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Increasing evidence supports the efficacy of conjoint therapies that focus on intimate partner violence for couples who engage in mild to moderate physical aggression but want to preserve the relationship and end the aggression. However, there has been no examination of how this population responds to couple therapy that does not have a specific focus on aggression. This lacuna in the research literature is of concern because couples with a history of low-level aggression often seek couple therapy, but couple therapy without a focus on violence is thought to potentially exacerbate aggression. In the current study, the authors examined the efficacy of non-aggression-focused behavioral couple therapy for couples with and without a history of mild physical aggression. One hundred thirty-four couples, 45% of whom had experienced low-level aggression in the year prior to therapy, completed up to 26 sessions of couple therapy and 2 years of follow-up assessments. Results demonstrated no significant differences in relationship and individual outcomes by history of aggression. In addition, couples maintained very low levels of physical aggression during and after treatment and showed reductions in psychological aggression when relationship and individual functioning improved.

This study investigated demand-withdraw communication among 68 severely distressed couples seeking therapy, 66 moderately distressed couples seeking therapy, and 48 nondistressed couples. Self-report and videotaped discussions replicated previous research, demonstrating that greater demand-withdraw during relationship problem discussions was associated with greater distress and that overall, wife-demand/husband-withdraw was greater than husband-demand/wife-withdraw. Results extended the conflict structure view of demand-withdraw by indicating that this gender polarity in demand-withdraw roles varied in strength and direction depending on who chose the topic for discussion, distress level, and marriage length. Further, in videotaped personal problem discussions, typical gender patterns of demand-withdraw were reversed. Across the relationship and personal problem discussions, a pattern of gender polarity emerged when husbands held the burden of changing.

Atkins, C. B. & Dickinson, W. W. 2007 (January): Landscape modification by meltwater channels at margins of cold-based glaciers, Dry Valleys, Antarctica. Boreas, Vol. 36, pp. 47–55. Oslo. ISSN 0300–9483. This article describes distinctive lateral meltwater channels at the margins of low-elevation cold-based glaciers in the Dry Valleys. The channels significantly modify the ground surface and indicate that cold-based glaciers can be active geomorphic agents. Summer meltwater from the glacier surface flows over ice-aprons and erodes into the frozen ground creating channels up to 3 m deep and 10 m wide adjacent to unmodified ground that is protected beneath the glacier itself. Rapid fluvial excavation in the channels leads to undercutting and collapse of channel walls, which is capable of overturning large boulders. During glacial retreat, a succession of channels is incised into newly exposed ground creating a distinctive series of nested lateral channels and ridges. These represent the most obvious and persistent geomorphological signature of cold-based glacier activity in the region. Cold-based glaciers may advance and retreat over the same area many times without necessarily destroying older features, thereby creating a complex series of channels, deposits and remnant surfaces with a disordered chronology. Recognizing the role of cold-based glaciers and their meltwater channels on landscape evolution is critical for interpreting the timing and style of glacial events in the Antarctic.

Daily college drinking data often have highly skewed distributions with many zeroes and a rising and falling pattern of use across the week. Alcohol researchers have typically relied on statistical models with dummy variables for either the weekend or all days of the week to handle weekly patterns of use. However, weekend versus weekday categorizations may be too simplistic and saturated dummy variable models too unwieldy, particularly when covariates of weekly patterns are included. In the present study we evaluate the feasibility of cyclical (sine and cosine) covariates in a multilevel hurdle count model for evaluating daily college alcohol use data. Results showed that the cyclical parameterization provided a more parsimonious approach than multiple dummy variables. The number of drinks when drinking had a smoothly rising and falling pattern that was reasonably approximated by cyclical terms, but a saturated set of dummy variables was a better model for the probability of any drinking. Combining cyclical terms and multilevel hurdle models is a useful addition to the data analyst toolkit when modeling longitudinal drinking with high zero counts. However, drinking patterns were not perfectly sinusoidal in the current application, highlighting the need to consider multiple models and carefully evaluate model fit.

Therapist language plays a critical role in influencing the overall quality of psychotherapy. Notably, it is a major contributor to the perceived level of empathy expressed by therapists, a primary measure for judging their efficacy. We explore psycholinguistics inspired features for predicting therapist empathy. These features model language which conveys information about affective and cognitive processes, which is central to the therapist expressing understanding of the patient’s perspective. We describe the dimensional features obtained based on psycholinguisitic norms, and their application to predicting empathy expressed in motivational interviewing sessions for addiction counseling. We compare these to standard lexical features (n-grams) and demonstrate that these features contain complementary information for predicting therapist empathy. The highest empathy prediction results achieved are 75.28% UAR and 0.6112 Spearman’s correlation.

The next generation of astrophysical missions will require fabrication technology capable of producing high angular resolution x-ray mirrors. A full-shell direct fabrication approach using modern robotic polishing machines has the potential for producing stiff and light-weight shells that can be heavily nested, to produce large collecting areas, and are easier to mount, align and assemble, giving improved angular resolution. This approach to mirror fabrication, is being pursued at MSFC. The current status of this direct fabrication technology is presented.

