Arthroscopic Versus Open Anterior Shoulder Stabilization: A Prospective Randomized Clinical Trial With 15-Year Follow-up With an Assessment of the Glenoid Being "On-Track" and "Off-Track" as a Predictor of Failure.

BACKGROUND: Recent studies have demonstrated equivalent short-term results when comparing arthroscopic versus open anterior shoulder stabilization. However, none have evaluated the long-term clinical outcomes of patients after arthroscopic or open anterior shoulder stabilization, with inclusion of an assessment of preoperative glenoid tracking. PURPOSE: To compare long-term clinical outcomes of patients with recurrent anterior shoulder instability randomized to open and arthroscopic stabilization groups. Additionally, preoperative magnetic resonance imaging (MRI) studies were used to assess whether the shoulders were "on-track" or "off-track" to ascertain a prediction of increased failure risk. STUDY DESIGN: Randomized controlled trial; Level of evidence, 1. METHODS: A consecutive series of 64 patients with recurrent anterior shoulder instability were randomized to receive either arthroscopic or open stabilization by a single surgeon. Follow-up assessments were performed at minimum 15-year follow-up using established postoperative evaluations. Clinical failure was defined as any recurrent dislocation postoperatively or subjective instability. Preoperative MRI scans were obtained to calculate the glenoid track and designate shoulders as on-track or off-track. These results were then correlated with the patients' clinical results at their latest follow-up. RESULTS: Of 64 patients, 60 (28 arthroscopic and 32 open) were contacted or examined for follow-up (range, 15-17 years). The mean age at the time of surgery was 25 years (range, 19-42 years), while the mean age at the time of this assessment was 40 years (range, 34-57 years). The rates of arthroscopic and open long-term failure were 14.3% (4/28) and 12.5% (4/32), respectively. There were no differences in subjective shoulder outcome scores between the treatment groups. Of the 56 shoulders, with available MRI studies, 8 (14.3%) were determined to be off-track. Of these 8 shoulders, there were 2 surgical failures (25.0%; 1 treated arthroscopically, 1 treated open). In the on-track group, 6 of 48 had failed surgery (12.5%; 3 open, 3 arthroscopic [P = .280]). CONCLUSION: Long-term clinical outcomes were comparable at 15 years postoperatively between the arthroscopic and open stabilization groups. The presence of an off-track lesion may be associated with a higher rate of recurrent instability in both cohorts at long-term follow-up; however, this study was underpowered to verify this situation.

Bringing Critical Race Praxis Into the Study of Electrophysiological Substrate of Sudden Cardiac Death: The ARIC Study.

Background Race is an established risk factor for sudden cardiac death (SCD). We sought to determine whether the association of electrophysiological substrate with SCD varies between black and white individuals. Methods and Results Participants from the ARIC (Atherosclerosis Risk in Communities) study with analyzable ECGs (n=14 408; age, 54±6 years; 74% white) were included. Electrophysiological substrate was characterized by ECG metrics. Two competing outcomes were adjudicated: SCD and non-SCD. Interaction of ECG metrics with race was studied in Cox proportional hazards and Fine-Gray competing risk models, adjusted for prevalent cardiovascular disease, risk factors, and incident nonfatal cardiovascular disease. At the baseline visit, adjusted for age, sex, and study center, blacks had larger spatial ventricular gradient magnitude (0.30 mV; 95% CI, 0.25-0.34 mV), sum absolute QRST integral (18.4 mV*ms; 95% CI, 13.7-23.0 mV*ms), and Cornell voltage (0.30 mV; 95% CI, 0.25-0.35 mV) than whites. Over a median follow-up of 24.4 years, SCD incidence was higher in blacks (2.86 per 1000 person-years; 95% CI, 2.50-3.28 per 1000 person-years) than whites (1.37 per 1000 person-years; 95% CI, 1.22-1.53 per 1000 person-years). Blacks with hypertension had the highest rate of SCD: 4.26 (95% CI, 3.66-4.96) per 1000 person-years. Race did not modify an association of ECG variables with SCD, except QRS-T angle. Spatial QRS-T angle was associated with SCD in whites (hazard ratio, 1.38; 95% CI, 1.25-1.53) and hypertension-free blacks (hazard ratio, 1.52; 95% CI, 1.09-2.12), but not in blacks with hypertension (hazard ratio, 1.15; 95% CI, 0.99-1.32) (P-interaction=0.004). Conclusions Race did not modify associations of electrophysiological substrate with SCD and non-SCD. Electrophysiological substrate does not explain racial disparities in SCD rate.

