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Clinical intuition suggests that personality disorders hinder the treatment of depression, but research findings are mixed. One reason for this might be the way in which current assessment measures conflate general aspects of personality disorders, such as overall severity, with specific aspects, such as stylistic tendencies. The goal of this study was to clarify the unique contributions of the general and specific aspects of personality disorders to depression outcomes.
Patients admitted to the Menninger Clinic, Houston, between 2012 and 2015 (N = 2352) were followed over a 6–8-week course of multimodal inpatient treatment. Personality disorder symptoms were assessed with the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, 4th edition Axis II Personality Screening Questionnaire at admission, and depression severity was assessed using the Patient Health Questionnaire-9 every fortnight. General and specific personality disorder factors estimated with a confirmatory bifactor model were used to predict latent growth curves of depression scores in a structural equation model.
The general factor predicted higher initial depression scores but not different rates of change. By contrast, the specific borderline factor predicted slower rates of decline in depression scores, while the specific antisocial factor predicted a U shaped pattern of change.
Personality disorder symptoms are best represented by a general factor that reflects overall personality disorder severity, and specific factors that reflect unique personality styles. The general factor predicts overall depression severity while specific factors predict poorer prognosis which may be masked in prior studies that do not separate the two.
Improving Access to Psychological Therapies (IAPT) services treat most patients in England who present to primary care with major depression. Psychodynamic psychotherapy is one of the psychotherapies offered. Dynamic Interpersonal Therapy (DIT) is a psychodynamic and mentalization-based treatment for depression. 16 sessions are delivered over approximately 5 months. Neither DIT's effectiveness relative to low-intensity treatment (LIT), nor the feasibility of randomizing patients to psychodynamic or cognitive-behavioural treatments (CBT) in an IAPT setting has been demonstrated.
147 patients were randomized in a 3:2:1 ratio to DIT (n = 73), LIT (control intervention; n = 54) or CBT (n = 20) in four IAPT treatment services in a combined superiority and feasibility design. Patients meeting criteria for major depressive disorder were assessed at baseline, mid-treatment (3 months) and post-treatment (6 months) using the Hamilton Rating Scale for Depression (HRSD-17), Beck Depression Inventory-II (BDI-II) and other self-rated questionnaire measures. Patients receiving DIT were also followed up 6 months post-completion.
The DIT arm showed significantly lower HRSD-17 scores at the 6-month primary end-point compared with LIT (d = 0.70). Significantly more DIT patients (51%) showed clinically significant change on the HRSD-17 compared with LIT (9%). The DIT and CBT arms showed equivalence on most outcomes. Results were similar with the BDI-II. DIT showed benefit across a range of secondary outcomes.
DIT delivered in a primary care setting is superior to LIT and can be appropriately compared with CBT in future RCTs.
We present a new experimental platform for studying laboratory astrophysics that combines a high-intensity, high-repetition-rate laser with the Large Plasma Device at the University of California, Los Angeles. To demonstrate the utility of this platform, we show the first results of volumetric, highly repeatable magnetic field and electrostatic potential measurements, along with derived quantities of electric field, charge density and current density, of the interaction between a super-Alfvénic laser-produced plasma and an ambient, magnetized plasma.
We have previously shown that the minor alleles of vascular endothelial growth factor A (VEGFA) single-nucleotide polymorphism rs833069 and superoxide dismutase 2 (SOD2) single-nucleotide polymorphism rs2758331 are both associated with improved transplant-free survival after surgery for CHD in infants, but the underlying mechanisms are unknown. We hypothesised that one or both of these minor alleles are associated with better systemic ventricular function, resulting in improved survival.
This study is a follow-up analysis of 422 non-syndromic CHD patients who underwent neonatal cardiac surgery with cardiopulmonary bypass. Echocardiographic reports were reviewed. Systemic ventricular function was subjectively categorised as normal, or as mildly, moderately, or severely depressed. The change in function was calculated as the change from the preoperative study to the last available study. Stepwise linear regression, adjusting for covariates, was performed for the outcome of change in ventricular function. Model comparison was performed using Akaike’s information criterion. Only variables that improved the model prediction of change in systemic ventricular function were retained in the final model.
Genetic and echocardiographic data were available for 335/422 subjects (79%). Of them, 33 (9.9%) developed worse systemic ventricular function during a mean follow-up period of 13.5 years. After covariate adjustment, the presence of the VEGFA minor allele was associated with preserved ventricular function (p=0.011).
These data support the hypothesis that the mechanism by which the VEGFA single-nucleotide polymorphism rs833069 minor allele improves survival may be the preservation of ventricular function. Further studies are needed to validate this genotype–phenotype association and to determine whether this mechanism is related to increased vascular endothelial growth factor production.
