This article outlines the evidence base for the use of paradoxical interventions (PIs) in individual psychotherapy. Often misunderstood, PIs have shown long-term (distal) impacts on clinical ...outcomes, yet a review of the existing literature on these interventions illustrates a trending decline in consideration and use within both research and applied settings. Definitions of PIs and their constituent elements are presented along with clinical examples. We conducted one meta-analysis comparing PIs with a placebo or control and another comparing PIs to other therapeutic methods. PIs demonstrated a large effect (d = 1.1, k = 17 studies) compared to controls and a medium effect size (d = .49, k = 17 studies) compared to other therapeutic methods. We included a review of several case studies using PIs as well. Among the salient findings, there is a lack of assessment measure to track the implementation of PIs in session or a method to track their in-session effects. Further, there is a dearth of contemporary quantitative experimental research and development of PIs. We further advocate for the development and integration of PI training and supervision into clinical education and posteducation programs, given the current data demonstrating clinical utility.
Clinical Impact Statement
Question: This article provides a review of the existing research investigating the clinical utility and efficacy of paradoxical interventions (PI) in psychotherapy. Findings: PIs were shown to have positive effects on patients' symptoms compared to either a control group or when compared to other techniques. Meaning: PIs are useful techniques that can be employed by clinicians in appropriate settings. Next Steps: Based on this study, the researchers advocate for continued research on and the development of PIs for modern practice, as well as the inclusion of PIs in modern training and supervision programs.
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Although emotion has long been considered important to psychotherapeutic process, empirical assessment of its impact has emerged only recently. The present study applied two meta-analyses to explore ...the association between therapist expression of emotion and psychotherapy outcome, and client expression of emotion and psychotherapy outcome. Overall, 66 studies (13 for the therapist meta-analysis and 43 for the client meta-analysis) were included. A significant medium effect size was found between the therapist's emotional expression and outcomes (d = 0.56) and a significant medium-to-large effect size between the client's emotional expression and outcomes (d = 0.85). Third-party rating of emotional expression emerged as a significant moderator of outcomes. Limitations of the research, diversity considerations, and therapeutic practices that conclude the article are then presented.
Clinical Impact Statement
Question: We attempted to address the question of what the relationship between client and therapist expressions of affect on therapeutic outcomes was. Findings: Therapist expression of affect had a medium effect on client outcome, whereas client expression of affect had a medium-to-large effect on client outcome. Meaning: Clinicians may wish to reexamine the role of the expression of affect in the therapeutic relationship. Next Steps: Training to recognize and facilitate client emotional expression, as well as training focused on appropriate therapist emotional expression, would be warranted.
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In an effort to more fully understand the full spectrum of human genetic variation, we generated deep single-molecule, real-time (SMRT) sequencing data from two haploid human genomes. By using an ...assembly-based approach (SMRT-SV), we systematically assessed each genome independently for structural variants (SVs) and indels resolving the sequence structure of 461,553 genetic variants from 2 bp to 28 kbp in length. We find that >89% of these variants have been missed as part of analysis of the 1000 Genomes Project even after adjusting for more common variants (MAF > 1%). We estimate that this theoretical human diploid differs by as much as ∼16 Mbp with respect to the human reference, with long-read sequencing data providing a fivefold increase in sensitivity for genetic variants ranging in size from 7 bp to 1 kbp compared with short-read sequence data. Although a large fraction of genetic variants were not detected by short-read approaches, once the alternate allele is sequence-resolved, we show that 61% of SVs can be genotyped in short-read sequence data sets with high accuracy. Uncoupling discovery from genotyping thus allows for the majority of this missed common variation to be genotyped in the human population. Interestingly, when we repeat SV detection on a pseudodiploid genome constructed in silico by merging the two haploids, we find that ∼59% of the heterozygous SVs are no longer detected by SMRT-SV. These results indicate that haploid resolution of long-read sequencing data will significantly increase sensitivity of SV detection.