Therapists can impact the likelihood a given patient will benefit from psychotherapy. However, therapists are rarely held accountable for their patients' outcomes. As a result, low-performing providers likely continue to practice alongside providers with high response rates. In the current study, we conducted a Monte Carlo simulation to illustrate a thought experiment-what happens to patient outcomes if therapists with the worst outcomes were removed from practice? We drew initial samples of 50 therapists from 3 simulated populations of 1,000 therapists with a mean patient response rate of 50% and different effect sizes for therapist variability in outcomes. We simulated 30 patient outcomes for each therapist, with outcome defined as response to treatment versus no response. We removed therapists with response rates in the bottom 5% and replaced them with a random sample of therapists from the population. Over 10 years, the difference in responses between the lowest and highest performing therapists was substantial (between 697 and 997 additional responses to treatment). After repeatedly removing the lowest performing providers 40 times (simulating a 10-year time span), response rates increased substantially. The cumulative number of patient responses (i.e., summing the total number of responses across 10 years) increased by 4,266, 6,404, and 9,307 when therapists accounted for 5%, 10%, or 20% of the patient outcome variance, respectively. These findings indicate that performance-based retention of therapists could improve the quality of psychotherapy in health systems by improving the average response rate and decreasing the probability that a patient will be treated by a therapist who consistently has poor outcomes.

Meta-analysis is a quantitative synthesis methodology aimed at systematically searching and screening relevant studies and integrating the findings from the eligible single studies to generate more robust and efficient estimates. Meta-analysis shows the magnitude and consistency of the overall effect size under investigation across studies. When the effect is consistent, it can then be generalized to a larger population. Reflecting this important utility, there has been a meteoric rise in the number of meta-analysis publications (Sutton & Higgins, 2008). Furthermore, meta-analysis is increasingly seen as a method to combat the current reproducibility crisis in preclinical and clinical trial research (Begley & Ellis, 2012; Ioannidis, 2005) and, more generally, as an important tool for open research practices (Cooper & VandenBos, 2013; Cumming, 2014; Eich, 2014; Open Science Collaboration, 2012). For these reasons, findings from meta-analyses weigh heavily in evidence-based decision making. Meta-analysis studies, however, are not without limitations, some of which may be inherent to a method that relies on aggregated data (AD) from published studies (Cooper & Patell, 2009). In addition, like all methodologies, meta-analysis must be applied properly to yield valid conclusions. The present review was motivated by a recent meta-analysis by Foxcroft, Coombes, Wood, Allen, and Almeida Santimano (2014) for the Cochrane Database of Systematic Reviews that evaluated the effectiveness of motivational interviewing (MI) interventions for heavy drinking among adolescents and young adults up to age 25. Their study included 66 randomized controlled trials of individuals between the ages of 15 and 25, of which 55 studies were quantitatively analyzed for alcohol outcomes. Foxcroft et al. concluded that: There are no substantive, meaningful benefits of MI interventions for the prevention of alcohol misuse. Although some significant effects were found, we interpret the effect sizes as being too small, given the measurement scales used in the studies included in the review, to be of relevance to policy or practice (p. 2). Foxcoft et al. further stated that the quality of evidence was low to moderate and, consequently, the reported effect sizes in their meta-analysis may be overestimated. The resulting press coverage declared “Counseling Has Limited Benefit on Young People Drinking Alcohol” (ScienceDaily news, 2014, August) and “Counseling Does Little to Deter Youth Drinking, Review Finds” (HealthDay news, 2014, August). Given the potential impact that Foxcroft et al. (2014) may have on intervention and policy development, as well as clients' understanding of their treatment options, it is important to critically examine the study's methodology and conclusion. The quality of evidence is just as important for meta-analysis reviews as for single studies when making recommendations to clinicians in the field (see the Grading of Recommendations Assessment, Development and Evaluation [GRADE] approach; Guyatt et al., 2008). In discussing Foxcroft et al. for the present article, we utilize available reporting guidelines for meta-analysis studies, such as the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA; Moher, Liberati, Tetzlaff, Altman, & The PRISMA group, 2009) of randomized controlled trials. The PRISMA has been adopted by many journals and organizations, including the Cochrane Collaboration, all BMC journals, and PloS One. The Meta-Analysis Reporting Standards (MARS) has been adopted by the American Psychological Association (APA) as part of the Journal Article Reporting Standards (JARS) by the APA Publications and Communications Board Working Group (2008). A new open access journal Archives of Scientific Psychology by APA (Cooper & VandenBos, 2013) further elaborates the MARS to help authors to improve the reporting of systematic reviews and meta-analyses. We also utilized other tutorial articles and textbooks (e.g., Borenstein, Hedges, Higgins, & Rothstein, 2009).

This study examined variability in Motivational Interviewing (MI) integrity among 15 providers for three years following training. Data come from an effectiveness trial in which providers were trained to deliver brief single-session MI interventions. Each session was audio-recorded and coded for MI integrity using the Motivational Interviewing Treatment Integrity (MITI) 3.1.1 rating system. Within-provider variation in MI integrity was large, especially for behavior count scores (e.g., open questions, complex reflections) and only slightly smaller for global session scores of MI Spirit and Empathy. Within-provider variability was in most cases larger than between-provider variability and there was no evidence that providers improved appreciably over time. These findings raise concerns about the quality of MI being delivered in large-scale implementation efforts and have implications for the monitoring and training of higher quality MI.

Rapid changes in technology are altering some of the basic ways in which we interact with our world, as seen in the evolution of the telephone to mobile phone to smart phone. These technological changes are ushering in new methods of data collection and analysis, which also open up new types of research questions and designs for couple researchers. This chapter reviews current and emerging methods for data acquisition and analysis in relationship science. Data acquisition methods include mobile technology and context-specific ecological momentary assessment, as well as behavioral signal-processing techniques to quantify such data. Analytic methods cover mixed models and actor–partner interdependence models, as well as a broad introduction to machine learning techniques that are appropriate for massive datasets.