Attitudes and awareness of suture anchor cost: a survey of shoulder surgeons performing rotator cuff repairs.

BACKGROUND: The cost of health care in the United States accounts for 18% of the nation's gross domestic product and is expected to reach 20% by 2020. Physicians are responsible for 60%-80% of decisions resulting in health care expenditures. Rotator cuff repairs account for $1.2-$1.6 billion in US health care expenditures annually. The purpose of this study is to assess surgeons' cost awareness in the setting of rotator cuff repairs. The hypothesis is that practice environment and training affect cost consciousness and incentivization will lead to more cost-effective choices. METHODS: In this cross-sectional study, a 21-item survey was distributed via the email list services of the American Shoulder and Elbow Surgeons and Arthroscopy Association of North America. Data collected included demographics, variables regarding rotator cuff repair (technique, number of companies used, procedures per month), and knowledge of costs. RESULTS: Responses from 345 surgeons in 23 countries were obtained with the majority (89%) being from the United States. Most surgeons were "cost-conscious" (275, 70.7%). Of these surgeons, 62.9% are willing to switch suture anchors brands to reduce overall costs if incentivized. Cost-conscious surgeons were more likely to be fellowship trained in shoulder and elbow (51.81% vs. 38.57%, P = .048), be paid based on productivity (73.53% vs. 61.43%, P = .047), and receive shared profits (85.4% vs. 75%, P = .02). CONCLUSION: The majority of orthopedic surgeons are both cost-conscious and willing to change their practice to reduce costs if incentivized to do so. A better understanding of implant costs combined with incentives may help reduce health care expenditure.

Linezolid pharmacokinetics in MDR-TB: a systematic review, meta-analysis and Monte Carlo simulation.

Objectives: The oxazolidinone linezolid is an effective component of drug-resistant TB treatment, but its use is limited by toxicity and the optimum dose is uncertain. Current strategies are not informed by clinical pharmacokinetic (PK)/pharmacodynamic (PD) data; we aimed to address this gap. Methods: We defined linezolid PK/PD targets for efficacy (fAUC0-24:MIC >119 mg/L/h) and safety (fCmin <1.38 mg/L). We extracted individual-level linezolid PK data from existing studies on TB patients and performed meta-analysis, producing summary estimates of fAUC0-24 and fCmin for published doses. Combining these with a published MIC distribution, we performed Monte Carlo simulations of target attainment. Results: The efficacy target was attained in all simulated individuals at 300 mg q12h and 600 mg q12h, but only 20.7% missed the safety target at 300 mg q12h versus 98.5% at 600 mg q12h. Although suggesting 300 mg q12h should be used preferentially, these data were reliant on a single centre. Efficacy and safety targets were missed by 41.0% and 24.2%, respectively, at 300 mg q24h and by 44.6% and 27.5%, respectively, at 600 mg q24h. However, the confounding effect of between-study heterogeneity on target attainment for q24h regimens was considerable. Conclusions: Linezolid dosing at 300 mg q12h may retain the efficacy of the 600 mg q12h licensed dosing with improved safety. Data to evaluate commonly used 300 mg q24h and 600 mg q24h doses are limited. Comprehensive, prospectively obtained PK/PD data for linezolid doses in drug-resistant TB treatment are required.

Optimized retroviral transduction of mouse T cells for in vivo assessment of gene function.

Retroviral (RV) expression of genes of interest (GOIs) is an invaluable tool and has formed the foundation of cellular engineering for adoptive cell therapy in cancer and other diseases. However, monitoring of transduced T cells long term (weeks to months) in vivo remains challenging because of the low frequency and often poor durability of transduced T cells over time when transferred without enrichment. Traditional methods often require additional overnight in vitro culture after transduction. Moreover, in vitro-generated effector CD8+ T cells enriched by sorting often have reduced viability, making it difficult to monitor the fate of transferred cells in vivo. Here, we describe an optimized mouse CD8+ T-cell RV transduction protocol that uses simple and rapid Percoll density centrifugation to enrich RV-susceptible activated CD8+ T cells. Percoll density centrifugation is simple, can be done on the day of transduction, requires minimal time, has low reagent costs and improves cell recovery (up to 60%), as well as the frequency of RV-transduced cells (∼sixfold over several weeks in vivo as compared with traditional methods). We have used this protocol to assess the long-term stability of CD8+ T cells after RV transduction by comparing the durability of T cells transduced with retroviruses expressing each of six commonly used RV reporter genes. Thus, we provide an optimized enrichment and transduction approach that allows long-term in vivo assessment of RV-transduced T cells. The overall procedure from T-cell isolation to RV transduction takes 2 d, and enrichment of activated T cells can be done in 1 h.