The Megamaser Cosmology Project (MCP) measures the Hubble Constant by determining geometric distances to circumnuclear 22 GHz H2O megamasers in galaxies at low redshift (z < 0.05) but well into the Hubble flow. In combination with the recent, exquisite observations of the Cosmic Microwave Background by WMAP and Planck, these measurements provide a direct test of the standard cosmological model and constrain the equation of state of dark energy. The MCP is a multi-year project that has recently completed observations and is currently working on final analysis. Based on distance measurements to the first four published megamasers in the sample, the MCP currently determines H0 = 69.3 ± 4.2 km s−1 Mpc−1. The project is finalizing analysis for five additional galaxies. When complete, we expect to achieve a ~4% measurement. Given the tension between the Planck prediction of H0 in the context of the standard cosmological model and astrophysical measurements based on standard candles, the MCP provides a critical and independent geometric measurement that does not rely on external calibrations or a distance ladder.
Due to the limited availability of selective herbicides to control Sumatran fleabane after soybean emergence, it is essential to develop new options that provide effective control prior to planting. A new herbicide formulation containing diclosulam+halauxifen-methyl was evaluated for effectiveness at two Sumatran fleabane plant heights (5 to 10 cm, and 10 to 50 cm) and for soybean selectivity when applied at 7 or 3 d before planting. Combined results from the two sites showed that diclosulam+halauxifen, applied either alone or in a tank mixture with glyphosate, and the tank mixture of diclosulam+2,4-D amine+glyphosate are effective at all rates tested to control Sumatran fleabane in preplant applications. Crop response was observed with applications 7 days before planting at only one of the sites. A rate-dependent crop response was observed for pre-plant applications performed 3 days before soybean planting. However, crop yield was not significantly affected for either timing across all rates. All rates tested of diclosulam+halauxifen in this study were considered safe to soybean.
A 9-year-old boy who was born with bicuspid aortic stenosis underwent two unsuccessful aortic valvuloplasty interventions, and by 2 years of age he developed restrictive cardiomyopathy caused by left ventricular endocardial fibroelastosis and diastolic dysfunction. The attending cardiologist referred the patient to a high-volume, high-profile congenital cardiac surgical programme 1000 miles away that has a team with considerable experience with left ventricular endocardial fibroelastosis resection and a reputation of achieving good results. Owing to problems with insurance coverage, the parents sought other options for the care of their child in their home state. Dr George Miller is a well-respected local congenital and paediatric cardiac surgeon with considerable experience with the Ross operation as well as with right ventricular endocardial fibroelastosis resection. When talking with Dr Miller, he implied that there is little difference between right ventricular endocardial fibroelastosis and left ventricular endocardial fibroelastosis resection, and stated that he would perform the operation with low mortality based on his overall experience. Dr Miller stated that the local institution could provide an equivalent surgical procedure with comparable outcomes, without the patient and family having to travel out of state. A fundamental dilemma that often arises in clinical surgical practice concerns the conduct of assessing and performing new procedures, especially in rare cases, for which the collective global experience is scant. Although Dr Miller has performed right ventricular endocardial fibroelastosis resection, this procedure differs from left ventricular endocardial fibroelastosis resection, and he cannot be sure that he will indeed be able to perform the procedure better than the high-volume surgeon. This ethical situation is best understood in terms of the principles of respect for patient autonomy, beneficence, non-maleficence, and justice. The tension between the imperatives of beneficence and the obligation to respect the autonomy of the patient by acting only with the patient’s best interest in mind is discussed.
Since its introduction in the late 19th century, symmetry breaking has been found to play a crucial role in physics. In particular, it appears as one key phenomenon controlling hydrodynamic and acoustic instabilities in problems with rotational symmetries. A previous paper investigated its desired potential application to the control of circumferential thermoacoustic modes in one annular cavity coupled with multiple flames (Bauerheim et al., J. Fluid Mech., vol. 760, 2014, pp. 431–465). The present paper focuses on a similar problem when symmetry breaking appears unintentionally, for example when uncertainties due to tolerances are taken into account. It yields a large uncertainty quantification (UQ) problem containing numerous uncertain parameters. To tackle this well-known ‘curse of dimensionality’, a novel UQ methodology is used. It relies on the active subspace approach to construct a reduced set of input variables. This strategy is applied on two annular cavities coupled by 19 flames to determine its modal risk factor, i.e. the probability of an azimuthal acoustic mode being unstable. Since each flame is modelled by two uncertain parameters, it leads to a large UQ problem involving 38 parameters. An acoustic network model is then derived, which yields a nonlinear dispersion relation for azimuthal modes. This nonlinear problem, subject to bifurcations, is solved quasi-analytically. Results show that the dimension of the probabilistic problem can be drastically reduced, from 38 uncertain parameters to only 3. Moreover, it is found that the three active variables are related to physical quantities, which unveils underlying phenomena controlling the stability of the two coupled cavities. The first active variable is associated with a coupling strength controlling the bifurcation of the system, while the two others correspond to a symmetry-breaking effect induced by the uncertainties. Thus, an additional destabilization effect appear caused by the non-uniform pattern of the uncertainty distribution, which breaks the initial rotating symmetry of the annular cavities. Finally, the active subspace is exploited by fitting the response surface with polynomials (linear, quadratic and cubic). By comparing accuracy and cost, results prove that 5 % error can be achieved with only 30 simulations on the reduced space, whereas 2000 are required on the complete initial space. It exemplifies that this novel UQ technique can accurately predict the risk factor of an annular configuration at low cost as well as unveil key parameters controlling the stability.
