resulting from anatomical variation of lumbrical muscles: imaging findings Abstract We report three cases of camptodactyly in adolescent patients, presenting with a passive flexion deformity of the fifth finger. Ultrasound findings include aberrant lumbrical insertion and decreased lumbrical size, confirmed with magnetic resonance imaging, and aberrant dynamics. Surgery confirmed these findings in one patient. To the best of our knowledge, these imaging findings have not been reported previously.

Comparison of PSMA-PET/CT, choline-PET/CT, NaF-PET/CT, MRI, and bone scintigraphy in the diagnosis of bone metastases in patients with prostate cancer: a systematic review and meta-analysis Abstract Objective A systematic review and meta-analysis to compare the diagnostic performance of prostate-specific membrane antigen (PSMA)-PET/CT, choline-PET/CT, Sodium Fluoride (NaF) PET/CT, MRI, and bone scintigraphy (BS) in detecting bone metastases in patients with prostate cancer. Methods We searched PubMed and Embase for articles published between January 1990 and September 2018. Two evaluators independently extracted the sensitivity, specificity, the numbers of true and false positives, and true and false negatives. We calculated the pooled sensitivity, specificity, and 95% confidence intervals (CI) for each method. We calculated the tests’ diagnostic odds ratios (DOR); drew the summary receiver operating characteristic (SROC) curves; and obtained the areas under the curves (AUC), Q* values, and 95% CIs. Results The per-patient pooled sensitivities of PSMA-PET/CT, choline-PET/CT, NaF-PET/CT, MRI, and BS were 0.97, 0.87, 0.96, 0.91, and 0.86, respectively. The pooled specificities were 1.00, 0.99, 0.97, 0.96, and 0.95, respectively. The pooled DOR values were 504.16, 673.67, 242.63, and 114.44, respectively. The AUC were 1.00, 0.99, 0.99, 0.98, and 0.95, respectively. The per-lesion pooled sensitivities of PSMA-PET/CT, choline-PET/CT, NaF-PET/CT, MRI, and bone imaging were 0.88, 0.80, 0.97, 0.81 and 0.68, respectively. Conclusions According to the meta-analysis, PSMA-PET/CT had the highest per-patient sensitivity and specificity in detecting bone metastases with prostate cancer. The sensitivities of NaF-PET/CT and MRI were better than those for choline-PET/CT and BS. The specificity of PSMA-PET/CT was significantly better than BS. Others were similar. For per-lesion, NaF-PET/CT had the highest sensitivity, PSMA-PET/CT had higher sensitivity than choline-PET/CT and MRI, and BS had the lowest sensitivity.

Radiographic signs of hook of hamate fracture: evaluation of diagnostic utility Abstract Objective Hook of hamate fracture, the most common swing-related wrist fracture, is commonly seen in high-level athletes. The fracture is rarely diagnosed on routine wrist radiographs, thus generally requiring CT or MR for diagnosis. Surgical excision has a high success rate, however diagnostic delay contributes to a high complication rate. Radiographic signs of hook of hamate fracture have been published, but uncertainty of the diagnostic accuracy limits application. The purpose of this study is to determine accuracy and interobserver reliability of radiographic signs of hook of hamate. Materials and methods This retrospective case-control study evaluated wrist radiographs of 50 patients, including 24 positive and 26 negative, for hook of hamate fracture, each proven by CT or MR. Five reviewers performed blinded, randomized evaluation of radiographs documenting whether the hook of hamate was normal or fractured, and if fractured, the radiographic signs present (ring sign, ghostly shadow, and diffuse sclerosis) and views that contributed to diagnosis. Results Radiographic signs demonstrated high sensitivity (85%; 95% CI: 77–91), specificity (92%; 95% CI: 86–96), and accuracy (89%; 95% CI: 84–92) with substantial interobserver reliability (k = 0.652). The ring sign was the most sensitive radiographic sign. Diagnosis was most often supported by the oblique view (38%) and rarely the lateral view (15%). Conclusions Radiographic signs of hook of hamate fracture on routine radiographs can accurately and reliably diagnose hook of hamate fractures. Evaluation for discontinuity of the cortical ring will optimize sensitivity, allowing for timely diagnosis and treatment, and a reduction of complications.

Longitudinal MRI structural findings observed in accelerated knee osteoarthritis: data from the Osteoarthritis Initiative Abstract Objective To analyze structural, longitudinal MRI findings during the development of accelerated knee osteoarthritis (AKOA) over 4 years. Materials and methods From the Osteoarthritis Initiative (OAI), knees with no radiographic osteoarthritis (KL 0/1) developing advanced-stage osteoarthritis (KL 3/4; AKOA) within a 4-year (y) timeframe were selected. MRIs were graded using the modified Whole-Organ Magnetic Resonance Imaging Score (WORMS) at the beginning of the 4-year timeframe (index visit), at 2-year, and 4-year follow-up. Morphological and clinical findings associated with KL 3/4 onset within 2 years compared to 4 years were assessed using generalized estimating equations. Results AKOA was found in 162 knees of 149 subjects (age 63.25 ± 8.3; 103 females; BMI 29.4 ± 3.9). Moderate to severe meniscal lesions WORMS ≥ 3 were present in 25% (41/162) at the index visit, 64% (104/162) at 2-year and 93% (151/162) at 4-year follow-up. Meniscal extrusion was the most prevalent finding (ranging from 18% at the index visit, 45% at 2-year and 94% at 4-year follow-up) and root tears were the most common types of tears (9% at the index visit; 22% at 2 years and 38% at 4 years). Risk factors associated with KL 3/4 onset within 2 years included root tears at the index visit (adjusted OR, 2.82; 95% CI: 1.33, 6.00; p = 0.007) and incident knee injury (42%, 49/116 vs. 24%, 11/46, p = 0.032). Conclusions Meniscal abnormalities, in particular extrusion and root tears, were the most prevalent morphological features found in subjects with AKOA. These results suggest that meniscal abnormalities have a significant role in accelerated progression of OA.

