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Objective: To provide a comprehensive assessment of the association between psychological treatment adherence/competence/integrity (ACI) and clinical outcomes. Method: The review protocol was preregistered (CRD42020193889). Studies that assessed ACI–outcome relationships for adult psychotherapy were searched across three databases (Scopus, PsycINFO, MEDLINE). Random effects meta-analyses were conducted on adherence–outcome, competence–outcome, and integrity–outcome relationships. Separate analyses were performed for studies with hierarchical (i.e., patients nested within therapist) versus nonhierarchical study designs. Moderator analyses were performed according to predefined clinical and methodological features. GRADE assessments rated the quality of each meta-analytic comparison. Results: The review identified 62 studies suitable for inclusion (45 adherence–outcome, 39 competence–outcome, and seven integrity–outcome effect sizes; N = 8,210 across all analyses). No significant adherence–outcome association was found. A small significant positive association was found only in nonhierarchical studies between competence and outcome, r = 0.17, 95% CI [0.07–0.26], p < .001, ∼d = .34, GRADE = moderate. Small-to-moderate significant positive associations between integrity and outcome were found for both nonhierarchical, r = 0.15, 95% CI [0.06–0.23], p < .001, ∼d = .30, GRADE = high, and hierarchical study designs, r = 0.23, 95% CI [0.01, 0.43], p < .044, ∼d = .47, GRADE = low. Diagnosis, treatment modality and year of publication significantly moderated the strength of ACI–outcome correlations. Conclusions: Competence and integrity are significantly associated with clinical outcome, with a magnitude comparable to wider common factors. Further research is required to study these process–outcome associations with greater precision in routine-care settings and to understand the role of moderating variables.

Psychological intervention outcomes depend in part on the therapist who provides the intervention (a therapist effect). However, recent reviews suggest that therapist effects may vary as a function of the context in which care is provided and therefore should not be generalized beyond that context. This study statistically analysed therapist effect differences between care sectors delivering psychological interventions. The sample comprised routine clinical data from 26,814 patients (69% female; mean age 38) and 466 therapists in five care sectors: primary care, secondary care, university, voluntary, and workplace. Therapist effects were analysed using multilevel models and Markov chain Monte Carlo credible intervals. The therapist effect was significantly larger in primary care (8.4%) than in any other sector (1.1%–2.3%) except secondary care (4.1%), after controlling for explanatory baseline and process variables as well as accounting for differences between clinics. There were no other significant differences detected between care sectors. These findings support the hypothesis that differences in effectiveness between therapists vary depending on the context in which psychological treatment is provided. Differences in relative therapist impact can vary by a factor of 4–8 across treatment sectors. This should be considered in the application of research evidence, treatment planning, and the design and delivery of psychological care provision.

Purpose\ud Individuals living in areas of higher deprivation are more likely to have requested mental health treatment but are less likely to have received treatment or benefitted from it. Less is known about the extent of access equality and treatment outcomes for individuals with a long-term health condition who experience mental health difficulties. The purpose of this paper is to evaluate the extent to which the neighbourhood Index of Multiple Deprivation predicted access to treatment, appointment attendance, treatment completion and clinical outcomes in a British health psychology clinic.\ud \ud Design/methodology/approach\ud Retrospective data were used from 479 individuals referred to a health psychology clinic over 12 months. Clinical outcomes were measured using the Clinical Outcomes in Routine Evaluation – Outcome Measure. Patient data were linked with their neighbourhood Index of Multiple Deprivation decile. Data were analysed using correlation, linear regression and Fisher’s exact test.\ud \ud Findings\ud There were no significant associations between deprivation and whether an individual attended assessment, attended treatment or completed treatment or between deprivation and patients’ clinical outcomes. Exploratory evidence indicated that individuals from higher deprivation neighbourhoods may be over-represented in clinic referrals, and individuals from lower deprivation neighbourhoods may be under-represented, compared with local population distribution estimates.\ud \ud Originality/value\ud This evaluation provides insights into treatment outcomes and deprivation in those with physical health difficulties. Further evaluation using a larger sample and comparing referrals with local prevalence estimates of comorbid mental and physical health problems would enable greater confidence in the conclusion that no evidence of inequality on the basis of neighbourhood deprivation was found.

Objective\ud We aimed to characterize the demographics of adults with dissociative (nonepileptic) seizures, placing emphasis on distribution of age at onset, male:female ratio, levels of deprivation, and dissociative seizure semiology.\ud \ud Methods\ud We collected demographic and clinical data from 698 adults with dissociative seizures recruited to the screening phase of the CODES (Cognitive Behavioural Therapy vs Standardised Medical Care for Adults With Dissociative Non‐Epileptic Seizures) trial from 27 neurology/specialist epilepsy clinics in the UK. We described the cohort in terms of age, age at onset of dissociative seizures, duration of seizure disorder, level of socioeconomic deprivation, and other social and clinical demographic characteristics and their associations.\ud \ud Results\ud In what is, to date, the largest study of adults with dissociative seizures, the overall modal age at dissociative seizure onset was 19 years; median age at onset was 28 years. Although 74% of the sample was female, importantly the male:female ratio varied with age at onset, with 77% of female but only 59% of male participants developing dissociative seizures by the age of 40 years. The frequency of self‐reported previous epilepsy was 27%; nearly half of these epilepsy diagnoses were retrospectively considered erroneous by clinicians. Patients with predominantly hyperkinetic dissociative seizures had a shorter disorder duration prior to diagnosis in this study than patients with hypokinetic seizures (P < .001); dissociative seizure type was not associated with gender. Predominantly hyperkinetic seizures were most commonly seen in patients with symptom onset in their late teens. Thirty percent of the sample reported taking antiepileptic drugs; this was more common in men. More than 50% of the sample lived in areas characterized by the highest levels of deprivation, and more than two‐thirds were unemployed.\ud \ud Significance\ud Females with dissociative seizures were more common at all ages, whereas the proportion of males increased with age at onset. This disorder was associated with socioeconomic deprivation. Those with hypokinetic dissociative seizures may be at risk for delayed diagnosis and treatment.