Multimodal Assessment of Body Pain in Orofacial Pain Patients.

OBJECTIVE: . Patients with complaints of orofacial pain (OFP) often have other body pain, yet many do not report these to their providers. Uncontrolled pain at any location may impact the successful management of an OFP complaint. The objective of this study was to determine the number of pain regions throughout the body, and the underreporting of pain, in patients who presented to a tertiary military OFP clinic. DESIGN: A retrospective chart review was conducted on 423 consecutive new patients. Patients were given three assessment opportunities to report their pain on a whole-body pain map: 1) prior to evaluation (Pt1), 2) following an explanatory statement by their provider on the relationship between pain and prognosis (Pt2), and 3) during directed pain inquiry of specific body regions (Pro). The pain map was divided into nine anatomical regions that were assessed for the presence of pain after Pt1, Pt2, and Pro. RESULTS: Initially, 60.5% of patients did not report all pain locations (Pt1). Following the explanatory statement (Pt2), 30.5% still did not report all pain. Following the completion of all assessment methods, the most commonly reported number of pain regions was five (17.0%), and 91.5% of patients reported multiple pain regions. CONCLUSIONS: Most patients had multiple pain complaints outside the chief complaint, yet the majority did not report these until multiple forms of assessment were utilized. These data encourage the use of a pain map, a verbal pain explanation, and directed pain questioning to more accurately capture pain location and facilitate multidisciplinary care.

Sociopolitical effects of bow and arrow technology in prehistoric coastal California.

Bow and arrow technology spread across California between ∼AD 250 and 1200, first appearing in the intermountain deserts of the Great Basin and later spreading to the coast. We critically evaluate the available data for the initial spread in bow and arrow technology and examine its societal effects on the well-studied Northern Channel Islands off the coast of Southern California. The introduction of this technology to these islands between AD 650 and 900 appears to predate the appearance of hereditary inequality between AD 900 and 1300. We conclude, based on the available data, that this technology did not immediately trigger intergroup warfare. We argue that the introduction of the bow and arrow contributed to sociopolitical instabilities that were on the rise within the context of increasing population levels and unstable climatic conditions, which stimulated intergroup conflict and favored the development of hereditary inequality. Population aggregation and economic intensification did occur with the introduction of the bow and arrow. This observation is consistent with the hypothesis that social coercion via intra-group "law enforcement" contributed to changes in societal scale that ultimately resulted in larger groups that were favored in inter-group conflict. We argue that the interplay between intra-group "law enforcement" and inter-group warfare were both essential for the ultimate emergence of social inequality between AD 900 and 1300.

Teaching cost-conscious medicine: impact of a simple educational intervention on appropriate abdominal imaging at a community-based teaching hospital.

BACKGROUND: Rising costs pose a major threat to US health care. Residency programs are being asked to teach residents how to provide cost-conscious medical care. METHODS: An educational intervention incorporating the American College of Radiology appropriateness criteria with lectures on cost-consciousness and on the actual hospital charges for abdominal imaging was implemented for residents at Scripps Mercy Hospital in San Diego, CA. We hypothesized that residents would order fewer abdominal imaging examinations for patients with complaints of abdominal pain after the intervention. We analyzed the type and number of abdominal imaging studies completed for patients admitted to the inpatient teaching service with primary abdominal complaints for 18 months before (738 patients) and 12 months following the intervention (632 patients). RESULTS: There was a significant reduction in mean abdominal computed tomography (CT) scans per patient (1.7-1.4 studies per patient, P < .001) and total abdominal radiology studies per patient (3.1-2.7 studies per patient, P  =  .02) following the intervention. The avoidance of charges solely due to the reduction in abdominal CT scans following the intervention was $129 per patient or $81,528 in total. CONCLUSIONS: A simple educational intervention appeared to change the radiologic test-ordering behavior of internal medicine residents. Widespread adoption of similar interventions by residency programs could result in significant savings for the health care system.

Accelerated approval of oncology products: the food and drug administration experience.