Subchondral insufficiency fracture of the knee: grading, risk factors, and outcome Abstract Objective To propose an magnetic resonance imaging (MRI) grading system for subchondral insufficiency fracture of the knee (SIFK) to predict outcome and assess risk factors. Materials and methods A total of 50 SIFK patients were retrospectively reviewed utilizing two MRI examinations approximately a year apart and compared them with 51 control subjects. A grading system was introduced that classifies lesions as low- vs high-grade. Lesion location 3D dimensions, extent of bone marrow edema (BME), location of meniscal tears and associated extrusion, degree of chondrosis and among other parameters were stratified according to lesion grade and compared with follow-up examinations. Statistical analyses were performed (Pearson’s correlation, binary logistic regression, and Chi-squared analysis). Results The majority of SIFK lesions were low-grade (LG; 78%) and most of them (70%) were observed in the medial femoral condyle. Predictor variables comparing low-grade and high-grade SIFK lesions included meniscal tear (p = 0.01), degree of extrusion (p < 0.003), chondrosis (p = 0.01), medial chondrosis grade (p = 0.001), medial femoral condyle (p = 0.01), surface collapse (p < 0.0001), marrow edema improvement (p < 0.0001), first MRI anteroposterior dimension (p = 0.001), transverse dimension (p < 0.001), and ellipsoid volume (p = 0.02). Predictor variables found to be significantly different between controls and patients were meniscal tear (p = 0.024), location of the medial meniscal tear (p < 0.0001), degree of extrusion (p < 0.0001), chondrosis (p < 0.0001), joint effusion (p < 0.0001), Baker’s cyst (p < 0.0001), knee lock (p = 0.03) and buckle (p = 0.01), and history of trauma (p = 0.01). Conclusion A SIFK grading system for MRI is introduced. Surrogate markers of high-grade lesions include medial meniscus posterior root tears with associated moderate to severe extrusion, high-grade chondrosis, larger lesion sizes (anteroposterior/transverse), and articular surface collapse. Improvement of BME on follow-up was highly predictive of low-grade disease.

The Dixon technique for MRI of the bone marrow Abstract Dixon sequences are established as a reliable MRI technique that can be used for problem-solving in the assessment of bone marrow lesions. Unlike other fat suppression methods, Dixon techniques rely on the difference in resonance frequency between fat and water and in a single acquisition, fat only, water only, in-phase and out-of-phase images are acquired. This gives Dixon techniques the unique ability to quantify the amount of fat within a bone lesion, allowing discrimination between marrow-infiltrating and non-marrow-infiltrating lesions such as focal nodular marrow hyperplasia. Dixon can be used with gradient echo and spin echo techniques, both two-dimensional and three-dimensional imaging. Another advantage is its rapid acquisition time, especially when using traditional two-point Dixon gradient echo sequences. Overall, Dixon is a robust fat suppression method that can also be used with intravenous contrast agents. After reviewing the available literature, we would like to advocate the implementation of additional Dixon sequences as a problem-solving tool during the assessment of bone marrow pathology.

Dual-layer spectral computerized tomography for metal artifact reduction: small versus large orthopedic devices Abstract Introduction Metal artifacts limit the diagnostic utility of computerized tomography (CT) for implant-related complications. Dual-layer spectral detector CT imaging has been suggested for artifact reduction. Our objective was to evaluate the utility of spectral CT in artifact reduction in patients with small and large metal implants. Methods In this prospective study, patients with metallic orthopedic implants underwent CT imaging using a prototype spectral detector CT scanner. Conventional images were generated with iterative reconstruction at 120 kVp, and virtual monochromatic images were generated at 20-keV intervals between 40 to 200 keV. Conventional and monochromatic images were compared quantitatively using signal-to-noise ratio (SNR) and artifact improvement. Qualitative analysis was performed independently by two musculoskeletal radiologists and included six image quality indicators. Results A total of 12 patients were scanned. In monochromatic images, as the energy level increased, the artifact size decreased progressively (p < 0.01). When conventional and monochromatic images were compared, maximum reduction was seen at 200 keV. Using qualitative assessments, 160 and 180 keV levels had the best overall diagnostic image quality. With increased energy level, there was improvement in qualitative ratings of bone-metal interface conspicuity (p = 0.002), degree of streak artifact (p = 0.010) and trabecular bone definition at 1 cm from implant (p = 0.023), and a trend towards significance for bone definition at 5 cm, soft tissue detail and overall diagnostic quality. Subgroup analysis revealed superior artifact reduction in small implants compared to large hardware. Discussion Our results support the utility of dual-layer spectral CT in metal artifact reduction. Virtual monochromatic images were diagnostically superior, especially for smaller implants. Virtual monoenergetic images at 160–180 keV are ideal for reducing artifacts.

Clinical utility of virtual noncalcium dual-energy CT in imaging of the pelvis and hip Abstract Dual-energy virtual noncalcium images are increasingly used to identify marrow edema which accompanies bony pelvic injuries and marrow pathology obscured by cancellous bone. We present a clinical perspective of our experience using virtual noncalcium images in the work up of pelvic osseous pathology.

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