Objective\ud \ud We aimed to characterize the demographics of adults with dissociative (nonepileptic) seizures, placing emphasis on distribution of age at onset, male:female ratio, levels of deprivation, and dissociative seizure semiology.\ud Methods\ud \ud We collected demographic and clinical data from 698 adults with dissociative seizures recruited to the screening phase of the CODES (Cognitive Behavioural Therapy vs Standardised Medical Care for Adults With Dissociative Non‐Epileptic Seizures) trial from 27 neurology/specialist epilepsy clinics in the UK. We described the cohort in terms of age, age at onset of dissociative seizures, duration of seizure disorder, level of socioeconomic deprivation, and other social and clinical demographic characteristics and their associations.\ud Results\ud \ud In what is, to date, the largest study of adults with dissociative seizures, the overall modal age at dissociative seizure onset was 19 years; median age at onset was 28 years. Although 74% of the sample was female, importantly the male:female ratio varied with age at onset, with 77% of female but only 59% of male participants developing dissociative seizures by the age of 40 years. The frequency of self‐reported previous epilepsy was 27%; nearly half of these epilepsy diagnoses were retrospectively considered erroneous by clinicians. Patients with predominantly hyperkinetic dissociative seizures had a shorter disorder duration prior to diagnosis in this study than patients with hypokinetic seizures (P < .001); dissociative seizure type was not associated with gender. Predominantly hyperkinetic seizures were most commonly seen in patients with symptom onset in their late teens. Thirty percent of the sample reported taking antiepileptic drugs; this was more common in men. More than 50% of the sample lived in areas characterized by the highest levels of deprivation, and more than two‐thirds were unemployed.\ud Significance\ud \ud Females with dissociative seizures were more common at all ages, whereas the proportion of males increased with age at onset. This disorder was associated with socioeconomic deprivation. Those with hypokinetic dissociative seizures may be at risk for delayed diagnosis and treatment.

Pricing single asset American options is a hard problem in mathematical finance. There are no closed form solutions available (apart from in the case of the perpetual option), so many approximations and numerical techniques have been developed. Pricing multi–asset (high dimensional) American options is still more difficult. We extend the method proposed theoretically by Glasserman and Yu (2004) by employing regression basis functions that are martingales under geometric Brownian motion. This results in more accurate Monte Carlo simulations, and computationally cheap lower and upper bounds to the American option price. We have implemented these models in QuantLib, the open–source derivatives pricing library. The code for many of the models discussed in this thesis can be downloaded from quantlib.org as part of a practical pricing and risk management library. We propose a new type of multi–asset option, the “Radial Barrier Option” for which we find analytic solutions. This is a barrier style option that pays out when a barrier, which is a function of the assets and their correlations, is hit. This is a useful benchmark test case for Monte Carlo simulations and may be of use in approximating multi–asset American options. We use Laplace transforms in this analysis which can be applied to give analytic results for the hitting times of Bessel processes. We investigate the asymptotic solution of the single asset Black–Scholes–Merton equation in the case of low volatility. This analysis explains the success of some American option approximations, and has the potential to be extended to basket options.

Multidrug-resistant Staphylococcus aureus infections pose a significant threat to human health. Antibiotic resistance is most commonly propagated by conjugative plasmids like pLW1043, the first vancomycin-resistant S. aureus vector identified in humans. We present the molecular basis for resistance transmission by the nicking enzyme in S. aureus (NES), which is essential for conjugative transfer. NES initiates and terminates the transfer of plasmids that variously confer resistance to a range of drugs, including vancomycin, gentamicin, and mupirocin. The NES N-terminal relaxase–DNA complex crystal structure reveals unique protein–DNA contacts essential in vitro and for conjugation in S. aureus. Using this structural information, we designed a DNA minor groove-targeted polyamide that inhibits NES with low micromolar efficacy. The crystal structure of the 341-residue C-terminal region outlines a unique architecture; in vitro and cell-based studies further establish that it is essential for conjugation and regulates the activity of the N-terminal relaxase. This conclusion is supported by a small-angle X-ray scattering structure of a full-length, 665-residue NES–DNA complex. Together, these data reveal the structural basis for antibiotic multiresistance acquisition by S. aureus and suggest novel strategies for therapeutic intervention.

We have established a plasmid-based system that enables tightly controlled gene expression and the generation of GFP fusion proteins in Staphylococcus aureus simply and rapidly. This system takes advantage of an Escherichia coli-S. aureus shuttle vector that contains the replication region of the S. aureus theta-mode multiresistance plasmid pSK41, and is therefore a stable low-copy-number plasmid in the latter organism. This vector also contains a multiple cloning site downstream of the IPTG-inducible Pspac promoter for insertion of the gene of interest. Production of encoded proteins can be stringently regulated in an IPTG-dependent manner by introducing a pE194-based plasmid, pGL485, carrying a constitutively expressed lacI gene. Using GFP fusions to two essential proteins of S. aureus, FtsZ and NusA, we showed that our plasmid allowed tightly controlled gene expression and accurate localization of fusion proteins with no detrimental effect on cells at low inducer concentrations. At higher IPTG concentrations, we obtained sixfold overproduction of protein compared with wild-type levels, with FtsZ-GFP-expressing cells showing lysis and delocalized fluorescence, while NusA-GFP showed only delocalized fluorescence. These results show that our system is capable of titratable induction of gene expression for localization or overexpression studies. © 2011 SGM.