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It remains unclear which individuals with subthreshold depression benefit most from psychological intervention, and what long-term effects this has on symptom deterioration, response and remission.
Aims
To synthesise psychological intervention benefits in adults with subthreshold depression up to 2 years, and explore participant-level effect-modifiers.
Method
Randomised trials comparing psychological intervention with inactive control were identified via systematic search. Authors were contacted to obtain individual participant data (IPD), analysed using Bayesian one-stage meta-analysis. Treatment–covariate interactions were added to examine moderators. Hierarchical-additive models were used to explore treatment benefits conditional on baseline Patient Health Questionnaire 9 (PHQ-9) values.
Results
IPD of 10 671 individuals (50 studies) could be included. We found significant effects on depressive symptom severity up to 12 months (standardised mean-difference [s.m.d.] = −0.48 to −0.27). Effects could not be ascertained up to 24 months (s.m.d. = −0.18). Similar findings emerged for 50% symptom reduction (relative risk = 1.27–2.79), reliable improvement (relative risk = 1.38–3.17), deterioration (relative risk = 0.67–0.54) and close-to-symptom-free status (relative risk = 1.41–2.80). Among participant-level moderators, only initial depression and anxiety severity were highly credible (P > 0.99). Predicted treatment benefits decreased with lower symptom severity but remained minimally important even for very mild symptoms (s.m.d. = −0.33 for PHQ-9 = 5).
Conclusions
Psychological intervention reduces the symptom burden in individuals with subthreshold depression up to 1 year, and protects against symptom deterioration. Benefits up to 2 years are less certain. We find strong support for intervention in subthreshold depression, particularly with PHQ-9 scores ≥ 10. For very mild symptoms, scalable treatments could be an attractive option.
The Hippoboscidae are ectoparasites of birds and mammals, which, as a group, are known to vector multiple diseases. Avipoxvirus (APV) is mechanically vectored by various arthropods and causes seasonal disease in wild birds in the United Kingdom (UK). Signs of APV and the presence of louse flies (Hippoboscidae) on Dunnocks Prunella modularis were recorded over a 16·5-year period in a rural garden in Somerset, UK. Louse flies collected from this site and other sites in England were tested for the presence of APV DNA and RNA sequences. Louse flies on Dunnocks were seen to peak seasonally three weeks prior to the peak of APV lesions, an interval consistent with the previously estimated incubation period of APV in Dunnocks. APV DNA was detected on 13/25 louse flies, Ornithomya avicularia and Ornithomya fringillina, taken from Dunnocks, both with and without lesions consistent with APV, at multiple sites in England. Collectively these data support the premise that louse flies may vector APV. The detection of APV in louse flies, from apparently healthy birds, and from sites where disease has not been observed in any host species, suggests that the Hippoboscidae could provide a non-invasive and relatively cheap method of monitoring avian diseases. This could provide advanced warnings of disease, including zoonoses, before they become clinically apparent.
Objectives/Goals: Manual skin assessment in chronic graft-versus-host disease (cGVHD) can be time consuming and inconsistent (>20% affected area) even for experts. Building on previous work we explore methods to use unmarked photos to train artificial intelligence (AI) models, aiming to improve performance by expanding and diversifying the training data without additional burden on experts. Methods/Study Population: Common to many medical imaging projects, we have a small number of expert-marked patient photos (N = 36, n = 360), and many unmarked photos (N = 337, n = 25,842). Dark skin (Fitzpatrick type 4+) is underrepresented in both sets; 11% of patients in the marked set and 9% in the unmarked set. In addition, a set of 20 expert-marked photos from 20 patients were withheld from training to assess model performance, with 20% dark skin type. Our gold standard markings were manual contours around affected skin by a trained expert. Three AI training methods were tested. Our established baseline uses only the small number of marked photos (supervised method). The semi-supervised method uses a mix of marked and unmarked photos with human feedback. The self-supervised method uses only unmarked photos without any human feedback. Results/Anticipated Results: We evaluated performance by comparing predicted skin areas with expert markings. The error was given by the absolute difference between the percentage areas marked by the AI model and expert, where lower is better. Across all test patients, the median error was 19% (interquartile range 6 – 34) for the supervised method and 10% (5 – 23) for the semi-supervised method, which incorporated unmarked photos from 83 patients. On dark skin types, the median error was 36% (18 – 62) for supervised and 28% (14 – 52) for semi-supervised, compared to a median error on light skin of 18% (5 – 26) for supervised and 7% (4 – 17) for semi-supervised. Self-supervised, using all 337 unmarked patients, is expected to further improve performance and consistency due to increased data diversity. Full results will be presented at the meeting. Discussion/Significance of Impact: By automating skin assessment for cGVHD, AI could improve accuracy and consistency compared to manual methods. If translated to clinical use, this would ease clinical burden and scale to large patient cohorts. Future work will focus on ensuring equitable performance across all skin types, providing fair and accurate assessments for every patient.