Haplotype-resolved or phased genome assembly provides a complete picture of genomes and their complex genetic variations. However, current algorithms for phased assembly either do not generate ...chromosome-scale phasing or require pedigree information, which limits their application. We present a method named diploid assembly (DipAsm) that uses long, accurate reads and long-range conformation data for single individuals to generate a chromosome-scale phased assembly within 1 day. Applied to four public human genomes, PGP1, HG002, NA12878 and HG00733, DipAsm produced haplotype-resolved assemblies with minimum contig length needed to cover 50% of the known genome (NG50) up to 25 Mb and phased ~99.5% of heterozygous sites at 98-99% accuracy, outperforming other approaches in terms of both contiguity and phasing completeness. We demonstrate the importance of chromosome-scale phased assemblies for the discovery of structural variants (SVs), including thousands of new transposon insertions, and of highly polymorphic and medically important regions such as the human leukocyte antigen (HLA) and killer cell immunoglobulin-like receptor (KIR) regions. DipAsm will facilitate high-quality precision medicine and studies of individual haplotype variation and population diversity.
The human fragile X mental retardation 1 (FMR1) gene contains a (CGG)(n) trinucleotide repeat in its 5' untranslated region (5'UTR). Expansions of this repeat result in a number of clinical disorders ...with distinct molecular pathologies, including fragile X syndrome (FXS; full mutation range, greater than 200 CGG repeats) and fragile X-associated tremor/ataxia syndrome (FXTAS; premutation range, 55-200 repeats). Study of these diseases has been limited by an inability to sequence expanded CGG repeats, particularly in the full mutation range, with existing DNA sequencing technologies. Single-molecule, real-time (SMRT) sequencing provides an approach to sequencing that is fundamentally different from other "next-generation" sequencing platforms, and is well suited for long, repetitive DNA sequences. We report the first sequence data for expanded CGG-repeat FMR1 alleles in the full mutation range that reveal the confounding effects of CGG-repeat tracts on both cloning and PCR. A unique feature of SMRT sequencing is its ability to yield real-time information on the rates of nucleoside addition by the tethered DNA polymerase; for the CGG-repeat alleles, we find a strand-specific effect of CGG-repeat DNA on the interpulse distance. This kinetic signature reveals a novel aspect of the repeat element; namely, that the particular G bias within the CGG/CCG-repeat element influences polymerase activity in a manner that extends beyond simple nearest-neighbor effects. These observations provide a baseline for future kinetic studies of repeat elements, as well as for studies of epigenetic and other chemical modifications thereof.
We present single-molecule, real-time sequencing data obtained from a DNA polymerase performing uninterrupted template-directed synthesis using four distinguishable fluorescently labeled ...deoxyribonucleoside triphosphates (dNTPs). We detected the temporal order of their enzymatic incorporation into a growing DNA strand with zero-mode waveguide nanostructure arrays, which provide optical observation volume confinement and enable parallel, simultaneous detection of thousands of single-molecule sequencing reactions. Conjugation of fluorophores to the terminal phosphate moiety of the dNTPs allows continuous observation of DNA synthesis over thousands of bases without steric hindrance. The data report directly on polymerase dynamics, revealing distinct polymerization states and pause sites corresponding to DNA secondary structure. Sequence data were aligned with the known reference sequence to assay biophysical parameters of polymerization for each template position. Consensus sequences were generated from the single-molecule reads at 15-fold coverage, showing a median accuracy of 99.3%, with no systematic error beyond fluorophore-dependent error rates.