We reviewed the regulatory history of the accelerated approval process and the US Food and Drug Administration (FDA) experience with accelerated approval of oncology products from its initiation in December 11, 1992, to July 1, 2010. The accelerated approval regulations allowed accelerated approval of products to treat serious or life-threatening diseases based on surrogate endpoints that are reasonably likely to predict clinical benefit. Failure to complete postapproval trials to confirm clinical benefit with due diligence could result in removal of the accelerated approval indication from the market. From December 11, 1992, to July 1, 2010, the FDA granted accelerated approval to 35 oncology products for 47 new indications. Clinical benefit was confirmed in postapproval trials for 26 of the 47 new indications, resulting in conversion to regular approval. The median time between accelerated approval and regular approval of oncology products was 3.9 years (range = 0.8-12.6 years) and the mean time was 4.7 years, representing a substantial time savings in terms of earlier availability of drugs to cancer patients. Three new indications did not show clinical benefit when confirmatory postapproval trials were completed and were subsequently removed from the market or had restricted distribution plans implemented. Confirmatory trials were not completed for 14 new indications. The five longest intervals from receipt of accelerated approval to July 1, 2010, without completion of trials to confirm clinical benefit were 10.5, 6.4, 5.5, 5.5, and 4.7 years. The five longest intervals between accelerated approval and successful conversion to regular approval were 12.6, 9.7, 8.1, 7.5, and 7.4 years. Trials to confirm clinical benefit should be part of the drug development plan and should be in progress at the time of an application seeking accelerated approval to prevent an ineffective drug from remaining on the market for an unacceptable time.

RhBMP-2 versus iliac crest bone graft for lumbar spine fusion in patients over 60 years of age: a cost-utility study.

STUDY DESIGN: Randomized clinical trial. OBJECTIVE: To perform a cost-utility analysis using actual cost data from a randomized clinical trial of patients over 60 years old who underwent posterolateral fusion using either rhBMP-2/ACS or iliac crest bone graft (ICBG). SUMMARY BACKGROUND DATA: Bone morphogenetic protein has been shown to be an effective bone graft substitute for spine fusion. However, a clinical trial-based economic analysis of rhBMP-2/ACS compared with iliac crest bone graft has not been done. METHODS: Patients over 60 years old requiring decompression and posterolateral fusion were randomized to rhBMP-2/ACS (n = 50) or ICBG (n = 52). A dedicated hospital coder and research nurse tracked each patient to determine direct costs of inpatient care and all postoperative healthcare encounters up to 2 years after surgery. Preoperative and 2-year-postoperative SF-6D utility scores for each patient were determined. A decision tree was created, which included the probability of complications, need for additional treatments and revision surgery; and the costs associated with initial surgery and treatment for complications and additional treatment for continued spine symptoms; and utility scores. RESULTS: The mean total 2-year cost for care (excluding complication and additional spine treatment costs) was $34,235 in the ICBG group and $36,530 in the rhBMP-2/ACS group. For the entire group, the mean cost to treat a major complication was $10,888, the cost of revision surgery for nonunion was $46,852, and additional treatment for spine-related events was $5892. In the ICBG group, 8 patients had complications; 20 had additional interventions, 5 of whom required revision for nonunion. In the rhBMP-2/ACS group, 6 patients had complications, 10 had additional interventions, and 1 required revision for nonunion. The cost of using rhBMP-2/ACS was $39,967 with a 0.11 mean improvement in SF-6D; and for ICBG the cost was $42,286 with a mean improvement of 0.10 in SF-6D. CONCLUSION: There are more complications, increased need for additional treatment and revision surgery in patients over 60 years old receiving ICBG compared with rhBMP-2/ACS. This may account for higher costs and lower improvements in utility seen in patients receiving ICBG compared with rhBMP-2/ACS in this study population.

RhBMP-2 versus iliac crest bone graft for lumbar spine fusion: a randomized, controlled trial in patients over sixty years of age.