The treatment of rare and expensive medical conditions is one of the defining qualities of paediatric cardiology and congenital heart surgery. Increasing concerns over healthcare resource allocation are challenging the merits of treating more expensive forms of congenital heart disease, and this trend will almost certainly continue. In this manuscript, the problems of resource allocation for rare and expensive medical conditions are described from philosophical and economic perspectives. The argument is made that current economic models are limited in the ability to assess the value of treating expensive and rare forms of congenital heart disease. Further, multi-disciplinary approaches are necessary to best determine the merits of treating a patient population such as those with significant congenital heart disease that sometimes requires enormous healthcare resources.
Respect for patient autonomy is an important and indispensable principle in the ethical practice of clinical medicine. Legal tenets recognise the centrality of this principle and the inherent right of patients of sound mind – properly informed – to make their own personal medical decisions. In the course of everyday medical practice, however, challenging cases may result in ethical dilemmas for the patient, the physician, and society. Resolution of these dilemmas requires a thorough understanding of the underlying principles that allow the clinician to make informed decisions and to offer considered therapeutic options to the patient. We argue in this paper that there is also need for a transition of moral competency from understanding principles to attaining virtue in the classic Aristotelian tradition. Achieving moral virtue is based on a lifetime of learning, practising, and watching how others, who have achieved virtue, act and perform their duties. We further claim that learning moral virtue in medical practice is best realised by incorporating the lessons learnt during daily rounds where frank discussions and considered resolutions can occur under the leadership of senior practitioners who have achieved a semblance of moral excellence.
Anomalous aortic origins of the coronary arteries comprise approximately one-third of all coronary artery anomalies and are characterised by coronary arteries with anomalies of aortic origin involving abnormal courses, stenoses, and compression that can lead to myocardial ischaemia and sudden death. Operative techniques to treat these anomalies have not been standardised yet. Moreover, the management of potential complications has not been addressed. Common and rare forms of anomalous aortic origins of the coronary arteries are reviewed and understood standard techniques for an uncomplicated unroofing procedure are illustrated. Also noted are techniques that can be applied to unexpected anatomical findings and unwanted complications that could prove to be life-threatening. Several technical recommendations are offered.
Placebo responses raise significant challenges for the design of clinical trials. We report changes in agitation outcomes in the placebo arm of a recent trial of citalopram for agitation in Alzheimer's disease (CitAD).
In the CitAD study, all participants and caregivers received a psychosocial intervention and 92 were assigned to placebo for nine weeks. Outcomes included Neurobehavioral Rating Scale agitation subscale (NBRS-A), modified AD Cooperative Study-Clinical Global Impression of Change (CGIC), Cohen-Mansfield Agitation Inventory (CMAI), the Neuropsychiatric Inventory (NPI) Agitation/Aggression domain (NPI A/A) and Total (NPI-Total) and ADLs. Continuous outcomes were analyzed with mixed-effects modeling and dichotomous outcomes with logistic regression.
Agitation outcomes improved over nine weeks: NBRS-A mean (SD) decreased from 7.8 (3.0) at baseline to 5.4 (3.2), CMAI from 28.7 (6.7) to 26.7 (7.4), NPI A/A from 8.0 (2.4) to 4.9 (3.8), and NPI-Total from 37.3 (17.7) to 28.4 (22.1). The proportion of CGI-C agitation responders ranged from 21 to 29% and was significantly different from zero. MMSE improved from 14.4 (6.9) to 15.7 (7.2) and ADLs similarly improved. Most of the improvement was observed by three weeks and was sustained through nine weeks. The major predictor of improvement in each agitation measure was a higher baseline score in that measure.