The current paper presents novel methods for collecting MISC data and accurately assessing reliability of behavior codes at the level of the utterance. The MISC 2.1 was used to rate MI interviews from five randomized trials targeting alcohol and drug use. Sessions were coded at the utterance-level. Utterance-based coding reliability was estimated using three methods and compared to traditional reliability estimates of session tallies. Session-level reliability was generally higher compared to reliability using utterance-based codes, suggesting that typical methods for MISC reliability may be biased. These novel methods in MI fidelity data collection and reliability assessment provided rich data for therapist feedback and further analyses. Beyond implications for fidelity coding, utterance-level coding schemes may elucidate important elements in the counselor-client interaction that could inform theories of change and the practice of MI.

Marijuana is currently approved for medical use in 23 states. Both clinicians and the lay public have questioned whether users of marijuana for medical purposes are different from users of marijuana for recreational purposes. This study examined similarities and differences in important clinical characteristics between users of medical marijuana and users of recreational marijuana.The sample consisted of 868 adult primary care patients in Washington State, who reported use of medical marijuana (n = 131), recreational marijuana (n = 525), or drugs other than marijuana (n = 212). Retention was over 87% at 3-, 6-, 9-, and 12-month assessments.The majority of medical, psychiatric, substance use, and service utilization characteristic comparisons were not significant. However, medical marijuana users had significantly more medical problems, a significantly larger proportion reported15 days medical problems in the past month, and significantly smaller proportions reported no pain and no mobility limitations (p .001). Medical marijuana users also had significantly lower drug problem severity, lower alcohol problem severity, and significantly larger proportions reported using marijuana alone and concomitant opioid use only (p .001). There was no significant difference between medical and recreational users in the percentage using marijuana with at least two additional substances (48% vs. 58%, respectively, p = .05).Although our results suggest that there are few distinct differences between medical and recreational users of marijuana, the differences observed, while mostly very small in effect size (.2), are consistent with at least some medical users employing marijuana to relieve symptoms and distress associated with medical illness.

Antarctica has not always been a frozen continent covered in large ice sheets. It has experienced vastly different climates, ranging from tropical to polar, over hundreds of millions of years. As climate changed, so did the types of plants and animals, the amount of ice, the composition of the air and water, and the geological processes depositing sediments. Traces of these changes became preserved in layers of rock and ice that accumulated over time. Detailed studies of these layers allow scientists to produce a picture of, or to reconstruct, environments and climate conditions that existed in the past and piece together how and why they changed.

Motivational Interviewing (MI) is an efficacious treatment for substance use disorders and other problem behaviors (Lundahl and Burke, 2009). However, little is known about the specific mechanisms that drive therapeutic change. A growing body of research has focused on coding within-session language to better understand how therapist and patient language mutually influence each other and predict successful (or unsuccessful) treatment outcomes. These studies typically use human raters, requiring considerable financial, time, and training costs for conducting such research. This paper describes the development and testing of a recursive neural network (RNN) model for rating 78,977 therapist and patient talk turns across 356 MI sessions. We assessed the accuracy of RNNs in predicting human ratings for client speech and compared them to standard n-gram models. The RNN model showed improvement over ngram models for some codes, but overall, all of the models performed well below human reliability, demonstrating the difficulty of the task.

The technology for evaluating patient-provider interactions in psychotherapy–observational coding–has not changed in 70 years. It is labor-intensive, error prone, and expensive, limiting its use in evaluating psychotherapy in the real world. Engineering solutions from speech and language processing provide new methods for the automatic evaluation of provider ratings from session recordings. The primary data are 200 Motivational Interviewing (MI) sessions from a study on MI training methods with observer ratings of counselor empathy. Automatic Speech Recognition (ASR) was used to transcribe sessions, and the resulting words were used in a text-based predictive model of empathy. Two supporting datasets trained the speech processing tasks including ASR (1200 transcripts from heterogeneous psychotherapy sessions and 153 transcripts and session recordings from 5 MI clinical trials). The accuracy of computationally-derived empathy ratings were evaluated against human ratings for each provider. Computationally-derived empathy scores and classifications (high vs. low) were highly accurate against human-based codes and classifications, with a correlation of 0.65 and F-score (a weighted average of sensitivity and specificity) of 0.86, respectively. Empathy prediction using human transcription as input (as opposed to ASR) resulted in a slight increase in prediction accuracies, suggesting that the fully automatic system with ASR is relatively robust. Using speech and language processing methods, it is possible to generate accurate predictions of provider performance in psychotherapy from audio recordings alone. This technology can support large-scale evaluation of psychotherapy for dissemination and process studies.

Infidelity can have devastating effects on couples’ relationships. Not only are couples typically confused and uncertain about how to proceed, but couple therapists also report that treating infidelity is one of their greatest clinical challenges. In the current article, we present a conceptual model of response to infidelity with a corresponding infidelity-specific, couple-based intervention. This intervention incorporates interventions from cognitive-behavioral, insight-oriented, trauma-based, and forgiveness approaches to working with couples. In addition to this intervention created specifically for treating infidelity, we discuss how existing, empirically supported couple therapies such as traditional behavioral couple therapy (TBCT) and integrative behavioral couple therapy (IBCT) approach the treatment of infidelity. Finally, we present preliminary findings from two small treatment studies that provide initial, encouraging findings for the utility of the infidelity-specific intervention as well as TBCT and IBCT for treating infidelity.