STUDY DESIGN: Prospective randomized controlled trial of rhBMP-2/ACS (Infuse bone graft) versus iliac crest bone graft (ICBG) for lumbar spine fusion in patients over 60 years of age. OBJECTIVE: To report on clinical, radiographic, and economic outcomes, at 2-year follow-up, in patients treated by posterolateral lumbar fusion with rhBMP-2/ACS versus ICBG. SUMMARY OF BACKGROUND DATA: RhBMP-2/ACS is widely used "off-label" for posterolateral spinal fusion. Despite encouraging initial reports, outstanding issues include the need for evidence regarding safety and efficacy in an older population; and an assessment of cost-effectiveness. METHODS: Patients over 60 years old were randomized to rhBMP-2/ACS (n = 50) or ICBG (n = 52). Oswestry Disability Index, Short Form-36, and numerical rating scales for back and leg pain were determined preoperatively and at 6, 12, and 24 months postoperatively. Fusion was evaluated by fine-cut computed tomography scan 2 years postoperatively by 3 reviewers. All in-patient and subsequent out-patient event costs were recorded by a dedicated hospital coder. RESULTS: Two-year postoperative improvement in Oswestry Disability Index averaged 15.8 in the rhBMP-2/ACS group and 13.0 in the ICBG group. Mean improvement in Short Form-36 physical component score was 6.6 in the rhBMP-2/ACS group and 7.5 in the ICBG group. There were 20 complications in the ICBG group and 8 complications in the rhBMP-2/ACS group (P = 0.014). Sixteen ICBG and 10 rhBMP-2/ACS patients required additional treatment for persistent back or leg symptoms. Two rhBMP-2/ACS patients had revision procedures, 1 for nonunion. Eight patients in the ICBG group had revision procedures, 5 for nonunion. Mean fusion grade on computed tomography scan was significantly (P = 0.030) better in the rhBMP-2/ACS (4.3) compared with the ICBG group (3.8). Mean cost of the initial admission was $36,530 in the rhBMP-2/ACS group and $34,235 in the iliac crest bone graft (ICBG) group. Total cost of care over 2 years was $42,574 for the ICBG group and $40,131 for the rhBMP-2/ACS group. CONCLUSION: RhBMP-2/ACS is a viable ICBG replacement in older patients in terms of safety, clinical efficacy, and cost-effectiveness.

Multi-disciplinary studies of viruses: the role of structure in shaping the questions and answers.

This contribution to the 50th anniversary issue of the Journal of Structural Biology traces a path in which the author evolved from seeing macromolecular structure as end in it self to a means of organizing and correlating data from many sources. The author looks at where we have been and where we are going in this enterprise and the role that structure plays in defining ever more ambitious biological questions and testing and refining models that incorporate data from many techniques. In this, essentially, personal account, the author reflects on 35 years of structural virology and the stages experienced; from "stand alone" crystallography of virus particles to the study of virus assembly and maturation in vitro and eventually into the entire virus infection process from particle cell entry to egress. In the process data from many sources were incorporated into reasonable and testable models based on structures ranging in resolution from near-atomic determined by crystallography, to nanometer, determined by electron cryo-microscopy and image reconstruction, to five nanometer tomographic studies in the cell. The technological development over this period, for structural studies at all resolutions and functional studies that were unimaginable three decades ago, has been astonishing. Here we look at an aspect of this development applied to virology.

The perioperative cost of Infuse bone graft in posterolateral lumbar spine fusion.

BACKGROUND CONTEXT: There is mounting evidence supporting the efficacy of bone morphogenetic protein (BMP) for both anterior interbody and posterolateral lumbar fusion. However, the relative cost of BMP remains an important concern for physicians, hospitals, and payers. PURPOSE: The purpose of this study is to report on the perioperative costs for patients treated with rhBMP-2 as compared with an iliac crest bone graft (ICBG) supplemented with graft extenders. STUDY DESIGN/SETTING: A prospective randomized controlled trial of rhBMP-2/ACS (Infuse Bone Graft; Medtronic Sofamor Danek, Memphis, TN) versus ICBG+/-graft extender for lumbar spine fusion in patients over 60 years old. PATIENT SAMPLE: One hundred two patients over 60 years old who required a posterolateral lumbar spine fusion randomized between receiving rhBMP-2/ACS or ICBG. OUTCOME MEASURES: All health-care costs over the first 3 months after surgery. METHODS: As part of a prospective randomized trial of rhBMP-2/ACS versus ICBG+/-graft extender for lumbar spine fusion, all costs over the first 3 months after surgery were directly recorded by a dedicated coder funded by Norton Healthcare, Louisville, KY. A dedicated research nurse also followed all patients throughout their hospital stay and posthospitalization recovery to identify any adverse events or additional outpatient medical care. RESULTS: Fifty patients received rhBMP-2/ACS and 52 underwent ICBG harvest. The mean hospital cost for the index admission was $24,736 for the rhBMP-2/ACS group and $21,138 for the ICBG group. Mean inpatient physician costs were $5,082 in the rhBMP-2/ACS group and $5,316 in the ICBG group. Costs associated with posthospital rehabilitation averaged $4,906 in the rhBMP-2/ACS group versus $6,820 in the ICBG group. Total payer expenditure for the 3-month perioperative period averaged $33,860 in the rhBMP-2/ACS group and $37,227 in the ICBG group. CONCLUSIONS: The hospital carries the cost burden associated with the utilization of rhBMP-2/ACS. In contrast, the payer in a Diagnosis-Related Group (DRG) model achieves a net savings, based primarily on the decreased payment for inpatient rehabilitation, but also on decreased hospital reimbursement, physician costs, and other outpatient services.