Haplotype-resolved genome assemblies are important for understanding how combinations of variants impact phenotypes. To date, these assemblies have been best created with complex protocols, such as ...cultured cells that contain a single-haplotype (haploid) genome, single cells where haplotypes are separated, or co-sequencing of parental genomes in a trio-based approach. These approaches are impractical in most situations. To address this issue, we present FALCON-Phase, a phasing tool that uses ultra-long-range Hi-C chromatin interaction data to extend phase blocks of partially-phased diploid assembles to chromosome or scaffold scale. FALCON-Phase uses the inherent phasing information in Hi-C reads, skipping variant calling, and reduces the computational complexity of phasing. Our method is validated on three benchmark datasets generated as part of the Vertebrate Genomes Project (VGP), including human, cow, and zebra finch, for which high-quality, fully haplotype-resolved assemblies are available using the trio-based approach. FALCON-Phase is accurate without having parental data and performance is better in samples with higher heterozygosity. For cow and zebra finch the accuracy is 97% compared to 80-91% for human. FALCON-Phase is applicable to any draft assembly that contains long primary contigs and phased associate contigs.
A comparison of the genomes of two “outbreak”
Vibrio cholerae
isolates from Haiti with those of other isolates indicates that this outbreak strain is distinct from circulating Latin American isolates ...and bears striking similarity to recent isolates from South Asia.
The outbreak of cholera that began in Haiti in late October 2010 illustrates the continued public health threat of this ancient scourge.
1
Cholera, an acutely dehydrating diarrheal disease that can rapidly kill its victims, is caused by
Vibrio cholerae,
a gram-negative bacterium.
2
This disease, which is usually transmitted through contaminated water, can and has spread in an explosive fashion. In the weeks since cases were first confirmed in the Artibonite province of Haiti on October 19, 2010, the disease has reached all 10 provinces in Haiti and has spread to the neighboring Dominican Republic on the island of Hispaniola. Of . . .
Objective
: The purpose of this paper is to describe an approach to dynamical systems (DS) using a set of differential equations, and how an application of these equations can be used to address a ...critical element of the therapeutic relationship. Using APA's Three Approaches to Psychotherapy with a Female Client: The Next Generation and Three Approaches to Psychotherapy with a Male Client: The Next Generation videos, DS models were created for each of the six sessions with expert clinicians (Judith Beck, Leslie Greenberg, and Nancy McWilliams) from the three theoretical approaches. Method
: A second-by-second observational coding system of the emotional exchanges of the therapists and clients was used as the data for the equations. Results: DS modeling allowed for a side-by-side comparison between the three approaches as well as between the two clients. Examining the graphs created by plotting the results of the DS equations (in particular, phase-space portraits) revealed that there were similarities among the three theoretical approaches, and there were notable differences between the two clients. Conclusions: DS modelling can provide researchers and clinicians with a powerful tool to investigate the complex phenomenon that is psychotherapy.
The therapeutic relationship continues to be one of the most important factors in therapeutic outcomes. Given the place of emotion in the definition of the therapeutic relationship, as well as the ...demonstrated positive impact that emotional expression has on therapeutic process and outcome, it stands to reason that studying the emotional exchange between the therapist and client further would be warranted.
This study used a validated observational coding system--the Specific Affect Coding System (SPAFF) and a theoretical mathematical model to analyze behaviors which make up the therapeutic relationship. Specifically, the researchers used to codify relationship-building behaviors between an expert therapist and his client over the course of six sessions. Dynamical systems mathematical modeling was also employed to create "phase space portraits" depicting the relational dynamics between the master therapist and his client over six sessions.
Statistical analysis was used to compare SPAFF codes and model parameters between the expert therapist and his client. The expert therapist showed stability in affect codes over six sessions while the client's affect codes appeared to be more flexible over time, though model parameters remained stable across the six sessions. Finally, phase space portraits depicted the evolution of the affective dynamics between the master therapist and his client as the relationship matured.
The clinician's ability to stay emotionally positive and relatively stable across the six sessions (relative to the client) was noteworthy. It formed the basis for a stable base from which she could explore alternative methods to relate to others that she had allowed to dictate her actions, which is in keeping with previous research on the role of therapist facilitation of the therapeutic relationship, emotional expression within the therapeutic relationship, and influence of these on client outcomes. These results provide a valuable foundation for future research on emotional expression as a key component of the therapeutic relationship in psychotherapy.
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