SUMMARY: Background: Diabetic nephropathy is a major global health problem. Progression to renal failure is common; however, the mechanisms are unknown. Experimental models suggest a role for macrophages. Therefore, macrophage accumulation and its relationship to the subsequent clinical course were studied. Methods: A retrospective study of baseline histology and the subsequent clinical course over at least 5 years involving 20 consecutive patients with a histological and clinical diagnosis of diabetic nephropathy was performed. The relationship between macrophage accumulation in renal biopsy tissue (KP-1/anti-CD68+ cells), baseline measures of known predictors of progression (proteinuria, tubulointerstitial damage, myofibroblast accumulation) and progression over 5 years (plot of reciprocal of serum creatinine) was quantified. Results: Accumulation of macrophages was apparent in the glomeruli (2.8 + 0.7/gcs vs 1.0 + 0.2 for normals, P = not significant) and interstitium (296.9 + 63.3/mm2vs 19.0 + 1.3/mm2 for normals, P = 0.002) of patients with diabetic nephropathy. Glomerular macrophage number correlated with baseline serum creatinine (r = 0.548, P = 0.012) but not with progression of renal failure as glomerular macrophages were prevalent in early, but not advanced diabetic nephropathy. Interstitial macrophage accumulation correlated strongly with serum creatinine (r = 0.649, P = 0.002), proteinuria (r = 0.779, P

The Trauma Symptom Inventory (TSI; Briere, 1995) is a 100-item self-report measure of posttraumatic symptomatology that includes an Atypical Response (ATR) validity scale designed to differentiate honest from malingered profiles. In this study, using an analogue design to experimentally manipulate honest and malingered responses on the TSI, we found that proposed ATR cut scores produce a significant risk of false positives. Furthermore, the functioning of proposed cut scores worsened when we used posttraumatic stress disorder relevant samples and low estimates of malingering base rates. In light of these findings, the TSI should be used with caution when assessing claims of posttraumatic stress in forensic or disability settings.

OBJECTIVES The Atherosclerosis and Folic Acid Supplementation Trial (ASFAST) aimed to establish whether high-dose folic acid would slow the progression of atherosclerosis and reduce cardiovascular events in patients with chronic renal failure (CRF). BACKGROUND Hyperhomocysteinemia is a potential contributor to the high rates of cardiovascular morbidity and mortality in patients with CRF. METHODS A total of 315 subjects with CRF, mean age 57 years (range 24 to 79 years) were randomized to 15 mg folic acid daily or placebo and followed for a median of 3.6 years. The primary intima-media thickness (IMT) and clinical end points were: rate of progression of mean maximum carotid IMT and a composite of myocardial infarction (MI), stroke, and cardiovascular death. Secondary end points included all cardiovascular events and change in pulse wave velocity, systemic arterial compliance and augmentation index. Data were analyzed by intention-to-treat. RESULTS Plasma total homocysteine was reduced by 19% in the folic acid group. There was no significant difference between the treatment groups in rate of change of IMT or any measure of artery function. Seventy-seven events occurred in the folic acid group (14.9 per 100 patient-years) as compared with 86 in the placebo group (16.3 per 100 patient-years). The rates of the primary and secondary clinical end points at five years were not significantly different after adjustment for baseline differences between the groups (adjusted hazard ratio for MI, stroke, and cardiovascular death: 0.98 [95% confidence interval: 0.66 to 1.47]; p = 0.94; for all cardiovascular events: 0.95 [95% confidence interval: 0.69 to 1.30]; p = 0.75). CONCLUSIONS High-dose folic acid does not slow atheroma progression or improve cardiovascular morbidity or mortality in patients with CRF.

The current pandemic of diabetes mellitus will inevitably be followed by an epidemic of chronic kidney disease. It is anticipated that 25-40% of patients with type 1 diabetes and 5-40% of patients with type 2 diabetes will ultimately develop diabetic kidney disease. The control of blood pressure represents a key component for the prevention and management of diabetic nephropathy. There is a strong epidemiological connection between hypertension in diabetes and adverse outcomes in diabetes. Hypertension is closely linked to insulin resistance as part of the 'metabolic syndrome'. Diabetic nephropathy may lead to hypertension through direct actions on renal sodium handling, vascular compliance and vasomotor function. Recent clinical trials also support the utility of blood pressure reduction in the prevention of diabetic kidney disease. In patients with normoalbuminuria, transition to microalbuminuria can be prevented by blood pressure reduction. This action appears to be significant regardless of whether patients have elevated blood pressure or not. The efficacy of ACE inhibition appears to be greater than that achieved by other agents with a similar degree of blood pressure reduction; although large observational studies suggest the risk of microalbuminuria may be reduced by blood pressure reduction, regardless of modality. In patients with established microalbuminuria, ACE inhibitors and angiotensin receptor antagonists (angiotensin receptor blockers [ARBs]) consistently reduce the risk of progression from microalbuminuria to macroalbuminuria, over and above their antihypertensive actions. The clinical utility of combining these strategies remains to be established. In patients with overt nephropathy, blood pressure reduction is associated with reduced urinary albumin excretion and, subsequently, a reduced risk of renal impairment or end stage renal disease. In addition to actions on systemic blood pressure, it is now clear that ACE inhibitors and ARBs also reduce proteinuria in patients with diabetes. This anti-proteinuric activity is distinct from other antihypertensive agents and diuretics. Although there is a clear physiological rationale for blockade of the renin angiotensin system, which is strongly supported by clinical studies, to achieve the optimal lowering of blood pressure, particularly in the setting of established diabetic renal disease, a number of different antihypertensive agents will always be needed. In the end, the choice of agents should be individualised to achieve the maximal tolerated reduction in blood pressure and albuminuria. Ultimately, no matter how it is achieved, so long as it is achieved, renal risk can be reduced by agents that lower blood pressure and albuminuria.