Underrepresentation of diverse populations in medical research undermines generalizability, exacerbates health disparities, and erodes trust in research institutions. This study aimed to identify a suitable survey instrument to measure trust in medical research among Black and Latino communities in Baltimore, Maryland.
Methods:
Based on a literature review, a committee selected two validated instruments for community evaluation: Perceptions of Research Trustworthiness (PoRT) and Trust in Medical Researchers (TiMRs). Both were translated into Spanish through a standardized process. Thirty-four individuals participated in four focus groups (two in English, two in Spanish). Participants reviewed and provided feedback on the instruments’ relevance and clarity. Discussions were recorded, transcribed, and analyzed thematically.
Results:
Initial reactions to the instruments were mixed. While 68% found TiMR easier to complete, 74% preferred PoRT. Key discussion themes included the relevance of the instrument for measuring trust, clarity of the questions, and concerns about reinforcing negative perceptions of research. Participants felt that PoRT better aligned with the research goal of measuring community trust in research, though TiMR was seen as easier to understand. Despite PoRT’s lower reading level, some items were found to be more confusing than TiMR items.
Conclusion:
Community feedback highlighted the need to differentiate trust in medical research, researchers, and institutions. While PoRT and TiMR are acceptable instruments for measuring trust in medical research, refinement of both may be beneficial. Development and validation of instruments in multiple languages is needed to assess community trust in research and inform strategies to improve diverse participation in research.
In this chapter, the Green’s function method is developed that shows how boundary values, initial conditions, and inhomogeneous terms in partial-differential equations act as source terms for response throughout a domain. The Green’s function of a given partial-differential equations is the response from an impulsive point source and satisfies homogeneous versions of whatever boundary conditions the actual response satisfies. The Green’s function propagates a response from source points to receiver points. After developing this method for the scalar wave and diffusion equations and obtaining the Green’s functions of these equations in infinite domains, the focus turns to the Green’s function method for the multitude of vectorial continuum responses governed by equations derived in Part I of the book. In particular, elastodynamics, elastostatics, slow viscous flow, and continuum electromagnetics are analyzed using the Green’s function method. The so-called Green’s tensors for each of these continuum applications in an infinite domain are obtained using the Fourier transform and contour integration.
The Fourier transform pair is derived and various conventions in its definition discussed. It is shown how to obtain forward and inverse Fourier transforms for specific functions, which results in the completeness relation being formally proven. The basic properties of the Fourier transform are derived which include the symmetry properties of the real and imaginary parts, the shifting property, the stretching property, the differentiation property, Parseval’s theorem, the convolution theorem, and the integral-moment relations. The Fourier transform pair is then used to derive the two most important theorems of probability theory: the central-limit theorem and the law of large numbers. The Fourier transform is then used to solve various initial-value problems involving the diffusion and wave equation. The chapter concludes with the way Fourier analysis is key to performing time-series analysis of recorded data, which includes both filtering of the data and topics related to the data being recorded at discrete time intervals.
In this first chapter of Part II of the book on the mathematical methods of continuum physics, the continuum governing equations in Part I are related to three simple partial-differential equations that are analyzed throughout Part II: (1) the scalar wave equation, (2) the scalar diffusion equation, and (3) the scalar Poisson (or Laplace) equation. The nature of the boundary and initial conditions required in specifying well-posed boundary-value problems for each type of partial-differential equation is derived. The three types of equations are then solved using the method of separation of variables. In so doing, the most essential things to remember about the nature of the solution to wave, diffusion, and potential boundary-value problems are presented.
The same volume-averaging procedure used in Chapter 2 shows how to transition from the Maxwell’s equations controlling the electromagnetic fields of fundamental particles in vacuum to the continuum form of Maxwell’s equations describing the electromagnetic fields averaged over large numbers of molecules. The Maxwell stress tensor is derived for the body forces acting on the molecules. The macroscopic form of Maxwell’s equations and the associated electromagnetic fields are obtained when the frame of reference is moving with the center of mass of each collection of molecules. The laws of reversible polarization are obtained by time differentiation of the electromagnetic energy density. The law of electromigration (Ohm’s law) is obtained from a nonequilibrium thermodynamics perspective. Conditions are obtained for the neglect of the material movement in the continuum theory of electromagnetism. Electromagnetic continuity conditions are derived and used on example problems. The continuum form of Newtonian gravity is derived. Expressions for the Coriolis and centrifugal forces are derived when the frame of reference is rotating about an axis.