Indoor and outdoor air quality assessment of four wastewater treatment plants.

The study assessed the air quality of four wastewater treatment plants (WWTPs) by monitoring levels of hydrogen sulfide (H2S) and endotoxin. Samples were taken over a 1-year period (2001-2002). The unit operations at each WWTP were categorized as: (a) grit removal, (b) primary clarification, (c) biological treatment, (d) secondary clarification, (e) sludge dewatering, and (f) digestion. Temperature and humidity were monitored simultaneously, whereas airborne H2S and endotoxin were monitored at each of the six unit operations in each plant. Carbonaceous biochemical oxygen demand (CBOD) and total incoming flow of the day of visit were also recorded. The geometric means of H2S concentration were less than 1 ppm and endotoxin ranged from 6-1247 EU/m3. A mixed model analysis of covariance (ANCOVA) was used for the statistical analysis. While temperature was not associated with the levels of both contaminants, humidity was influential on the level of H2S (p < 0.01) but not of endotoxin. CBOD did not affect the levels of either contaminant; however, incoming flows showed an association with the levels of H2S (p < 0.05). The concentrations of H2S in the six unit operations were statistically different, whereas endotoxin did not show any differences in concentrations between units. Individual comparisons proved that concentrations of H2S in the grit removal and sludge dewatering unit operations were statistically higher than the other operations. Overall, the concentrations of H2S varied depending on total incoming flow, humidity, and different unit operations. This trend was not observed for endotoxin. The results showed that the factors analyzed affected concentrations of H2S and endotoxin differently. Therefore, different control methods for endotoxin and H2S need to be considered to effectively reduce their concentrations at WWTPs.

Capacity building for the clinical investigation of AIDS malignancy in East Africa.

PURPOSE: To build capacity in the resource-poor setting to support the clinical investigation and treatment of AIDS-related malignancies in a region of the world hardest hit by the AIDS pandemic. METHODS: An initial MEDLINE database search for international collaborative partnerships dedicated to AIDS malignancies in developing countries failed to identify any leads. This search prompted us to report progress on our collaboration in this aspect of the epidemic. Building on the formal Uganda-Case Western Reserve University (Case) Research Collaboration dating back to 1987, established NIH-supported centers of research excellence at Case, and expanding activities in Kenya, scientific and training initiatives, research capital amongst our institutions are emerging to sustain a international research enterprise focused on AIDS and other viral-related malignancies. RESULTS: A platform of clinical research trials with pragmatic design has been developed to further enhance clinical care and sustain training initiatives with partners in East Africa and the United States. An oral chemotherapy feasibility trial in AIDS lymphoma is near completion; a second lymphoma trial of byrostatin and vincristine is anticipated and a feasibility trial of indinavir for endemic Kaposi's sarcoma is planned. CONCLUSIONS: In the absence of published reports of evolving international partnerships dedicated to AIDS malignancy in resource constrained settings, we feel it important for such progress on similar or related international collaborative pursuits to be published. The success of this effort is realized by the long-term international commitment of the collaborating investigators and institutions to sustain this effort in keeping with ethical and NIH standards for the conduct of research; the provision of formal training of investigators and research personnel on clinical problems our East African partners are faced with in practice and the development of pragmatic clinical trials and therapeutic intervention to facilitate technology transfer and enhance clinical practice.

Organizational merger and cultural change for better outcomes: the first five years of the New York State Office of Children and Family Services.

Since its creation, New York State Office of Children and Family Services (OCFS) has used child and family development research to bridge the chasm between child welfare and juvenile justice policy and practice. OCFS's major challenges have been to help the staff and stakeholders of the merged child welfare and juvenile justice agencies develop a common culture and design new financial and programmatic infrastructures to promote better outcomes for children and families.