Antidepressant medication is considered the current standard for severe depression, and cognitive therapy is the most widely investigated psychosocial treatment for depression. However, not all patients want to take medication, and cognitive therapy has not demonstrated consistent efficacy across trials. Moreover, dismantling designs have suggested that behavioral components may account for the efficacy of cognitive therapy. The present study tested the efficacy of behavioral activation by comparing it with cognitive therapy and antidepressant medication in a randomized placebo-controlled design in adults with major depressive disorder (N = 241). In addition, it examined the importance of initial severity as a moderator of treatment outcome. Among more severely depressed patients, behavioral activation was comparable to antidepressant medication, and both significantly outperformed cognitive therapy. The implications of these findings for the evaluation of current treatment guidelines and dissemination are discussed.

Diabetic nephropathy involves a renal inflammatory response induced by the diabetic milieu. Macrophages accumulate in diabetic kidneys in association with the local upregulation of monocyte chemoattractant protein-1 (MCP-1); however, the contribution of macrophages to renal injury and the importance of MCP-1 to their accrual are unclear. Therefore, we examined the progression of streptozotocin (STZ)-induced diabetic nephropathy in mice deficient in MCP-1 in order to explore the role of MCP-1-mediated macrophage accumulation in the development of diabetic kidney damage. Renal pathology was examined at 2, 8, 12 and 18 weeks after STZ treatment in MCP-1 intact (+/+) and deficient (-/-) mice with equivalent blood glucose and hemoglobin A1c levels. In MCP-1(+/+) mice, the development of diabetic nephropathy was associated with increased kidney MCP-1 production, which occurred mostly in tubules, consistent with our in vitro finding that elements of the diabetic milieu (high glucose and advanced glycation end products) directly stimulate tubular MCP-1 secretion. Diabetes of 18 weeks resulted in albuminuria and elevated plasma creatinine in MCP-1(+/+) mice, but these aspects of renal injury were largely suppressed in MCP-1(-/-) mice. Protection from nephropathy in diabetic MCP-1(-/-) mice was associated with marked reductions in glomerular and interstitial macrophage accumulation, histological damage and renal fibrosis. Diabetic MCP-1(-/-) mice also had a smaller proportion of kidney macrophages expressing markers of activation (inducible nitric oxide synthase or sialoadhesin) compared to diabetic MCP-1(+/+) mice. In conclusion, our study demonstrates that MCP-1-mediated macrophage accumulation and activation plays a critical role in the development of STZ-induced mouse diabetic nephropathy.

This article provides an overview of a study that synthesizes multiple, independently collected alcohol intervention studies for college students into a single, multisite longitudinal data set. This research embraced innovative analytic strategies (i.e., integrative data analysis or meta-analysis using individual participant-level data), with the overall goal of answering research questions that are difficult to address in individual studies such as moderation analysis, while providing a built-in replication for the reported efficacy of brief motivational interventions for college students. Data were pooled across 24 intervention studies, of which 21 included a comparison or control condition and all included one or more treatment conditions. This yielded a sample of 12,630 participants (42% men; 58% first-year or incoming students). The majority of the sample identified as White (74%), with 12% Asian, 7% Hispanic, 2% Black, and 5% other/mixed ethnic groups. Participants were assessed 2 or more times from baseline up to 12 months, with varying assessment schedules across studies. This article describes how we combined individual participant-level data from multiple studies, and discusses the steps taken to develop commensurate measures across studies via harmonization and newly developed Markov chain Monte Carlo (MCMC) algorithms for 2-parameter logistic item response theory models and a generalized partial credit model. This innovative approach has intriguing promises, but significant barriers exist. To lower the barriers, there is a need to increase overlap in measures and timing of follow-up assessments across studies, better define treatment and control groups, and improve transparency and documentation in future single intervention studies.

Macrophage accumulation has long been recognized as a feature of allograft rejection, yet the role of macrophages in rejection remains underappreciated. Macrophages contribute to both the innate and acquired arms of the alloimmune response and thus may be involved in all aspects of acute and chronic allograft rejection. Recent advances in macrophage biology have allowed a better understanding of the mechanisms of macrophage accumulation, their state of activation and the pleuripotent roles they play in allograft rejection. Therapeutic attention to macrophages, in addition to T lymphocytes, may lead to improved outcomes in organ transplantation.

BACKGROUND : The degree to which transplant recipients are immunosuppressed influences their risks of rejection, infection and cancer. Current measures of immune suppression are crude (clinical events) or indirect (drug exposure). We assessed a direct measure of immune status, leukocyte phenotype and function (LPF, a composite measure of five aspects of peripheral blood leukocyte phenotype and function), as a predictor of infection. METHODS : A double-blind, prospective, cohort study was conducted, to determine the burden of infection in stable renal transplant recipients with moderate-severe (Group I, n = 34) or minimal (Group II, n = 36) impairment of LPF, a composite score of: (i) CD4 count; (ii) lymphocyte proliferation in response to phytohaemagglutinin A (PHA); (iii) serum Ig concentrations; (iv) neutrophil phagocytic function; and (v) reactive oxygen species generation. Subjects completed a 6 month diary and each recorded infection was scored 1-4: 1, minor undefined infection (e.g. URTI); 2, minor, microbiologically defined infection (e.g. UTI); 3, major defined infection (requiring hospitalization); 4, opportunistic infection (e.g. Herpes zoster). Final infection score was the sum of all infective episodes. Subjects were then followed-up for 5 years for outcome measures. RESULTS : Groups were well matched for age, sex, diabetes, serum creatinine, rejection and trough cyclosporin concentrations. Group I (moderate to severe impairment of LPF) recorded a higher infection score, 2.4+/-2.8 vs 1.2+/-1.2 for Group II, P = 0.02, due to a higher incidence of moderate to severe infection. This relationship was confirmed by multivariate analysis (OR 1.83, CI 1.08, 3.11, P = 0.03 per unit increase in infection score). During the 5 year follow-up period they had significantly more episodes of admission to hospital, and twice as many admissions due to infections, but no difference in malignancy, graft or patient outcome. CONCLUSION : LPF testing prospectively identified a cohort who incurred a higher burden of infection. Further studies are required to determine the predictive value of LPF for acute rejection, infection and cancer, and to determine whether adjustments to therapy on the basis of LPF can lead to improved outcomes.