Nonequilibrium transport equations are derived for two types of diffusive systems: (1) viscous fluids made of a single molecular species that support thermal flux and (2) two-component (solute and solvent) miscible fluids that support solute flux and thermal flux. The general statement of energy conservation for any viscous fluid is derived and used to obtain the statement of entropy conservation for each system type. This identifies the irreversible entropy production of each system, which in turn produces linear transport laws relating the nonequilibrium diffusive flux to the gradients in the intensive parameters. The matrix of transport coefficients in the transport laws is proven to be symmetric (Onsager symmetry) using the continuum governing equations and requires the direction of flow to be reversed to obtain symmetry. Capillary physics is treated using Cahn–Hilliard theory that resolves the gradients in concentration across transition layers separating two immiscible, or partially miscible, fluid. The rules of contact-line movement (imbibition and drainage) in conduits are derived from a more macroscopic perspective where the transition layers are modeled as sharp interfaces.
This chapter shows how to transition exactly from discrete molecular dynamics to the averaged continuum dynamics controlling the movement of the center of mass of large numbers of molecules. Discrete particle dynamics is described from the classical Newton–Maxwell perspective and from the quantum perspective with an emphasis on how quantum effects control the force interactions between molecules. Representing atoms using the Dirac delta function in three dimensions (a field) is introduced along with the volume-averaging theorem that defines the macroscopic gradient of volume-averaged fields. The continuum statements of the conservation of mass and momentum of large numbers of atoms are derived. It is shown that the forces causing the center of mass of a collection of molecules to move come entirely from molecules that lie outside the collection. In so doing, the stress tensor is obtained as sums over the molecular-force interactions and a sum over the thermal (random) kinetic energy of the molecules. Body forces are defined as the long-range force fields of electromagnetism and gravity acting on each collection of molecules.
The law of Newtonian viscosity is derived and the suite of continuum equations controlling the mechanics of fluids presented. Conditions for viscous flow to be considered incompressible are derived and the Navier–Stokes equations defined. Dimensional analysis is described along with the idea of similarity of two flow fields occurring on different spatial and temporal scales. The nature of the boundary and initial conditions for a flow domain are obtained that result in unique solutions of the linear form of the Navier–Stokes equations along with the specific boundary conditions on the flow fields that hold at fluid–solid and fluid–fluid interfaces. Analytical solutions of viscous flow are obtained for a range a specific, and simple, steady-state flow geometries. Time harmonic flow in straight conduits is determined as is the magnetohydrodynamic flow taking place in straight conduits filled with an electrically conducting fluid and a magnetic field applied perpendicularly to the conduit. In the guided exercises, the lubrication approximation is used to obtain approximate solutions for a range of flow scenarios.
In this chapter, the student learns how to perform certain classes of definite integrals using contour integration methods. Although the integration variable is real for most integrals of interest, such as the inverse Fourier transform, analysis of the integral is extended to complex values of the integration variable and theorems related to integrating around closed contours on the complex plane are used to solve classes of definite integrals. The key theorems include Cauchy’s theorem for integrating so-called analytic functions, Jordan’s lemma, and the residue theorem for the important case where inside a closed contour on the complex plane, the integrand has places called singularities at which the function is not well behaved. Contour integration is used to analyze and derive results for the constitutive laws of a material when the current response depends not just on current forcing but also on the history of the forcing. This topic is called delayed linear response, which is developed at length. Contour integration, when combined with Fourier transforms, provides the solution of various types of initial-value and boundary-value problems in infinite and semi infinite domains.
The rules of macroscopic elastic response are derived in an exact way by first stating the time rate at which mechanical work is performed in deforming a collection of molecules, which is the time rate at which internal elastic energy is being reversibly stored in the molecular bonds. From this work rate, the definition of the average stress tensor is obtained as well as the exact statement of the strain rate. An additional time derivative of the average stress tensor then gives Hooke’s law in its most general nonlinear form. How the elastic stiffnesses in Hooke’s law change with changing strain is derived. Displacement is defined and the shape change and volume change of a sample are understood through how the displacements of the surface bounding the sample are related to the strain tensor. Elastodynamic plane body-wave response is obtained, as is reflection and refraction of plane body waves from an interface and evanescent surface waves. It is shown how sources of elastodynamic waves such as cracking and explosions are represented as equivalent body forces.
This chapter is meant to be a student’s first introduction to tensors. Self-contained and complete, the student learns how tensors are defined, written, and used. The scalar and vector products are defined along with the physical meaning of the divergence and curl differential operations that act on tensors of any order. The integro-differential theorems are introduced in three dimensions, which include the fundamental theorem of calculus in three dimensions, Stokes’ theorem and the Reynolds’ transport theorem. The student learns how to derive a long list of tensor-calculus product rules that are valid in any coordinate system. The Taylor series in three-dimensional space is derived, which involves tensors of all orders. Functions of second-order tensors are defined. Isotropic tensors of all tensorial orders are obtained and used in proving Curie’s principle for the constitutive laws in an isotropic material. Tensor calculus in orthogonal curvilinear coordinates is developed. Finally, the Dirac delta function is introduced along with its integral and differential properties and uses.