We observed significant placebo response which may be due to regression to the mean, response to a psychosocial intervention, natural course of symptoms, or nonspecific benefits of participation in a trial.
We report on the composition of turn-off stars in the intriguing open cluster, NGC 6791, which is old, but super-metal-rich using Keck/HIRES spectra. We find [Fe/H] = +0.30 ±0.02[O/Fe]n −0.06 ±0.02,[Mg/Fe], [Si/Fe], [Ca/Fe], and [Ti/Fe] near solar and the two Fe-peak elements, Cr and Ni, are consistent with Fe.
The tricuspid valve is being increasingly recognised as an important safeguard to the heart with congenital heart disease. Both structural anomalies of the valve and functional burdens from other malformations of the right heart can lead to major haemodynamic consequences both upstream and downstream. The indications to surgically intervene on the tricuspid valve are evolving and vary depending on the malformation. The extant surgical techniques and their applications to corresponding frequent congenital anomalies of the tricuspid valve are reviewed.
Operations for left ventricular outflow tract abnormalities are centred on hemodynamic conditions that relate to subvalvar stenosis, valvar stenosis/regurgitation, aortic annular hypoplasia, and supravalvar aortic stenosis. Operative interventions over the years have evolved because the intervening outcomes proved to be unsatisfactory. The resection for subvalvar aortic stenosis has progressed from a fibrous “membrane” resection to a more extensive fibromuscular resection. Operative solutions for valvar aortic stenosis and regurgitation have resulted in operative interventions that depend on simple commissurotomy, leaflet extensions, prosthetic mechanical valve replacement, biologic valve replacement, including the pulmonary autograft, and operations to treat aortic annular stenosis. Although there are enthusiastic proponents for all of these strategies, the fact remains that none have proven to be curative; patients can expect to undergo further procedures during their lifetimes. The short- and mid-term solutions to these left ventricular outflow tract abnormalities have improved based on operations that have been attended by increasing operative complexity. The purpose of this review is to chronicle the operative steps of the Ross operation, the Konno–Rastan operation, the modified Konno operation, the Ross–Konno operation, and the modified Ross–Konno operation.
Agitation is common across neuropsychiatric disorders and contributes to disability, institutionalization, and diminished quality of life for patients and their caregivers. There is no consensus definition of agitation and no widespread agreement on what elements should be included in the syndrome. The International Psychogeriatric Association formed an Agitation Definition Work Group (ADWG) to develop a provisional consensus definition of agitation in patients with cognitive disorders that can be applied in epidemiologic, non-interventional clinical, pharmacologic, non-pharmacologic interventional, and neurobiological studies. A consensus definition will facilitate communication and cross-study comparison and may have regulatory applications in drug development programs.
The ADWG developed a transparent process using a combination of electronic, face-to-face, and survey-based strategies to develop a consensus based on agreement of a majority of participants. Nine-hundred twenty-eight respondents participated in the different phases of the process.
Agitation was defined broadly as: (1) occurring in patients with a cognitive impairment or dementia syndrome; (2) exhibiting behavior consistent with emotional distress; (3) manifesting excessive motor activity, verbal aggression, or physical aggression; and (4) evidencing behaviors that cause excess disability and are not solely attributable to another disorder (psychiatric, medical, or substance-related). A majority of the respondents rated all surveyed elements of the definition as “strongly agree” or “somewhat agree” (68–88% across elements). A majority of the respondents agreed that the definition is appropriate for clinical and research applications.
A provisional consensus definition of agitation has been developed. This definition can be used to advance interventional and non-interventional research of agitation in patients with cognitive impairment.
This paper considers an endogenous growth model with public capital and heterogeneous agents. Heterogeneity is due to differences in discount factors and inherent abilities. This allows us to closely approximate the 2007 U.S. income and wealth distributions. Government expenditures, including public investment, are financed through a progressive income tax along with a flat tax on consumption. Three revenue-neutral fiscal policy reforms are considered: (i) an increase in the degree of progressivity of the tax schedule that reduces the after-tax income distribution Gini coefficient to its lowest value over the period 1979–2009, (ii) a reduction in the progressivity ratio that causes the Gini coefficient of the wealth distribution to come close to 1, and (iii) an increase in the fraction of output allocated to public investment that has the same positive impact on the growth rate as reform (ii). It is shown that increasing investment in public capital is the only type of policy that simultaneously enhances growth and reduces both types of inequality (income and wealth). We also find that the public-investment-to-output ratio that maximizes social welfare crucially depends on the elasticity of the labor supply. With a more elastic labor supply the optimal ratio is 4.40%, whereas with a less elastic labor supply it is 5.53%.