Diabetic nephropathy is a leading cause of end-stage renal failure and is a growing concern given the increasing incidence of type 2 diabetes. Diabetic nephropathy is associated with progressive kidney macrophage accumulation and experimental studies suggest that intercellular adhesion molecule (ICAM)-1 facilitates kidney macrophage recruitment during type 1 diabetes. To ascertain the importance of ICAM-1 in promoting type 2 diabetic nephropathy, the development of renal injury in ICAM-1 intact and deficient db/db mice with equivalent hyperglycemia and obesity between ages 2 and 8 mo was examined and compared with results with normal db/+ mice. Increases in albuminuria (11-fold), glomerular leukocytes (10-fold), and interstitial leukocytes (three-fold) consisting of predominantly CD68+ macrophages were identified at 8 mo in diabetic db/db mice compared with nondiabetic db/+ mice. In comparison to db/db mice, ICAM-1-deficient db/db mice had marked reductions in albuminuria at 6 mo (77% downward arrow) and 8 mo (85% downward arrow). There was also a significant decrease in glomerular (63% downward arrow) and interstitial (83% downward arrow) leukocytes in ICAM-1-deficient db/db mice, which were associated with reduced glomerular hypertrophy and hypercellularity and tubular damage. The development of renal fibrosis (expression of TGF-beta1, collagen IV, and interstitial alpha-smooth muscle actin) was also strikingly attenuated in the ICAM-1-deficient db/db mice. Additional in vitro studies showed that macrophage activation by high glucose or advanced glycation end products could promote ICAM-1 expression on tubular cells and macrophage production of active TGF-beta1. Thus, ICAM-1 appears to be a critical promoter of nephropathy in mouse type 2 diabetes by facilitating kidney macrophage recruitment.

What have we learned from clinical trials on prevention ? The incidence of end-stage renal disease is increasing at an alarming rate. While diabetes is now the most common cause of renal failure, hypertension commonly coexists, exacerbating renal damage and the other vascular complications of diabetes. Clinical trials have shown the benefits of intervention strategies that target not only the retardation of renal disease, but also the primary prevention of the conditions known to cause renal damage. These strategies include: lifestyle modification programs to prevent diabetes and hypertension; aggressive treatment of established hypertension; combination antihypertensive regimens; and the use of angiotensin-converting-enzyme inhibitors and angiotensin II receptor blockers for additional renoprotection beyond that of blood pressure control. In addition, albuminuria and proteinuria have emerged as powerful predictors of progression of renal disease. The present paper reviews the results of available clinical trials and meta-analyses on these interventional strategies, and highlights the potential of albuminuria and proteinuria in predicting renal and cardiovascular outcomes.

Components of the therapeutic process have been shown to be moderately strong predictors of change in patients’ global interpersonal functioning during therapy. The authors sought to extend this research by examining how the therapeutic process in time-limited dynamic psychotherapy related to change in patients’ perceptions of a specific relationship as rated by the Structural Analysis of Social Behavior. Results showed that ratings of therapist warmth at Session 3 predicted increased warmth and decreased hostility in patient behavior at posttreatment. Therapist warmth at Session 16 was predictive of a decrease in submissive behavior by patients toward their significant other. The importance of the association between the therapeutic process and patients’ important interpersonal relationships is discussed.

When a partner has been unfaithful, an important therapeutic task is to assess factors that contributed to the affair and that may affect the individual's and couple's healing. This article provides a framework to assess multiple factors and their influence on an affair over time, as well as on responses to an affair. We address factors related to the person involved in an affair, his or her partner, their relationship, and the external context. These factors are considered across six phases of an affair: predisposition, approach, initial involvement, maintenance, disclosure or discovery, and response. A case study is presented to illustrate the usefulness of the framework in working with couples in which there has been an affair.

In a sample of 134 married couples randomly assigned to traditional or integrative behavioral couple therapy (TBCT vs. IBCT), a multivariate hierarchical growth curve analysis using latent variable regression revealed that measures of communication, behavior frequency, and emotional acceptance acted as mechanisms of change. TBCT led to greater changes in frequency of targeted behavior early in therapy, whereas IBCT led to greater changes in acceptance of targeted behavior both early and late in therapy. In addition, change in behavioral frequency was strongly related to improvements in satisfaction early in therapy; however, in the 2nd half of therapy, emotional acceptance was more strongly related to changes in satisfaction. Research and clinical implications are discussed.

SUMMARY: Background: Determinants of native arteriovenous fistula (AVF) placement have been well studied. Little is known on whether these factors impact on subsequent blood flow (Qa) in the mature AVF. Methods: Arteriovenous fistula Qa and cardiac index (CI) were determined by ultrasound dilution. Multiple linear regression was used to assess independent predictors of AVF Qa. Results: Of the 148 patients available for the analysis, 68% were male, with 61% using a radiocephalic AVF. Aetiology of renal disease was: 38% glomerulonephritis (GN), 22% diabetes mellitus (DM), 9% hypertension/ischaemic (HTN) and 31% other. Thirty per cent had coronary artery disease (CAD), 10% cerebrovascular disease and 11% peripheral vascular disease (PVD). Median (iqr) Qa was 1185 mL/min (790–1650) and CI was 3.15 L/min per 1.73 m2 (2.60–3.93). On univariable analysis, log CI (0.98, P

Inflammation and fibrosis are pathological mechanisms that are partially regulated by cell signalling through the p38 mitogen-activated protein kinase (MAPK) pathway. Elements of the diabetic milieu such as high glucose and advanced glycation end-products induce activation of this pathway in renal cells. Therefore, we examined whether p38 MAPK signalling is associated with the development of human and experimental diabetic nephropathy.Immunostaining identified phosphorylated (active) p38 MAPK in human biopsies with no abnormality ( n=6) and with Type 2 diabetic nephropathy ( n=12). Changes in kidney levels of phosphorylated p38 were assessed by immunostaining and western blotting in mice with streptozotocin-induced Type 1 diabetes that had been killed after 0.5, 2, 3, 4 and 8 months, and in Type 2 diabetic db/db mice at 2, 4, 6 and 8 months of age.Phosphorylated p38 was detected in some intrinsic cells in normal human kidney, including podocytes, cortical tubules and occasional interstitial cells. Greater numbers of these phosphorylated p38+ cells were observed in diabetic patients, and phosphorylated p38 was identified in accumulating interstitial macrophages and myofibroblasts. A similar pattern of p38 activation was observed in both mouse models of diabetes. In mice, kidney levels of phosphorylated p38 increased (2-6 fold) following the onset of Type 1 and Type 2 diabetes. In both mouse models, interstitial phosphorylated p38+ cells were associated with hyperglycaemia, increased HbA(1)c levels and albuminuria. Further assessment of streptozotocin-induced diabetic nephropathy showed that interstitial phosphorylated p38+ cells correlated with interstitial fibrosis (myofibroblasts, collagen).Increased p38 MAPK signalling is a feature of human and experimental diabetic nephropathy. Time course studies in mouse models suggest that phosphorylation of p38 plays a pathological role, particularly in the development of interstitial fibrosis.

Objective: To evaluate the efficacy and safety of monotherapy with adalimumab in patients with RA for whom previous DMARD treatment has failed. Methods: In a 26 week, double blind, placebo controlled, phase III trial, 544 patients with RA were randomised to monotherapy with adalimumab 20 mg every other week, 20 mg weekly, 40 mg every other week, 40 mg weekly, or placebo. The primary efficacy end point was ≥20% improvement in the ACR core criteria (ACR20 response). Secondary efficacy end points included ACR50, ACR70, EULAR responses, and the Disability Index of the Health Assessment Questionnaire (HAQ DI). Results: After 26 weeks, patients treated with adalimumab 20 mg every other week, 20 mg weekly, 40 mg every other week, and 40 mg weekly had significantly better response rates than those treated with placebo: ACR20 (35.8%, 39.3%, 46.0%, 53.4%, respectively v 19.1%; p⩽0.01); ACR50 (18.9%, 20.5%, 22.1%, 35.0% v 8.2%; p⩽0.05); ACR70 (8.5%, 9.8%, 12.4%, 18.4% v 1.8%; p⩽0.05). Moderate EULAR response rates were significantly greater with adalimumab than with placebo (41.5%, 48.2%, 55.8%, 63.1% v 26.4%; p⩽0.05). Patients treated with adalimumab achieved better improvements in mean HAQ DI than those receiving placebo (−0.29, −0.39, −0.38, −0.49 v −0.07; p⩽0.01). No significant differences were found between adalimumab and placebo treated patients for serious adverse events, serious infections, or malignancies. Injection site reaction occurred in 10.6% and 0.9% of adalimumab and placebo treated patients, respectively (p⩽0.05). Conclusion: Among patients with RA for whom previous DMARD treatment had failed, adalimumab monotherapy achieved significant, rapid, and sustained improvements in disease activity and improved physical function and was safe and well tolerated.

Arterial function after successful renal transplantation. Background Renal transplantation is increasingly the preferred method of renal replacement therapy. Cardiovascular disease is the major barrier to long-term survival for transplant recipients. The aim of this study was to determine whether the increased arterial stiffness of patients with chronic renal failure is improved after successful renal transplantation. Methods The study involved a group of 36 patients, aged 27 to 68years (mean ± SD, 46 ± 11years) who had cardiovascular risk assessment and measurements of carotid artery intima-media thickness (IMT), arterial pulse wave velocity [aorto-femoral (PWV a-f) and femoral-dorsalis pedis (PWV f-d)], systemic arterial compliance (SAC), and arterial wave reflection (augmentation index, AI x ) performed before and 12months after successful renal transplantation. B-mode ultrasound measurements were used to determine mean carotid IMT and applanation tonometry techniques to determine SAC, AI x , PWV (a-f), PWV (f-d), and central pressures. On each occasion the following were also measured: fasting lipids, homocysteine (tHcy), red cell folate, cobalamin, and fibrinogen levels. Results One year after transplantation, mean serum creatinine was 143 ± 47 μmol/L, and creatinine clearance 60 ± 16mL/min/1.74m 2 (range 25 to 104mL/min/1.74m 2 ). Total and low-density lipoprotein (LDL) cholesterol were significantly reduced. tHcy was decreased by 38% and normalized in 45%. Systolic and diastolic blood pressure and mean arterial pressure were all improved. From baseline to 12months' post-transplantation, there was no significant change in carotid IMT (mean IMT 0.76 ± 0.11 vs. 0.75 ± 0.14mm, P = 0.28) or SAC (0.45 ± 0.23 vs. 0.46 ± 0.22 units, P = 0.95), but PWV [PWV (a-f) 9.6 ± 2.6 vs. 8.8 ± 2.2 m/sec, P = 0.007; PWV (f-d) 10.7 ± 1.8 vs. 8.4 ± 1.7 m/sec, P x (24.3 ± 13.4 vs. 15.9 ± 11.4%, P = 0.003) improved. After adjusting for the differences in blood pressure, the changes in PWV (a-f) were no longer significant, but the differences in PWV (f-d) persisted. The change in AI x remained significant after adjusting for differences in heart rate, and the fall in AI x was greater in patients on immunosuppression with tacrolimus compared with those on cyclosporine. Conclusion One year after successful renal transplantation, improvement in cardiovascular risk factors was associated with improvement in indices of arterial stiffness.

Native arteriovenous fistula (AVF) prevalence varies significantly among different populations and countries. Physician practice patterns may have a strong influence on access type. We assessed differences in vascular access practice patterns across all treating centers in New Zealand.Adult (ageor = 18 years) patients on hemodialysis therapy in the year ending September 30, 2001, were studied from the Australian and New Zealand Dialysis and Transplant Association Registry. Multinomial logistic regression was used to assess factors associated with arteriovenous graft (AVG) and catheter use.Of 772 patients available for analysis, 461 patients (60%) underwent dialysis using an AVF; 122 patients (16%), an AVG; and 189 patients (24%), a catheter. On multivariable analysis, female sex (odds ratio, 5.92; P0.001), coronary artery disease (odds ratio, 1.89; P0.05), body mass index greater than 30 (odds ratio, 2.55; P0.05), and age (odds ratio, 1.03 per year increase; P0.001) were associated with an increased likelihood of AVG use. Maori and Pacific Island patients were less likely to use an AVG compared with Caucasians (odds ratio, 0.47; P0.05). Predictors of greater likelihood of catheter use were female sex (odds ratio, 3.9; P0.001), late referral (odds ratio, 1.60; P0.05), and age (odds ratio, 1.02 per year increase; P0.001). Proportions of access types varied significantly across the 7 treating centers (AVFs, 32% to 86%; AVGs, 2% to 32%; catheters, 9% to 33%; P0.001). After adjusting for confounding factors, significant differences persisted among access types in some centers and the national average.Certain patient characteristics, such as age and female sex, are associated strongly with increased AVG and catheter use. However, the significant variation in risk across centers suggests more attention needs to be given to physician practice patterns to increase AVF use rates.

The p38 mitogen-activated protein kinase (MAPK) pathway transduces external stress stimuli and is important in extracellular matrix synthesis in cell types in vitro; however, its role in renal fibrosis is not known. Explored was the role the p38 MAPK pathway in rat unilateral ureteric obstruction (UUO), a model of renal fibrosis induced by a noninflammatory surgical insult. In a time-course study, a marked increase in phosphorylation (activation) of p38 in both interstitial myofibroblasts and tubules was shown. Rats were then treated daily with a specific inhibitor of p38alpha, NPC 31169, from the time of UUO surgery until being killed 7 d later. Compared with vehicle, NPC 31169-treated rats had a significant reduction in renal fibrosis assessed by interstitial volume, collagen IV deposition, and mRNA levels. This was primarily due to a reduction in the accumulation of interstitial myofibroblasts, as shown by a reduction in the area of immunostaining for alpha-smooth muscle actin and heat shock protein 47. The increase in renal TGF-beta1 mRNA and protein levels in UUO was unaltered with NPC 31169 treatment; however, connective tissue growth factor mRNA was reduced. These results demonstrate that p38alpha MAPK plays an important role in renal fibrosis, acting downstream of TGF-beta1. Blockade of p38 MAPK reduces extracellular matrix production and may be considered a potential therapeutic option in the treatment of renal fibrosis.

Background: In this systematic review of randomized controlled trials (RCTs), we assess the benefits and harm of current treatments for diffuse proliferative lupus nephritis (DPLN). Methods: The Cochrane Controlled Trial Registry, MEDLINE, and EMBASE were searched for RCTs of treatment for DPLN. All available RCTs of patients with biopsy-proven DPLN were included, and data were extracted for overall mortality, end-stage renal disease, doubling of serum creatinine level, relapse, major infection, herpes zoster infection, ovarian failure, malignancy, and bladder toxicity. Treatment effects on these outcomes were summarized as relative risk (RR) with 95% confidence interval (CI) and pooled by using a random-effects model. Results: Twenty-five of 920 articles identified were eligible RCTs and were included. The majority compared cyclophosphamide or azathioprine plus steroids versus steroids alone. Cyclophosphamide plus steroids reduced the risk for doubling of serum creatinine level (4 RCTs, 228 patients; RR, 0.59; 95% CI, 0.40 to 0.88) compared with steroids alone, but had no impact on overall mortality (5 RCTs, 226 patients; RR, 0.98; 95% CI, 0.53 to 1.82). However, risk for ovarian failure was increased significantly (3 RCTs, 147 patients; RR, 2.18; 95% CI, 1.10 to 4.34). In studies from the 1970s, azathioprine plus steroids reduced the risk for all-cause mortality compared with steroids alone (3 RCTs, 78 patients; RR, 0.60; 95% CI, 0.36 to 0.99), but had no effect on renal outcomes. Neither therapy was associated with increased risk for major infection. The addition of plasma exchange to these treatments offered no benefit, and information on other agents, including mycophenolate mofetil, was insufficient for analysis. Conclusion: Until future RCTs of newer agents are completed, the current use of cyclophosphamide combined with steroids remains the best option to preserve renal function in patients with DPLN. The smallest effective dose and shortest duration of treatment should be used to minimize gonadal toxicity without compromising efficacy.